Sorption between nanoparticles(NPs)and minerals may critically affect the migration of associated elements as well as the environmental impact of NPs.Since illite is widely present in soil,sediment,and water,we have e...Sorption between nanoparticles(NPs)and minerals may critically affect the migration of associated elements as well as the environmental impact of NPs.Since illite is widely present in soil,sediment,and water,we have experimentally investigated the sorption behavior of citrate-coated gold nanoparticles(AuNPs)as model NPs on illite under different pH and mineral mass conditions.We demonstrated that sorption of these negatively charged AuNPs strongly depended on the suspension pH.At pH above 8,which coincided with the apparent point of zero charge(pH 7.9)of our illite sample,only marginal sorption of AuNPs was observed.At pH 3-8,significant sorption of AuNPs on illite was found,with almost complete sorption occurring at more acidic conditions(pH 3-4).TEM observations revealed that sorption took place through the attachment AuNPs on illite edges.At pH 2,AuNPs mostly formed chain-like fused structures and precipitated out of the suspension.Based upon the above pH dependence,residual organic ligand content after sorption,and complementary sorption results with positively charged AuNPs,we conclude that the sorption process is mainly driven by the electrostatic attraction between negatively charged AuNPs and positively charged illite edges,with possible competitive involvement of citrate molecules.We expect that our findings will improve our understanding of NP-mineral interaction and the environmental fate of NPs.展开更多
Enrichment of As and Au at the overgrowth rims of arsenian pyrite is a distinctive feature of Carlin-type gold ores.Revealing distribution of such key elements in high resolution is of fundamental importance yet often...Enrichment of As and Au at the overgrowth rims of arsenian pyrite is a distinctive feature of Carlin-type gold ores.Revealing distribution of such key elements in high resolution is of fundamental importance yet often proves challenging.In this study,repeated non-oxidative acid etching of ore samples from Shuiyindong gold deposit was applied to enable elemental depth profiling of goldbearing arsenian pyrite grains.ICP-OES and AAS were used to determine the dissolved Fe,As,and Au concentrations in each of the etching solutions,and XPS was carried out to exam the etched mineral surfaces.In contrast to conventional ion beam etching that may cause substantial sample damage,our acid etching method does not seem to significantly alter the composition and chemical state of the samples.The etched depths directly converted from the measured elemental concentrations can reproducibly reach a very high resolution of~1 nm,and can be conveniently controlled through varying the etching time.While the Fe and As depth profiles consistently reflect the surface oxidation property of arsenian pyrite,the Au profile displaying an obvious upward trend reveals the ore fluid evolution at the late stage of mineralization.Based on our experimental results,we demonstrate that our wet chemistry method is capable of effective depth profiling of gold ore and perhaps other geological samples,with advantages surpassing many instrumental techniques including negligible sample damage,nanoscale resolution as well as isotropic etching.展开更多
While engineered nanoparticles are widely used and maybe eventually released into the environment,natural nanoparticles are also commonly found in the Earth system.Nanoparticles may critically affect the geochemical m...While engineered nanoparticles are widely used and maybe eventually released into the environment,natural nanoparticles are also commonly found in the Earth system.Nanoparticles may critically affect the geochemical migration of associated elements and pose potential threats to the ecological environment.It is necessary to establish an accurate and reliable method for measuring the concentration of nanoparticles.AAS is one of the most commonly used methods for the concentration determination of nanoparticles.However,till now,there has been no systematic report on how experimental variables affect AAS measurements.In this study,we used gold nanoparticles(AuNPs) as an example and studied the influences of a list of factors on the concentration determination of AuNPs by AAS,including digestion method,ionization interference,acidic medium,background correction method,and organic matter.We demonstrate that all these factors may have varying degrees of influence on the measured gold concentrations.When the gold colloid is digested at room temperature for more than 8 h or at 60℃ for more than 2 h,and the system contains a low concentration of organic matter,AAS can accurately measure the AuNP concentration at ppm-level.The deuterium lamp background deduction method is not recommended to use for samples with lower gold concentrations.展开更多
