Morphology of hydraulic fracture surface has significant effects on oil and gas flow,proppant migration and fracture closure,which plays an important role in oil and gas fracturing stimulation.In this paper,we analyze...Morphology of hydraulic fracture surface has significant effects on oil and gas flow,proppant migration and fracture closure,which plays an important role in oil and gas fracturing stimulation.In this paper,we analyzed the fracture surface characteristics induced by supercritical carbon dioxide(SC-CO_(2))and water in open-hole and perforation completion conditions under triaxial stresses.A simple calculation method was proposed to quantitatively analyze the fracture surface area and roughness in macro-level based on three-dimensional(3D)scanning data.In micro-level,scanning electron micrograph(SEM)was used to analyze the features of fracture surface.The results showed that the surface area of the induced fracture increases with perforation angle for both SC-CO_(2)and water fracturing,and the surface area of SC-CO_(2)-induced fracture is 6.49%e58.57%larger than that of water-induced fracture.The fractal dimension and surface roughness of water-induced fractures increase with the increase in perforation angle,while those of SC-CO_(2)-induced fractures decrease with the increasing perforation angle.A considerable number of microcracks and particle peeling pits can be observed on SC-CO_(2)-induced fracture surface while there are more flat particle surfaces in water-induced fracture surface through SEM images,indicating that fractures tend to propagate along the boundary of the particle for SC-CO_(2)fracturing while water-induced fractures prefer to cut through particles.These findings are of great significance for analyzing fracture mechanism and evaluating fracturing stimulation performance.展开更多
A slug flow model considering the dispersed bubbles entrained from the tail of Taylor bubble(TB) and recoalesced with the successive TB was proposed. Experiment was conducted to test the validity of this model by usin...A slug flow model considering the dispersed bubbles entrained from the tail of Taylor bubble(TB) and recoalesced with the successive TB was proposed. Experiment was conducted to test the validity of this model by using a high-speed camcorder and particle image velocimetry(PIV). It was found that the model was valid for predicting the characteristics of slug flow in airlift pump within average error of 14%. Moreover, large pipe diameter was found to accelerate the rise velocity of TB and decreases void fraction in liquid slug by a small margin.展开更多
Tunnel though coal seam is one of the most difficult tunnels since its risk of coal and gas outburst and the complex geological conditions.According to the directional cutting of water jet and the characteristic of th...Tunnel though coal seam is one of the most difficult tunnels since its risk of coal and gas outburst and the complex geological conditions.According to the directional cutting of water jet and the characteristic of the coal seam and rock mass,this paper presents a new method of tunnelling though coal seam assisted by water jet slotting,which can be divided into improving permeability of coal seam and directional cracking in the rock mass.The mechanism of improving permeability of coal seam was stated,and the crack criterion of rock during blasting was established based on fracture theory.Then,the evolution law of pressure wave and the crack propagation were simulated by FEM software ANSYS/LS-DYNA,the results show that the shape of the crush zone formed by stress wave is different between the normal borehole blasting and the slotted borehole blasting,and the tension is the main factor which let crack propagation.What is more,for normal borehole blasting,the tension concentration occurred along the direction of 45 degrees and let crack expand,while for slotted borehole blasting the tension concentration occurred along the direction of 0 degrees and 90 degrees,and the maximum tension along the direction of 0 degrees is larger than the maximum tension along the direction of 90 degrees,and the main crack expand along the direction of 0 degrees,which prove that the existence of the slot play a good role of orientation for directional cracking.展开更多
Experiments were conducted to investigate the flow characteristics in the riser pipe and the suction pipe of airlift pump at a series of air flow rates and submergence ratios by using a high speed camcorder and a Lase...Experiments were conducted to investigate the flow characteristics in the riser pipe and the suction pipe of airlift pump at a series of air flow rates and submergence ratios by using a high speed camcorder and a Laser Doppler Velocimetvy system (LDV). A modified model was developed to predict the performance of airlift pump operating in gas-liquid two-phase flow, The results show that an unstable flow structure composed by a water falling film, a bubbly mixture, a water ascending film appearing alternately in riser pipe dominates the performance of airlift pump at large air flow rates. The bubbly mixture with a strongest capacity for pumping water first increases to its maximum and then slightly decreases. In suction pipe, the average velocity shows a flat profile and increases with increasing submergence ratio. Moreover, the predicted results of modified model are in good agreement with the experimental data in a margin of ± 12%.展开更多
