Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders....Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.展开更多
The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin a...The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.展开更多
Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata...Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of life.Researchers con...Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of life.Researchers continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPSCNS/PCs)into spinal cord injured tissues.展开更多
Chinese President Xi Jinping,also General Secretary of the Communist Party of China Central Committee and Chairman of the Central Military Commission,delivers an important speech at a central conference on work relate...Chinese President Xi Jinping,also General Secretary of the Communist Party of China Central Committee and Chairman of the Central Military Commission,delivers an important speech at a central conference on work related to neighboring countries in Beijing,capital of China.The conference was held on April 8-9,2025.展开更多
Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional ...Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.展开更多
This eastern province sets an example in rural revitalization through green development.THE Green Rural Revival Program is an innovative initiative launched by east China’s Zhejiang Pro-vince.It aims to promote compr...This eastern province sets an example in rural revitalization through green development.THE Green Rural Revival Program is an innovative initiative launched by east China’s Zhejiang Pro-vince.It aims to promote comprehensive rural revitalization by focusing on environmental conservation and sustainable development.展开更多
Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve ...Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.展开更多
The Global Navigation Satellite System(GNSS)has been widely adopted in numerous fields,including intelligent transportation,remote sensing,and aeronautical and astronautical engineering.As new navigation approaches,te...The Global Navigation Satellite System(GNSS)has been widely adopted in numerous fields,including intelligent transportation,remote sensing,and aeronautical and astronautical engineering.As new navigation approaches,technologies,and applications continue to emerge,they attract significant global attention.Ensuring reliable positioning solutions with high accuracy,strong anti-interference capabilities,high availability and low integrity risks has become increasingly critical.展开更多
Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis(ALS)and other neurodegenerative diseases.While current studies have primarily focused on gene regulation mediated by full-...Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis(ALS)and other neurodegenerative diseases.While current studies have primarily focused on gene regulation mediated by full-length nuclear TDP-43,the potential effects of cytoplasmic TDP-43 fragments remain less explored.Our previous findings demonstrated that primate-specific cleavage of TDP-43 contributes to its cytoplasmic localization,prompting further investigation into its pathological effects.In the cynomolgus monkey brain,we observed that mutant or truncated TDP-43 was transported onto the ribosome organelle.Ribosome-associated transcriptomic analysis revealed dysregulation of apoptosis-and lysosome-related genes,indicating that cytoplasmic TDP-43 induces neurotoxicity by binding to ribosomes and disrupting mRNA expression.These findings provide mechanistic insights into the gain-of-function effects of pathological TDP-43.展开更多
An integrity monitoring framework is proposed to ensure the quality of the real-time Precise Point Positioning(PPP)correction data at the service end.The key contributions are designing quantitative metrics to charact...An integrity monitoring framework is proposed to ensure the quality of the real-time Precise Point Positioning(PPP)correction data at the service end.The key contributions are designing quantitative metrics to characterize the integrity status of the precise Orbit,Clock(OC)and Code Bias(OCB)corrections,and deriving the corresponding algorithms to detect and exclude anomalies,and to evaluate the real-time accuracy levels of the OCB.Compared to many prior works whose interests focused on analyzing and improving the averaged long-term accuracy,this work is established from integrity perspective.In particular,a two-layer fault detection and identification approach is developed to reduce the miss detection and false alert probabilities.The test statistics are constructed based on the raw observations from a network of worldwide sparsely distributed monitor stations.In addition,a realistic data-driven model is established to compute the Quality Indicators(QI)for healthy OCB products.The proposed scheme is validated respectively for multi-constellation OC and code bias,using historical correction data.The results suggest that the detection algorithms can effectively identify and alert the faults,so that the remaining correction errors approximate well to Gaussian distributions.Moreover,the computed QI are shown to be consistent with the truth error variations in real time.Most importantly,the position domain verification shows noticeable positioning accuracy and robustness improvements under both nominal and faulty conditions of the OCB correction data.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
Antenna Group Delay Variation(AGDV)is a hardware error source that affects the performance of Dual-Frequency Multi-Constellation(DFMC)Ground-based Augmentation System(GBAS),and these errors are difficult to distinguis...Antenna Group Delay Variation(AGDV)is a hardware error source that affects the performance of Dual-Frequency Multi-Constellation(DFMC)Ground-based Augmentation System(GBAS),and these errors are difficult to distinguish from multipath errors.Currently,AGDV is usually modeled as a part of the multipath error,which is called the multipath-AGDV model.However,because of the inconsistency of AGDV and multipath when switching among different positioning modes of GBAS,and because the traditional model does not consider the impact of the azimuth on AGDV,using the traditional multipath-AGDV model will cause the protection levels to be inaccurately calculated.In this paper,azimuth-based modeling of AGDV is conducted by using anechoic chamber measurements.The biases and standard deviations of AGDV based on azimuths are analyzed and modeled,and the calculation method for the DFMC GBAS protection level is optimized.The results show that the azimuth-based AGDV model and protection level optimization algorithm can better avoid the error exceeding the protection level than the multipath-AGDV model.Compared with AGDV elevation model,the VPLs of the B1C signal are increased by 0.24 m and 0.06 m,and the VPLs of the B2a signal are reduced by 0.01 m and 0.16 m using the 100 s and 600 s DFree filtering positioning modes,respectively.The changes in the B1C and B2a protection levels reflect the changes in AGDV corresponding to the azimuth for the respective frequencies,further ensuring the integrity of airborne users,especially when they turn near the airport.展开更多
