Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global an...Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.展开更多
Cold atmospheric plasma shows a satisfactory ability to inactivate bacterial biofilms that are difficult to remove using conventional methods in some cases. However, the researches on the inactivation mechanism are no...Cold atmospheric plasma shows a satisfactory ability to inactivate bacterial biofilms that are difficult to remove using conventional methods in some cases. However, the researches on the inactivation mechanism are not quite sufficient. Poly-β-1–6-N-acetylglucosamine(PNAG),which is one of the important components in some biofilms, was used as the research subject,and the related mechanism of action triggered by different concentrations of the OH in plasma was studied using reactive molecular dynamics simulations. The results showed that OH radicals could not only trigger the hydrogen abstraction reaction leading to cleavage of the PNAG molecular structure, but undergo an OH addition reaction with PNAG molecules. New reaction pathways appeared in the simulations as the OH concentration increased, but the reaction efficiency first increased and then decreased. The simulation study in this paper could, to some extent, help elucidate the microscopic mechanism of the interaction between OH radicals in plasma and bacterial biofilms at the atomic level.展开更多
Background:Largely due to incidental detection,asymptomatic pancreatic cystic le-sions(PCLs)have become prevalent in recent years.Among them,intraductal papillary mucinous neoplasm(IPMN)infrequently advances to pancre...Background:Largely due to incidental detection,asymptomatic pancreatic cystic le-sions(PCLs)have become prevalent in recent years.Among them,intraductal papillary mucinous neoplasm(IPMN)infrequently advances to pancreatic ductal adenocarcinoma(PDAC).Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients.Because RNF43 loss-of-function mutations and KRAS gain-of-function mutations concur in a subset of IPMN and PDAC,their biological significance and therapeutic potential should be elucidated.Methods:Pancreatic Rnf43 knockout and Kras activated mice(Rnf43^(−/−);Kras^(G12D))were generated to evaluate their clinical significance in pancreatic pre-neoplastic initiation and malignant transformation.Results:Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice.The Wnt/β-catenin signaling pathway was activated in pan-creatic Kras^(G12D)and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly.Conclusions:Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation.This genetically reconstituted autochthonous pancreatic Rnf43^(−/−);Kras^(G12D)preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β-catenin signaling.Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs,patients with these genetic anomalies warrant surveillance,surgery,and/or targeted therapeutics such as Wnt/β-catenin inhibitors.展开更多
Reintroduction is an important strategy to restore or re-establish wild populations of endangered species.Pre-release training is a necessary step to ensure postreintroduction survival.However,studies reported contrad...Reintroduction is an important strategy to restore or re-establish wild populations of endangered species.Pre-release training is a necessary step to ensure postreintroduction survival.However,studies reported contradicting outcomes after pre-release training of juveniles and adults.This study used farmed and feral American mink(Neovison vison)to analyze the influence of captive breeding on the morphology,structure and efficiency of the two major hindlimb levers,the femur and tibia pivoted by hip and knee joints that are essential for locomotion.Results showed that captive breeding did not alter the sexual dimorphism of the two levers that are related to survival in the wild.Captive-bred mink showed slightly altered morphology of the femur and fundamental structure of the hindlimb levers that improved efficiency,but this resulted in reduction of performance related to foraging in both terrestrial and aquatic environments,especially for females.These findings suggest that reintroduction of mustelid as exampled by the mink here should focus on juveniles because the skeletal alterations associated with captive rearing were recorded only among adults and are irreversible in adulthood.In contrast,captive-reared juveniles showed no skeletal alterations and would be expected to recovery from any atrophy of the muscular system caused by captive rearing for shorter durations.Our results support the application of pre-release training of juveniles in enriched environments as a method for alleviating structural alteration of appendages and enhancing locomotion to increase survival probability in complex habitats.展开更多