Objective： The aim of this study was to evaluate L-J （Lo＂wenstein-Jensen） medium culture, MGIT 960 culture anddifferent specimen types in diagnosis of BJTB （bone and joint tuberculosis）. Methods：： Specimens of...Objective： The aim of this study was to evaluate L-J （Lo＂wenstein-Jensen） medium culture, MGIT 960 culture anddifferent specimen types in diagnosis of BJTB （bone and joint tuberculosis）. Methods：： Specimens of pus, caseous necrosis,tuberculous granuloma and sequestrum were collected from 52 BJTB patients. All specimens were cultured using both MGIT 960system and L-J medium; and all pus were amplified using real-time PCR to detect the presence of M. tuberculosis DNA. KeyFindings： A total of 191 specimens were collected. Granuloma had better chance to produce positive outcomes by L-J mediumculture, while for sequestrum MGIT 960 culture had higher yield, but there was no significant difference in the recovery rates amongdifferent types of specimen either by L-J culture （Z2 = 0.638, P = 0.888） or by MGIT960 culture （Z2 = 1.399, P = 0.706）. MGIT960culture had significantly higher recovery rate than L-J culture, With a combined culture and PCR-based test, the recovery rate of pusspecimen was significantly higher than that of either method alone （P 〈 0.05）. Conclusion： MGIT 960 culture is superior to L-Jculture in BJTB diagnosis; pus, sequestrum, granuloma and caseous necrosis are usable specimen for mycobacterial culture;combination of culture and molecular techniques can provide a better diagnostic significance.展开更多
The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a s...The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.展开更多
Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2...Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.展开更多
Background Parkinson’s disease(PD)is characterised by degeneration of ventral midbrain dopaminergic(DA)neurons and abnormal deposition ofα-synuclein(α-syn)in neurons.Activation of the innate immune pathogen recogni...Background Parkinson’s disease(PD)is characterised by degeneration of ventral midbrain dopaminergic(DA)neurons and abnormal deposition ofα-synuclein(α-syn)in neurons.Activation of the innate immune pathogen recognition receptor toll-like receptor 2(TLR2)is associated with exacerbation ofα-syn pathology.TLR2 is increased on neurons in the PD brain,and its activation results in the accumulation and propagation ofα-syn through autophagy inhibition in neurons.In addition to the aggregation and propagation of pathologicalα-syn,dysfunction of astrocytes may contribute to DA neuronal death and subsequent clinical progression of PD.However,the role of astrocytes in TLR2-mediated PD pathology is less explored but important to address,given that TLR2 is a potential therapeutic target for PD.Methods Induced pluripotent stem cells from three controls and three PD patients were differentiated into a midbrain model comprised of neurons(including DA neurons)and astrocytes.Cells were treated with or without the TLR2 agonist Pam3CSK4,andα-syn pathology was seeded using pre-formed fibrils.Confocal imaging was used to assess lysosomal function andα-syn pathology in the different cell types,as well as DA neuron health and astrocyte activation.Results TLR2 activation acutely impaired the autophagy lysosomal pathway,and potentiatedα-syn pathology seeded by pre-formed fibrils in PD neurons and astrocytes,leading to degeneration and loss of DA neurons.The astrocytes displayed impaired chaperone-mediated autophagy reducing their ability to clear accumulatedα-syn,and increases of A1 neurotoxic phenotypic proteins SerpinG1,complement C3,PSMB8 and GBP2.Moreover,the phenotypic changes in astrocytes correlated with a specific loss of DA neurons.Conclusions Taken together,these results support a role for astrocyte dysfunction inα-syn accumulation and DA neuronal loss following TLR2 activation in PD.展开更多
Background Parkinson’s disease(PD)and multiple system atrophy(MSA)are classified asα-synucleinopathies and are primarily differentiated by their clinical phenotypes.Delineating these diseases based on their specific...Background Parkinson’s disease(PD)and multiple system atrophy(MSA)are classified asα-synucleinopathies and are primarily differentiated by their clinical phenotypes.Delineating these diseases based on their specificα-synuclein(α-Syn)proteoform pathologies is crucial for accurate antemortem biomarker diagnosis.Newly identifiedα-Syn pathologies in PD raise questions about whether MSA exhibits a similar diversity.This prompted the need for a comparative study focusing onα-Syn epitope-specific immunoreactivities in both diseases,which could clarify the extent of pathological overlap and diversity,and guide more accurate biomarker development.Methods We utilised a multiplex immunohistochemical approach to detect multiple structural domains ofα-Syn proteoforms across multiple regions prone to pathological accumulation in MSA(n=10)and PD(n=10).Comparison of epitope-specificα-Syn proteoforms was performed in the MSA medulla,inferior olivary nucleus,substantia nigra,hippocampus,and cerebellum,and in the PD olfactory bulb,medulla,substantia nigra,hippocampus,and