The rapid development of electric vehicles and portable energy storage systems demands improvements in the energy density and cost-effectiveness of lithium-ion batteries,a domain in which Lithium-rich layered cathode(...The rapid development of electric vehicles and portable energy storage systems demands improvements in the energy density and cost-effectiveness of lithium-ion batteries,a domain in which Lithium-rich layered cathode(LLO)materials inherently excel.However,these materials face practical challenges,such as low initial Coulombic efficiency,inferior cycle/rate performance,and voltage decline during cycling,which limit practical application.Our study introduces a surface multi-component integration strategy that incorporates oxygen vacancies into the pristine LLO material Li1.2Mn_(0.6)Ni_(0.2)O_(2).This process involves a brief citric acid treatment followed by calcination,aiming to explore rate-dependent degradation behavior.The induced surface oxygen vacancies can reduce surface oxygen partial pressure and diminish the generation of O_(2)and other highly reactive oxygen species on the surface,thereby facilitating the activation of Li ions trapped in tetrahedral sites while overcoming transport barriers.Additionally,the formation of a spinel-like phase with 3D Li+diffusion channels significantly improves Li^(+)diffusion kinetics and stabilizes the surface structure.The optimally modified sample boasts a discharge capacity of 299.5 mA h g^(-1)at a 0.1 C and 251.6 mA h g^(-1)at a 1 C during the initial activation cycle,with an impressive capacity of 222.1 mA h g^(-1)at a 5 C.Most notably,it retained nearly 70%of its capacity after 300 cycles at this elevated rate.This straightforward,effective,and highly viable modification strategy provides a crucial resolution for overcoming challenges associated with LLO materials,making them more suitable for practical application.展开更多
Cation-disordered rocksalt oxides(DRX)have been identified as promising cathode materials for high energy density applications owing to their variable elemental composition and cationic-anionic redox activity.However,...Cation-disordered rocksalt oxides(DRX)have been identified as promising cathode materials for high energy density applications owing to their variable elemental composition and cationic-anionic redox activity.However,their practical implementation has been impeded by unwanted phenomena such as irrepressible transition metal migration/dissolution and O_(2)/CO_(2)evolution,which arise due to parasitic reactions and densification-degradation mechanisms during extended cycling.To address these issues,a micron-sized DRX cathode Li_(1.2)Ni_(1/3)Ti_(1/3)W_(2/15)O_(1.85)F_(0.15)(SLNTWOF)with F substitution and ultrathin LiF coating layer is developed by alcohols assisted sol-gel method.Within this fluorination-induced integrated structure design(FISD)strategy,in-situ F substitution modifies the activity/reversibility of the cationic-anionic redox reaction,while the ultrathin LiF coating and single-crystal structure synergistically mitigate the cathode/electrolyte parasitic reaction and densification-degradation mechanism.Attributed to the multiple modifications and size effect in the FISD strategy,the SLNTWOF sample exhibits reversible cationic-anionic redox chemistry with a meliorated reversible capacity of 290.3 mA h g^(-1)at 0.05C(1C=200 mA g^(-1)),improved cycling stability of 78.5%capacity retention after 50 cycles at 0.5 C,and modified rate capability of 102.8 mA h g^(-1)at 2 C.This work reveals that the synergistic effects between bulk structure modification,surface regulation,and engineering particle size can effectively modulate the distribution and evolution of cationic-anionic redox activities in DRX cathodes.展开更多
Phaeocystis globosa is an important harmful algal bloom causative species distributing widely in temperate and tropical coastal waters in the world.The morphological,physiological,and biochemical characteristics are d...Phaeocystis globosa is an important harmful algal bloom causative species distributing widely in temperate and tropical coastal waters in the world.The morphological,physiological,and biochemical characteristics are different among geographic strains,which can not be distinguished with nuclear ribosomal DNA markers at present.Therefore,the genetic distance and phylogeographic relationships of nuclear 28S rDNA D1–D2 and ITS regions,and three chloroplast intergenic spacers(petN-trnS1,trnM1-psbA,and rbcS-rpl27)were analyzed and compared among 13 strains of P.globosa isolated from the Pacific Ocean and Atlantic Ocean in this study.In addition,the nucleotide polymorphisms of 28S rDNA D1–D2,ITS,and rbcS-rpl27 regions were evaluated in two