The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as ph...The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.展开更多
Special skills are required in portrait painting, such as imagining geometric structures and facial detail for final portrait designs. This makes it a difficult task for users, especially novices without prior artisti...Special skills are required in portrait painting, such as imagining geometric structures and facial detail for final portrait designs. This makes it a difficult task for users, especially novices without prior artistic training, to draw freehand portraits with high-quality details. In this paper, we propose dualFace, a portrait drawing interface to assist users with different levels of drawing skills to complete recognizable and authentic face sketches. Inspired by traditional artist workflows for portrait drawing, dualFace gives two-stages of drawing assistance to provide global and local visual guidance. The former helps users draw contour lines for portraits (i.e., geometric structure), and the latter helps users draw details of facial parts, which conform to the user-drawn contour lines. In the global guidance stage, the user draws several contour lines, and dualFace then searches for several relevant images from an internal database and displays the suggested face contour lines on the background of the canvas. In the local guidance stage, we synthesize detailed portrait images with a deep generative model from user-drawn contour lines, and then use the synthesized results as detailed drawing guidance. We conducted a user study to verify the effectiveness of dualFace, which confirms that dualFace significantly helps users to produce a detailed portrait sketch.展开更多
Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy an...Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields.Accordingly,the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management.A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials.However,these drugs are ineffective for all patients,as evidenced by the fact that only a minority of patients in these trials showed prolonged survival.Furthermore,there are several published phase III clinical trials that involve immune checkpoint inhibitors,peptide vaccines,dendritic cell vaccines,and virotherapy.Accordingly,this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.展开更多
Gliomas,the most common primary tumors in the central nervous system(CNS),can be categorized into 4 grades according to the World Health Organization.The most malignant glioma type is gradeⅣ,also named glioblastoma m...Gliomas,the most common primary tumors in the central nervous system(CNS),can be categorized into 4 grades according to the World Health Organization.The most malignant glioma type is gradeⅣ,also named glioblastoma multiforme(GBM).However,the standard treatment of concurrent temozolomide(TMZ)chemotherapy and radiotherapy after maximum resection does not improve overall survival in patients with GBM.Targeting components of the CNS microenvironment represents a new strategy for improving the efficacy of glioma treatment.Most recent studies focused on T cells.However,there is a growing body of evidence that tumor-associated macrophages(TAMs)play an important role in tumor progression and can be regulated by a wide array of cytokines or chemokines.New TAM-associated immunotherapies may improve clinical outcomes by blocking tumor progression and prolonging survival.However,understanding the exact roles and possible mechanisms of TAMs in the tumor environment is necessary for developing this promising therapeutic target and identifying potential diagnostic markers for improved prognosis.This review summarizes the possible interactions between TAMs and glioma progression and discusses the potential therapeutic directions for TAM-associated immunotherapies.展开更多
基金supported by Yunnan Province Innovation Team of Prevention and Treatment for Brain Disease with Acupuncture and Tuina,No.202405AS350007Youth Top Talent Project of 10-thousand Talent Plan in Yunnan Province,No.YNWR-QNBJ-2018-345+3 种基金the National Natural Science Foundation of China,No.81960731Joint Special Project of Traditional Chinese Medicine in Science and Technology Department of Yunnan Province,Nos.2019FF002[-008],202001AZ070001-002 and 202001AZ070001-030Yunnan Province University Innovation Team Projects No.2019YGC04Yunnan Province Project Education Fund,Nos.2024Y406,2024Y414(all to PZ)。
文摘The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.
基金supported by Grant from Tateishi Science and Technology Foundation,JSPS KAKENHI grant JP20K19845 and JP19K20316,Japan.
文摘Special skills are required in portrait painting, such as imagining geometric structures and facial detail for final portrait designs. This makes it a difficult task for users, especially novices without prior artistic training, to draw freehand portraits with high-quality details. In this paper, we propose dualFace, a portrait drawing interface to assist users with different levels of drawing skills to complete recognizable and authentic face sketches. Inspired by traditional artist workflows for portrait drawing, dualFace gives two-stages of drawing assistance to provide global and local visual guidance. The former helps users draw contour lines for portraits (i.e., geometric structure), and the latter helps users draw details of facial parts, which conform to the user-drawn contour lines. In the global guidance stage, the user draws several contour lines, and dualFace then searches for several relevant images from an internal database and displays the suggested face contour lines on the background of the canvas. In the local guidance stage, we synthesize detailed portrait images with a deep generative model from user-drawn contour lines, and then use the synthesized results as detailed drawing guidance. We conducted a user study to verify the effectiveness of dualFace, which confirms that dualFace significantly helps users to produce a detailed portrait sketch.
基金Clinical Major Specialty Projects of BeijingNational High Level Hospital Clinical Research Funding,Grant/Award Number:2022-PUMCH-A-019。
文摘Glioblastoma(GBM)is the most common primary central nervous system tumor,whose prognosis remains poor under the sequential standard of care,such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields.Accordingly,the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management.A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials.However,these drugs are ineffective for all patients,as evidenced by the fact that only a minority of patients in these trials showed prolonged survival.Furthermore,there are several published phase III clinical trials that involve immune checkpoint inhibitors,peptide vaccines,dendritic cell vaccines,and virotherapy.Accordingly,this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.
文摘Gliomas,the most common primary tumors in the central nervous system(CNS),can be categorized into 4 grades according to the World Health Organization.The most malignant glioma type is gradeⅣ,also named glioblastoma multiforme(GBM).However,the standard treatment of concurrent temozolomide(TMZ)chemotherapy and radiotherapy after maximum resection does not improve overall survival in patients with GBM.Targeting components of the CNS microenvironment represents a new strategy for improving the efficacy of glioma treatment.Most recent studies focused on T cells.However,there is a growing body of evidence that tumor-associated macrophages(TAMs)play an important role in tumor progression and can be regulated by a wide array of cytokines or chemokines.New TAM-associated immunotherapies may improve clinical outcomes by blocking tumor progression and prolonging survival.However,understanding the exact roles and possible mechanisms of TAMs in the tumor environment is necessary for developing this promising therapeutic target and identifying potential diagnostic markers for improved prognosis.This review summarizes the possible interactions between TAMs and glioma progression and discusses the potential therapeutic directions for TAM-associated immunotherapies.
