Intensivists are often plagued with the challenges of managing critically ill patients in the neurocritical intensive care unit(neuro ICU);one such challenge is the level of illness and the need for sedation,inhibitin...Intensivists are often plagued with the challenges of managing critically ill patients in the neurocritical intensive care unit(neuro ICU);one such challenge is the level of illness and the need for sedation,inhibiting the provider’s ability to adequately assess the patient.Most sedatives alter neurological and physical exam findings,only compounding potential barriers to providing the best care for each patient.It is important to emphasize that even in the altered mentation of these patients,physical and neurological exams reign supreme as diagnostic tools and should be used in conjunction with multimodal neuromonitoring methods,rather than labs or imaging alone.Additionally,selecting the appropriate analgesic(s)and sedative(s)based on these findings are highly important when determining the best course of individualized management.Thus,providers in the neuro ICU should be highly familiar with the appropriate analgesic and sedative options available in order to determine not only which may be best for each patient,but to also better understand how each drug may impact assessment findings.This comprehensive review aims to provide a structured overview of the pertinent sedatives commonly used in neuro ICUs,their risks and benefits,and how providers can best utilize each in practice to further improve patient outcomes.The novel contribution of this work provides comparative drug tables,dosing guidance for pediatric and very elderly(>85-years-old)populations,and an exploration into the future possibilities of utilizing artificial intelligence and the human gut microbiome to further enhance the prospects of precision medicine.展开更多
Human Activity Recognition(HAR)in drone-captured videos has become popular because of the interest in various fields such as video surveillance,sports analysis,and human-robot interaction.However,recognizing actions f...Human Activity Recognition(HAR)in drone-captured videos has become popular because of the interest in various fields such as video surveillance,sports analysis,and human-robot interaction.However,recognizing actions from such videos poses the following challenges:variations of human motion,the complexity of backdrops,motion blurs,occlusions,and restricted camera angles.This research presents a human activity recognition system to address these challenges by working with drones’red-green-blue(RGB)videos.The first step in the proposed system involves partitioning videos into frames and then using bilateral filtering to improve the quality of object foregrounds while reducing background interference before converting from RGB to grayscale images.The YOLO(You Only Look Once)algorithm detects and extracts humans from each frame,obtaining their skeletons for further processing.The joint angles,displacement and velocity,histogram of oriented gradients(HOG),3D points,and geodesic Distance are included.These features are optimized using Quadratic Discriminant Analysis(QDA)and utilized in a Neuro-Fuzzy Classifier(NFC)for activity classification.Real-world evaluations on the Drone-Action,Unmanned Aerial Vehicle(UAV)-Gesture,and Okutama-Action datasets substantiate the proposed system’s superiority in accuracy rates over existing methods.In particular,the system obtains recognition rates of 93%for drone action,97%for UAV gestures,and 81%for Okutama-action,demonstrating the system’s reliability and ability to learn human activity from drone videos.展开更多
The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） ra...The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） rats were treated intra-gastrically with different doses of MC-LR for 90 d, the locomotor activity, spatial learning and memory function were evaluated in the rats after treatment using open field tests and Morris water maze tests. The results show that MC-LR exposure can lead to impairment of the spatial learning capacity and locomotor activity in rats at the dose of 2. 00 p,g/kg. The levels of NAA in the hippocampus were measured by magnetic resonance spectroscopy （MRI）. A significant decrease of NAA/Cr ratio （ P 〈 0. 05） was observed in the hippocampous. This study indicates that intra-gastrical exposure to low-doses of MC-LR has adverse effects on neuronal behavior and NAA levels in the hippocampous.展开更多
Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging...Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.展开更多
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tra...Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.展开更多
Two kinds of neuro-fuzzy gust response alleviation control laws are designed for a flexible large-aspect-ratio wing model. Simulations and comparisons of random gust alleviation using the two control laws are performe...Two kinds of neuro-fuzzy gust response alleviation control laws are designed for a flexible large-aspect-ratio wing model. Simulations and comparisons of random gust alleviation using the two control laws are performed. Based on the better neuro-fuzzy control law,experiments and simulations of sinusoidal gust alleviation using one-control-surface control system and two-control-surface control system are developed. The investigations show that the two kinds of neuro-fuzzy gust response alleviation control laws can alleviate random gust responses effectively. The neuro-fuzzy gust response alleviation control law including a modifying factor is better than the other one without it. Further,the better one has good effects on the sinusoidal gust alleviation at different frequencies and flow velocities. The two-control-surface control system has better effects on gust response alleviation than the one-control-surface control system when the gust is strong. The simulation results agree well with the experimental results. These results can be usefully referenced to the design of actual gust alleviation control systems.展开更多