P.globosa strains.The various levels of nucleotide polymorphism were in the nuclear 28S rDNA D1–D2 region and ITS region,but no polymorphism was in the chloroplast rbcS-rpl27 intergenic spacer.A reasonable intraspecific phylogeographic relationship was presented by rbcS-rpl27 intergenic spacer,which had the strongest distinction to geographic strains compared to those of 28S rDNA D1–D2 and ITS regions.In the phylogenetic tree of rbcS-rpl27 intergenic spacer,the two strains from the North Sea of the Atlantic Ocean were divided firstly from the species of P.globosa,and then formed an independent clade,while the other Atlantic strains and all of Pacific strains joined up to build the other clade.It was implied that at least two genetically distant populations of P.globosa existed in the Atlantic coastal regions.This study provided a high-resolution chloroplast marker to analyze intraspecific phylogeographic populations of P.globosa,and preliminarily clarified the genetic relationships of the Pacific and Atlantic strains of P.globosa.展开更多
Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiven...Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.展开更多
Adipose browning has demonstrated therapeutic potentials in several diseases.Here,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse in...Adipose browning has demonstrated therapeutic potentials in several diseases.Here,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold condition.All major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling.Our findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to cold.The adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is potentiated.Furthermore,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)adipocyte.Beige adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold.Our data reveal fundamental changes during cold-evoked adipose browning.展开更多
This work presents a brief review of our recent research on an antiresonant mechanism named core antiresonant reflection(CARR),which leads to a broadband terahertz(THz)spectrum output with periodic dips at resonant fr...This work presents a brief review of our recent research on an antiresonant mechanism named core antiresonant reflection(CARR),which leads to a broadband terahertz(THz)spectrum output with periodic dips at resonant frequencies after its transmission along a hollow-core tubular structure(e.g.,a paper tube).The CARR theory relies only on parameters of the tube core(e.g.,the inner diameter)rather than the cladding,thus being distinct from existing principles such as the traditional antiresonant reflection inside optical waveguides(ARROWs).We demonstrate that diverse tubular structures,including cylindrical,polyhedral,spiral,meshy,and notched hollow tubes with either transparent or opaque cladding materials,as well as a thick-walled hole,could indeed become CARR-type resonators.Based on this CARR effect,we also perform various applications,such as pressure sensing with paper-folded THz cavities,force/magnetism-driven chiral polarization modulations,and single-pulse measurements of the angular dispersion of THz beams.In future studies,the proposed CARR method promises to support breakthroughs in multiple fields by means of being extended to more kinds of tubular entities for enhancing their interactions with light waves in an antiresonance manner.展开更多
Oncolytic viruses have emerged as new powerful therapeutic agents for cancer therapy by specifically lysing cancer cells while activating innate immune responses at the same time.However,due to the thorny issues of sa...Oncolytic viruses have emerged as new powerful therapeutic agents for cancer therapy by specifically lysing cancer cells while activating innate immune responses at the same time.However,due to the thorny issues of safety concerns and host immune reaction,the clinical application of oncolytic viruses is still limited.Herein,we report a rationally designed oncolytic virus-like nanoparticles(OV-NPs)composed of stimulator of interferon genes(STING)-stimulating polymer loaded with therapeutic genes for cancer immunotherapy.After injection into tumor,the OV-NPs carrying OX40L plasmid could reprogram tumor cells to express OX40L immune checkpoint molecules and activate the STING pathway for cooperatively enhancing antitumor immunity,with a tumor suppression rate of 92.3%in B16F10 tumor model and 78.7%in MC38 tumor model without causing any toxicity.The OV-NPs could be further applied in carrying other plasmids(IL-12)and utilization in gene combination therapy.This study should inspire designing synthetic OV-NPs as alternative strategies for extending oncolytic virus application in cancer immunotherapy.展开更多