The pattern of thematic progression,reflecting the semantic relationships between contextual two sentences,is an important subject in discourse analysis.We introduce a new corpus of Chinese news discourses annotated w...The pattern of thematic progression,reflecting the semantic relationships between contextual two sentences,is an important subject in discourse analysis.We introduce a new corpus of Chinese news discourses annotated with thematic progression information and explore some computational methods to automatically extracting the discourse structural features of simplified thematic progression pattern(STPP)between contextual sentences in a text.Furthermore,these features are used in a hybrid approach to a major discourse analysis task,Chinese coreference resolution.This novel approach is built up via heuristic sieves and a machine learning method that comprehensively utilizes both the top-down STPP features and the bottom-up semantic features.Experimental results on the intersection of the CoNLL-2012 task shared dataset and the CDTC corpus demonstrate the effectiveness of our proposed approach.展开更多
本科生的科研经历可以有效地吸引和帮助他们今后在专业上的发展。在本科教学中引入适当的科研题目,可以更好地激发学生的学习兴趣,从而为他们今后的职业发展做足准备。由于资源等客观条件的限制,美国高校本科生可以参与融入高端科研课...本科生的科研经历可以有效地吸引和帮助他们今后在专业上的发展。在本科教学中引入适当的科研题目,可以更好地激发学生的学习兴趣,从而为他们今后的职业发展做足准备。由于资源等客观条件的限制,美国高校本科生可以参与融入高端科研课题的机会有限。普渡大学Calumet分校(Purdue University Calumet)在2015年获得美国国家科学基金(NSF)支持,创立了本科生科研教学基地。基地在2015-2017年中每个夏季学期,向全美高校本科生提供为期9周的全日制培训。一支高校教师队伍将和学员一起对当前热门科研议题——可持续发展无线网络科技进行研究。2015届夏季培训已经成功举办,教学评估显示不同专业程度及背景的学生都能够从这个培训中受益,取得更丰富的专业知识和难能可贵的科研经历。展开更多
Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regenera...Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface,graft necrosis and sclerosis.However,poor gap integration is a serious concern,which eventually leads to deterioration of joint function.To deal with such complications,this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl(GelMA)hydrogel(BSN-GelMA).A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty,as early as six weeks.Moreover,the International Cartilage Repair Society score,histology score,glycosaminoglycan content,subchondral bone volume,and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group.This improved outcome was due to bio-interactive materials,which acted as tissue fillers to bridge the gap,prevent cartilage degeneration,and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel.This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty.It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.展开更多
3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while th...3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury(SCI)has been relatively overlooked.Herein,living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy.The living nerve-like fibers are comprised of neural stem cells(NSCs)embedded within a designed hydrogel that mimics the extracellular matrix(ECM),assembled into a highly spatial ordered architecture,similar to densely arranged bundles of the nerve fibers.The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model.Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation,angiogenesis,neurogenesis,neural relay formations,and neural circuit remodeling,leading to outstanding functional reconstruction,revealing an evolution process of this living construct after implantation.This effective strategy,based on biomimetic living constructs,opens a new perspective on SCI therapies.展开更多
The coexistence of superconductivity and charge inhomogeneity was observed in many cuprate superconductors.The relationship between those two is still controversial.Similarly,in the graphene sheets of the intercalated...The coexistence of superconductivity and charge inhomogeneity was observed in many cuprate superconductors.The relationship between those two is still controversial.Similarly,in the graphene sheets of the intercalated graphitic superconductor CaC_(6),the charge inhomogeneity was also observed.We simulate such a system by constructing the Hubbard model on the honeycomb lattice with charge inhomogeneity imposed by force.Utilizing the finite-temperature determinant quantum Monte Carlo algorithm,we examine the relationship between the superconducting pairing and the charge inhomogeneity.An optimal charge inhomogeneity for the d+id-wave pairing is found.While for other artificial charge inhomogeneities,the d+id-wave pairing is monotonically suppressed.The possibleπ-phase shift induced by charge inhomogeneity is also examined.展开更多
Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects(15 mm in rats and 25 mm in humans),which can be improved by a beneficial intraluminal microenvironment.However,indiv...Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects(15 mm in rats and 25 mm in humans),which can be improved by a beneficial intraluminal microenvironment.However,individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves.Herein,an aligned fibrin/functionalized self-assembling peptide(AFG/fSAP)interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly.The hydrogel possesses an aligned structure,high water content,appropriate mechanical properties and suitable biodegradation capabilities for nerve repair,which enhances the alignment and neurotrophin secretion of primary Schwann cells(SCs)in vitro,and successfully bridges a 15-mm sciatic nerve gap in rats in vivo.The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles.The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts.Moreover,the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve.Altogether,the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.展开更多
Nanostructured transition metal oxides are promising alternative anodes for lithium ion batteries.Li-ion storage performance is expected to improve if high packing density energy particles are available.Herein,Mn_2O_3...Nanostructured transition metal oxides are promising alternative anodes for lithium ion batteries.Li-ion storage performance is expected to improve if high packing density energy particles are available.Herein,Mn_2O_3 microspheres with a ca.18 μm diameter and a tapped density of 1.33 g/cm^3 were synthesized by a facile solvothermal-thermal coversion route.Spherical MnCO_3 precursors were obtained through solvothermal treatment and they decomposed and converted into Mn_2O_3 microspheres at an annealing temperature of 700 C.The Mn_2O_3 microspheres consisted of Mn_2O_3 nanoparticles with an average 40 nm diameter.These porous Mn_2O_3 microspheres allow good electrolyte penetration and provide an ion buffer reservoir to ensure a constant electrolyte supply.The Mn_2O_3 microspheres have reversible capacities of590 and 320 mAh/g at 50 and 400 mA/g,respectively.We thus report an efficient route for the fabrication of energy particles for advanced energy storage.展开更多
Kuümmell disease(KD)causes serious vertebral body collapse in patients.However,only a few case reports have been conducted and the number of patients with KD investigated was limited.Additionally,the frequently u...Kuümmell disease(KD)causes serious vertebral body collapse in patients.However,only a few case reports have been conducted and the number of patients with KD investigated was limited.Additionally,the frequently used poly(methyl methacrylate)(PMMA)bone cement for KD is limited by excessive modulus and poor biocompatibility.Herein,we aimed to modify PMMA bone cement with mineralized collagen(MC),and compare the clinical effects,image performance and finite ele-ment analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD.Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed.The surgical procedure,intraoperative blood loss,hospital stay and complications were compared between different groups.Visual analog scale,Oswestry disability index,anterior verte-bral height,posterior vertebral height,computed tomography value,adjacent vertebral re-fracture,Cobb angle and wedge-shaped correction angle were evaluated.Additionally,the representative sample was selected for finite element analysis.We found that the MC-modified PMMA bone ce-ment could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.展开更多
The quality of measurement data is critical to the accuracy of both outdoor and indoor localization methods.Due to the inevitable measurement error,the analytics on the error data is critical to evaluate localization ...The quality of measurement data is critical to the accuracy of both outdoor and indoor localization methods.Due to the inevitable measurement error,the analytics on the error data is critical to evaluate localization methods and to find the effective ones.For indoor localization,Received Signal Strength(RSS)is a convenient and low-cost measurement that has been adopted in many localization approaches.However,using RSS data for localization needs to solve a fundamental problem,that is,how accurate are these methods?The reason of the low accuracy of the current RSS-based localization methods is the oversimplified analysis on RSS measurement data.In this proposed work,we adopt a generalized measurement model to find optimal estimators whose estimated error is equal to the Cram′er-Rao Lower Bound(CRLB).Through mathematical techniques,the key factors that affect the accuracy of RSS-based localization methods are revealed,and the analytics expression that discloses the proportional relationship between the localization accuracy and these factors is derived.The significance of our discovery has two folds:First,we present a general expression for localization error data analytics,which can explain and predict the accuracy of range-based localization algorithms;second,the further study on the general analytics expression and its minimum can be used to optimize current localization algorithms.展开更多