目的优化LipofectamineTM2000介导外源基因转染Neuro-2a(N-2a)细胞的条件,以提高转染效率。方法将携带增强型绿色荧光蛋白(Enhanced green fluorescent protein,EGFP)的真核表达载体pEGFP-N1在LipofectamineTM2000介导下转染N-2a细胞,...目的优化LipofectamineTM2000介导外源基因转染Neuro-2a(N-2a)细胞的条件,以提高转染效率。方法将携带增强型绿色荧光蛋白(Enhanced green fluorescent protein,EGFP)的真核表达载体pEGFP-N1在LipofectamineTM2000介导下转染N-2a细胞,对转染时间、细胞融合度、质粒质量与脂质体体积比例及培养基pH值进行优化,荧光显微镜观察EGFP的表达,并计算转染效率。结果在细胞融合度达80%,质粒质量与脂质体体积比为1∶3的条件下转染48 h,EGFP的阳性率最高(P<0.05);培养基pH值为8.0左右时,EGFP的阳性率较高,且细胞凋亡率较低。结论优化了LipofectamineTM2000转染N-2a细胞的条件,提高了转染效率,为外源基因高效转染N-2a细胞奠定了基础。展开更多
Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and dis...Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.展开更多
Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A ...Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.展开更多
Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation...Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation.To address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A cells.The results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A cells.To identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or inhibitors.Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth.Moreover,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this effect.These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.展开更多
文摘Intensivists are often plagued with the challenges of managing critically ill patients in the neurocritical intensive care unit(neuro ICU);one such challenge is the level of illness and the need for sedation,inhibiting the provider’s ability to adequately assess the patient.Most sedatives alter neurological and physical exam findings,only compounding potential barriers to providing the best care for each patient.It is important to emphasize that even in the altered mentation of these patients,physical and neurological exams reign supreme as diagnostic tools and should be used in conjunction with multimodal neuromonitoring methods,rather than labs or imaging alone.Additionally,selecting the appropriate analgesic(s)and sedative(s)based on these findings are highly important when determining the best course of individualized management.Thus,providers in the neuro ICU should be highly familiar with the appropriate analgesic and sedative options available in order to determine not only which may be best for each patient,but to also better understand how each drug may impact assessment findings.This comprehensive review aims to provide a structured overview of the pertinent sedatives commonly used in neuro ICUs,their risks and benefits,and how providers can best utilize each in practice to further improve patient outcomes.The novel contribution of this work provides comparative drug tables,dosing guidance for pediatric and very elderly(>85-years-old)populations,and an exploration into the future possibilities of utilizing artificial intelligence and the human gut microbiome to further enhance the prospects of precision medicine.
基金funded by the Open Access Initiative of the University of Bremen and the DFG via SuUB Bremen.Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2024R348),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Human Activity Recognition(HAR)in drone-captured videos has become popular because of the interest in various fields such as video surveillance,sports analysis,and human-robot interaction.However,recognizing actions from such videos poses the following challenges:variations of human motion,the complexity of backdrops,motion blurs,occlusions,and restricted camera angles.This research presents a human activity recognition system to address these challenges by working with drones’red-green-blue(RGB)videos.The first step in the proposed system involves partitioning videos into frames and then using bilateral filtering to improve the quality of object foregrounds while reducing background interference before converting from RGB to grayscale images.The YOLO(You Only Look Once)algorithm detects and extracts humans from each frame,obtaining their skeletons for further processing.The joint angles,displacement and velocity,histogram of oriented gradients(HOG),3D points,and geodesic Distance are included.These features are optimized using Quadratic Discriminant Analysis(QDA)and utilized in a Neuro-Fuzzy Classifier(NFC)for activity classification.Real-world evaluations on the Drone-Action,Unmanned Aerial Vehicle(UAV)-Gesture,and Okutama-Action datasets substantiate the proposed system’s superiority in accuracy rates over existing methods.In particular,the system obtains recognition rates of 93%for drone action,97%for UAV gestures,and 81%for Okutama-action,demonstrating the system’s reliability and ability to learn human activity from drone videos.
