Background:Geographical distribution of endemic species and its multiple scale drivers are an important topic in biodiversity conservation,because these species are especially vulnerable to climate change and habitat ...Background:Geographical distribution of endemic species and its multiple scale drivers are an important topic in biodiversity conservation,because these species are especially vulnerable to climate change and habitat degradation,and therefore have high conservation priority.Here,for the first time,we simultaneously linked glacial-interglacial climate change,contemporary climate,plant species richness and altitudinal range with endemic bird distribution in China.Methods:Ordinary least squares models and simultaneous autoregressive models were used to assess the associations between endemic bird richness,endemic bird ratio and each explanatory variable.Structural Equation Models were also performed to test the direct and indirect effects of these variables on endemic bird richness and endemic bird ratio.Results:Higher endemic bird richness and endemic bird ratio occurred in regions with stable glacial-interglacial temperature,i.e.,southwest China.Plant species richness and altitudinal range were also positively correlated with endemic bird richness and endemic bird ratio.Glacial-interglacial temperature change,contemporary precipitation,plant species richness and altitudinal range were all included in the best combination of variables for endemic bird richness.Importantly,glacial-interglacial temperature change had strong direct effects on both endemic bird richness and endemic bird ratio,while plant species richness only had a direct effect on endemic bird richness.Conclusions:Our results indicate that endemic birds in China concentrate in southwest regions where there are stable glacial-interglacial temperature,more plant species and larger altitudinal range.Notably,while stable climate has strong direct effects on both endemic bird richness and endemic bird ratio,plant species may affect endemic bird richness through its effect on overall bird species richness.Importantly,the recent anthropogenic activities have also significantly intensified in this region,which would pose huge challenge for biodiversity conservation in China.展开更多
Humic-like substances(HULIS)are a major component of brown carbon and consequently play a major role in climate change.In this study,70 PM_(2.5) samples were collected from Xi'an in winter 2019 and summer 2020.Neu...Humic-like substances(HULIS)are a major component of brown carbon and consequently play a major role in climate change.In this study,70 PM_(2.5) samples were collected from Xi'an in winter 2019 and summer 2020.Neutral HULIS(HULIS-n),acidic HULIS(HULIS-a),and high-polarity water-soluble organic compounds(HP-WSOC)were analyzed to determine their carbon concentrations and measure their ultraviolet-visible absorption and infrared spectra.Of the three components,HULIS-n had the highest carbon content in both winter(3.29±1.45μg m^(-3))and in summer(1.38±1.10μg m^(-3)).The semi-quantitative results for the functional groups revealed that HP-WSOC was rich in carboxylic acids and had high aromaticity in winter,whereas HULIS-n was rich in carboxylic acids in summer.Moreover,HULJS-a was richer in nitrate esters and saturated aliphatic hydrocarbons in summer than in winter.The results for specific ultraviolet absorbance(SUVA)and E_(250)/E_(365) revealed that HULIS had higher molecular weight and aromaticity in winter than in summer.HULIS-n dominated in the total light absorption of HULIS+HP-WSOC in both winter(73.08%)and summer(48.57%).Overall,the results on the carbon content,optical properties,and functional groups of WSOCs with differing polarity can improve un-derstanding of environmental and climatic effects.展开更多
In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH...In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH)is reported,comprising Gd-containing layered double hydroxide nanosheets(Gd-LDH,as a drug nanocarrier/MRI contrast agent),atorvastatin(ATO,as a neuroprotective drug)and the ferritin heavy subunit(FTH,as a blood brain barrier transport agent).Experiments revealed AFGd-LDH to possess outstanding antioxidant activity,neuroprotective properties,blood‒brain barrier transit properties,and biocompatibility.In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be~90%,surpassing CeO_(2)(50%,a ROS scavenger)and edaravone(52%,a clinical neuroprotective drug).Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion,reducing the infarct area by 67%and lowering the neurological deficit score from 3.2 to 0.9.AFGd-LDH also offered outstanding MRI performance,thus enabling simultaneous imaging and ischemia reperfusion therapy.展开更多
Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB...Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.展开更多
In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy...In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.展开更多
Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is charact...Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is characterized by wide clinical variability,including multiple café-au-lait macules(CALMs),fibromatous tumors,axillary or inguinal freckling,Lisch nodules(iris hamartomas),skeletal anomalies,and cognitive impairments(Monroe et al.,2017).展开更多
Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resul...Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.展开更多
基金supported by the National Natural Science Foundation of China(No.41861004 granted to GF,and 31870506 to ML)the Inner Mongolia Grassland Talent(12000-12102228 to GF)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB31000000 granted to ML)Natural Science Foundation of Jiangsu Province(BK20181398 granted to ML)。
文摘Background:Geographical distribution of endemic species and its multiple scale drivers are an important topic in biodiversity conservation,because these species are especially vulnerable to climate change and habitat degradation,and therefore have high conservation priority.Here,for the first time,we simultaneously linked glacial-interglacial climate change,contemporary climate,plant species richness and altitudinal range with endemic bird distribution in China.Methods:Ordinary least squares models and simultaneous autoregressive models were used to assess the associations between endemic bird richness,endemic bird ratio and each explanatory variable.Structural Equation Models were also performed to test the direct and indirect effects of these variables on endemic bird richness and endemic bird ratio.Results:Higher endemic bird richness and endemic bird ratio occurred in regions with stable glacial-interglacial temperature,i.e.,southwest China.Plant species richness and altitudinal range were also positively correlated with endemic bird richness and endemic bird ratio.Glacial-interglacial temperature change,contemporary precipitation,plant species richness and altitudinal range were all included in the best combination of variables for endemic bird richness.Importantly,glacial-interglacial temperature change had strong direct effects on both endemic bird richness and endemic bird ratio,while plant species richness only had a direct effect on endemic bird richness.Conclusions:Our results indicate that endemic birds in China concentrate in southwest regions where there are stable glacial-interglacial temperature,more plant species and larger altitudinal range.Notably,while stable climate has strong direct effects on both endemic bird richness and endemic bird ratio,plant species may affect endemic bird richness through its effect on overall bird species richness.Importantly,the recent anthropogenic activities have also significantly intensified in this region,which would pose huge challenge for biodiversity conservation in China.
