Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To d...Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To date,the utilization of biomaterials to aid in cartilage regeneration,especially through the use of injectable scaffolds,has attracted considerable attention.Various materials,therapeutics and fabrication approaches have emerged with a focus on manipulating the cartilage microenvironment to induce the formation of cartilaginous structures that have similar properties to the native tissues.In particular,the design and fabrication of injectable hydrogel-based scaffolds have advanced in recent years with the aim of enhancing its therapeutic efficacy and improving its ease of administration.This review summarizes recent progress in these efforts,including the structural improvement of scaffolds,network cross-linking techniques and strategies for controlled release,which present new opportunities for the development of injectable scaffolds for cartilage regeneration.展开更多
Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and suppor...Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and support dermal cell growth.Here,ε-PL was incorporated into polycaprolactone(PCL)/gelatin electrospun scaffolds collected at varying rotation speeds.Then,the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity.The morphological study showed that the electrospun wound dressings were smooth,continuous,and bead-free,with a mean diameter ranging from 267±7 to 331±8 nm for all random and aligned nanofibers.The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus.Moreover,nanofiber mats are highly hydro-philic,which is crucial for an efficient wound dressing.The samples also demonstrated high antimicrobial properties against common wound bacterial strains,including methicillin-resistant Staphylococcus aureus(MRSA),Staphylococcus aureus(SA),Escherichia coli(EC),Acinetobacter baumannii(AB),and Pseudomonas aeruginosa(PA).Mammalian cell prolifera-tion and morphology assays involving primary human dermal fibroblasts(hDFs)and immortalized keratinocytes(HaCaT)showed excellent biocompatibility of the electrospun mats and remarkably aligned mats.Furthermore,aligned mats showed more cell migration than randomly oriented mats,which is desirable for more efficient wound healing.Therefore,it can be concluded that aligned PCL/gelatin mats containingε-PL are promising for potential use in wound dressings.展开更多
Recent advances in deep neural networks have shed new light on physics,engineering,and scientific computing.Reconciling the data-centered viewpoint with physical simulation is one of the research hotspots.The physicsi...Recent advances in deep neural networks have shed new light on physics,engineering,and scientific computing.Reconciling the data-centered viewpoint with physical simulation is one of the research hotspots.The physicsinformedneural network(PINN)is currently the most general framework,which is more popular due to theconvenience of constructing NNs and excellent generalization ability.The automatic differentiation(AD)-basedPINN model is suitable for the homogeneous scientific problem;however,it is unclear how AD can enforce fluxcontinuity across boundaries between cells of different properties where spatial heterogeneity is represented bygrid cells with different physical properties.In this work,we propose a criss-cross physics-informed convolutionalneural network(CC-PINN)learning architecture,aiming to learn the solution of parametric PDEs with spatialheterogeneity of physical properties.To achieve the seamless enforcement of flux continuity and integration ofphysicalmeaning into CNN,a predefined 2D convolutional layer is proposed to accurately express transmissibilitybetween adjacent cells.The efficacy of the proposedmethodwas evaluated through predictions of several petroleumreservoir problems with spatial heterogeneity and compared against state-of-the-art(PINN)through numericalanalysis as a benchmark,which demonstrated the superiority of the proposed method over the PINN.展开更多
Herein we computationally explore the modulation of the release kinetics of an encapsulated guest molecule from the cucurbit[7]uril(CB7)cavity by ligands binding to the host portal.We uncovered a correlation between t...Herein we computationally explore the modulation of the release kinetics of an encapsulated guest molecule from the cucurbit[7]uril(CB7)cavity by ligands binding to the host portal.We uncovered a correlation between the ligand-binding affinity with CB7 and the guest residence time,allowing us to rapidly predict the release kinetics through straightforward energy minimization calculations.These high-throughput predictions in turn enable a Monte-Carlo Tree Search(MCTS)to de novo design a series of cap-shaped ligand molecules with large binding affinities and boosting guest residence times by up to 7 orders of magnitude.Notably,halogenated aromatic compounds emerge as top-ranking ligands.Detailed modeling suggests the presence of halogen-bonding between the ligands and the CB7 portal.Meanwhile,the binding of top-ranked ligands is supported by^(1)H NMR and 2D DOSY-NMR.Our findings open up possibilities in gating of molecular transport through a nanoscale cavity with potential applications in nanopore technology and controlled drug release.展开更多