The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained in...The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.展开更多
Hair and feathers are composed of keratin and are indigestible, inalimental and unpalatable for carnivores. However, carnivores often ingest hair and feathers during feeding or when grooming. We hypothesized tha...Hair and feathers are composed of keratin and are indigestible, inalimental and unpalatable for carnivores. However, carnivores often ingest hair and feathers during feeding or when grooming. We hypothesized that ingestion of hair and feathers changes species diversity and relative abundance of bacteria in the gut of carnivores. To test this hypothesis, we added disinfected poultry down feathers to the normal diet of captive Arctic foxes (Alopex lagopus). We then used fluorescently labeled terminal restriction fragments (T-RFs) to examine changes in fecal bacterial diversity and abundance. The results showed that the number of bacterial species increased significantly after feather ingestion, but that total abundance was unchanged. This demonstrated that addition of disinfected feathers to the diet stimulated increased production among less abundant bacteria, resulting in a balancing of relative abundance of different bacterial species, or that some newly-ingested microbial species would colonize the gut because a suitable microhabitat had become available. This implies that the overall production of bacterial metabolites would be made up of a greater range of substances after feather ingestion. On one hand, the host’s immune response would be more diverse, increasing the capacity of the immune system to regulate gut microflora. On the other hand, the animal’s physiological performance would also be affected. For wild animals, such altered physiological traits would be subjected to natural selection, and, hence, persistent geographic differences in the character of ingested feathers or fur would drive speciation.展开更多
A hierarchically aligned fibrin hydrogel(AFG)that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo.However,its potential in pro...A hierarchically aligned fibrin hydrogel(AFG)that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo.However,its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified.Here,the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored.Histologically obvious white matter regeneration consisting of a large area of consecutive,compact and aligned nerve fibers is induced by AFG,leading to a significant motor functional restoration.The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks.Moreover,high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group.Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion,pointing out its promising prospect in clinic practice.展开更多
Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widel...Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widely proven to promote bone regeneration,their weak mechanical properties limit the clinical applications in cranioplasty.Herein,we applied two previously developed mineralized collagen-based bone scaffolds(MC),porous MC(pMC)and compact MC(cMC)to construct a biphasic MC composite bone scaffold(bMC)to repair the large-sized cranial bone defect in developing sheep.A supporting frame composed of cMC phase in the shape of tic–tac–toe structure was fabricated first and then embedded in pMC phase.The two phases had good interfacial bond,attributing to the formation of an interfacial zone.The in vivo performance of the bMC scaffold was evaluated by using a cranial bone defect model in 1-month-old sheep.The computed tomography imaging,X-ray scanning and histological evaluation showed that the pMC phase in the bMC scaffold,similar to the pMC scaffold,was gradually replaced by the regenerative bone tissues with comprehensively increased bone mineral density and complete connection of bone bridge in the whole region.The cMC frame promoted new bone formation beneath the frame without obvious degradation,thus providing appropriate mechanical protection and ensuring the structural integrity of the implant.In general,the sheep with bMC implantation exhibited the best status of survival,growth and the repair effect.The biphasic structural design may be a prospective strategy for developing new generation of cranioplasty materials to regenerate cranial bone defect in clinic.展开更多
基金National Key R&D program of China,Grant/Award Number:2021YFC2500700The National Natural Science Foundation of China+1 种基金Grant/Award Number:81730078The Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-049。
文摘Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.
