Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
In this work,a portable floating-electrode dielectric barrier discharge(FE-DBD)device is designed with a rechargeable battery as the power supply.The characteristics of the FE-DBD with a metal electrode and human hand...In this work,a portable floating-electrode dielectric barrier discharge(FE-DBD)device is designed with a rechargeable battery as the power supply.The characteristics of the FE-DBD with a metal electrode and human hand are studied and compared.The human contact safety is verified by calculating the current through the human body based on the equivalent circuit model.Escherichia coli inactivation experiments confirm the efficacy of the FE-DBD device in the envisaged applications.展开更多
Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncod...Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, lnc_217, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of lnc_217 was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of lnc_217 not only decreased de novo lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid β- oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that lnc_217 may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.展开更多
The large size of lasers limits their applications in confined spaces,such as in biosensing and in vivo brain tissue imaging.In this regard,micron-sized lasers have been developed.They exhibit great potential for biol...The large size of lasers limits their applications in confined spaces,such as in biosensing and in vivo brain tissue imaging.In this regard,micron-sized lasers have been developed.They exhibit great potential for biological detecting,remote sensing,and depth tracking due to their small sizes,sensitive properties of their spectral fingerprints,and flexible positional modulation in the microenvironment.Lanthanide-based luminescent materials that possess long excited-state lifetime,narrow emission bandwidth,and upconversion behaviors are promising as gain mediums for novel microlasers.In addition,lanthanide-based microlasers could be generated under natural ambient conditions with pumped or continuous light sources,which significantly promotes the practical applications of microlasers.Recent progress in the design,synthesis,and biomedical applications of lanthanide-based microlasers has been outlined in this review.Lanthanide ions doped and upconverted lanthanide-based microlasers are highlighted,which exhibit advantageous structures,miniaturized dimensions,and high lasing performance.The applications of lanthanide-based microlasers are further discussed,the upconverted microlasers show great advantages for biological applications owing to their tunable excitation and emission characteristics and excellent environmental stability.Moreover,perspectives and challenges in the field of lanthanide-based microlasers are presented.展开更多
The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting ...The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.展开更多
3D printed polyether-ether-ketone(PEEK)implant has become a popular clinical alternative to implants made of titanium alloy for cranial bone substitutes due to its bone-match properties,however its biological inert hi...3D printed polyether-ether-ketone(PEEK)implant has become a popular clinical alternative to implants made of titanium alloy for cranial bone substitutes due to its bone-match properties,however its biological inert hin-dered the progress of clinical applications of such material.To enhance the tissue integration capability of PEEK implants and promote their long-term stability,cranial implants of gradient porous structures were designed and manufactured via fused filament fabrication(FFF)3D printing technology in both PEEK and PEEK/HA com-posites materials,then functionally evaluation of the implants on the tissue in-growth and the osteointegration mechanisms was conducted via animal tests.The 3D printed PEEK scaffold was found to have 2-5 folds of the compressive strength to those of the natural cranial bone.The in vivo studies verified that the porous PEEK/HA scaffold could effectively induce the bone ingrowth to form a stable biointegration boundary surrounding the host bone tissue after 4 weeks of implantation.Moreover,the PEEK/HA scaffold showed no significant advantages in improving the soft tissue in-growth,only making its distribution more evenly.It is also interestingly to find out that the vertically connective pores throughout the implant did not enhance the tissue binding force even though it did promote the nutrient transportation.In conclusion,the use of PEEK/HA composite material and a well-designed porous structure was proved to be an effective approach to improve the biointegration between the implant and host tissues.展开更多