entorhinal cortex.Results N-terminus and C-terminus antibodies detected significantly moreα-Syn pathology in MSA than antibodies for phosphorylated(pS129)α-Syn,which are classically used to detectα-Syn.Importantly,C-terminus immunolabelling is more pronounced in MSA compared to PD.Meanwhile,N-terminus immunolabelling consistently detected the highest percentage ofα-Syn across pathologically burdened regions of both diseases,which could be of biological significance.As expected,oligodendroglial involvement distinguished MSA from PD,but in contrast to PD,no substantial astrocytic or microglialα-Syn accumulation in MSA occurred.These data confirm glial-specific changes between these diseases when immunolabelling the N-terminus epitope.In comparison,N-terminus neuronalα-Syn was present in PD and MSA,with most MSA neurons lacking pS129α-Syn proteoforms.This explains why characterisation of neuronal MSA pathologies is lacking and challenges the reliance on pS129 antibodies for the accurate quantification ofα-Syn pathological load acrossα-synucleinopathies.Conclusions These findings underscore the necessity of utilising a multiplex approach to detectα-Syn,most importantly including the N-terminus,to capture the entire spectrum ofα-Syn proteoforms inα-synucleinopathies.The data provide novel insights toward the biological differentiation of theseα-synucleinopathies and pave the way for more refined antemortem diagnostic methods to facilitate early identification and intervention of these neurodegenerative diseases.展开更多
基金financially supported by the National Natural Science Foundation of China(41872046)Doctoral Research Startup Project in 2017 of Guizhou Normal University in ChinaProject of Science and Technology Supporting Plan,Guizhou Province(Qian Sci.Co.[2017],No.2580)。
文摘Sorption between nanoparticles(NPs)and minerals may critically affect the migration of associated elements as well as the environmental impact of NPs.Since illite is widely present in soil,sediment,and water,we have experimentally investigated the sorption behavior of citrate-coated gold nanoparticles(AuNPs)as model NPs on illite under different pH and mineral mass conditions.We demonstrated that sorption of these negatively charged AuNPs strongly depended on the suspension pH.At pH above 8,which coincided with the apparent point of zero charge(pH 7.9)of our illite sample,only marginal sorption of AuNPs was observed.At pH 3-8,significant sorption of AuNPs on illite was found,with almost complete sorption occurring at more acidic conditions(pH 3-4).TEM observations revealed that sorption took place through the attachment AuNPs on illite edges.At pH 2,AuNPs mostly formed chain-like fused structures and precipitated out of the suspension.Based upon the above pH dependence,residual organic ligand content after sorption,and complementary sorption results with positively charged AuNPs,we conclude that the sorption process is mainly driven by the electrostatic attraction between negatively charged AuNPs and positively charged illite edges,with possible competitive involvement of citrate molecules.We expect that our findings will improve our understanding of NP-mineral interaction and the environmental fate of NPs.
基金Financial supports from the B-type Strategic Priority Program of the Chinese Academy of Sciences(Grant No.XDB41000000)the National Natural Science Foundation of China(41872046,41902041 and 41173074)the Natural Science Research Project of Education Department of Guizhou Province(No.KY[2018]004)are sincerely acknowledged.
文摘Enrichment of As and Au at the overgrowth rims of arsenian pyrite is a distinctive feature of Carlin-type gold ores.Revealing distribution of such key elements in high resolution is of fundamental importance yet often proves challenging.In this study,repeated non-oxidative acid etching of ore samples from Shuiyindong gold deposit was applied to enable elemental depth profiling of goldbearing arsenian pyrite grains.ICP-OES and AAS were used to determine the dissolved Fe,As,and Au concentrations in each of the etching solutions,and XPS was carried out to exam the etched mineral surfaces.In contrast to conventional ion beam etching that may cause substantial sample damage,our acid etching method does not seem to significantly alter the composition and chemical state of the samples.The etched depths directly converted from the measured elemental concentrations can reproducibly reach a very high resolution of~1 nm,and can be conveniently controlled through varying the etching time.While the Fe and As depth profiles consistently reflect the surface oxidation property of arsenian pyrite,the Au profile displaying an obvious upward trend reveals the ore fluid evolution at the late stage of mineralization.Based on our experimental results,we demonstrate that our wet chemistry method is capable of effective depth profiling of gold ore and perhaps other geological samples,with advantages surpassing many instrumental techniques including negligible sample damage,nanoscale resolution as well as isotropic etching.