基金supported by National Natural Science Foundation of China(Grant No.11675095)the Fundamental Research Funds of Shandong University(Grant No.2017JC017)。
文摘Cold atmospheric plasma shows a satisfactory ability to inactivate bacterial biofilms that are difficult to remove using conventional methods in some cases. However, the researches on the inactivation mechanism are not quite sufficient. Poly-β-1–6-N-acetylglucosamine(PNAG),which is one of the important components in some biofilms, was used as the research subject,and the related mechanism of action triggered by different concentrations of the OH in plasma was studied using reactive molecular dynamics simulations. The results showed that OH radicals could not only trigger the hydrogen abstraction reaction leading to cleavage of the PNAG molecular structure, but undergo an OH addition reaction with PNAG molecules. New reaction pathways appeared in the simulations as the OH concentration increased, but the reaction efficiency first increased and then decreased. The simulation study in this paper could, to some extent, help elucidate the microscopic mechanism of the interaction between OH radicals in plasma and bacterial biofilms at the atomic level.
基金The National Natural Science Foundation of China(81872287,81730078)the Chinese Academy of Medical Sciences Initiative for Innovative Medicine(2021-1-I2M-018).
文摘Background:Largely due to incidental detection,asymptomatic pancreatic cystic le-sions(PCLs)have become prevalent in recent years.Among them,intraductal papillary mucinous neoplasm(IPMN)infrequently advances to pancreatic ductal adenocarcinoma(PDAC).Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients.Because RNF43 loss-of-function mutations and KRAS gain-of-function mutations concur in a subset of IPMN and PDAC,their biological significance and therapeutic potential should be elucidated.Methods:Pancreatic Rnf43 knockout and Kras activated mice(Rnf43^(−/−);Kras^(G12D))were generated to evaluate their clinical significance in pancreatic pre-neoplastic initiation and malignant transformation.Results:Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice.The Wnt/β-catenin signaling pathway was activated in pan-creatic Kras^(G12D)and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly.Conclusions:Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation.This genetically reconstituted autochthonous pancreatic Rnf43^(−/−);Kras^(G12D)preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β-catenin signaling.Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs,patients with these genetic anomalies warrant surveillance,surgery,and/or targeted therapeutics such as Wnt/β-catenin inhibitors.
基金funded by China State Forestry and Grassland Administration Project for Rescue and Captive Breeding of Endangered and Rare Wildlife(2018).
文摘Reintroduction is an important strategy to restore or re-establish wild populations of endangered species.Pre-release training is a necessary step to ensure postreintroduction survival.However,studies reported contradicting outcomes after pre-release training of juveniles and adults.This study used farmed and feral American mink(Neovison vison)to analyze the influence of captive breeding on the morphology,structure and efficiency of the two major hindlimb levers,the femur and tibia pivoted by hip and knee joints that are essential for locomotion.Results showed that captive breeding did not alter the sexual dimorphism of the two levers that are related to survival in the wild.Captive-bred mink showed slightly altered morphology of the femur and fundamental structure of the hindlimb levers that improved efficiency,but this resulted in reduction of performance related to foraging in both terrestrial and aquatic environments,especially for females.These findings suggest that reintroduction of mustelid as exampled by the mink here should focus on juveniles because the skeletal alterations associated with captive rearing were recorded only among adults and are irreversible in adulthood.In contrast,captive-reared juveniles showed no skeletal alterations and would be expected to recovery from any atrophy of the muscular system caused by captive rearing for shorter durations.Our results support the application of pre-release training of juveniles in enriched environments as a method for alleviating structural alteration of appendages and enhancing locomotion to increase survival probability in complex habitats.
基金This research has been supported by the National Natural Science Foundation of China under grant 61728205,61673290,61672371,61750110534,61876217Science&Technology Development Project of Suzhou under grant SYG201817.
文摘The pattern of thematic progression,reflecting the semantic relationships between contextual two sentences,is an important subject in discourse analysis.We introduce a new corpus of Chinese news discourses annotated with thematic progression information and explore some computational methods to automatically extracting the discourse structural features of simplified thematic progression pattern(STPP)between contextual sentences in a text.Furthermore,these features are used in a hybrid approach to a major discourse analysis task,Chinese coreference resolution.This novel approach is built up via heuristic sieves and a machine learning method that comprehensively utilizes both the top-down STPP features and the bottom-up semantic features.Experimental results on the intersection of the CoNLL-2012 task shared dataset and the CDTC corpus demonstrate the effectiveness of our proposed approach.