Graphene has attracted great interest in optoelectronics, owing to its high carrier mobility and broadband absorption. However, a graphene photodetector exhibits low photoresponsivity because of its weak light absorpt...Graphene has attracted great interest in optoelectronics, owing to its high carrier mobility and broadband absorption. However, a graphene photodetector exhibits low photoresponsivity because of its weak light absorption. In this work, we designed a graphene/MoSe_2 heterostructure photodetector, which exhibits photoresponse ranging from visible to near infrared and an ultrahigh photoresponsivity up to 1.3 × 104 A·W^(-1) at 550 nm. The electron–hole pairs are excited in a few-layered MoSe2 and separated by the built-in electric field. A large number of electrons shift to graphene, while the holes remain in the MoSe_2, which creates a photogating effect.展开更多
In the present study,we aimed to investigate the hepatoprotective effect of Chinese herbal medicine Polygonatum sibiricum(PS).In this study,a rat acute liver injury(ALI)model was established by a single intraperitonea...In the present study,we aimed to investigate the hepatoprotective effect of Chinese herbal medicine Polygonatum sibiricum(PS).In this study,a rat acute liver injury(ALI)model was established by a single intraperitoneal injection of 50%CCl_(4) oil solution,and the rats were treated intragastrically with Polygonatum sibiricum aqueous extract(PSAE).The results showed that PSAE significantly decreased the serum levels of ALT,AST and ALP,increased the activities of glutathione(GSH)and superoxide dismutase(SOD),decreased malondialdehyde(MDA)activity in hepatic tissue,and decreased the reactive oxygen species(ROS)level in hepatocytes.The expressions of Nrf2,NQO-1,HO-1,Bcl-2,Bcl-x L mRNA,and HO-1 proteins were elevated,and the expression of p53 mRNA was decreased.In conclusion,PSAE exerted a powerful protective action against CCl_(4)-induced ALI in rats via effectively regulating the expressions of Nrf2-Keap1-ARE related genes and proteins,and inhibiting hepatocyte apoptosis.These outcomes provided evidence that PS had apparent hepatoprotective effect.展开更多
Brain diseases, including tumors and neurodegenerative disorders, are among the most serious health problems. Non-invasively high-resolution imaging methods are required to gain anatomical structures and information o...Brain diseases, including tumors and neurodegenerative disorders, are among the most serious health problems. Non-invasively high-resolution imaging methods are required to gain anatomical structures and information of the brain. In addition, efficient diagnosis technology is also needed to treat brain disease. Rare-earth based materials possess unique optical properties, superior magnetism, and high X-ray absorption abilities, enabling high-resolution imaging of the brain through magnetic resonance imaging, computed tomography imaging, and fluorescence imaging technologies. In addition, rare-earth based materials can be used to detect, treat, and regulate of brain diseases through fine modulation of their structures and functions. Importantly, rare-earth based materials coupled with biomolecules such as antibodies, peptides, and drugs can overcome the blood-brain barrier and be used for targeted treatment. Herein, this review highlights the rational design and application of rare-earth based materials in brain imaging, therapy, monitoring, and neuromodulation. Furthermore, the development prospect of rare-earth based materials is briefly introduced.展开更多
Polypeptides consisting of amino acid(AA)sequences are suitable for high-density information storage.However,the lack of suitable encoding systems,which accommodate the characteristics of polypeptide synthesis,storage...Polypeptides consisting of amino acid(AA)sequences are suitable for high-density information storage.However,the lack of suitable encoding systems,which accommodate the characteristics of polypeptide synthesis,storage and sequencing,impedes the application of polypeptides for large-scale digital data storage.To address this,two reliable and highly efficient encoding systems,i.e.RaptorQ-Arithmetic-Base64-Shuffle-RS(RABSR)and RaptorQArithmetic-Huffman-Rotary-Shuffle-RS(RAHRSR)systems,are developed for polypeptide data storage.The two encoding systems realized the advantages of compressing data,correcting errors of AA chain loss,correcting errors within AA chains,eliminating homopolymers,and pseudo-randomized encrypting.The coding efficiency without arithmetic compression and error correction of audios,pictures and texts by the RABSR system was 3.20,3.12 and 3.53 Bits/AA,respectively.While that using the RAHRSR system reached 4.89,4.80 and 6.84 Bits/AA,respectively.When implemented with redundancy for error correction and arithmetic compression to reduce redundancy,the coding efficiency of audios,pictures and texts by the RABSR system was 4.43,4.36 and 5.22 Bits/AA,respectively.This efficiency further increased to 7.24,7.11 and 9.82 Bits/AA by the RAHRSR system,respectively.Therefore,the developed hexadecimal polypeptide-based systems may provide a new scenario for highly reliable and highly efficient data storage.展开更多
