Multifocal pontine glioblastoma exhibiting an exophytic growth pattern in the cerebello-pontine angle(CPA) is rare.We present a case of a 5-year-old girl with consecutive neurological imaging and other clinical findin...Multifocal pontine glioblastoma exhibiting an exophytic growth pattern in the cerebello-pontine angle(CPA) is rare.We present a case of a 5-year-old girl with consecutive neurological imaging and other clinical findings indicating progressive multifocal exophytic pontine glioblastoma.Three lesions were reported,of which two were initially presented,and one was developed 2 months later.One lesion demonstrated a progressing exophytic extension in the cistern of the left side of the CPA.The other two lesions were located and confined within the pons.Initial magnetic resonance imaging and positron emission tomography-computed tomography indicated low-grade glioma or inflammatory disease.However,2 and 3 months later,subsequent magnetic resonance spectroscopy(MRS) displayed elevated choline and depressed N-acetyl aspartate peaks compared with the peaks on the initial MRS,indicating a high-grade glioma.Subtotal resection was performed for the CPA lesion.Histopathologic examination showed discrepant features of different parts of the CPA lesion.The patient received no further chemotherapy or radiotherapy and died 2 months after surgery.The multifocal and exophytic features of this case and the heterogeneous manifestations on neurological images were rare and confusing for both diagnosis and surgical decision-making.Our case report may contribute knowledge and helpful guidance for other medical doctors.展开更多
Cavefi sh can be important models for understanding the relationships among evolution,adaptation,and development in extreme environments.However,cavefi sh remain poorly studied,particularly at the genome level.Here,we...Cavefi sh can be important models for understanding the relationships among evolution,adaptation,and development in extreme environments.However,cavefi sh remain poorly studied,particularly at the genome level.Here,we sequenced the complete mitogenome of three cavefi sh in the family Nemacheilidae(Paranemachilus pingguoensis,Oreonectes polystigmus,and Heminoemacheilus longibarbatus),which were collected from karst caves in South China.The mitogenomes each contained 37 genes(13 protein coding,22 tRNA,and two rRNA genes)and a single control region,with the same genetic arrangement and distribution as those found in vertebrates.The non-synonymous/synonymous mutation ratios(Ka/Ks)of the mitogenomes indicated that the protein-coding genes(PCGs)of the three cavefi sh evolved under purifying selection.The mitogenomes of the three cavefi sh exhibit nucleotide composition biases for PCGs,tRNAs,rRNAs,and the whole genome,indicating that the mitochondrial DNA might have been subjected to evolutionary selection in response to extreme cave environments.Divergence time and evolutionary history analyses suggested that the speciation and diversifi cation of the cavefi sh coincided with the Miocene uplift of the southern Qinghai-Tibet Plateau,which greatly changed cave habitats.Overall,our study sheds light on the mitogenomes,phylogeny,and evolutionary history of nemacheilid cavefi sh.展开更多
Glioblastoma multiforme(GBM)is a highly aggressive brain tumor with an extremely low survival rate.New and effective approaches for treatment are therefore urgently needed.Here,we successfully developed M1-like macrop...Glioblastoma multiforme(GBM)is a highly aggressive brain tumor with an extremely low survival rate.New and effective approaches for treatment are therefore urgently needed.Here,we successfully developed M1-like macrophage-derived extracellular vesicles(M1EVs)that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients:enrichment of M2 macrophages in GBM;and origination of a majority of infiltrating macrophage from peripheral blood.To maximize the synergistic effect,we further functionalized the membranes of M1EVs with two hydrophobic agents(the chemical excitation source CPPO(C)and the photosensitizer Ce6(C))and loaded the hydrophilic hypoxiaactivated prodrug AQ4N(A)into the inner core of the M1EVs.After intravenous injection,the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration,and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization,which increased hydrogen peroxide(H_(2)O_(2))levels.Furthermore,the reaction between H_(2)O_(2) and CPPO produced chemical energy,which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy(CDT).As this reaction consumed oxygen,the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy.Therefore,CCA-M1EVs achieved synergistic immunomodulation,CDT,and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect.Finally,we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models,underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM.展开更多
