Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by ra...Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining homeostasis.Hence,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful response.Anti-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for survival.At the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral tissues.Additionally,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).展开更多
Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct ro...Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.展开更多
Effects of plasma equilibrium parameters on the alpha particle loss with the toroidal field ripple based on the CFETR steady-state scenario have been numerically investigated by the orbit-following code GYCAVA. It is ...Effects of plasma equilibrium parameters on the alpha particle loss with the toroidal field ripple based on the CFETR steady-state scenario have been numerically investigated by the orbit-following code GYCAVA. It is found that alpha particle losses decrease and loss regions become narrower with the plasma current increasing or with the magnetic field decreasing. It is because the ripple stochastic transport and the ripple well loss of alpha particle are reduced with the safety factor decreasing. Decrease of the plasma density and temperature can reduce alpha particle losses due to enhancement of the slowing-down effect. The direction of the toroidal magnetic field can significantly affect heat loads induced by lost alpha particle. The vertical asymmetry of heat loads induced by the clockwise and counter-clockwise toroidal magnetic fields are due to the fact that the ripple distribution is asymmetric about the mid-plane, which can be explained by the typical orbits of alpha particle. The maximal heat load of alpha particle for the clockwise toroidal magnetic field is much smaller than that for the counter-clockwise one.展开更多
In 2018 and 2021,the Drift-Towing Ocean Profilers(DTOP)provided extensive temperature and salinity data on the upper 120m ocean through their drifts over the Alpha Ridge north of the Canada Basin.The thickness and tem...In 2018 and 2021,the Drift-Towing Ocean Profilers(DTOP)provided extensive temperature and salinity data on the upper 120m ocean through their drifts over the Alpha Ridge north of the Canada Basin.The thickness and temperature maximum of Alaska Coastal Water(ACW)ranged from 20m to 40m and-1.5℃to-0.8℃,respectively,and the salinity generally maintained from 30.2 to 32.5.Comparison with World Ocean Atlas 2018’s climatology manifested a 40m-thick and warm ACW roughly ex-ceeding the temperature maximum by 0.4–0.5℃in June–August 2021.This anomalously warm ACW was highly related to the ex-pansion of the Beaufort Gyre in the negative Arctic Oscillation phase.During summer,the under-ice oceanic heat flux F_(w)^(OHF)was elevated,with a maximum value of above 25Wm^(-2).F_(w)^(OHF)was typically low in the freezing season,with an average value of 1.2Wm^(-2).The estimates of upward heat flux contributed by ACW to the sea ice bottom F_(w)^(OHF)were in the range of 3–4Wm^(-2)in June–August 2021,when ACW contained a heat content of more than 80MJm^(-2).The heat loss over this period was driven by a weak stratification upon the ACW layer associated with a surface mixed layer(SML)approaching the ACW core.After autumn,F_(w)^(OHF)was reduced(<2 Wm^(-2))except during rare events when it elevated F_(w)^(OHF)slightly.In addition,the intensive and widespread Ekman suction,which created a violent upwelling north of the Canada Basin,was largely responsible for the substantial cooling and thinning of the ACW layer in the summer of 2021.展开更多
Drinking good quality water is essential for better health. It is therefore essential to assess the radiological quality of all water consumed in the District of Abidjan in order to prevent related hazards. Thus, the ...Drinking good quality water is essential for better health. It is therefore essential to assess the radiological quality of all water consumed in the District of Abidjan in order to prevent related hazards. Thus, the objective of this study was to assess the risk of cancer due to the ingestion of alpha and beta emitting radionuclides in the different types of water consumed in the region. A total of 63 water samples with 43 tap