A disintegrin and metalloproteinase(ADAM)12 was previously found to be expressed in T cells in the inflamed brain.However,the function of ADAM12 in T-cell responses in general and in tissue inflammation has not been e...A disintegrin and metalloproteinase(ADAM)12 was previously found to be expressed in T cells in the inflamed brain.However,the function of ADAM12 in T-cell responses in general and in tissue inflammation has not been examined.Here,we studied the role of ADAM12 in T-cell responses,fate determination on activation,and its functions in T cells to mediate tissue inflammation.We identified ADAM12 as a costimulatory molecule that is expressed on naive T cells and downregulated on stimulation.ADAM12 mimics CD28 costimulatory signaling to activate and induce the proliferation of T-helper 1(Th1)cells.Monoclonal ADAM12 Fab antibodies trigger T-cell activation by amplifying TCR signaling to stimulate T-bet-mediated IFNγproduction.Lack of genomic ADAM12 and its knockdown in T cells diminished T-bet and IFNγproduction in Th1 cells,whereas other T cells,including Th17 cells,were unaffected.ADAM12 had similar functions in vivo on myelin antigen(MOG_(35-55))-induced T-cell activation.We found that genetic loss of ADAM12 profoundly alleviated Th1-mediated neuroinflammation and thus disease severity in experimental autoimmune encephalomyelitis,a model of multiple sclerosis.Transcriptomic profiling of MOG_(35-55)-specific ADAM12^(−/−)T cells revealed differentially expressed genes that are important for T-cell activation,proliferation,and costimulatory signaling and Th1 pathogenicity,consistent with their inability to cause T-cell-mediated skin inflammation in a model of adoptive delayed-type hypersensitivity.We conclude that ADAM12 is a T-cell costimulatory molecule that contributes to the pathogenesis of tissue inflammation and a potential target for the treatment of Th1-mediated diseases.展开更多
Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes.Although neuronal morphology and local distribution of neurons/blood vessels in th...Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes.Although neuronal morphology and local distribution of neurons/blood vessels in the brain have been known,the subcellular structures of cells remain challenging,especially in the live brain.In addition,the complicated brain functions involve numerous functional molecules,but the concentrations,distributions and interactions of these molecules in the brain are still poorly understood.In this review,frontier techniques available for multiscale structure imaging from organelles to the whole brain are first overviewed,including magnetic resonance imaging(MRI),computed tomography(CT),positron emission tomography(PET),serial-section electron microscopy(ss EM),light microscopy(LM)and synchrotron-based X-ray microscopy(XRM).Specially,XRM for three-dimensional(3D)imaging of large-scale brain tissue with high resolution and fast imaging speed is highlighted.Additionally,the development of elegant methods for acquisition of brain functions from electrical/chemical signals in the brain is outlined.In particular,the new electrophysiology technologies for neural recordings at the single-neuron level and in the brain are also summarized.We also focus on the construction of electrochemical probes based on dual-recognition strategy and surface/interface chemistry for determination of chemical species in the brain with high selectivity and long-term stability,as well as electrochemophysiological microarray for simultaneously recording of electrochemical and electrophysiological signals in the brain.Moreover,the recent development of brain MRI probes with high contrast-to-noise ratio(CNR)and sensitivity based on hyperpolarized techniques and multi-nuclear chemistry is introduced.Furthermore,multiple optical probes and instruments,especially the optophysiological Raman probes and fiber Raman photometry,for imaging and biosensing in live brain are emphasized.Finally,a brief perspective on existing challenges and further research development is provided.展开更多
Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recogn...Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.展开更多
