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
Attention deficit hyperactivity disorder(ADHD)turns into a common neuro progressional disorder.Although gender identity has obtained increasing attention in ADHD researches,its role in ADHD presentation and treatment ...Attention deficit hyperactivity disorder(ADHD)turns into a common neuro progressional disorder.Although gender identity has obtained increasing attention in ADHD researches,its role in ADHD presentation and treatment response remains underexplored.Our review seeks to mainly delve into the effect of gender identity on ADHD,exploring the unique needs of individuals with various gender identities in the context of ADHD symptoms,diagnostic assessment,and treatment,with the goal of supplying theoretical support and practical recommendations for future research and clinical practice.The primary content includes,specifically:(1)Symptom expression differences:Gender identity significantly affects ADHD symptoms;male-identified individuals commonly perform worse in task orientation and attention stability,while female-identified individuals may demonstrate more variability in attention control and executive functions;(2)Diagnosis and treatment:Clinical practice generally neglects the impact of gender identity on ADHD management,with personalized needs of gender-identified individuals frequently not adequately addressed,potentially,affecting treatment outcomes;and(3)Future research directions:Future studies should further assess how gender identity affects the specific mechanisms of ADHD,conduct researches in multicultural contexts,and engage in long-term follow-up studies to evaluate the long-term impact of gender identity on ADHD progression.Besides,enhanced funding and public education on the relationship between gender identity and ADHD are needed to advance the field.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
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
BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal trac...BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.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
Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patientsdue to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are lar...Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patientsdue to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci® robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer(and less aggressive tumors), with particular attention to the oncological results and widespread reproducibility of each technique.展开更多
An adaptive neuro fuzzy inference system was used for classifying water quality status of river.It applied several physical and inorganic chemical indicators including dissolved oxygen,chemical oxygen demand,and ammon...An adaptive neuro fuzzy inference system was used for classifying water quality status of river.It applied several physical and inorganic chemical indicators including dissolved oxygen,chemical oxygen demand,and ammonia-nitrogen.A data set(nine weeks,total 845 observations)was collected from 100 monitoring stations in all major river basins in China and used for training and validating the model.Up to 89.59%of the data could be correctly classified using this model.Such performance was more competitive when compared with artificial neural networks.It is applicable in evaluation and classification of water quality status.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
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Supported by the Central Guiding Local Science and Technology Development Fund Project,No.YDZX2022091。
文摘Attention deficit hyperactivity disorder(ADHD)turns into a common neuro progressional disorder.Although gender identity has obtained increasing attention in ADHD researches,its role in ADHD presentation and treatment response remains underexplored.Our review seeks to mainly delve into the effect of gender identity on ADHD,exploring the unique needs of individuals with various gender identities in the context of ADHD symptoms,diagnostic assessment,and treatment,with the goal of supplying theoretical support and practical recommendations for future research and clinical practice.The primary content includes,specifically:(1)Symptom expression differences:Gender identity significantly affects ADHD symptoms;male-identified individuals commonly perform worse in task orientation and attention stability,while female-identified individuals may demonstrate more variability in attention control and executive functions;(2)Diagnosis and treatment:Clinical practice generally neglects the impact of gender identity on ADHD management,with personalized needs of gender-identified individuals frequently not adequately addressed,potentially,affecting treatment outcomes;and(3)Future research directions:Future studies should further assess how gender identity affects the specific mechanisms of ADHD,conduct researches in multicultural contexts,and engage in long-term follow-up studies to evaluate the long-term impact of gender identity on ADHD progression.Besides,enhanced funding and public education on the relationship between gender identity and ADHD are needed to advance the field.
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.
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.
文摘BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.
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.
文摘Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patientsdue to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci® robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer(and less aggressive tumors), with particular attention to the oncological results and widespread reproducibility of each technique.
基金supported by the National Natural Science Foundation of China(No.50778009)
文摘An adaptive neuro fuzzy inference system was used for classifying water quality status of river.It applied several physical and inorganic chemical indicators including dissolved oxygen,chemical oxygen demand,and ammonia-nitrogen.A data set(nine weeks,total 845 observations)was collected from 100 monitoring stations in all major river basins in China and used for training and validating the model.Up to 89.59%of the data could be correctly classified using this model.Such performance was more competitive when compared with artificial neural networks.It is applicable in evaluation and classification of water quality status.
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.