water samples, 5 bottled mineral water and 15 sachet water samples was collected and taken to GAEC laboratory for analysis. The low background Gas-less Automatic Alpha/Beta counting system (Canberra iMatic<sup>TM</sup>) was used to determine alpha and beta activity concentrations. Activity concentrations of both gross alpha and gross beta obtained in water sample were respectively lower than the WHO recommended limits of 0.1 Bq/l and 1 Bq/l. Also, the annual effective dose and total equivalent effective dose found in mineral bottled water samples were higher than in other types of water. The assessment of radiological lifetime risk has shown values of cancer risk due to ingestion alpha and beta emitters lower than recommended limit. These results indicate that there is no health hazard associated to consumption of water in the District of Abidjan.展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood ...Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.展开更多
自动调制识别在无线通信领域发挥了巨大作用。多数研究中假设的加性高斯白噪声信道已不再满足实际信道环境的准确描述。实际中,由于闪电、雷暴、多用户干扰、设备故障等原因,信道环境中广泛存在Alpha稳定分布噪声。因此对其开展研究更...自动调制识别在无线通信领域发挥了巨大作用。多数研究中假设的加性高斯白噪声信道已不再满足实际信道环境的准确描述。实际中,由于闪电、雷暴、多用户干扰、设备故障等原因,信道环境中广泛存在Alpha稳定分布噪声。因此对其开展研究更符合实际且具有挑战性。该文针对Alpha稳定分布噪声提出了一种预处理联合轻量级网络的调制识别方法。首先,通过对数域映射及阈值限制对接收信号进行预处理,抑制由Alpha稳定分布噪声带来的尖锐脉冲将信号幅度控制到合理范围;然后,提出一种基于Ghost模块的轻量级网络来完成信号的调制识别分类任务。实验结果表明,与现有的CLDNN(Convolutional Long Short-term Deep Neural Network)、CNN(Convolutional Neural Network)、ResNe(t Residual Network)相比,本文所提方法具有较高的识别准确率及较低的计算复杂度。展开更多
基金supported by grants from the Spanish Ministry of Education and Science(RYC-2017-22412,PID2019-107989RB-I00 and MDM-2017-0720)FundacióTV3(248/C/2020)(to AM).
文摘Inflammatory reflex and cholinergic anti-inflammatory pathway:Innate immune system triggers a local inflammatory response following an injury or a pathogen invasion.Likewise,this inflammatory response is limited by rapid,localized,and adaptive anti-inflammatory responses which are crucial for maintaining homeostasis.Hence,the loss of these responses converts a limited and protective inflammatory response into an excessive and harmful response.Anti-inflammatory responses are integrated into the central nervous system,since the central nervous system accumulates information about harmful events,activates defenses,and builds memory for survival.At the same time,it has been demonstrated that hypothalamic neuronal signaling can be altered by inflammation in peripheral tissues.Additionally,immune cells release neuropeptides and neurotransmitters such as acetylcholine(ACh),the main neurotransmitter of the parasympathetic autonomic nervous system,evidencing the communication between the immune and nervous systems(Tracey,2002).
文摘Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.12175034 and 12005063)the National Key Research and Development Program of China (Grant No.2019YFE03030001)the Fundamental Research Funds for the Central Universities (Grant No.2232022G-10)。
文摘Effects of plasma equilibrium parameters on the alpha particle loss with the toroidal field ripple based on the CFETR steady-state scenario have been numerically investigated by the orbit-following code GYCAVA. It is found that alpha particle losses decrease and loss regions become narrower with the plasma current increasing or with the magnetic field decreasing. It is because the ripple stochastic transport and the ripple well loss of alpha particle are reduced with the safety factor decreasing. Decrease of the plasma density and temperature can reduce alpha particle losses due to enhancement of the slowing-down effect. The direction of the toroidal magnetic field can significantly affect heat loads induced by lost alpha particle. The vertical asymmetry of heat loads induced by the clockwise and counter-clockwise toroidal magnetic fields are due to the fact that the ripple distribution is asymmetric about the mid-plane, which can be explained by the typical orbits of alpha particle. The maximal heat load of alpha particle for the clockwise toroidal magnetic field is much smaller than that for the counter-clockwise one.
基金supported by the National Natural Science Foundation of China(Nos.42276239 and 41941012)the National Key R&D Program of China(No.2019YFC1509101)the Fundamental Research Funds for the Central Universities(No.202165005).