Poly(butylene succinate-co-furandicarboxylate)(PBSF)and poly(butylene adipateco-furandicarboxylate)(PBAF)are novel furandicarboxylic acid-based biodegradable copolyesters with great potential to replace fossil-derived...Poly(butylene succinate-co-furandicarboxylate)(PBSF)and poly(butylene adipateco-furandicarboxylate)(PBAF)are novel furandicarboxylic acid-based biodegradable copolyesters with great potential to replace fossil-derived terephthalic acid-based copolyesters such as poly(butylene succinate-co-terephthalate)(PBST)and poly(butylene adipate-co-terephthalate)(PBAT).In this study,quantum chemistry techniques after molecular dynamics simulations are employed to investigate the degradationmechanism of PBSF and PBAF catalyzed by Candida antarctica lipase B(CALB).Computational analysis indicates that the catalytic reaction follows a four-step mechanism resembling the ping-pong bibi mechanism,with the initial two steps being acylation reactions and the subsequent two being hydrolysis reactions.Notably,the first step of the hydrolysis is identified as the rate-determining step.Moreover,by introducing single-point mutations to expand the substrate entrance tunnel,the catalytic distance of the first acylation step decreases.Additionally,energy barrier of the rate-determining step is decreased in the PBSF system by site-directed mutations on key residues increasing hydrophobicity of the enzyme’s active site.This study unprecedently show the substrate binding pocket and hydrophobicity of the enzyme’s active site have the potential to be engineered to enhance the degradation of copolyesters catalyzed by CALB.展开更多
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
基金supported by National Natural Science Foundation of China(Nos.51907088,51677019)。
文摘In this work,a portable floating-electrode dielectric barrier discharge(FE-DBD)device is designed with a rechargeable battery as the power supply.The characteristics of the FE-DBD with a metal electrode and human hand are studied and compared.The human contact safety is verified by calculating the current through the human body based on the equivalent circuit model.Escherichia coli inactivation experiments confirm the efficacy of the FE-DBD device in the envisaged applications.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.32130050,32201064,and 82170838)the Natural Science Research Project of Universities in Jiangsu Province(Grant No.21KJB180003).
文摘Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, lnc_217, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of lnc_217 was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of lnc_217 not only decreased de novo lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid β- oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that lnc_217 may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.
基金supported by the National Natural Science Foundation of China(Nos.22020102003,22207104,and 22125701)the National Key R&D Program of China(Nos.2022YFF071000 and 2021YFF0701800)+2 种基金Natural Science Foundation of Jilin Province(No.20230101102JC)China Postdoctoral Science Foundation(Nos.2020M681055 and 2022T150634)Young Elite Scientists Sponsorship Program by CAST(Nos.2021-2023QNRC and YESS20210067).
文摘The large size of lasers limits their applications in confined spaces,such as in biosensing and in vivo brain tissue imaging.In this regard,micron-sized lasers have been developed.They exhibit great potential for biological detecting,remote sensing,and depth tracking due to their small sizes,sensitive properties of their spectral fingerprints,and flexible positional modulation in the microenvironment.Lanthanide-based luminescent materials that possess long excited-state lifetime,narrow emission bandwidth,and upconversion behaviors are promising as gain mediums for novel microlasers.In addition,lanthanide-based microlasers could be generated under natural ambient conditions with pumped or continuous light sources,which significantly promotes the practical applications of microlasers.Recent progress in the design,synthesis,and biomedical applications of lanthanide-based microlasers has been outlined in this review.Lanthanide ions doped and upconverted lanthanide-based microlasers are highlighted,which exhibit advantageous structures,miniaturized dimensions,and high lasing performance.The applications of lanthanide-based microlasers are further discussed,the upconverted microlasers show great advantages for biological applications owing to their tunable excitation and emission characteristics and excellent environmental stability.Moreover,perspectives and challenges in the field of lanthanide-based microlasers are presented.
基金the Natural Science Foundation of Guangdong Province,China(No.2022A1515012552)Shenzhen Science and Technology Innovation Committee of China(SZSTI+3 种基金No.JCYJ20220818102611025)Research Initiation Project of Shunde Hospital,Southern Medical University(No.CRSP2022002)Research Initiation Project of the First Affiliated Hospital of Gannan Medical University(No.QD202316)Beijing Sisco Clinical Oncology Research Foundation of China(No.Y-2022METAZMS-0118).
文摘The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.
基金supported by National Natural Science Foundation of China(Grant.Nos.51835010,12202347)Natural Science Basic Research Program of Shaanxi Province of China(Grant.No.2022JQ-378)+1 种基金Fundamental Research Funds for the Central Universities and the Program for Innovation Team of Shaanxi Province of China(Grant.No.2023-CX-TD-17)Natural Science Foundation of Guangdong Province of China(Grant.No.2022A1515012552).