文摘本科生的科研经历可以有效地吸引和帮助他们今后在专业上的发展。在本科教学中引入适当的科研题目,可以更好地激发学生的学习兴趣,从而为他们今后的职业发展做足准备。由于资源等客观条件的限制,美国高校本科生可以参与融入高端科研课题的机会有限。普渡大学Calumet分校(Purdue University Calumet)在2015年获得美国国家科学基金(NSF)支持,创立了本科生科研教学基地。基地在2015-2017年中每个夏季学期,向全美高校本科生提供为期9周的全日制培训。一支高校教师队伍将和学员一起对当前热门科研议题——可持续发展无线网络科技进行研究。2015届夏季培训已经成功举办,教学评估显示不同专业程度及背景的学生都能够从这个培训中受益,取得更丰富的专业知识和难能可贵的科研经历。
基金supported by the National Key Research and Development Program of China(2016YFB0700804)National Natural Science Foundation of China(NO.T2121004,31830029).
文摘Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface,graft necrosis and sclerosis.However,poor gap integration is a serious concern,which eventually leads to deterioration of joint function.To deal with such complications,this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl(GelMA)hydrogel(BSN-GelMA).A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty,as early as six weeks.Moreover,the International Cartilage Repair Society score,histology score,glycosaminoglycan content,subchondral bone volume,and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group.This improved outcome was due to bio-interactive materials,which acted as tissue fillers to bridge the gap,prevent cartilage degeneration,and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel.This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty.It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.
基金The authors thank the financial support from the National Natural Science Foundation of China(Grant No.32271414 and 82201521)the Tsinghua Precision Medicine Foundation(Grant No.2022TS001)the National Key Research and Development Program of China(Grant No.2020YFC1107600).
文摘3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner.To date,various emergences of living constructs have been bioprinted for in vitro applications,while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury(SCI)has been relatively overlooked.Herein,living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy.The living nerve-like fibers are comprised of neural stem cells(NSCs)embedded within a designed hydrogel that mimics the extracellular matrix(ECM),assembled into a highly spatial ordered architecture,similar to densely arranged bundles of the nerve fibers.The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model.Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation,angiogenesis,neurogenesis,neural relay formations,and neural circuit remodeling,leading to outstanding functional reconstruction,revealing an evolution process of this living construct after implantation.This effective strategy,based on biomimetic living constructs,opens a new perspective on SCI therapies.
基金sponsored by the Natural Science Foundation of Chongqing,China(Grant No.cstc2021jcyj-msxmX1009)the Joint Guiding Project of Natural Science Foundation of Heilongjiang Province(Grant No.LH2019A011).
文摘The coexistence of superconductivity and charge inhomogeneity was observed in many cuprate superconductors.The relationship between those two is still controversial.Similarly,in the graphene sheets of the intercalated graphitic superconductor CaC_(6),the charge inhomogeneity was also observed.We simulate such a system by constructing the Hubbard model on the honeycomb lattice with charge inhomogeneity imposed by force.Utilizing the finite-temperature determinant quantum Monte Carlo algorithm,we examine the relationship between the superconducting pairing and the charge inhomogeneity.An optimal charge inhomogeneity for the d+id-wave pairing is found.While for other artificial charge inhomogeneities,the d+id-wave pairing is monotonically suppressed.The possibleπ-phase shift induced by charge inhomogeneity is also examined.
