KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to eva...KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to evaluate the influence of varying hydrothermal synthesis temperatures on the physicochemical properties of both the KIT-5/Beta supports and the resulting catalysts.The catalytic performances of catalysts were evaluated under reaction conditions of 320℃,4 MPa H_(2)pressure,and a weight hourly space velocity(WHSV)of 4.8 h^(-1)for hydrodenitrogenation(HDN)of quinoline.The results indicated that the specific surface area and pore structure of the materials could be effectively regulated by adjusting the hydrothermal synthesis temperature,which in turn influenced the number of active sites on the catalyst.The NiW/KB-125 catalyst,synthesized at 125℃,presented the highest quinoline HDN efficiency(96.8%),which can be attributed to its favorable pore channel structure,greater Brønsted acid number,higher degree of metal sulfidation(80.12%)and appropriate metal-support interaction(MSI).展开更多
SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by neurotoxic amyloid beta(Aβ)deposition in the brain.Neurons can internalize and exocytose Aβ;however,the molecular pathways governing Aβreleas...Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by neurotoxic amyloid beta(Aβ)deposition in the brain.Neurons can internalize and exocytose Aβ;however,the molecular pathways governing Aβrelease remain poorly understood.To identify key regulators of Aβ42 transport,we applied formaldehyde cross-linking of protein complexes combined with co-immunoprecipitation and mass spectrometry analysis to identify TMED10 as a novel Aβ42-interacting protein.In cultured neurons,TMED10 knockdown(KD)increased intracellular Aβ42 levels by preventing Aβ42 exocytosis.TMED10 expression was significantly reduced in the cortex of AD patients.Overexpression of TMED10 in primary neurons mitigated the toxic effects of exogenous Aβ42.In 5×FAD mice,overexpression of TMED10 via tail vein injection of a brain-penetrable adeno-associated virus improved cognitive function and reduced Aβ42 plaque accumulation.Together,these findings position TMED10 as a potential regulator of Aβ42 exocytosis and underscore the need for further studies to evaluate its therapeutic potential in AD.展开更多
Habitat loss driven by land-use change is a major factor shaping the dynamics of urban bird community structures.However,the potential mechanisms by which the spatial configuration and composition of blue-green infras...Habitat loss driven by land-use change is a major factor shaping the dynamics of urban bird community structures.However,the potential mechanisms by which the spatial configuration and composition of blue-green infrastructure,recognized as biodiversity hotspots in urban landscapes,influence urban bird beta diversity remain insufficiently understood.This study was conducted in the built-up area of Yinchuan,an internationally recognized wetland city in Northwest China.From December 2023 to June 2024,we systematically surveyed bird communities during both the breeding and wintering periods across 29 blue-green space mosaics.We quantified taxonomic,functional,and phylogenetic beta diversity,along with their turnover component and nestedness-resultant component,based on both pairwise beta diversity and multiple-site beta diversity.We further assessed the relative importance of landscape variables and spatial geographic distance in shaping beta diversity patterns and used hierarchical modeling of species communities(HMSC)to explore the responses of bird occurrence and functional traits to landscape variables.Our results revealed that species turnover was the dominant driver of taxonomic,functional,and phylogenetic beta diversity.Seasonal differences were observed in the effects of spatial geographic distance and landscape structure on beta diversity and its components,with landscape variables showing higher explanatory power than geographic isolation.In the breeding period,landscape diversity and waterbody area had positive effects on bird occurrence,whereas in the wintering period,most landscape features—except for landscape diversity—exerted neutral or negative influences.Regarding functional traits,we found that reproductive traits,flight ability,and foraging characteristics responded significantly to landscape structure,and that some small-bodied species active in aerial and canopy layers were more adaptable to habitat fragmentation.This study provides novel insights into the assembly processes and driving mechanisms of urban bird communities and offers scientific support for the notion that designing and maintaining blue-green infrastructure can contribute to urban biodiversity conservation.展开更多
Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the col...Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown t...Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.展开更多
Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson...Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.展开更多
Ambient light has profound effects on early seedling de-etiolation through red and far-red light-absorbing phytochromes and blue and UV-A light-absorbing cryptochromes. Subsequent integration of various light signal t...Ambient light has profound effects on early seedling de-etiolation through red and far-red light-absorbing phytochromes and blue and UV-A light-absorbing cryptochromes. Subsequent integration of various light signal trans- duction pathways leads to changes in gene expression and morphogenic responses. Here, we report the isolation of a new Arabidopsis light-signaling component, HYPOSENSITIVE TO LIGHT or HTL. Both htl-1 and htl-2 alleles displayed a long hypocotyl phenotype under red, far-red, and blue light, whereas overexpression of HTL caused a short hypocotyl pheno- type under similar light conditions. The mutants also showed other photomorphogenic defects such as elongated petioles, retarded cotyledon and leaf expansion, reduced accumulation of chlorophyll and anthocyanin pigments, and attenuated expression of light-responsive CHLOROPHYLL A/B BINDING PROTEIN 3 and CHALCONE SYNTHASE genes. HTL belongs to an alpha/beta fold protein family and is localized strongly in the nucleus and weakly in the cytosol. The expression of HTL was strongly induced by light of various wavelengths and this light induction was impaired in elongated hypocotyl 5. HY5 directly bound to both a C/G-box and a G-box in the HTL promoter but with a greater affinity toward the C/G-box. HTL, therefore, represents a new signaling step downstream of HY5 in phy- and cry-mediated de-etiolation responses.展开更多
基金Supported by the Autonomous Research Project of SKLCC(2024BWZ003)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA0390401)the Doctoral Research Start-up Funding of Shanxi Institute of Technology(026012).
文摘KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to evaluate the influence of varying hydrothermal synthesis temperatures on the physicochemical properties of both the KIT-5/Beta supports and the resulting catalysts.The catalytic performances of catalysts were evaluated under reaction conditions of 320℃,4 MPa H_(2)pressure,and a weight hourly space velocity(WHSV)of 4.8 h^(-1)for hydrodenitrogenation(HDN)of quinoline.The results indicated that the specific surface area and pore structure of the materials could be effectively regulated by adjusting the hydrothermal synthesis temperature,which in turn influenced the number of active sites on the catalyst.The NiW/KB-125 catalyst,synthesized at 125℃,presented the highest quinoline HDN efficiency(96.8%),which can be attributed to its favorable pore channel structure,greater Brønsted acid number,higher degree of metal sulfidation(80.12%)and appropriate metal-support interaction(MSI).
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
基金supported by research grants from the National Key Research and Development Program of China(2020YFA0804502)the National Natural Science Foundation of China(82101545)+1 种基金the CAMS Innovation Fund for Medical Sciences(2022-I2M-1-002)National High-Level Hospital Clinical Research Funding(2022-PUMCH-D-002).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by neurotoxic amyloid beta(Aβ)deposition in the brain.Neurons can internalize and exocytose Aβ;however,the molecular pathways governing Aβrelease remain poorly understood.To identify key regulators of Aβ42 transport,we applied formaldehyde cross-linking of protein complexes combined with co-immunoprecipitation and mass spectrometry analysis to identify TMED10 as a novel Aβ42-interacting protein.In cultured neurons,TMED10 knockdown(KD)increased intracellular Aβ42 levels by preventing Aβ42 exocytosis.TMED10 expression was significantly reduced in the cortex of AD patients.Overexpression of TMED10 in primary neurons mitigated the toxic effects of exogenous Aβ42.In 5×FAD mice,overexpression of TMED10 via tail vein injection of a brain-penetrable adeno-associated virus improved cognitive function and reduced Aβ42 plaque accumulation.Together,these findings position TMED10 as a potential regulator of Aβ42 exocytosis and underscore the need for further studies to evaluate its therapeutic potential in AD.