基金supported by Guizhou Provincial Science and Technology Foundation (Qian Sci.Co.ZK[2021] No.198)Doctoral Research Startup Project in 2017 of Guizhou Normal University in China+1 种基金the B-type Strategic Priority Program of the Chinese Academy of Sciences (Grant No.XDB41000000)the National Natural Science Foundation of China (41872046,41173074 and 42063008)。
文摘While engineered nanoparticles are widely used and maybe eventually released into the environment,natural nanoparticles are also commonly found in the Earth system.Nanoparticles may critically affect the geochemical migration of associated elements and pose potential threats to the ecological environment.It is necessary to establish an accurate and reliable method for measuring the concentration of nanoparticles.AAS is one of the most commonly used methods for the concentration determination of nanoparticles.However,till now,there has been no systematic report on how experimental variables affect AAS measurements.In this study,we used gold nanoparticles(AuNPs) as an example and studied the influences of a list of factors on the concentration determination of AuNPs by AAS,including digestion method,ionization interference,acidic medium,background correction method,and organic matter.We demonstrate that all these factors may have varying degrees of influence on the measured gold concentrations.When the gold colloid is digested at room temperature for more than 8 h or at 60℃ for more than 2 h,and the system contains a low concentration of organic matter,AAS can accurately measure the AuNP concentration at ppm-level.The deuterium lamp background deduction method is not recommended to use for samples with lower gold concentrations.
文摘Objective： The aim of this study was to evaluate L-J （Lo＂wenstein-Jensen） medium culture, MGIT 960 culture anddifferent specimen types in diagnosis of BJTB （bone and joint tuberculosis）. Methods：： Specimens of pus, caseous necrosis,tuberculous granuloma and sequestrum were collected from 52 BJTB patients. All specimens were cultured using both MGIT 960system and L-J medium; and all pus were amplified using real-time PCR to detect the presence of M. tuberculosis DNA. KeyFindings： A total of 191 specimens were collected. Granuloma had better chance to produce positive outcomes by L-J mediumculture, while for sequestrum MGIT 960 culture had higher yield, but there was no significant difference in the recovery rates amongdifferent types of specimen either by L-J culture （Z2 = 0.638, P = 0.888） or by MGIT960 culture （Z2 = 1.399, P = 0.706）. MGIT960culture had significantly higher recovery rate than L-J culture, With a combined culture and PCR-based test, the recovery rate of pusspecimen was significantly higher than that of either method alone （P 〈 0.05）. Conclusion： MGIT 960 culture is superior to L-Jculture in BJTB diagnosis; pus, sequestrum, granuloma and caseous necrosis are usable specimen for mycobacterial culture;combination of culture and molecular techniques can provide a better diagnostic significance.
基金National Natural Science Foundation of China,Grant/Award Numbers:92249305,82120108010,81930028,31921003Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF/R11/1010National Institutes of Health,Grant/Award Number:R01DA056739。
文摘The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.
基金This study was partially supported by grant PR093728(DoD to B.S.)the National Natural Science Foundation of China(grant numbers 31470845 and 81430033 to B.S.,31422020 to F.L.and 31600704 to H.H.Z.)+2 种基金grant 13JC1404700 from the Program of Science and Technology Commission of Shanghai Municipality(B.S.)the Ministry of Science and Technology of China(Program 2014CB943600,F.L.)Chinese Mega Project on Infectious Diseases(No.2018ZX10302301).
文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.
基金funded by a bequest from Francis Patrick Gill, the University of Sydney.F.W and L.H are funded by PhD scholarships from the University of Sydney.G.M.H.is a NHMRC Senior Leadership Fellow(#1176607).