Facial emotion recognition achieves great success with the help of large neural models but also fails to be applied in practical situations due to the large model size of neural methods.To bridge this gap,in this pape...Facial emotion recognition achieves great success with the help of large neural models but also fails to be applied in practical situations due to the large model size of neural methods.To bridge this gap,in this paper,we combine two mainstream model compression methods(pruning and quantization)together,and propose a pruningthen-quantization framework to compress the neural models for facial emotion recognition tasks.Experiments on three datasets show that our model could achieve a high model compression ratio and maintain the model’s high performance well.Besides,We analyze the layer-wise compression performance of our proposed framework to explore its effect and adaptability in fine-grained modules.展开更多
Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials ...Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.展开更多
In this work, it has been demonstrated that in order to fully understand the terahertz(THz) pulse generation process during femtosecond laser filamentation, the interaction between THz wave and air plasma has to be ta...In this work, it has been demonstrated that in order to fully understand the terahertz(THz) pulse generation process during femtosecond laser filamentation, the interaction between THz wave and air plasma has to be taken into account. This interaction is mainly associated with the spatial confinement of the THz pulse by the plasma column, which could be described by the one-dimensional negative dielectric(1DND) waveguide model. By combining the 1 DND model with the conventional four-wave mixing(4WM) and photocurrent(PC) models,the variation of THz spectral amplitude and width obtained in experiments could be better understood. Finally, a three-step procedure, with 1DND bridging 4WM and PC processes, has been established for the first time to describe the underlying mechanism of THz radiation from plasma sources.展开更多
Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancre...Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis.In this work,we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.PAK1-targeted inhibition is therefore a new potential therapeutic strategy for pancreatic cancer.Our small molecule screening identified a relatively specific PAK1-targeted inhibitor,CP734.Pharmacological and biochemical studies indicated that CP734 targets residue V342 of PAK1 to inhibit its ATPase activity.Further in vitro and in vivo studies elucidated that CP734 suppresses pancreatic tumor growth through depleting PAK1 kinase activity and its downstream signaling pathways.Little toxicity of CP734 was observed in murine models.Combined with gemcitabine or 5-fluorouracil,CP734 also showed synergistic effects on the anti-proliferation of pancreatic cancer cells.All these favorable results indicated that CP734 is a new potential therapeutic candidate for pancreatic cancer.展开更多
High-energy and safe lithium ion batteries(LIBs)are in increasing need as the rapid development of electronic devices,electric vehicles,as well as energy storage station.Li-rich oxides have attracted a lot of attentio...High-energy and safe lithium ion batteries(LIBs)are in increasing need as the rapid development of electronic devices,electric vehicles,as well as energy storage station.Li-rich oxides have attracted a lot of attention due to their high capacity and low cost as cathode material for LIBs.However,they still suffer from the vulnerable cathode/electrolyte interface,which presents the huge challenges of surface degradation and gas release,particularly at high state of charge.Some issues of Li-rich cathode materials,such as moderate cycle stability and voltage decay,are in tight connection with electrode-electrolyte interfacial side reactions.Research in the area of interfacial degradation mechanism and optimization strategies is of great significance as for Li-rich cathode,and extensive efforts have been poured.This review aims to understand the degradation mechanism of Li-rich cathode materials,and summarize the corresponding valuable and effective optimization strategies.Based on these considerations,we also have discussed the remaining challenges and the future research direction.展开更多
Dear Editor,Gastric cancer(GC)is one of the most common malignant tumors of the digestive system and the second leading cause of cancer death worldwide1.Despite the gradually declining morbidity and mortality,GC still...Dear Editor,Gastric cancer(GC)is one of the most common malignant tumors of the digestive system and the second leading cause of cancer death worldwide1.Despite the gradually declining morbidity and mortality,GC still burdens many countries in East Asia1.Understanding the GC pathological process is vital for the successful diagnosis,treatment and prevention of this disease.展开更多
Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the ...Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.展开更多
We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecu...We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.展开更多
基金supported by the National Key R&D Program of China(2021YFB2401800)the National Natural Science Foundation of China(21875022,22179008)+4 种基金the Yibin‘Jie Bang Gua Shuai’(2022JB004)the support from the Beijing Nova Program(20230484241)the support from the Postdoctoral Fellowship Program of CPSF(GZB20230931)the support from the 4B7B beam line of Beijing Synchrotron Radiation Facility(2021-BEPC-PT-005924,2021-BEPC-PT-005967)BL08U1A beam line of Shanghai Synchrotron Radiation Facility(2021-SSRF-PT-017710)。
文摘The rapid development of electric vehicles and portable energy storage systems demands improvements in the energy density and cost-effectiveness of lithium-ion batteries,a domain in which Lithium-rich layered cathode(LLO)materials inherently excel.However,these materials face practical challenges,such as low initial Coulombic efficiency,inferior cycle/rate performance,and voltage decline during cycling,which limit practical application.Our study introduces a surface multi-component integration strategy that incorporates oxygen vacancies into the pristine LLO material Li1.2Mn_(0.6)Ni_(0.2)O_(2).This process involves a brief citric acid treatment followed by calcination,aiming to explore rate-dependent degradation behavior.The induced surface oxygen vacancies can reduce surface oxygen partial pressure and diminish the generation of O_(2)and other highly reactive oxygen species on the surface,thereby facilitating the activation of Li ions trapped in tetrahedral sites while overcoming transport barriers.Additionally,the formation of a spinel-like phase with 3D Li+diffusion channels significantly improves Li^(+)diffusion kinetics and stabilizes the surface structure.The optimally modified sample boasts a discharge capacity of 299.5 mA h g^(-1)at a 0.1 C and 251.6 mA h g^(-1)at a 1 C during the initial activation cycle,with an impressive capacity of 222.1 mA h g^(-1)at a 5 C.Most notably,it retained nearly 70%of its capacity after 300 cycles at this elevated rate.This straightforward,effective,and highly viable modification strategy provides a crucial resolution for overcoming challenges associated with LLO materials,making them more suitable for practical application.
基金supported by the National Key R&D Program of China(2021YFB2401800)the National Natural Science Foundation of China(22179008,21875022)+2 种基金the Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0589,cstc2020jcyjmsxmX0654)the support from Beijing Institute of Technology Research Fund Program for Young Scholarsthe 4B7B beamlines radiation equipment of Beijing Synchrotron Radiation Facility(2021-BEPC-PT-005924,2021-BEPC-PT-005967)。
文摘Cation-disordered rocksalt oxides(DRX)have been identified as promising cathode materials for high energy density applications owing to their variable elemental composition and cationic-anionic redox activity.However,their practical implementation has been impeded by unwanted phenomena such as irrepressible transition metal migration/dissolution and O_(2)/CO_(2)evolution,which arise due to parasitic reactions and densification-degradation mechanisms during extended cycling.To address these issues,a micron-sized DRX cathode Li_(1.2)Ni_(1/3)Ti_(1/3)W_(2/15)O_(1.85)F_(0.15)(SLNTWOF)with F substitution and ultrathin LiF coating layer is developed by alcohols assisted sol-gel method.Within this fluorination-induced integrated structure design(FISD)strategy,in-situ F substitution modifies the activity/reversibility of the cationic-anionic redox reaction,while the ultrathin LiF coating and single-crystal structure synergistically mitigate the cathode/electrolyte parasitic reaction and densification-degradation mechanism.Attributed to the multiple modifications and size effect in the FISD strategy,the SLNTWOF sample exhibits reversible cationic-anionic redox chemistry with a meliorated reversible capacity of 290.3 mA h g^(-1)at 0.05C(1C=200 mA g^(-1)),improved cycling stability of 78.5%capacity retention after 50 cycles at 0.5 C,and modified rate capability of 102.8 mA h g^(-1)at 2 C.This work reveals that the synergistic effects between bulk structure modification,surface regulation,and engineering particle size can effectively modulate the distribution and evolution of cationic-anionic redox activities in DRX cathodes.