Solid-state lithium-metal-batteries(SSLMBs)using garnet Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZTO)as the solid electrolyte are expected to conquer the safety concerns of high energy Li batteries with organic liquid e...Solid-state lithium-metal-batteries(SSLMBs)using garnet Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZTO)as the solid electrolyte are expected to conquer the safety concerns of high energy Li batteries with organic liquid electrolytes owing to its nonflammable nature and good mechanical strength.However,the poor interfacial contact between the Li anode and LLZTO greatly restrains the practical applications of the electrolyte,because large polarization,dendritic Li formation and penetration can occur at the interfaces.Here,an effective method is proposed to improve the wettability of the LLZTO toward lithium and reduce the interfacial resistance by engineering universal lithiophilic interfacial layers.Thanks to the in-situ formed lithiophilic and ionic conductive Co/Li_(2)O interlayers,the symmetric Li/CoO-LLZTO/Li batteries present much smaller overpotential,ultra-low areal specific resistance(ASR,12.3 X cm^(2)),high critical current density(CCD,1.1 mA cm^(-2)),and outstanding cycling performance(1696 h at a current density of 0.3 mA cm^(-2))at 25℃.Besides,the solid-state Li/CoO-LLZTO/LFP cells deliver an excellent electrochemical performance with a high coulombic efficiency of~100%and a long cycling time over 185 times.Surprisingly,the high-voltage(4.6 V)solid state Li/CoO-LLZTO/Li_(1.4)Mn_(0.6)Ni_(0.2)Co_(0.2)O_(2.4)(LMNC622)batteries can also realize an ultra-high specific capacity(232.5 mAh g-1)under 0.1 C at 25℃.This work paves an effective way for practical applications of the dendrite-free SSLMBs.展开更多
Rational design of highly efficient,robust and nonprecious electrocatalysts for the oxygen reduction reaction(ORR),oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is highly demanded and challenging.H...Rational design of highly efficient,robust and nonprecious electrocatalysts for the oxygen reduction reaction(ORR),oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is highly demanded and challenging.Here,heterostructural Co_(3O)_(4)@Ni_(2)P arrays with numerous reaction sites,unique interfacial electronic structure and fast charge transfer kinetics are developed as electrocatalysts for rechargeable Zn-air batteries and overall water splitting.Both density functional theory calculation and X-ray absorption fine structure analysis manifest that the synergistic structural and abundant electronic modulations interfaces are formed,thus simultaneously promoting the electrocatalytic kinetics,activities and stabilities.Specifically,it can achieve an ultralow overpotential of 270 m V and 28 m V at 10 m A cm^(-2) for OER and HER,respectively.The water electrolyzer delivers a current density of 10 m A cm^(-2) at 1.563 V;furthermore,rechargeable Zn-air batteries triggered by this heterostructure can achieve excellent cyclic stability of 177 h(2 h per cycle)at 10 m A cm^(-2);both devices are superior to the Pt/C+Ir/C.This work not only designs an efficient trifunctional electrocatalyst but also paves an avenue to understand the heterostructure engineering for catalysts development and disclose the underlying relationship of interfacial electronic structures and catalytic properties.展开更多
Dear Editor,Among all the essential trace metals,zinc is of particular importance for its huge panoply of biological functions.As a pivotal element for hundreds of enzymes,either scarcity or accumulation of body zinc ...Dear Editor,Among all the essential trace metals,zinc is of particular importance for its huge panoply of biological functions.As a pivotal element for hundreds of enzymes,either scarcity or accumulation of body zinc can lead to severe disorders(Maret,2017).Therefore,body zinc must be tightly regulated in order to keep a precise amount that is sufficient for cells’survival but does not cause toxicity.As diet is the major source of trace elements including zinc,animals must adjust their feeding amount and preference to avoid scarcity or accumulation.However,how animal utilize their gustatory organs to detect zinc in food and whether the taste is regulated with body zinc level are unknown.Metals often cause the sense of taste termed as metallic taste.While sodium of certain concentration range delivers hedonic salty taste,salt solutions of most metals taste aversive.It was reported that zinc,copper and other heavy metal ions trigger an unpleasant sense of astringent/drying,sour or bitter.Although taste receptor cells were found essential for the detection of some divalent ions,the molecular mechanisms for this detection are largely elusive.Recently,the receptors for calcium were unambiguously identified in fruit fly(Lee et al.,2018).However,a full repertoire of receptors for sensing divalent ions is still lacking.展开更多
文摘Multifocal pontine glioblastoma exhibiting an exophytic growth pattern in the cerebello-pontine angle(CPA) is rare.We present a case of a 5-year-old girl with consecutive neurological imaging and other clinical findings indicating progressive multifocal exophytic pontine glioblastoma.Three lesions were reported,of which two were initially presented,and one was developed 2 months later.One lesion demonstrated a progressing exophytic extension in the cistern of the left side of the CPA.The other two lesions were located and confined within the pons.Initial magnetic resonance imaging and positron emission tomography-computed tomography indicated low-grade glioma or inflammatory disease.However,2 and 3 months later,subsequent magnetic resonance spectroscopy(MRS) displayed elevated choline and depressed N-acetyl aspartate peaks compared with the peaks on the initial MRS,indicating a high-grade glioma.Subtotal resection was performed for the CPA lesion.Histopathologic examination showed discrepant features of different parts of the CPA lesion.The patient received no further chemotherapy or radiotherapy and died 2 months after surgery.The multifocal and exophytic features of this case and the heterogeneous manifestations on neurological images were rare and confusing for both diagnosis and surgical decision-making.Our case report may contribute knowledge and helpful guidance for other medical doctors.