文摘Background Parkinson’s disease(PD)is characterised by degeneration of ventral midbrain dopaminergic(DA)neurons and abnormal deposition ofα-synuclein(α-syn)in neurons.Activation of the innate immune pathogen recognition receptor toll-like receptor 2(TLR2)is associated with exacerbation ofα-syn pathology.TLR2 is increased on neurons in the PD brain,and its activation results in the accumulation and propagation ofα-syn through autophagy inhibition in neurons.In addition to the aggregation and propagation of pathologicalα-syn,dysfunction of astrocytes may contribute to DA neuronal death and subsequent clinical progression of PD.However,the role of astrocytes in TLR2-mediated PD pathology is less explored but important to address,given that TLR2 is a potential therapeutic target for PD.Methods Induced pluripotent stem cells from three controls and three PD patients were differentiated into a midbrain model comprised of neurons(including DA neurons)and astrocytes.Cells were treated with or without the TLR2 agonist Pam3CSK4,andα-syn pathology was seeded using pre-formed fibrils.Confocal imaging was used to assess lysosomal function andα-syn pathology in the different cell types,as well as DA neuron health and astrocyte activation.Results TLR2 activation acutely impaired the autophagy lysosomal pathway,and potentiatedα-syn pathology seeded by pre-formed fibrils in PD neurons and astrocytes,leading to degeneration and loss of DA neurons.The astrocytes displayed impaired chaperone-mediated autophagy reducing their ability to clear accumulatedα-syn,and increases of A1 neurotoxic phenotypic proteins SerpinG1,complement C3,PSMB8 and GBP2.Moreover,the phenotypic changes in astrocytes correlated with a specific loss of DA neurons.Conclusions Taken together,these results support a role for astrocyte dysfunction inα-syn accumulation and DA neuronal loss following TLR2 activation in PD.
文摘Background Parkinson’s disease(PD)and multiple system atrophy(MSA)are classified asα-synucleinopathies and are primarily differentiated by their clinical phenotypes.Delineating these diseases based on their specificα-synuclein(α-Syn)proteoform pathologies is crucial for accurate antemortem biomarker diagnosis.Newly identifiedα-Syn pathologies in PD raise questions about whether MSA exhibits a similar diversity.This prompted the need for a comparative study focusing onα-Syn epitope-specific immunoreactivities in both diseases,which could clarify the extent of pathological overlap and diversity,and guide more accurate biomarker development.Methods We utilised a multiplex immunohistochemical approach to detect multiple structural domains ofα-Syn proteoforms across multiple regions prone to pathological accumulation in MSA(n=10)and PD(n=10).Comparison of epitope-specificα-Syn proteoforms was performed in the MSA medulla,inferior olivary nucleus,substantia nigra,hippocampus,and cerebellum,and in the PD olfactory bulb,medulla,substantia nigra,hippocampus,and entorhinal cortex.Results N-terminus and C-terminus antibodies detected significantly moreα-Syn pathology in MSA than antibodies for phosphorylated(pS129)α-Syn,which are classically used to detectα-Syn.Importantly,C-terminus immunolabelling is more pronounced in MSA compared to PD.Meanwhile,N-terminus immunolabelling consistently detected the highest percentage ofα-Syn across pathologically burdened regions of both diseases,which could be of biological significance.As expected,oligodendroglial involvement distinguished MSA from PD,but in contrast to PD,no substantial astrocytic or microglialα-Syn accumulation in MSA occurred.These data confirm glial-specific changes between these diseases when immunolabelling the N-terminus epitope.In comparison,N-terminus neuronalα-Syn was present in PD and MSA,with most MSA neurons lacking pS129α-Syn proteoforms.This explains why characterisation of neuronal MSA pathologies is lacking and challenges the reliance on pS129 antibodies for the accurate quantification ofα-Syn pathological load acrossα-synucleinopathies.Conclusions These findings underscore the necessity of utilising a multiplex approach to detectα-Syn,most importantly including the N-terminus,to capture the entire spectrum ofα-Syn proteoforms inα-synucleinopathies.The data provide novel insights toward the biological differentiation of theseα-synucleinopathies and pave the way for more refined antemortem diagnostic methods to facilitate early identification and intervention of these neurodegenerative diseases.