Aims: To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs(NSAIDs) in primary care between 2000 and 2004; to determine these r...Aims: To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs(NSAIDs) in primary care between 2000 and 2004; to determine these risks in patients with and without pre-existing coronary heart disease and in those taking and not taking aspirin. Design: Nested case-control study. Setting: 367 general practices contributing to the UK QRESEARCH database and spread throughout every strategic health authority and health board in England, Wales, and Scotland. Subjects: 9218 cases with a first ever diagnosis of myocardial infarction during the four year study period; 86 349 controls matched for age, calendar year, sex, and practice. Outcome measures: Unadjusted and adjusted odds ratios with 95%confidence intervals for myocardial infarction associated with rofecoxib, celecoxib, naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDs. Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use of statins, aspirin, and antidepressants. Results: A significantly increased risk of myocardial infarction was associated with current use of rofecoxib(adjusted odds ratio 1.32, 95%confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac(1.55, 1.39 to 1.72); and with current use of ibuprofen(1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at< 0.05 rather than< 0.01 for current use but significant at< 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease. Conclusion: These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of 展开更多
基金the Projects of International Cooperation and Exchanges NSFC(81420108021)Key Program of NSFC(81730067),Excellent Young Scholars NSFC(81622033)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation and UCLA’s start-up package to Z.G.
文摘Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To date,the utilization of biomaterials to aid in cartilage regeneration,especially through the use of injectable scaffolds,has attracted considerable attention.Various materials,therapeutics and fabrication approaches have emerged with a focus on manipulating the cartilage microenvironment to induce the formation of cartilaginous structures that have similar properties to the native tissues.In particular,the design and fabrication of injectable hydrogel-based scaffolds have advanced in recent years with the aim of enhancing its therapeutic efficacy and improving its ease of administration.This review summarizes recent progress in these efforts,including the structural improvement of scaffolds,network cross-linking techniques and strategies for controlled release,which present new opportunities for the development of injectable scaffolds for cartilage regeneration.
基金support from the Singapore International Graduate Award(SINGA).R.L.thanks funding support from the Duke-NUS Khoo Bridge Funding Award(Duke-NUS-KBrFA/2021/0044)N.K.V.acknowledges funding support from the Singapore Ministry of Education(MOE)under its MOE Academic Research Fund(AcRF)Tier 1 Grant(RG26/20)the Agency for Science,Technology and Research(A*STAR)under its Wound Care Innovation for the Tropics(WCIT)Industry Alignment Fund Pre-Positioning(IAF-PP)Grant(H17/01/a0/0K9)。
文摘Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and support dermal cell growth.Here,ε-PL was incorporated into polycaprolactone(PCL)/gelatin electrospun scaffolds collected at varying rotation speeds.Then,the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity.The morphological study showed that the electrospun wound dressings were smooth,continuous,and bead-free,with a mean diameter ranging from 267±7 to 331±8 nm for all random and aligned nanofibers.The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus.Moreover,nanofiber mats are highly hydro-philic,which is crucial for an efficient wound dressing.The samples also demonstrated high antimicrobial properties against common wound bacterial strains,including methicillin-resistant Staphylococcus aureus(MRSA),Staphylococcus aureus(SA),Escherichia coli(EC),Acinetobacter baumannii(AB),and Pseudomonas aeruginosa(PA).Mammalian cell prolifera-tion and morphology assays involving primary human dermal fibroblasts(hDFs)and immortalized keratinocytes(HaCaT)showed excellent biocompatibility of the electrospun mats and remarkably aligned mats.Furthermore,aligned mats showed more cell migration than randomly oriented mats,which is desirable for more efficient wound healing.Therefore,it can be concluded that aligned PCL/gelatin mats containingε-PL are promising for potential use in wound dressings.
基金the National Natural Science Foundation of China(No.52274048)Beijing Natural Science Foundation(No.3222037)+1 种基金the CNPC 14th Five-Year Perspective Fundamental Research Project(No.2021DJ2104)the Science Foundation of China University of Petroleum,Beijing(No.2462021YXZZ010).