Radio Frequency Fingerprint Identification(RFFI)technology provides a means of identifying spurious signals.This technology has been widely used in solving Automatic Dependent Surveillance–Broadcast(ADS-B)signal spoo...Radio Frequency Fingerprint Identification(RFFI)technology provides a means of identifying spurious signals.This technology has been widely used in solving Automatic Dependent Surveillance–Broadcast(ADS-B)signal spoofing problems.However,the effects of circuit changes over time often lead to a decline in identification accuracy within open-time set.This paper proposes an ADS-B transmitter identification method to solve the degradation of identification accuracy.First,a real-time data processing system is established to receive and store ADS-B signals to meet the conditions for open-time set.The system possesses the following functionalities:data collection,data parsing,feature extraction,and identity recognition.Subsequently,a two-dimensional TimeFrequency Feature Diagram(TFFD)is proposed as a signal pre-processing method.The TFFD is constructed from the received ADS-B signal and the reconstructed signal for input to the recognition model.Finally,incorporating a frequency offset layer into the Swin Transformer architecture,a novel recognition network framework is proposed.This integration can enhance the network recognition accuracy and robustness by tailoring to the specific characteristics of ADSB signals.Experimental results indicate that the proposed recognition architecture achieves recognition accuracy of 95.86%in closed-time set and 84.33%in open-time set,surpassing other algorithms.展开更多
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金supported by the Key Project of Guangzhou City,No.202206060002Science and Technology Project of Guangdong Province,No.2018B030332001Guangdong Provincial Pearl River Project,No.2021ZT09Y552 (all to GC)。
文摘Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.
基金supported by the National Natural Science Foundation of China,Nos.32070534(to WY),32370567(to WY),82371874(to XL),81830032(to XL),82071421(to SL)Key Field Research and Development Program of Guangdong Province,No.2018B030337001(to XL)+2 种基金Guangzhou Key Research Program on Brain Science,No.202007030008(to XL)Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(to XL)Guangdong Basic and Applied Basic Research Foundation,Nos.2022A1515012301(to WY),2023B1515020031(to WY).
文摘The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration.However,it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains.This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals.Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin.Recently,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate brain.In the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate brain.We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains.PINK1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable distribution.Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress.These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.
文摘Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024).
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金supported by the Keio University Medical Science Fund(to YO)the General Insurance Association of Japan(to YK)+1 种基金the Takeda Science Foundation(to YK)grants from the Japan Agency for Medical Research and Development(AMED)(Grant JP24bm1123037 and JP24ym0126118)(to HO)。
文摘Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of life.Researchers continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPSCNS/PCs)into spinal cord injured tissues.
文摘Chinese President Xi Jinping,also General Secretary of the Communist Party of China Central Committee and Chairman of the Central Military Commission,delivers an important speech at a central conference on work related to neighboring countries in Beijing,capital of China.The conference was held on April 8-9,2025.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010689)National Natural Science Foundation of China(82394422,82371874,82071421,82271902)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006)。
文摘Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.
文摘This eastern province sets an example in rural revitalization through green development.THE Green Rural Revival Program is an innovative initiative launched by east China’s Zhejiang Pro-vince.It aims to promote comprehensive rural revitalization by focusing on environmental conservation and sustainable development.
基金supported by Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology(20200730009)the National Natural Science Foundation of China(81870656)the Natural Science Foundation of Guangdong Province of China(2017A030313610 and 2023A1515012397).
文摘Dear Editor,Traumatic optic neuropathy(TON)is a severe vision-threatening condition,with an incidence rate ranging from 0.7% to 2.5%[1].The limited regenerative capacity of the optic nerve and the challenges of nerve transplantation result in substantial and irreversible visual loss in patients with TON.
文摘The Global Navigation Satellite System(GNSS)has been widely adopted in numerous fields,including intelligent transportation,remote sensing,and aeronautical and astronautical engineering.As new navigation approaches,technologies,and applications continue to emerge,they attract significant global attention.Ensuring reliable positioning solutions with high accuracy,strong anti-interference capabilities,high availability and low integrity risks has become increasingly critical.