文摘3D printed polyether-ether-ketone(PEEK)implant has become a popular clinical alternative to implants made of titanium alloy for cranial bone substitutes due to its bone-match properties,however its biological inert hin-dered the progress of clinical applications of such material.To enhance the tissue integration capability of PEEK implants and promote their long-term stability,cranial implants of gradient porous structures were designed and manufactured via fused filament fabrication(FFF)3D printing technology in both PEEK and PEEK/HA com-posites materials,then functionally evaluation of the implants on the tissue in-growth and the osteointegration mechanisms was conducted via animal tests.The 3D printed PEEK scaffold was found to have 2-5 folds of the compressive strength to those of the natural cranial bone.The in vivo studies verified that the porous PEEK/HA scaffold could effectively induce the bone ingrowth to form a stable biointegration boundary surrounding the host bone tissue after 4 weeks of implantation.Moreover,the PEEK/HA scaffold showed no significant advantages in improving the soft tissue in-growth,only making its distribution more evenly.It is also interestingly to find out that the vertically connective pores throughout the implant did not enhance the tissue binding force even though it did promote the nutrient transportation.In conclusion,the use of PEEK/HA composite material and a well-designed porous structure was proved to be an effective approach to improve the biointegration between the implant and host tissues.
基金financially supported by the National Natural Science Foundation of China(No.61575010)the Natural Science Foundation of Beijing(No.4162016)+1 种基金the Beijing Municipal Science and Technology Commission(No.Z151100003315018)the Beijing Nova Program(No.Z141109001814053)
文摘Graphene has attracted great interest in optoelectronics, owing to its high carrier mobility and broadband absorption. However, a graphene photodetector exhibits low photoresponsivity because of its weak light absorption. In this work, we designed a graphene/MoSe_2 heterostructure photodetector, which exhibits photoresponse ranging from visible to near infrared and an ultrahigh photoresponsivity up to 1.3 × 104 A·W^(-1) at 550 nm. The electron–hole pairs are excited in a few-layered MoSe2 and separated by the built-in electric field. A large number of electrons shift to graphene, while the holes remain in the MoSe_2, which creates a photogating effect.
基金Natural Science Foundation of the Anhui Higher Education Institutions of China(Grant No.KJ2019A0166)the National Natural Science Foundation of China(Grant No.31772786)。
文摘In the present study,we aimed to investigate the hepatoprotective effect of Chinese herbal medicine Polygonatum sibiricum(PS).In this study,a rat acute liver injury(ALI)model was established by a single intraperitoneal injection of 50%CCl_(4) oil solution,and the rats were treated intragastrically with Polygonatum sibiricum aqueous extract(PSAE).The results showed that PSAE significantly decreased the serum levels of ALT,AST and ALP,increased the activities of glutathione(GSH)and superoxide dismutase(SOD),decreased malondialdehyde(MDA)activity in hepatic tissue,and decreased the reactive oxygen species(ROS)level in hepatocytes.The expressions of Nrf2,NQO-1,HO-1,Bcl-2,Bcl-x L mRNA,and HO-1 proteins were elevated,and the expression of p53 mRNA was decreased.In conclusion,PSAE exerted a powerful protective action against CCl_(4)-induced ALI in rats via effectively regulating the expressions of Nrf2-Keap1-ARE related genes and proteins,and inhibiting hepatocyte apoptosis.These outcomes provided evidence that PS had apparent hepatoprotective effect.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29040201)the National Natural Science Foundation of China(NSFC)(81901680)。
基金the National Key R&D Program of China(2020YFA0908900,2021YFB3502300,and 2020YFA0712102)National Natural Science Foundation of China(Grant No.21834007,22020102003,22107097,21907088,and 22125701)+1 种基金Youth Innovation Promotion Association of CAS(Grant No.2020228,2021226)China Postdoctoral Science Foundation(2020M681055).
