α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Multimodal image fusion plays an important role in image analysis and applications.Multimodal medical image fusion helps to combine contrast features from two or more input imaging modalities to represent fused inform...Multimodal image fusion plays an important role in image analysis and applications.Multimodal medical image fusion helps to combine contrast features from two or more input imaging modalities to represent fused information in a single image.One of the critical clinical applications of medical image fusion is to fuse anatomical and functional modalities for rapid diagnosis of malignant tissues.This paper proposes a multimodal medical image fusion network(MMIF-Net)based on multiscale hybrid attention.The method first decomposes the original image to obtain the low-rank and significant parts.Then,to utilize the features at different scales,we add amultiscalemechanism that uses three filters of different sizes to extract the features in the encoded network.Also,a hybrid attention module is introduced to obtain more image details.Finally,the fused images are reconstructed by decoding the network.We conducted experiments with clinical images from brain computed tomography/magnetic resonance.The experimental results show that the multimodal medical image fusion network method based on multiscale hybrid attention works better than other advanced fusion methods.展开更多
ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant...ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of Gal R2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress(CMS) decreased the expression of both ETS-1 and Gal R2 in the ventral hippocampus of rats. Meanwhile,we demonstrated that overexpression of ETS-1 increased the expression of Gal R2 in primary hippocampal neurons.Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2(p-ERK1/2) of Gal R2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats,which might be mediated by increasing the level of Gal R2 and its downstream p-ERK1/2 in the ventral hippocampus.展开更多
Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these ...Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.展开更多
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by Qingdao Huanghai University School-Level ScientificResearch Project(2023KJ14)Undergraduate Teaching Reform Research Project of Shandong Provincial Department of Education(M2022328)+1 种基金National Natural Science Foundation of China under Grant(42472324)Qingdao Postdoctoral Foundation under Grant(QDBSH202402049).
文摘Multimodal image fusion plays an important role in image analysis and applications.Multimodal medical image fusion helps to combine contrast features from two or more input imaging modalities to represent fused information in a single image.One of the critical clinical applications of medical image fusion is to fuse anatomical and functional modalities for rapid diagnosis of malignant tissues.This paper proposes a multimodal medical image fusion network(MMIF-Net)based on multiscale hybrid attention.The method first decomposes the original image to obtain the low-rank and significant parts.Then,to utilize the features at different scales,we add amultiscalemechanism that uses three filters of different sizes to extract the features in the encoded network.Also,a hybrid attention module is introduced to obtain more image details.Finally,the fused images are reconstructed by decoding the network.We conducted experiments with clinical images from brain computed tomography/magnetic resonance.The experimental results show that the multimodal medical image fusion network method based on multiscale hybrid attention works better than other advanced fusion methods.
基金supported by grants from the National Natural Science Foundation of China (31271154, 31171032, and 81671345)the Beijing Natural Science Foundation (7162016)+1 种基金the Special Project on Natural Chronic Non-infectious Diseases (2016YFC1307202)the Beijing Municipal Science and Technology Commission (Z181100001518001)
文摘ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of Gal R2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress(CMS) decreased the expression of both ETS-1 and Gal R2 in the ventral hippocampus of rats. Meanwhile,we demonstrated that overexpression of ETS-1 increased the expression of Gal R2 in primary hippocampal neurons.Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2(p-ERK1/2) of Gal R2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats,which might be mediated by increasing the level of Gal R2 and its downstream p-ERK1/2 in the ventral hippocampus.
基金the authors are supported by grants from Natural Science Foundation of China(81671244,81371200,and 81401042)a special fund from Key Laboratory of Neurodegenerative Disease,Ministry of Education(PXM2019_026283_000002)+1 种基金Beijing Municipal Science and Technology Commission(Z161100005116011,Z171100000117013)Beijing Municipal commission of Health and Family Planning(PXM2017_026283_000002).
文摘Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.