基金Supported by the National Key Research and Development Plan Project,the Sino-Australian Centre for Healthy Coasts(No.2016YFE0101500)the Science&Technology Basic Resources Investigation Program(No.2018FY100206)the National Natural Science Foundation of China(Nos.41576121,41776127)。
文摘Phaeocystis globosa is an important harmful algal bloom causative species distributing widely in temperate and tropical coastal waters in the world.The morphological,physiological,and biochemical characteristics are different among geographic strains,which can not be distinguished with nuclear ribosomal DNA markers at present.Therefore,the genetic distance and phylogeographic relationships of nuclear 28S rDNA D1–D2 and ITS regions,and three chloroplast intergenic spacers(petN-trnS1,trnM1-psbA,and rbcS-rpl27)were analyzed and compared among 13 strains of P.globosa isolated from the Pacific Ocean and Atlantic Ocean in this study.In addition,the nucleotide polymorphisms of 28S rDNA D1–D2,ITS,and rbcS-rpl27 regions were evaluated in two P.globosa strains.The various levels of nucleotide polymorphism were in the nuclear 28S rDNA D1–D2 region and ITS region,but no polymorphism was in the chloroplast rbcS-rpl27 intergenic spacer.A reasonable intraspecific phylogeographic relationship was presented by rbcS-rpl27 intergenic spacer,which had the strongest distinction to geographic strains compared to those of 28S rDNA D1–D2 and ITS regions.In the phylogenetic tree of rbcS-rpl27 intergenic spacer,the two strains from the North Sea of the Atlantic Ocean were divided firstly from the species of P.globosa,and then formed an independent clade,while the other Atlantic strains and all of Pacific strains joined up to build the other clade.It was implied that at least two genetically distant populations of P.globosa existed in the Atlantic coastal regions.This study provided a high-resolution chloroplast marker to analyze intraspecific phylogeographic populations of P.globosa,and preliminarily clarified the genetic relationships of the Pacific and Atlantic strains of P.globosa.
基金supported by the National Natural Science Foundation of China (22222509, 52025035, 52103194, and 22105199)The Ministry of Science and Technology of China (2022YFE0110200)+3 种基金Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029)Jilin Province Science and Technology Development Plan (YDZJ202101ZYTS131, 20220402037GH, and 20210508049RQ)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH)The Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)。
文摘Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.
基金National Natural Science Foundation of China(NSFC)-Excellent Young Scientists Fund(81922079)Hong Kong Research Grants Council General Research Fund(17123419)Lo Kwee-Seong Biomedical Research Start-up Fund(7106480 and 7106481).
文摘Adipose browning has demonstrated therapeutic potentials in several diseases.Here,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold condition.All major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling.Our findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to cold.The adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is potentiated.Furthermore,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)adipocyte.Beige adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold.Our data reveal fundamental changes during cold-evoked adipose browning.
基金supported by the National Natural Science Foundation of China(Nos.61988102 and 62335012)the Youth Sci-Tech“Qimingxing”Program of Shanghai(No.22QC1400300)the National Key Research and Development Program of China(No.2022YFA1404004)。
文摘This work presents a brief review of our recent research on an antiresonant mechanism named core antiresonant reflection(CARR),which leads to a broadband terahertz(THz)spectrum output with periodic dips at resonant frequencies after its transmission along a hollow-core tubular structure(e.g.,a paper tube).The CARR theory relies only on parameters of the tube core(e.g.,the inner diameter)rather than the cladding,thus being distinct from existing principles such as the traditional antiresonant reflection inside optical waveguides(ARROWs).We demonstrate that diverse tubular structures,including cylindrical,polyhedral,spiral,meshy,and notched hollow tubes with either transparent or opaque cladding materials,as well as a thick-walled hole,could indeed become CARR-type resonators.Based on this CARR effect,we also perform various applications,such as pressure sensing with paper-folded THz cavities,force/magnetism-driven chiral polarization modulations,and single-pulse measurements of the angular dispersion of THz beams.In future studies,the proposed CARR method promises to support breakthroughs in multiple fields by means of being extended to more kinds of tubular entities for enhancing their interactions with light waves in an antiresonance manner.