文摘In 2018 and 2021,the Drift-Towing Ocean Profilers(DTOP)provided extensive temperature and salinity data on the upper 120m ocean through their drifts over the Alpha Ridge north of the Canada Basin.The thickness and temperature maximum of Alaska Coastal Water(ACW)ranged from 20m to 40m and-1.5℃to-0.8℃,respectively,and the salinity generally maintained from 30.2 to 32.5.Comparison with World Ocean Atlas 2018’s climatology manifested a 40m-thick and warm ACW roughly ex-ceeding the temperature maximum by 0.4–0.5℃in June–August 2021.This anomalously warm ACW was highly related to the ex-pansion of the Beaufort Gyre in the negative Arctic Oscillation phase.During summer,the under-ice oceanic heat flux F_(w)^(OHF)was elevated,with a maximum value of above 25Wm^(-2).F_(w)^(OHF)was typically low in the freezing season,with an average value of 1.2Wm^(-2).The estimates of upward heat flux contributed by ACW to the sea ice bottom F_(w)^(OHF)were in the range of 3–4Wm^(-2)in June–August 2021,when ACW contained a heat content of more than 80MJm^(-2).The heat loss over this period was driven by a weak stratification upon the ACW layer associated with a surface mixed layer(SML)approaching the ACW core.After autumn,F_(w)^(OHF)was reduced(<2 Wm^(-2))except during rare events when it elevated F_(w)^(OHF)slightly.In addition,the intensive and widespread Ekman suction,which created a violent upwelling north of the Canada Basin,was largely responsible for the substantial cooling and thinning of the ACW layer in the summer of 2021.
文摘Drinking good quality water is essential for better health. It is therefore essential to assess the radiological quality of all water consumed in the District of Abidjan in order to prevent related hazards. Thus, the objective of this study was to assess the risk of cancer due to the ingestion of alpha and beta emitting radionuclides in the different types of water consumed in the region. A total of 63 water samples with 43 tap water samples, 5 bottled mineral water and 15 sachet water samples was collected and taken to GAEC laboratory for analysis. The low background Gas-less Automatic Alpha/Beta counting system (Canberra iMatic<sup>TM</sup>) was used to determine alpha and beta activity concentrations. Activity concentrations of both gross alpha and gross beta obtained in water sample were respectively lower than the WHO recommended limits of 0.1 Bq/l and 1 Bq/l. Also, the annual effective dose and total equivalent effective dose found in mineral bottled water samples were higher than in other types of water. The assessment of radiological lifetime risk has shown values of cancer risk due to ingestion alpha and beta emitters lower than recommended limit. These results indicate that there is no health hazard associated to consumption of water in the District of Abidjan.
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
文摘2024年5月8日出版的《自然》报道了AlphaFold 3能以较高准确率预测蛋白质与其他生物分子相互作用的结构。AlphaFold 3是该人工智能模型的最新迭代,准确率与之前的专用工具相比显著提升,该模型由谷歌DeepMind和Isomorphic实验室的团队研发。这一最新模型能够预测蛋白质数据库(Protein Data Bank)内几乎所有分子类型复合物的结构。
文摘Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.
文摘自动调制识别在无线通信领域发挥了巨大作用。多数研究中假设的加性高斯白噪声信道已不再满足实际信道环境的准确描述。实际中,由于闪电、雷暴、多用户干扰、设备故障等原因,信道环境中广泛存在Alpha稳定分布噪声。因此对其开展研究更符合实际且具有挑战性。该文针对Alpha稳定分布噪声提出了一种预处理联合轻量级网络的调制识别方法。首先,通过对数域映射及阈值限制对接收信号进行预处理,抑制由Alpha稳定分布噪声带来的尖锐脉冲将信号幅度控制到合理范围;然后,提出一种基于Ghost模块的轻量级网络来完成信号的调制识别分类任务。实验结果表明,与现有的CLDNN(Convolutional Long Short-term Deep Neural Network)、CNN(Convolutional Neural Network)、ResNe(t Residual Network)相比,本文所提方法具有较高的识别准确率及较低的计算复杂度。