基金The National Natural Science Foundation of China(No.8107225881273123)
文摘The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） rats were treated intra-gastrically with different doses of MC-LR for 90 d, the locomotor activity, spatial learning and memory function were evaluated in the rats after treatment using open field tests and Morris water maze tests. The results show that MC-LR exposure can lead to impairment of the spatial learning capacity and locomotor activity in rats at the dose of 2. 00 p,g/kg. The levels of NAA in the hippocampus were measured by magnetic resonance spectroscopy （MRI）. A significant decrease of NAA/Cr ratio （ P 〈 0. 05） was observed in the hippocampous. This study indicates that intra-gastrical exposure to low-doses of MC-LR has adverse effects on neuronal behavior and NAA levels in the hippocampous.
基金supported by the Charles H.“Skip”Smith Endowment Fund and the Verne M.Willaman Endowment Fund from the Pennsylvania State University to G.C。
文摘Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.
基金supported by the National Glaucoma Research Program of the Bright Focus Foundationsupported by an unrestricted research grant from Research to Prevent BlindnessNIH center grant EY014801
文摘Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.
基金National Natural Science Foundation of China(90716006)
文摘Two kinds of neuro-fuzzy gust response alleviation control laws are designed for a flexible large-aspect-ratio wing model. Simulations and comparisons of random gust alleviation using the two control laws are performed. Based on the better neuro-fuzzy control law,experiments and simulations of sinusoidal gust alleviation using one-control-surface control system and two-control-surface control system are developed. The investigations show that the two kinds of neuro-fuzzy gust response alleviation control laws can alleviate random gust responses effectively. The neuro-fuzzy gust response alleviation control law including a modifying factor is better than the other one without it. Further,the better one has good effects on the sinusoidal gust alleviation at different frequencies and flow velocities. The two-control-surface control system has better effects on gust response alleviation than the one-control-surface control system when the gust is strong. The simulation results agree well with the experimental results. These results can be usefully referenced to the design of actual gust alleviation control systems.
文摘目的优化LipofectamineTM2000介导外源基因转染Neuro-2a(N-2a)细胞的条件,以提高转染效率。方法将携带增强型绿色荧光蛋白(Enhanced green fluorescent protein,EGFP)的真核表达载体pEGFP-N1在LipofectamineTM2000介导下转染N-2a细胞,对转染时间、细胞融合度、质粒质量与脂质体体积比例及培养基pH值进行优化,荧光显微镜观察EGFP的表达,并计算转染效率。结果在细胞融合度达80%,质粒质量与脂质体体积比为1∶3的条件下转染48 h,EGFP的阳性率最高(P<0.05);培养基pH值为8.0左右时,EGFP的阳性率较高,且细胞凋亡率较低。结论优化了LipofectamineTM2000转染N-2a细胞的条件,提高了转染效率,为外源基因高效转染N-2a细胞奠定了基础。
文摘Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.
基金the National Natural Science Foundation of China, No.30903123, 30901329the Project of Science and Technology of Jilin Province, No.20090741, 20090185
文摘Activin A, which was first described in 1986, has been shown to maintain hippocampal neuronal survival. Activin A increases intracellular free Ca2＋ via L-type Ca2＋ channels. Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion. The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period, and that activin A was shown to increase voltage-gated Na＋ current （/Na） in Neuro-2a cells, which was recorded by patch clamp technique. The present study revealed a novel mechanism for activin A, as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase.
基金supported by the Natural Science Foundation of Shanghai of China,No.16ZR1410500(to SZD)
文摘Retinoic acid can cause many types of cells,including mouse neuroblastoma Neuro-2 A cells,to differentiate into neurons.However,it is still unknown whether microRNAs(miRNAs)play a role in this neuronal differentiation.To address this issue,real-time polymerase chain reaction assays were used to detect the expression of several differentiation-related miRNAs during the differentiation of retinoic acid-treated Neuro-2 A cells.The results revealed that miR-124 and miR-9 were upregulated,while miR-125 b was downregulated in retinoic acid-treated Neuro-2 A cells.To identify the miRNA that may play a key role,miR-124 expression was regulated by transfection of miRNA mimics or inhibitors.Morphological analysis results showed that inhibition of miR-124 expression reversed the effects of retinoic acid on neurite outgrowth.Moreover,miR-124 overexpression alone caused Neuro-2 A cells to differentiate into neurons,and its inhibitor could block this effect.These results suggest that miR-124 plays an important role in retinoic acid-induced differentiation of Neuro-2 A cells.