基金the financial support from the National Key R&D Program of China(No.2020YFC1107600,2018YFB0704304,and 2018YFB1105504)Shandong Province Key R&D Program of China(No.2019JZZY011106)+3 种基金the National Natural Science Foundation of China(No.31771056 and 31800813)the Key Laboratory of Trauma and Neural Regeneration(Peking University),the Ministry of Education(No.BMU2019XY007-01)the Ministry of Education Innovation Program of China(No.IRT_16R01)Shenzhen Science and Technology Program(No.20190806162205278).
文摘Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects(15 mm in rats and 25 mm in humans),which can be improved by a beneficial intraluminal microenvironment.However,individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves.Herein,an aligned fibrin/functionalized self-assembling peptide(AFG/fSAP)interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly.The hydrogel possesses an aligned structure,high water content,appropriate mechanical properties and suitable biodegradation capabilities for nerve repair,which enhances the alignment and neurotrophin secretion of primary Schwann cells(SCs)in vitro,and successfully bridges a 15-mm sciatic nerve gap in rats in vivo.The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles.The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts.Moreover,the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve.Altogether,the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.
基金supported by the National Natural Science Foundation of China(21422604)the PetroChina Technology R&D Project on New Technology and the Method for Oil & Gas Development(2011A-1006)CNPC Innovation Foundation (2014D-5006-0207)
文摘Nanostructured transition metal oxides are promising alternative anodes for lithium ion batteries.Li-ion storage performance is expected to improve if high packing density energy particles are available.Herein,Mn_2O_3 microspheres with a ca.18 μm diameter and a tapped density of 1.33 g/cm^3 were synthesized by a facile solvothermal-thermal coversion route.Spherical MnCO_3 precursors were obtained through solvothermal treatment and they decomposed and converted into Mn_2O_3 microspheres at an annealing temperature of 700 C.The Mn_2O_3 microspheres consisted of Mn_2O_3 nanoparticles with an average 40 nm diameter.These porous Mn_2O_3 microspheres allow good electrolyte penetration and provide an ion buffer reservoir to ensure a constant electrolyte supply.The Mn_2O_3 microspheres have reversible capacities of590 and 320 mAh/g at 50 and 400 mA/g,respectively.We thus report an efficient route for the fabrication of energy particles for advanced energy storage.
基金This work was supported by National Key R&D Program of China(No.2018YFC1105202)the Key research and development plan in Zhejiang prov-ince(No.2020C03041)+1 种基金National Nature Science Fund of China(No.81871797)Natural Science Fund of Zhejiang Province(LY17H060001).
文摘Kuümmell disease(KD)causes serious vertebral body collapse in patients.However,only a few case reports have been conducted and the number of patients with KD investigated was limited.Additionally,the frequently used poly(methyl methacrylate)(PMMA)bone cement for KD is limited by excessive modulus and poor biocompatibility.Herein,we aimed to modify PMMA bone cement with mineralized collagen(MC),and compare the clinical effects,image performance and finite ele-ment analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD.Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed.The surgical procedure,intraoperative blood loss,hospital stay and complications were compared between different groups.Visual analog scale,Oswestry disability index,anterior verte-bral height,posterior vertebral height,computed tomography value,adjacent vertebral re-fracture,Cobb angle and wedge-shaped correction angle were evaluated.Additionally,the representative sample was selected for finite element analysis.We found that the MC-modified PMMA bone ce-ment could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.
基金partially supported by the National Key Research and Development Program of China(No.2016YFE0121800)
文摘The quality of measurement data is critical to the accuracy of both outdoor and indoor localization methods.Due to the inevitable measurement error,the analytics on the error data is critical to evaluate localization methods and to find the effective ones.For indoor localization,Received Signal Strength(RSS)is a convenient and low-cost measurement that has been adopted in many localization approaches.However,using RSS data for localization needs to solve a fundamental problem,that is,how accurate are these methods?The reason of the low accuracy of the current RSS-based localization methods is the oversimplified analysis on RSS measurement data.In this proposed work,we adopt a generalized measurement model to find optimal estimators whose estimated error is equal to the Cram′er-Rao Lower Bound(CRLB).Through mathematical techniques,the key factors that affect the accuracy of RSS-based localization methods are revealed,and the analytics expression that discloses the proportional relationship between the localization accuracy and these factors is derived.The significance of our discovery has two folds:First,we present a general expression for localization error data analytics,which can explain and predict the accuracy of range-based localization algorithms;second,the further study on the general analytics expression and its minimum can be used to optimize current localization algorithms.
