Amyotrophic lateral sclerosis(ALS)is a fatal,late-onset neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the motor cortex,brainstem,and spinal cord(Feldman et al.,2022).
Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(C...Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(Cleveland and Rothstein,2001).Frontotemporal lobar degeneration(FTLD)is a neurodegenerative disease affecting the frontal and temporal lobes of the brain,leading to changes in behavior,personality,and language(Van Langenhove et al.,2012).Both ALS and FTLD are classified as proteinopathies in which abnormal protein aggregation and accumulation in neurons contribute to the disease pathogenesis.Fused in sarcoma(FUS)is a DNA/RNA-binding protein involved in various cellular processes,including transcriptional regulation,RNA splicing,and DNA repair.Mutations in the FUS gene have been linked to familial ALS,highlighting the importance of FUS in the disease pathogenesis(Vance et al.,2009).In ALS and FTLD,aberrant post-translational modifications(PTMs)of FUS,such as phosphorylation,acetylation,and methylation,have been implicated in the promotion of FUS aggregation and neurotoxicity(Choi et al.,2023).Therefore,understanding the regulatory mechanisms of FUS PTMs is crucial for developing targeted therapies against these diseases.展开更多
Objective Brown and beige adipocytes dissipate energy through thermogenesis,and the impaired thermogenic function of these adipocytes is a key driver of obesity and related metabolic disorders.However,the molecular me...Objective Brown and beige adipocytes dissipate energy through thermogenesis,and the impaired thermogenic function of these adipocytes is a key driver of obesity and related metabolic disorders.However,the molecular mechanisms governing adipocyte thermogenesis are not fully understood.This study investigated the role of inorganic pyrophosphatase 1(PPA1)in regulating adipocyte thermogenesis and assessed its potential as a therapeutic target for obesity and metabolic disorders.Methods To investigate the function of PPA1 in adipose tissue thermogenesis,we generated adipose-specific heterozygous PPA1 knockout mice via the Cre-loxP system and established cold exposure models.PPA1 deletion effects were assessed by hematoxylin and eosin(H&E)staining,immunofluorescence,quantitative polymerase chain reaction(qPCR),and immunoblotting.Mitochondrial changes during browning were further characterized via transmission electron microscopy(TEM),mitochondrial DNA(mtDNA)quantification,qPCR,and Western blotting.The molecular mechanisms involved were subsequently dissected via mass spectrometry,coimmunoprecipitation(Co-IP),and immunofluorescence colocalization.Results Adi-PPA1^(fl/+)mice presented impaired adipose tissue thermogenesis upon cold exposure.Mechanistically,PPA1 deficiency impaired adipose browning in an enzyme activity-independent manner.PPA1 knockdown promoted the aberrant translocation and accumulation of fused in sarcoma(FUS)to mitochondria,which triggered mitochondrial dysfunction and suppressed browning.Crucially,silencing FUS effectively rescued the mitochondrial defects caused by PPA1 depletion.Conclusion PPA1 functions as a nonenzymatic positive regulator of adipocyte thermogenesis by interacting with FUS to prevent its mitochondrial mislocalization,thereby maintaining mitochondrial function and promoting adipose browning.These findings highlight PPA1 as a potential therapeutic avenue for obesity and metabolic disorders.展开更多
At present, multi-se nsor fusion is widely used in object recognition and classification, since this technique can efficiently improve the accuracy and the ability of fault toleranc e. This paper describes a multi-se...At present, multi-se nsor fusion is widely used in object recognition and classification, since this technique can efficiently improve the accuracy and the ability of fault toleranc e. This paper describes a multi-sensor fusion system, which is model-based and used for rotating mechanical failure diagnosis. In the data fusion process, the fuzzy neural network is selected and used for the data fusion at report level. By comparing the experimental results of fault diagnoses based on fusion data wi th that on original separate data,it is shown that the former is more accurate than the latter.展开更多
A data fusion method of online multisensors is prop os ed in this paper based on artificial neuron. First, the dynamic data fusion mode l on artificial neuron is built. Then the calibration of data fusion is discusse ...A data fusion method of online multisensors is prop os ed in this paper based on artificial neuron. First, the dynamic data fusion mode l on artificial neuron is built. Then the calibration of data fusion is discusse d with self-adaptive weighing technique. Finally performance of the method is d emonstrated by an online vibration measurement case. The results show that the f used data are more stable, sensitive, accurate, reliable than that of single sen sor data.展开更多
基金supported by the Else Kröner-Fresenius-Stiftung(2021-EKSE.95)the Deutsche Forschungsgemeinschaft(CRC1678 and Germany’s Excellence Strategy-CECAD,EXC 2030-390661388)(to DV).