基金supported by the Key R&D project of Shaanxi Province(grant No.2022zDLSF06-07)Chinese Academy of Sciences(CAS)“Light of West China”Program(grant No.XAB2021YN06)the State Key Laboratory of Loess and Quaternary Geology,Institute of Earth Environment,CAs(grant No.SKLLQG2103,SKLLQG2110)was also thanked.
文摘Humic-like substances(HULIS)are a major component of brown carbon and consequently play a major role in climate change.In this study,70 PM_(2.5) samples were collected from Xi'an in winter 2019 and summer 2020.Neutral HULIS(HULIS-n),acidic HULIS(HULIS-a),and high-polarity water-soluble organic compounds(HP-WSOC)were analyzed to determine their carbon concentrations and measure their ultraviolet-visible absorption and infrared spectra.Of the three components,HULIS-n had the highest carbon content in both winter(3.29±1.45μg m^(-3))and in summer(1.38±1.10μg m^(-3)).The semi-quantitative results for the functional groups revealed that HP-WSOC was rich in carboxylic acids and had high aromaticity in winter,whereas HULIS-n was rich in carboxylic acids in summer.Moreover,HULJS-a was richer in nitrate esters and saturated aliphatic hydrocarbons in summer than in winter.The results for specific ultraviolet absorbance(SUVA)and E_(250)/E_(365) revealed that HULIS had higher molecular weight and aromaticity in winter than in summer.HULIS-n dominated in the total light absorption of HULIS+HP-WSOC in both winter(73.08%)and summer(48.57%).Overall,the results on the carbon content,optical properties,and functional groups of WSOCs with differing polarity can improve un-derstanding of environmental and climatic effects.
基金support from National Natural Science Foundation of China(7172070,81771233,21805293,U20A20254,52072253)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019027)+2 种基金the Director Foundation of the Technical Institute of Physics and Chemistry,Chinese Academy of SciencesBeijing Science and Technology Plan subject:Beijing‒Tianjin‒Hebei collaborative innovation promotion project(No.Z181100009618035)National Key Research and Development Program(2018YFC1311602,2018YFC1312801,2016YF1301500).
文摘In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH)is reported,comprising Gd-containing layered double hydroxide nanosheets(Gd-LDH,as a drug nanocarrier/MRI contrast agent),atorvastatin(ATO,as a neuroprotective drug)and the ferritin heavy subunit(FTH,as a blood brain barrier transport agent).Experiments revealed AFGd-LDH to possess outstanding antioxidant activity,neuroprotective properties,blood‒brain barrier transit properties,and biocompatibility.In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be~90%,surpassing CeO_(2)(50%,a ROS scavenger)and edaravone(52%,a clinical neuroprotective drug).Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion,reducing the infarct area by 67%and lowering the neurological deficit score from 3.2 to 0.9.AFGd-LDH also offered outstanding MRI performance,thus enabling simultaneous imaging and ischemia reperfusion therapy.
基金This work was financially supported by the National Natural Science Foundation of China(No.81788101)the National Key Research and Development Program of China(No.2016YFC0905100)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-002)the Natural Science Foundation of Beijing(No.7172167).
文摘Epidermolysis bullosa(EB)is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation.Here,we investigated five Chinese families with EB,and eight variants including a novel nonsense variant(c.47G>A,p.W16*)in LAMA3,a known recurrent variant(c.74C>T,p.P25L)in KRT5,2 novel(c.2531T>A,p.V844E;c.6811_6814del,p.R2271fs)and 4 known(c.6187C>T,p.R2063W;c.7097G>A,p.G2366D;c.8569G>T,p.E2857*;c.3625_3635del,p.S1209fs)variants in COL7A1 were detected.Notably,this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay.Our study expands the mutation spectra of Chinese patients with EB.
基金the financial support from the National Natural Science Foundation of China(No.21571013,52073023,and 21805293)the National Basic Research Program(No.2014CB932101)+2 种基金the Program for Chang Jiang Scholars,Innovative Research Team in University(No.IRT1205)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019027)the Director Foundation of the Technical Institute of Physics and Chemistry,Chinese Academy of Sciences.
文摘In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.
基金supported by the National Key Research and Development Program of China(2016YFC0905100 and 2016YFC1000504)the National Natural Science Foundation of China(81788101)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1002)the Natural Science Foundation of Beijing(7172167)。
文摘Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is characterized by wide clinical variability,including multiple café-au-lait macules(CALMs),fibromatous tumors,axillary or inguinal freckling,Lisch nodules(iris hamartomas),skeletal anomalies,and cognitive impairments(Monroe et al.,2017).
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.82001221 and 81788101)the National Key Research and Development Program of China(Nos.2022YFC2703900 and 2022YFC2703903)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-018,2022-I2M-JB-004 and 2017-I2M-B&R-05).
文摘Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.