基金supported by the National Natural Science Foundation of China (22222509,52025035,51973215,22375198,52103194)Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029)+5 种基金Jilin Province Science and Technology DevelopmentPlan (YDZJ202101ZYTS131,20220402037GH,20210508049RQ)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH)Changchun Science and Technology Development Plan (21ZY09,21ZGY30)the China Postdoctoral Science Foundation (E21S2101)the Youth Talents Promotion Project of Jilin Province (QT202103)the Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)。
文摘Oncolytic viruses have emerged as new powerful therapeutic agents for cancer therapy by specifically lysing cancer cells while activating innate immune responses at the same time.However,due to the thorny issues of safety concerns and host immune reaction,the clinical application of oncolytic viruses is still limited.Herein,we report a rationally designed oncolytic virus-like nanoparticles(OV-NPs)composed of stimulator of interferon genes(STING)-stimulating polymer loaded with therapeutic genes for cancer immunotherapy.After injection into tumor,the OV-NPs carrying OX40L plasmid could reprogram tumor cells to express OX40L immune checkpoint molecules and activate the STING pathway for cooperatively enhancing antitumor immunity,with a tumor suppression rate of 92.3%in B16F10 tumor model and 78.7%in MC38 tumor model without causing any toxicity.The OV-NPs could be further applied in carrying other plasmids(IL-12)and utilization in gene combination therapy.This study should inspire designing synthetic OV-NPs as alternative strategies for extending oncolytic virus application in cancer immunotherapy.
基金supported in part by the Technological Breakthrough Project of Science,Technology and Innovation Commission of Shenzhen Municipality(No.JSGG20201102162000001)InnoHK Initiative of Hong Kong SAR Government,and the Laboratory for AI-Powered Financial Technologies Ltd.
文摘Facial emotion recognition achieves great success with the help of large neural models but also fails to be applied in practical situations due to the large model size of neural methods.To bridge this gap,in this paper,we combine two mainstream model compression methods(pruning and quantization)together,and propose a pruningthen-quantization framework to compress the neural models for facial emotion recognition tasks.Experiments on three datasets show that our model could achieve a high model compression ratio and maintain the model’s high performance well.Besides,We analyze the layer-wise compression performance of our proposed framework to explore its effect and adaptability in fine-grained modules.
基金supported by the National Key Research and Development Program of China(2016YFC1101400)the National Natural Science Foundation of China(No.81930025,81620108007,81901010)Open Foundation of Shandong Provincial Key Laboratory of Oral Tissue Regeneration(No.SDKQ201904).
文摘Reconstruction of bone defects,especially the critical-sized defects,with mechanical integrity to the skeleton is important for a patient's rehabilitation,however,it still remains challenge.Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties.However,not only efficacious and safe but also costeffective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success.Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine.Taking inspiration from the role and multicomponent construction of native extracellular matrix(ECM)for cell accommodation,the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration.On the other hand,with the going deep in understanding of mesenchymal stem cells(MSCs),they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization,systemic/local infusion of MSCs for cytotherapy,biomaterials-based approaches,cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system,all of them have been shown can improve MSCsmediated regeneration in preclinical studies and several clinical trials.Here,following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCsmediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration.
基金National Key R&D Program of China(2017YFC0821300)National Natural Science Foundation of China(NSFC)(11704252,11574160,61722111)+6 种基金National Program on Key Basic Research Project of China(973Program)(2014CB339802,2014CB339806)Major National Development Project of Scientific Instrument and Equipment(2017YFF0106300,2016YFF0100503)Tianjin Research Program of Application Foundation and Advanced Technology(15JCZDJC31700)Key Scientific and Technological Project of Science and Technology Commission of Shanghai Municipality(STCSM)(15DZ0500102)Shanghai Leading Talent(2016-019)Young Yangtze River Scholar(Q2016212)Tianjin Special Program for Talent Development
文摘In this work, it has been demonstrated that in order to fully understand the terahertz(THz) pulse generation process during femtosecond laser filamentation, the interaction between THz wave and air plasma has to be taken into account. This interaction is mainly associated with the spatial confinement of the THz pulse by the plasma column, which could be described by the one-dimensional negative dielectric(1DND) waveguide model. By combining the 1 DND model with the conventional four-wave mixing(4WM) and photocurrent(PC) models,the variation of THz spectral amplitude and width obtained in experiments could be better understood. Finally, a three-step procedure, with 1DND bridging 4WM and PC processes, has been established for the first time to describe the underlying mechanism of THz radiation from plasma sources.