基金Supported by the Open Fund of Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture(No.GXKEYLA2019-05)the National Natural Science Foundation of China(No.41806170)the China-ASEAN Maritime Cooperation Fund(No.CAMC-2018F)。
文摘Cavefi sh can be important models for understanding the relationships among evolution,adaptation,and development in extreme environments.However,cavefi sh remain poorly studied,particularly at the genome level.Here,we sequenced the complete mitogenome of three cavefi sh in the family Nemacheilidae(Paranemachilus pingguoensis,Oreonectes polystigmus,and Heminoemacheilus longibarbatus),which were collected from karst caves in South China.The mitogenomes each contained 37 genes(13 protein coding,22 tRNA,and two rRNA genes)and a single control region,with the same genetic arrangement and distribution as those found in vertebrates.The non-synonymous/synonymous mutation ratios(Ka/Ks)of the mitogenomes indicated that the protein-coding genes(PCGs)of the three cavefi sh evolved under purifying selection.The mitogenomes of the three cavefi sh exhibit nucleotide composition biases for PCGs,tRNAs,rRNAs,and the whole genome,indicating that the mitochondrial DNA might have been subjected to evolutionary selection in response to extreme cave environments.Divergence time and evolutionary history analyses suggested that the speciation and diversifi cation of the cavefi sh coincided with the Miocene uplift of the southern Qinghai-Tibet Plateau,which greatly changed cave habitats.Overall,our study sheds light on the mitogenomes,phylogeny,and evolutionary history of nemacheilid cavefi sh.
基金the National Natural Science Foundation of China(82003303,to X.W.,82102205,to H.D.,81772685,to W.L.,21821005,to G.M.,U2001224,to W.W.)the National Key R&D Program of China(2017YFA0207900,to W.W.)+1 种基金the National Key Research and Development Program of China(2020YFC1316900,2020YFC1316901)the Science and Technology Innovation Committee of Shenzhen Municipality(ZDSYS20140509173142601,ZDSYS201707281114196,ZDSYS20200811142600003,JSGG20191129144225464).
文摘Glioblastoma multiforme(GBM)is a highly aggressive brain tumor with an extremely low survival rate.New and effective approaches for treatment are therefore urgently needed.Here,we successfully developed M1-like macrophage-derived extracellular vesicles(M1EVs)that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients:enrichment of M2 macrophages in GBM;and origination of a majority of infiltrating macrophage from peripheral blood.To maximize the synergistic effect,we further functionalized the membranes of M1EVs with two hydrophobic agents(the chemical excitation source CPPO(C)and the photosensitizer Ce6(C))and loaded the hydrophilic hypoxiaactivated prodrug AQ4N(A)into the inner core of the M1EVs.After intravenous injection,the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration,and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization,which increased hydrogen peroxide(H_(2)O_(2))levels.Furthermore,the reaction between H_(2)O_(2) and CPPO produced chemical energy,which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy(CDT).As this reaction consumed oxygen,the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy.Therefore,CCA-M1EVs achieved synergistic immunomodulation,CDT,and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect.Finally,we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models,underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM.