文摘Amyotrophic lateral sclerosis(ALS)is a fatal,late-onset neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the motor cortex,brainstem,and spinal cord(Feldman et al.,2022).
基金supported by the BK21 FOUR(Fostering Outstanding Universities for Research)and the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(MOE)and the Ministry of Science and ICT(MSIT)(NRF-2022R1A2C1004204,RS-2023-00219563,2023-DD-UP-0007)by the Soonchunhyang University Research Fund(to KK)。
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disorder characterized by the degeneration of motor neurons in the brain and spinal cord,leading to muscle weakness,paralysis,and ultimately death(Cleveland and Rothstein,2001).Frontotemporal lobar degeneration(FTLD)is a neurodegenerative disease affecting the frontal and temporal lobes of the brain,leading to changes in behavior,personality,and language(Van Langenhove et al.,2012).Both ALS and FTLD are classified as proteinopathies in which abnormal protein aggregation and accumulation in neurons contribute to the disease pathogenesis.Fused in sarcoma(FUS)is a DNA/RNA-binding protein involved in various cellular processes,including transcriptional regulation,RNA splicing,and DNA repair.Mutations in the FUS gene have been linked to familial ALS,highlighting the importance of FUS in the disease pathogenesis(Vance et al.,2009).In ALS and FTLD,aberrant post-translational modifications(PTMs)of FUS,such as phosphorylation,acetylation,and methylation,have been implicated in the promotion of FUS aggregation and neurotoxicity(Choi et al.,2023).Therefore,understanding the regulatory mechanisms of FUS PTMs is crucial for developing targeted therapies against these diseases.
基金supported by Basic-Clinical Cooperation Program from Capital Medical University(No.PYZ24119)the National Natural Science Foundation of China(Nos.82270874,82370855).
文摘Objective Brown and beige adipocytes dissipate energy through thermogenesis,and the impaired thermogenic function of these adipocytes is a key driver of obesity and related metabolic disorders.However,the molecular mechanisms governing adipocyte thermogenesis are not fully understood.This study investigated the role of inorganic pyrophosphatase 1(PPA1)in regulating adipocyte thermogenesis and assessed its potential as a therapeutic target for obesity and metabolic disorders.Methods To investigate the function of PPA1 in adipose tissue thermogenesis,we generated adipose-specific heterozygous PPA1 knockout mice via the Cre-loxP system and established cold exposure models.PPA1 deletion effects were assessed by hematoxylin and eosin(H&E)staining,immunofluorescence,quantitative polymerase chain reaction(qPCR),and immunoblotting.Mitochondrial changes during browning were further characterized via transmission electron microscopy(TEM),mitochondrial DNA(mtDNA)quantification,qPCR,and Western blotting.The molecular mechanisms involved were subsequently dissected via mass spectrometry,coimmunoprecipitation(Co-IP),and immunofluorescence colocalization.Results Adi-PPA1^(fl/+)mice presented impaired adipose tissue thermogenesis upon cold exposure.Mechanistically,PPA1 deficiency impaired adipose browning in an enzyme activity-independent manner.PPA1 knockdown promoted the aberrant translocation and accumulation of fused in sarcoma(FUS)to mitochondria,which triggered mitochondrial dysfunction and suppressed browning.Crucially,silencing FUS effectively rescued the mitochondrial defects caused by PPA1 depletion.Conclusion PPA1 functions as a nonenzymatic positive regulator of adipocyte thermogenesis by interacting with FUS to prevent its mitochondrial mislocalization,thereby maintaining mitochondrial function and promoting adipose browning.These findings highlight PPA1 as a potential therapeutic avenue for obesity and metabolic disorders.
文摘At present, multi-se nsor fusion is widely used in object recognition and classification, since this technique can efficiently improve the accuracy and the ability of fault toleranc e. This paper describes a multi-sensor fusion system, which is model-based and used for rotating mechanical failure diagnosis. In the data fusion process, the fuzzy neural network is selected and used for the data fusion at report level. By comparing the experimental results of fault diagnoses based on fusion data wi th that on original separate data,it is shown that the former is more accurate than the latter.
文摘A data fusion method of online multisensors is prop os ed in this paper based on artificial neuron. First, the dynamic data fusion mode l on artificial neuron is built. Then the calibration of data fusion is discusse d with self-adaptive weighing technique. Finally performance of the method is d emonstrated by an online vibration measurement case. The results show that the f used data are more stable, sensitive, accurate, reliable than that of single sen sor data.