基金support from the National Key R&D Program of China(Nos.2020YFC1107600 and 2018YFB0704304)the National Natural Science Foundation of China(Nos.31771056 and 31771052)Shandong Province Key R&D Program of China(No.2019JZZY011106).
文摘The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.
文摘Hair and feathers are composed of keratin and are indigestible, inalimental and unpalatable for carnivores. However, carnivores often ingest hair and feathers during feeding or when grooming. We hypothesized that ingestion of hair and feathers changes species diversity and relative abundance of bacteria in the gut of carnivores. To test this hypothesis, we added disinfected poultry down feathers to the normal diet of captive Arctic foxes (Alopex lagopus). We then used fluorescently labeled terminal restriction fragments (T-RFs) to examine changes in fecal bacterial diversity and abundance. The results showed that the number of bacterial species increased significantly after feather ingestion, but that total abundance was unchanged. This demonstrated that addition of disinfected feathers to the diet stimulated increased production among less abundant bacteria, resulting in a balancing of relative abundance of different bacterial species, or that some newly-ingested microbial species would colonize the gut because a suitable microhabitat had become available. This implies that the overall production of bacterial metabolites would be made up of a greater range of substances after feather ingestion. On one hand, the host’s immune response would be more diverse, increasing the capacity of the immune system to regulate gut microflora. On the other hand, the animal’s physiological performance would also be affected. For wild animals, such altered physiological traits would be subjected to natural selection, and, hence, persistent geographic differences in the character of ingested feathers or fur would drive speciation.
基金supported by the Chinese National Natural Science Foundation(31771056,31771052)National Key Research and Development Project(2018YFB0704304,2020YFC1107600).
文摘A hierarchically aligned fibrin hydrogel(AFG)that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo.However,its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified.Here,the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored.Histologically obvious white matter regeneration consisting of a large area of consecutive,compact and aligned nerve fibers is induced by AFG,leading to a significant motor functional restoration.The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks.Moreover,high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group.Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion,pointing out its promising prospect in clinic practice.
基金financial support from the National Key R&D Program of China(2020YFC1107602)Shandong Province Key R&D Program of China(2019JZZY011106)the National Natural Science Foundation of China(No.81660214,81960238,82160250).
文摘Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widely proven to promote bone regeneration,their weak mechanical properties limit the clinical applications in cranioplasty.Herein,we applied two previously developed mineralized collagen-based bone scaffolds(MC),porous MC(pMC)and compact MC(cMC)to construct a biphasic MC composite bone scaffold(bMC)to repair the large-sized cranial bone defect in developing sheep.A supporting frame composed of cMC phase in the shape of tic–tac–toe structure was fabricated first and then embedded in pMC phase.The two phases had good interfacial bond,attributing to the formation of an interfacial zone.The in vivo performance of the bMC scaffold was evaluated by using a cranial bone defect model in 1-month-old sheep.The computed tomography imaging,X-ray scanning and histological evaluation showed that the pMC phase in the bMC scaffold,similar to the pMC scaffold,was gradually replaced by the regenerative bone tissues with comprehensively increased bone mineral density and complete connection of bone bridge in the whole region.The cMC frame promoted new bone formation beneath the frame without obvious degradation,thus providing appropriate mechanical protection and ensuring the structural integrity of the implant.In general,the sheep with bMC implantation exhibited the best status of survival,growth and the repair effect.The biphasic structural design may be a prospective strategy for developing new generation of cranioplasty materials to regenerate cranial bone defect in clinic.