基金supported by the National Natural Science Foundation of China(32401409)the Central Government’s Special Fund for National Key Protected Wildlife Conservation Projects in Yinchuan City(HXCG-ZC2023148,XZ-2024-16)。
文摘Habitat loss driven by land-use change is a major factor shaping the dynamics of urban bird community structures.However,the potential mechanisms by which the spatial configuration and composition of blue-green infrastructure,recognized as biodiversity hotspots in urban landscapes,influence urban bird beta diversity remain insufficiently understood.This study was conducted in the built-up area of Yinchuan,an internationally recognized wetland city in Northwest China.From December 2023 to June 2024,we systematically surveyed bird communities during both the breeding and wintering periods across 29 blue-green space mosaics.We quantified taxonomic,functional,and phylogenetic beta diversity,along with their turnover component and nestedness-resultant component,based on both pairwise beta diversity and multiple-site beta diversity.We further assessed the relative importance of landscape variables and spatial geographic distance in shaping beta diversity patterns and used hierarchical modeling of species communities(HMSC)to explore the responses of bird occurrence and functional traits to landscape variables.Our results revealed that species turnover was the dominant driver of taxonomic,functional,and phylogenetic beta diversity.Seasonal differences were observed in the effects of spatial geographic distance and landscape structure on beta diversity and its components,with landscape variables showing higher explanatory power than geographic isolation.In the breeding period,landscape diversity and waterbody area had positive effects on bird occurrence,whereas in the wintering period,most landscape features—except for landscape diversity—exerted neutral or negative influences.Regarding functional traits,we found that reproductive traits,flight ability,and foraging characteristics responded significantly to landscape structure,and that some small-bodied species active in aerial and canopy layers were more adaptable to habitat fragmentation.This study provides novel insights into the assembly processes and driving mechanisms of urban bird communities and offers scientific support for the notion that designing and maintaining blue-green infrastructure can contribute to urban biodiversity conservation.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
文摘Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by grants from Tianjin Scientific Research Project in Key Areas of Traditional Chinese Medicine,Tianjin Municipal Health Commission,No.2024012(to JL)Tianjin Municipal Education Commission Project,No.2021KJ217(to CS)。
文摘Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.
基金supported by the Spanish Ministry of Science and Innovation via a doctoral grant[FPU22/03656].supported by the Spanish Ministry of Science and Innovation(PID2022-137963OB-I00)Generalitat de Catalunya(2021-SGR-00635 AGAUR)+1 种基金CERCA Programme(Generalitat de Catalunya)by ICREA,ICREA-Academia 2020(to SV)。
文摘Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.
基金This work was supported by the National Science Foundation,by the Plant Biological Sciences Doctoral Dissertation Fellowship and Summer Fellowship from the University of Minnesota
文摘Ambient light has profound effects on early seedling de-etiolation through red and far-red light-absorbing phytochromes and blue and UV-A light-absorbing cryptochromes. Subsequent integration of various light signal trans- duction pathways leads to changes in gene expression and morphogenic responses. Here, we report the isolation of a new Arabidopsis light-signaling component, HYPOSENSITIVE TO LIGHT or HTL. Both htl-1 and htl-2 alleles displayed a long hypocotyl phenotype under red, far-red, and blue light, whereas overexpression of HTL caused a short hypocotyl pheno- type under similar light conditions. The mutants also showed other photomorphogenic defects such as elongated petioles, retarded cotyledon and leaf expansion, reduced accumulation of chlorophyll and anthocyanin pigments, and attenuated expression of light-responsive CHLOROPHYLL A/B BINDING PROTEIN 3 and CHALCONE SYNTHASE genes. HTL belongs to an alpha/beta fold protein family and is localized strongly in the nucleus and weakly in the cytosol. The expression of HTL was strongly induced by light of various wavelengths and this light induction was impaired in elongated hypocotyl 5. HY5 directly bound to both a C/G-box and a G-box in the HTL promoter but with a greater affinity toward the C/G-box. HTL, therefore, represents a new signaling step downstream of HY5 in phy- and cry-mediated de-etiolation responses.