文摘Brain diseases, including tumors and neurodegenerative disorders, are among the most serious health problems. Non-invasively high-resolution imaging methods are required to gain anatomical structures and information of the brain. In addition, efficient diagnosis technology is also needed to treat brain disease. Rare-earth based materials possess unique optical properties, superior magnetism, and high X-ray absorption abilities, enabling high-resolution imaging of the brain through magnetic resonance imaging, computed tomography imaging, and fluorescence imaging technologies. In addition, rare-earth based materials can be used to detect, treat, and regulate of brain diseases through fine modulation of their structures and functions. Importantly, rare-earth based materials coupled with biomolecules such as antibodies, peptides, and drugs can overcome the blood-brain barrier and be used for targeted treatment. Herein, this review highlights the rational design and application of rare-earth based materials in brain imaging, therapy, monitoring, and neuromodulation. Furthermore, the development prospect of rare-earth based materials is briefly introduced.
基金supported by the National Key Research and Development Program of China (2018YFA0902600,2021YFF1200300,and 2020YFA0712102)the National Natural Science Foundation of China (21877104,21834007,22107097,21878258,22020102003,and 22125701)+2 种基金K.C.Wong Education Foundation (GJTD-2018-09)the Youth Innovation Promotion Association of CAS (2021226)the Zhejiang Provincial Natural Science Foundation of China (Y20B060027).
文摘Polypeptides consisting of amino acid(AA)sequences are suitable for high-density information storage.However,the lack of suitable encoding systems,which accommodate the characteristics of polypeptide synthesis,storage and sequencing,impedes the application of polypeptides for large-scale digital data storage.To address this,two reliable and highly efficient encoding systems,i.e.RaptorQ-Arithmetic-Base64-Shuffle-RS(RABSR)and RaptorQArithmetic-Huffman-Rotary-Shuffle-RS(RAHRSR)systems,are developed for polypeptide data storage.The two encoding systems realized the advantages of compressing data,correcting errors of AA chain loss,correcting errors within AA chains,eliminating homopolymers,and pseudo-randomized encrypting.The coding efficiency without arithmetic compression and error correction of audios,pictures and texts by the RABSR system was 3.20,3.12 and 3.53 Bits/AA,respectively.While that using the RAHRSR system reached 4.89,4.80 and 6.84 Bits/AA,respectively.When implemented with redundancy for error correction and arithmetic compression to reduce redundancy,the coding efficiency of audios,pictures and texts by the RABSR system was 4.43,4.36 and 5.22 Bits/AA,respectively.This efficiency further increased to 7.24,7.11 and 9.82 Bits/AA by the RAHRSR system,respectively.Therefore,the developed hexadecimal polypeptide-based systems may provide a new scenario for highly reliable and highly efficient data storage.
基金This study was supported by funding from the Danish Council For Independent Research(DFF)-Medical Science(DFF-4183–00427B),Danish Multiple Sclerosis Society,and Lundbeck Foundation to S.Issazadeh-Navikas and the MS International Federation-McDonald Fellowship to M.H.
文摘A disintegrin and metalloproteinase(ADAM)12 was previously found to be expressed in T cells in the inflamed brain.However,the function of ADAM12 in T-cell responses in general and in tissue inflammation has not been examined.Here,we studied the role of ADAM12 in T-cell responses,fate determination on activation,and its functions in T cells to mediate tissue inflammation.We identified ADAM12 as a costimulatory molecule that is expressed on naive T cells and downregulated on stimulation.ADAM12 mimics CD28 costimulatory signaling to activate and induce the proliferation of T-helper 1(Th1)cells.Monoclonal ADAM12 Fab antibodies trigger T-cell activation by amplifying TCR signaling to stimulate T-bet-mediated IFNγproduction.Lack of genomic ADAM12 and its knockdown in T cells diminished T-bet and IFNγproduction in Th1 cells,whereas other T cells,including Th17 cells,were unaffected.ADAM12 had similar functions in vivo on myelin antigen(MOG_(35-55))-induced T-cell activation.We found that genetic loss of ADAM12 profoundly alleviated Th1-mediated neuroinflammation and thus disease severity in experimental autoimmune encephalomyelitis,a model of multiple sclerosis.Transcriptomic profiling of MOG_(35-55)-specific ADAM12^(−/−)T cells revealed differentially expressed genes that are important for T-cell activation,proliferation,and costimulatory signaling and Th1 pathogenicity,consistent with their inability to cause T-cell-mediated skin inflammation in a model of adoptive delayed-type hypersensitivity.We conclude that ADAM12 is a T-cell costimulatory molecule that contributes to the pathogenesis of tissue inflammation and a potential target for the treatment of Th1-mediated diseases.