基金supported by the National Natural Science Foundation of China (21603019 and 201503025)Program for the Hundred Talents Program of Chongqing University。
文摘Solid-state lithium-metal-batteries(SSLMBs)using garnet Li_(6.4)La_(3)Zr_(1.4)Ta_(0.6)O_(12)(LLZTO)as the solid electrolyte are expected to conquer the safety concerns of high energy Li batteries with organic liquid electrolytes owing to its nonflammable nature and good mechanical strength.However,the poor interfacial contact between the Li anode and LLZTO greatly restrains the practical applications of the electrolyte,because large polarization,dendritic Li formation and penetration can occur at the interfaces.Here,an effective method is proposed to improve the wettability of the LLZTO toward lithium and reduce the interfacial resistance by engineering universal lithiophilic interfacial layers.Thanks to the in-situ formed lithiophilic and ionic conductive Co/Li_(2)O interlayers,the symmetric Li/CoO-LLZTO/Li batteries present much smaller overpotential,ultra-low areal specific resistance(ASR,12.3 X cm^(2)),high critical current density(CCD,1.1 mA cm^(-2)),and outstanding cycling performance(1696 h at a current density of 0.3 mA cm^(-2))at 25℃.Besides,the solid-state Li/CoO-LLZTO/LFP cells deliver an excellent electrochemical performance with a high coulombic efficiency of~100%and a long cycling time over 185 times.Surprisingly,the high-voltage(4.6 V)solid state Li/CoO-LLZTO/Li_(1.4)Mn_(0.6)Ni_(0.2)Co_(0.2)O_(2.4)(LMNC622)batteries can also realize an ultra-high specific capacity(232.5 mAh g-1)under 0.1 C at 25℃.This work paves an effective way for practical applications of the dendrite-free SSLMBs.
基金the National Natural Science Foundation of China(Nos.22179014 and 21603019)the Fundamental Research Funds for the Central Universities(No.2021CDJQY-051)+1 种基金the Key Program for International Science and Technology Cooperation Projects of Ministry of Science and Technology of China(No.2016YFE0125900)the Hundred Talents Program of Chongqing University。
文摘Rational design of highly efficient,robust and nonprecious electrocatalysts for the oxygen reduction reaction(ORR),oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)is highly demanded and challenging.Here,heterostructural Co_(3O)_(4)@Ni_(2)P arrays with numerous reaction sites,unique interfacial electronic structure and fast charge transfer kinetics are developed as electrocatalysts for rechargeable Zn-air batteries and overall water splitting.Both density functional theory calculation and X-ray absorption fine structure analysis manifest that the synergistic structural and abundant electronic modulations interfaces are formed,thus simultaneously promoting the electrocatalytic kinetics,activities and stabilities.Specifically,it can achieve an ultralow overpotential of 270 m V and 28 m V at 10 m A cm^(-2) for OER and HER,respectively.The water electrolyzer delivers a current density of 10 m A cm^(-2) at 1.563 V;furthermore,rechargeable Zn-air batteries triggered by this heterostructure can achieve excellent cyclic stability of 177 h(2 h per cycle)at 10 m A cm^(-2);both devices are superior to the Pt/C+Ir/C.This work not only designs an efficient trifunctional electrocatalyst but also paves an avenue to understand the heterostructure engineering for catalysts development and disclose the underlying relationship of interfacial electronic structures and catalytic properties.
文摘Dear Editor,Among all the essential trace metals,zinc is of particular importance for its huge panoply of biological functions.As a pivotal element for hundreds of enzymes,either scarcity or accumulation of body zinc can lead to severe disorders(Maret,2017).Therefore,body zinc must be tightly regulated in order to keep a precise amount that is sufficient for cells’survival but does not cause toxicity.As diet is the major source of trace elements including zinc,animals must adjust their feeding amount and preference to avoid scarcity or accumulation.However,how animal utilize their gustatory organs to detect zinc in food and whether the taste is regulated with body zinc level are unknown.Metals often cause the sense of taste termed as metallic taste.While sodium of certain concentration range delivers hedonic salty taste,salt solutions of most metals taste aversive.It was reported that zinc,copper and other heavy metal ions trigger an unpleasant sense of astringent/drying,sour or bitter.Although taste receptor cells were found essential for the detection of some divalent ions,the molecular mechanisms for this detection are largely elusive.Recently,the receptors for calcium were unambiguously identified in fruit fly(Lee et al.,2018).However,a full repertoire of receptors for sensing divalent ions is still lacking.