基金supported by the National Natural Science Foundation of China(81873057,81973527)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)grant(China).
文摘Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis.In this work,we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.PAK1-targeted inhibition is therefore a new potential therapeutic strategy for pancreatic cancer.Our small molecule screening identified a relatively specific PAK1-targeted inhibitor,CP734.Pharmacological and biochemical studies indicated that CP734 targets residue V342 of PAK1 to inhibit its ATPase activity.Further in vitro and in vivo studies elucidated that CP734 suppresses pancreatic tumor growth through depleting PAK1 kinase activity and its downstream signaling pathways.Little toxicity of CP734 was observed in murine models.Combined with gemcitabine or 5-fluorouracil,CP734 also showed synergistic effects on the anti-proliferation of pancreatic cancer cells.All these favorable results indicated that CP734 is a new potential therapeutic candidate for pancreatic cancer.
基金This work was supported by the National Key R&D Program of China(2016YFB0100301)National Natural Science Foundation of China(21875022,51802020,51802019)+1 种基金Science and Technology Innovation Foundation(2020CX5100006)Young Elite Scien-tists Sponsorship Program by CAST(2018QNRC001).L.Chen and N.Li acknowledge the support from Bijig Institute of Technology Research Fund Program for Young Scholars.
文摘High-energy and safe lithium ion batteries(LIBs)are in increasing need as the rapid development of electronic devices,electric vehicles,as well as energy storage station.Li-rich oxides have attracted a lot of attention due to their high capacity and low cost as cathode material for LIBs.However,they still suffer from the vulnerable cathode/electrolyte interface,which presents the huge challenges of surface degradation and gas release,particularly at high state of charge.Some issues of Li-rich cathode materials,such as moderate cycle stability and voltage decay,are in tight connection with electrode-electrolyte interfacial side reactions.Research in the area of interfacial degradation mechanism and optimization strategies is of great significance as for Li-rich cathode,and extensive efforts have been poured.This review aims to understand the degradation mechanism of Li-rich cathode materials,and summarize the corresponding valuable and effective optimization strategies.Based on these considerations,we also have discussed the remaining challenges and the future research direction.
基金supported by the China Postdoctoral Science Foundation(No.2018M642211)the Chinese Science and Technology Major Project of China(2015ZX09102023-003)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BE2016737)the Research and Development Fund of Kangda College,Nanjing Medical University(No.KD2017KYJJZD011).
文摘Dear Editor,Gastric cancer(GC)is one of the most common malignant tumors of the digestive system and the second leading cause of cancer death worldwide1.Despite the gradually declining morbidity and mortality,GC still burdens many countries in East Asia1.Understanding the GC pathological process is vital for the successful diagnosis,treatment and prevention of this disease.
基金supported by the National Natural Science Foundation of China(Nos.51973215,52025035,52003268,51829302,and 51833010)Bureau of International Cooperation Chinese Academy of Sciences(No.121522KYSB20200029)+1 种基金the Jilin Province Science and Technology Development Plan(No.2020122331JC)support from the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020232).
文摘Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.
基金the Bureau of International Cooperation Chinese Academy of Sciences(grant no.121522KYSB20200029)National Natural Science Foundation of China(grant nos.22222509,52025035,52003268,and 51973215)+3 种基金Jilin Province Science and Technology Development Plan(grant nos.YDZJ202101-ZYTS131 and 20220402037GH)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(grant no.20210504001GH)Changchun Science and Technology Development Plan(grant no.21ZY09)the Youth Innovation Promotion Association of Chinese Academy of Sciences(grant no.2020232).
文摘We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.