基金supported by the National Natural Science Foundation of China(32270564 to P.Y.,82394422 to X.J.L.,82371178 to B.L.)Guangdong Basic and Applied Basic Research(2022A1515011205 and 2023A1515010811 to P.Y.,2021ZT09Y007 and 2018B030337001 to X.J.L.)。
文摘Cytoplasmic accumulation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis(ALS)and other neurodegenerative diseases.While current studies have primarily focused on gene regulation mediated by full-length nuclear TDP-43,the potential effects of cytoplasmic TDP-43 fragments remain less explored.Our previous findings demonstrated that primate-specific cleavage of TDP-43 contributes to its cytoplasmic localization,prompting further investigation into its pathological effects.In the cynomolgus monkey brain,we observed that mutant or truncated TDP-43 was transported onto the ribosome organelle.Ribosome-associated transcriptomic analysis revealed dysregulation of apoptosis-and lysosome-related genes,indicating that cytoplasmic TDP-43 induces neurotoxicity by binding to ribosomes and disrupting mRNA expression.These findings provide mechanistic insights into the gain-of-function effects of pathological TDP-43.
基金supported by supported by the National Key Research and Development Plan,China(No.2023YFB3906501)the National Natural Science Foundation of China(No.42227802)the Fundamental Research Funds for the Central Universities,China(No.501JCGG2024133001)。
文摘An integrity monitoring framework is proposed to ensure the quality of the real-time Precise Point Positioning(PPP)correction data at the service end.The key contributions are designing quantitative metrics to characterize the integrity status of the precise Orbit,Clock(OC)and Code Bias(OCB)corrections,and deriving the corresponding algorithms to detect and exclude anomalies,and to evaluate the real-time accuracy levels of the OCB.Compared to many prior works whose interests focused on analyzing and improving the averaged long-term accuracy,this work is established from integrity perspective.In particular,a two-layer fault detection and identification approach is developed to reduce the miss detection and false alert probabilities.The test statistics are constructed based on the raw observations from a network of worldwide sparsely distributed monitor stations.In addition,a realistic data-driven model is established to compute the Quality Indicators(QI)for healthy OCB products.The proposed scheme is validated respectively for multi-constellation OC and code bias,using historical correction data.The results suggest that the detection algorithms can effectively identify and alert the faults,so that the remaining correction errors approximate well to Gaussian distributions.Moreover,the computed QI are shown to be consistent with the truth error variations in real time.Most importantly,the position domain verification shows noticeable positioning accuracy and robustness improvements under both nominal and faulty conditions of the OCB correction data.
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the National Key Research and Development Program of China(No.2023YFB3907001)the financial support from the National Natural Science Foundation of China(Nos.62371029,U2233217 and 62101019)the Civil Aviation Security Capacity Building Fund Project of China(Nos.CAAC Contract 2021(77)and CAAC Contract 2022(110)).
文摘Antenna Group Delay Variation(AGDV)is a hardware error source that affects the performance of Dual-Frequency Multi-Constellation(DFMC)Ground-based Augmentation System(GBAS),and these errors are difficult to distinguish from multipath errors.Currently,AGDV is usually modeled as a part of the multipath error,which is called the multipath-AGDV model.However,because of the inconsistency of AGDV and multipath when switching among different positioning modes of GBAS,and because the traditional model does not consider the impact of the azimuth on AGDV,using the traditional multipath-AGDV model will cause the protection levels to be inaccurately calculated.In this paper,azimuth-based modeling of AGDV is conducted by using anechoic chamber measurements.The biases and standard deviations of AGDV based on azimuths are analyzed and modeled,and the calculation method for the DFMC GBAS protection level is optimized.The results show that the azimuth-based AGDV model and protection level optimization algorithm can better avoid the error exceeding the protection level than the multipath-AGDV model.Compared with AGDV elevation model,the VPLs of the B1C signal are increased by 0.24 m and 0.06 m,and the VPLs of the B2a signal are reduced by 0.01 m and 0.16 m using the 100 s and 600 s DFree filtering positioning modes,respectively.The changes in the B1C and B2a protection levels reflect the changes in AGDV corresponding to the azimuth for the respective frequencies,further ensuring the integrity of airborne users,especially when they turn near the airport.
基金supported by the National Key Research and Development Program of China(No.2022YFB4300902)。
文摘Radio Frequency Fingerprint Identification(RFFI)technology provides a means of identifying spurious signals.This technology has been widely used in solving Automatic Dependent Surveillance–Broadcast(ADS-B)signal spoofing problems.However,the effects of circuit changes over time often lead to a decline in identification accuracy within open-time set.This paper proposes an ADS-B transmitter identification method to solve the degradation of identification accuracy.First,a real-time data processing system is established to receive and store ADS-B signals to meet the conditions for open-time set.The system possesses the following functionalities:data collection,data parsing,feature extraction,and identity recognition.Subsequently,a two-dimensional TimeFrequency Feature Diagram(TFFD)is proposed as a signal pre-processing method.The TFFD is constructed from the received ADS-B signal and the reconstructed signal for input to the recognition model.Finally,incorporating a frequency offset layer into the Swin Transformer architecture,a novel recognition network framework is proposed.This integration can enhance the network recognition accuracy and robustness by tailoring to the specific characteristics of ADSB signals.Experimental results indicate that the proposed recognition architecture achieves recognition accuracy of 95.86%in closed-time set and 84.33%in open-time set,surpassing other algorithms.