基金supported by the National Natural Science Foundation of China(22004037 for Liu Z22022410 and 82050005 for Zhu Y+9 种基金22022402 and 21974051 for Zhang L21635003 and21811540027 for Tian Y22125701 and 21834007 for Liu K22020102003for Zhang H91859206 and 21921004 for Zhou X)the Innovation Program of Shanghai Municipal Education Commission(201701070005E00020 for Tian Y)the Research Funds of Happiness Flower ECNU(2020JK2103 for Tian Y)the Shanghai Municipal Science and Technology Commission(19JC1410300 for Fan C)the Youth Innovation Promotion Association of CAS(2016236 for Zhu Y)the National Key Research and Development Project of China(2018YFA0704000 for Zhou X)。
文摘Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes.Although neuronal morphology and local distribution of neurons/blood vessels in the brain have been known,the subcellular structures of cells remain challenging,especially in the live brain.In addition,the complicated brain functions involve numerous functional molecules,but the concentrations,distributions and interactions of these molecules in the brain are still poorly understood.In this review,frontier techniques available for multiscale structure imaging from organelles to the whole brain are first overviewed,including magnetic resonance imaging(MRI),computed tomography(CT),positron emission tomography(PET),serial-section electron microscopy(ss EM),light microscopy(LM)and synchrotron-based X-ray microscopy(XRM).Specially,XRM for three-dimensional(3D)imaging of large-scale brain tissue with high resolution and fast imaging speed is highlighted.Additionally,the development of elegant methods for acquisition of brain functions from electrical/chemical signals in the brain is outlined.In particular,the new electrophysiology technologies for neural recordings at the single-neuron level and in the brain are also summarized.We also focus on the construction of electrochemical probes based on dual-recognition strategy and surface/interface chemistry for determination of chemical species in the brain with high selectivity and long-term stability,as well as electrochemophysiological microarray for simultaneously recording of electrochemical and electrophysiological signals in the brain.Moreover,the recent development of brain MRI probes with high contrast-to-noise ratio(CNR)and sensitivity based on hyperpolarized techniques and multi-nuclear chemistry is introduced.Furthermore,multiple optical probes and instruments,especially the optophysiological Raman probes and fiber Raman photometry,for imaging and biosensing in live brain are emphasized.Finally,a brief perspective on existing challenges and further research development is provided.
基金supported by the National Natural Science Foundation of China(No.82103140,81773290)China Postdoctoral Science Foundation(No.2020M682803)President Foundation of Nanfang Hospital,Southern Medical University,Guangdong,China(No.2020C009).
文摘Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.
基金supported by the Joint Funds of the National Natural Science Foundation of China(No.U21A20320)the National Natural Science Foundation of China(No.22106102)was also sponsored by the special fund of State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants(No.SEPKLEHIAEC-202203).
文摘Poly(butylene succinate-co-furandicarboxylate)(PBSF)and poly(butylene adipateco-furandicarboxylate)(PBAF)are novel furandicarboxylic acid-based biodegradable copolyesters with great potential to replace fossil-derived terephthalic acid-based copolyesters such as poly(butylene succinate-co-terephthalate)(PBST)and poly(butylene adipate-co-terephthalate)(PBAT).In this study,quantum chemistry techniques after molecular dynamics simulations are employed to investigate the degradationmechanism of PBSF and PBAF catalyzed by Candida antarctica lipase B(CALB).Computational analysis indicates that the catalytic reaction follows a four-step mechanism resembling the ping-pong bibi mechanism,with the initial two steps being acylation reactions and the subsequent two being hydrolysis reactions.Notably,the first step of the hydrolysis is identified as the rate-determining step.Moreover,by introducing single-point mutations to expand the substrate entrance tunnel,the catalytic distance of the first acylation step decreases.Additionally,energy barrier of the rate-determining step is decreased in the PBSF system by site-directed mutations on key residues increasing hydrophobicity of the enzyme’s active site.This study unprecedently show the substrate binding pocket and hydrophobicity of the enzyme’s active site have the potential to be engineered to enhance the degradation of copolyesters catalyzed by CALB.