文摘Recent advances in deep neural networks have shed new light on physics,engineering,and scientific computing.Reconciling the data-centered viewpoint with physical simulation is one of the research hotspots.The physicsinformedneural network(PINN)is currently the most general framework,which is more popular due to theconvenience of constructing NNs and excellent generalization ability.The automatic differentiation(AD)-basedPINN model is suitable for the homogeneous scientific problem;however,it is unclear how AD can enforce fluxcontinuity across boundaries between cells of different properties where spatial heterogeneity is represented bygrid cells with different physical properties.In this work,we propose a criss-cross physics-informed convolutionalneural network(CC-PINN)learning architecture,aiming to learn the solution of parametric PDEs with spatialheterogeneity of physical properties.To achieve the seamless enforcement of flux continuity and integration ofphysicalmeaning into CNN,a predefined 2D convolutional layer is proposed to accurately express transmissibilitybetween adjacent cells.The efficacy of the proposedmethodwas evaluated through predictions of several petroleumreservoir problems with spatial heterogeneity and compared against state-of-the-art(PINN)through numericalanalysis as a benchmark,which demonstrated the superiority of the proposed method over the PINN.
基金H.L.and T.-C.L.are grateful to the studentship funded by the A*STAR-UCL Research Attachment Programme through the EPSRC Centre for Doctoral Training in Molecular Modelling and Materials Science(Grant EP/L015862/1)T.-C.L.is grateful to the Research Project Grant(Grant RPG-2016-393)funded by the Leverhulme Trust+1 种基金We acknowledge the use of the UCL Myriad High Performance Computing Facility(Myriad@UCL),and associated support services,in the completion of this workThis work is partially supported financially by the Agency for Science,Technology and Research(A^(*)STAR)under grant AMDM A1898b0043,and A^(*)STAR SERC CRF Award.
文摘Herein we computationally explore the modulation of the release kinetics of an encapsulated guest molecule from the cucurbit[7]uril(CB7)cavity by ligands binding to the host portal.We uncovered a correlation between the ligand-binding affinity with CB7 and the guest residence time,allowing us to rapidly predict the release kinetics through straightforward energy minimization calculations.These high-throughput predictions in turn enable a Monte-Carlo Tree Search(MCTS)to de novo design a series of cap-shaped ligand molecules with large binding affinities and boosting guest residence times by up to 7 orders of magnitude.Notably,halogenated aromatic compounds emerge as top-ranking ligands.Detailed modeling suggests the presence of halogen-bonding between the ligands and the CB7 portal.Meanwhile,the binding of top-ranked ligands is supported by^(1)H NMR and 2D DOSY-NMR.Our findings open up possibilities in gating of molecular transport through a nanoscale cavity with potential applications in nanopore technology and controlled drug release.
文摘Aims: To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs(NSAIDs) in primary care between 2000 and 2004; to determine these risks in patients with and without pre-existing coronary heart disease and in those taking and not taking aspirin. Design: Nested case-control study. Setting: 367 general practices contributing to the UK QRESEARCH database and spread throughout every strategic health authority and health board in England, Wales, and Scotland. Subjects: 9218 cases with a first ever diagnosis of myocardial infarction during the four year study period; 86 349 controls matched for age, calendar year, sex, and practice. Outcome measures: Unadjusted and adjusted odds ratios with 95%confidence intervals for myocardial infarction associated with rofecoxib, celecoxib, naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDs. Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use of statins, aspirin, and antidepressants. Results: A significantly increased risk of myocardial infarction was associated with current use of rofecoxib(adjusted odds ratio 1.32, 95%confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac(1.55, 1.39 to 1.72); and with current use of ibuprofen(1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at< 0.05 rather than< 0.01 for current use but significant at< 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease. Conclusion: These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of
基金资助（Funding） ： This study received no external funding. The authors did the work either in their personal time or during the course of their normal employment. The corresponding author （JH-C） and CC had access to all the data in the study, and all authors agreed and share responsibility for the decision to submit for publication.