Thermally-induced changes in the fracture properties of geological reservoir rocks can influence their stability,transport characteristics,and performance related to various deep subsurface energy projects.The modifie...Thermally-induced changes in the fracture properties of geological reservoir rocks can influence their stability,transport characteristics,and performance related to various deep subsurface energy projects.The modified maximum tangential stress(MMTS)criterion is a classical theory for predicting the fracture instability of rocks.However,there is a lack of research on the accuracy of MMTS theory when rocks are subjected to different temperatures.In this study,mechanical theoretical analysis and failure and fracture mechanics experiments of granite under the influence of temperatures ranging from 20℃to 600℃are carried out.The results showed that the theoretical estimated value of MMTS differs significantly from the experimental data at 20℃-600℃.The Keff/KIC ratio is less than the experimental test value due to the critical crack growth radius(rc)estimated by the conventional method being larger than the critical crack growth radius(rce)derived from the experimental data.Varied temperatures affect the fracture process zone size of fine-grained,compact granite,and the MMTS theoretical estimation results.Therefore,it is essential to modify the critical crack growth radius for MMTS theory to accurately predict the fracture characteristics of thermally damaged rocks.In addition,the variation of the rock’s me-chanical properties with temperature and its causes are obtained.Between 20℃and 600℃,the mode-Ⅰ,mode-Ⅱ,and mixed-mode(a-30℃and 45℃)fracture toughness and Brazilian splitting strength of the granite decrease by 80%and 73%,respectively.When the rock is heated above 400℃,its deterioration is mainly caused by a widening of its original cracks.展开更多
Depth discontinuity edge affects the visual quality of synthesized images in 3D image warping.However,it suffers from accuracy degradation when up-sampled from low-resolution depth maps,especially at large scaling fac...Depth discontinuity edge affects the visual quality of synthesized images in 3D image warping.However,it suffers from accuracy degradation when up-sampled from low-resolution depth maps,especially at large scaling factors.To preserve the accuracy of depth discontinuity,a novel joint bilateral depth super-resolution with intensity guidance method is proposed.Particularly,the fast local intensity classification is exploited to estimate depth coefficients in joint bilateral up-sampling for depth maps,so as to eliminate depth discontinuity edge misalignment.Additionally,the proposed method is accelerated on graphic processing units(GPUs)to meet the requirement of realtime application.Experiments demonstrate that our method can preserve the accuracy of depth discontinuity edges after super resolution,leveraging the visual quality of synthesized image in 3D image warping.展开更多
Background Methamphetamine(METH)addiction causes a huge burden on society.The prefrontal cortex(PFC),associated with emotion and cognitive behaviours,is also involved in addiction neurocircuitry.Although bulk RNA sequ...Background Methamphetamine(METH)addiction causes a huge burden on society.The prefrontal cortex(PFC),associated with emotion and cognitive behaviours,is also involved in addiction neurocircuitry.Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC,the impact on different cell types remains unknown.Aims To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders.Methods We performed single-nucleus RNA sequencing(snRNA-seq)to examine the transcriptomes of 20465 nuclei isolated from the PFC of chronic METH-treated and control mice.Main cell types and differentially expressed genes(DEGs)were identified and confirmed by RNA fluorescence in situ hybridization(FISH).Results Six main cell types were identified depending on the single-cell nucleus sequencing;of particular interest were the mature oligodendrocytes in the PFC.The DEGs of mature oligodendrocytes were enriched in the myelin sheath,adenosine triphosphate(ATP)metabolic process,mitochondrial function and components,and so on.The messenger RNA levels of Aldoc and Atp5l(FISH)and the protein level of the mitochondrial membrane pore subunit TOM40(immunofluorescence)decreased in the mature oligodendrocytes.Fast blue staining and transmission electron microscopy image indicated myelin damage,and the myelin thickness decreased in METH brains.Conclusions snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment,underscoring potential relationships with psychiatric disorders.展开更多
世居高原藏族已形成独特的适应低氧环境的机制,低氧诱导因子(hypoxia-inducible factor,HIF)通路基因内皮PAS结构域蛋白1(endothelial PAS domain protein 1,EPAS1)的遗传变异已被阐明与其低氧适应密切相关.脑耗氧量高,因此最容易受到...世居高原藏族已形成独特的适应低氧环境的机制,低氧诱导因子(hypoxia-inducible factor,HIF)通路基因内皮PAS结构域蛋白1(endothelial PAS domain protein 1,EPAS1)的遗传变异已被阐明与其低氧适应密切相关.脑耗氧量高,因此最容易受到高原低氧的影响.本研究旨在探讨HIF通路基因遗传变异与世居高原藏族脑结构和功能网络的关系.本研究招募了135名世居高原藏族人(19.9±1.1岁)作为研究对象,匹配的65名平原汉族人作为基因遗传变异的对照人群.首先,根据文献选择EPAS1基因中12个单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行基因分型.其次,通过脑磁共振成像(magnetic resonance imaging,MRI)扫描获得藏族脑T1结构像和静息态功能MRI(functional MRI,fMRI).藏族人群中单倍型GA和CAAA的频率显著高于平原汉族,具有这些高频率单倍型的适应较好藏族人群的脑皮层表面积在左中央后回、右距状旁回、右额中回和右后扣带回显著增加,皮层体积在左距状旁回和右颞上回显著增加,脑功能连接主要在躯体运动、腹侧注意、视觉和默认模式网络上显著增加.总之,本研究揭示了EPAS1基因适应性遗传变异与世居高原藏族脑结构和功能网络的关系,发现基因上适应较好的藏族人群脑的变化集中在功能活跃的视觉感知和运动控制脑区及其相关功能神经网络以及默认模式网络.脑的这些变化有助于调节藏族的高原活动.展开更多
Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promisin...Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promising for the therapy of these diseases.We have conceptualized a strategy,named dephosphorylation-targeting chimeras(DEPTACs),for specifically hijacking phosphatases to tau to debilitate its hyperphosphorylation.Here,we conducted the step-by-step optimization of each constituent motif to generate DEPTACs with reasonable effectiveness in facilitating the dephosphorylation and subsequent clearance of pathological tau.Specifically,for one of the selected chimeras,D16,we demonstrated its significant efficiency in rescuing the neurodegeneration caused by neurotoxic K18-tau seeds in vitro.Moreover,intravenous administration of D16 also alleviated tau pathologies in the brain and improved memory deficits in AD mice.These results suggested DEPTACs as targeted modulators of tau phosphorylation,which hold therapeutic potential for AD and other tauopathies.展开更多
Light is a critical environmental cue that regulates a variety of diverse plant developmental processes.Cryptochrome 1(CRY1)is the major photoreceptor that mediates blue light-dependent photomorphogenic responses such...Light is a critical environmental cue that regulates a variety of diverse plant developmental processes.Cryptochrome 1(CRY1)is the major photoreceptor that mediates blue light-dependent photomorphogenic responses such as the inhibition of hypocotyl elongation.Gibberellin(GA)participates in the repression of photomorphogenesis and promotes hypocotyl elongation.However,the antagonistic interaction between blue light and GA is not well understood.Here,we report that blue light represses GA-induced degradation of the DELLA proteins(DELLAs),which are key negative regulators in the GA signaling pathway,via CRY1,thereby inhibiting the GA response during hypocotyl elongation.Both in vitro and in vivo biochemical analyses demonstrated that CRY1 physically interacts with GA receptors-GA-INSENSITIVE DWARF 1 proteins(GID1s)-and DELLAs in a blue light-dependent manner.Furthermore,we showed that CRY1 inhibits the association between GID1s and DELLAs.Genetically,CRY1 antagonizes the function of GID1s to repress the expression of cell elongation-related genes and thus hypocotyl elongation.Taken together,our findings demonstrate that CRY1 coordinates blue light and GA signali ng for plant photomorphogenesis by stabilizing DELLAs through the binding and in activation of GID1s,providing new in sights into the mechanism by which blue light antagonizes the function of GA in photomorphogenesis.展开更多
Accumulation of impaired mitochondria and energy metabolism disorders are non-negligible features of both aging and age-related neurodegeneration,including Alzheimer’s disease(AD).A growing number of studies suggest ...Accumulation of impaired mitochondria and energy metabolism disorders are non-negligible features of both aging and age-related neurodegeneration,including Alzheimer’s disease(AD).A growing number of studies suggest that mitophagy disorders play an important role in AD occurrence and development.The interaction between mitophagy deficits and Aβor Tau pathology may form a vicious cycle and cause neuronal damage and death.Elucidating the molecular mechanism of mitophagy and its role in AD may provide insights into the etiology and mechanisms of AD.Defective mitophagy is a potential target for AD prevention and treatment.展开更多
Accumulating evidence indicates that RIPK1 is associated with inflammation and apoptotic.RIPK1 deficiency leads to proinflammatory signaling impaired.However,only few patients with homozygous loss-of-function mutation...Accumulating evidence indicates that RIPK1 is associated with inflammation and apoptotic.RIPK1 deficiency leads to proinflammatory signaling impaired.However,only few patients with homozygous loss-of-function mutation in RIPK1 gene had been reported until now.Here,we report a Chinese combined immunodeficiency patient.He had recurrent infection,diarrhea after 3 months old.Immune function indicated that T,B and NK cells decreased significantly but immunoglobulins approximately remained normal.Whole-exome sequencing indicated that he had novel compound heterozygous mutations(c.998 C>A from his mother and c.1934 C>T from his father)in RIPK1 gene,which were confirmed by Sanger sequencing.Our study reports novel mutations in RIPK1 gene and new phenotype of patient with RIPK1 deficiency.展开更多
As a major public health problem in modern society,Alzheimer’s disease(AD)is currently the most widely prevalent neurodegenerative disease,which will indubitably increase dramatically in the coming years,unless drugs...As a major public health problem in modern society,Alzheimer’s disease(AD)is currently the most widely prevalent neurodegenerative disease,which will indubitably increase dramatically in the coming years,unless drugs that can prevent or cure the disease become available.Because AD is characterized histopathologically by extracellular deposition of amyloid beta(Aβ)surrounded by dystrophic neuritis forming senile plaques(SPs).展开更多
Depth-image-based rendering(DIBR) is widely used in 3 DTV, free-viewpoint video, and interactive 3 D graphics applications. Typically, synthetic images generated by DIBR-based systems incorporate various distortions, ...Depth-image-based rendering(DIBR) is widely used in 3 DTV, free-viewpoint video, and interactive 3 D graphics applications. Typically, synthetic images generated by DIBR-based systems incorporate various distortions, particularly geometric distortions induced by object dis-occlusion. Ensuring the quality of synthetic images is critical to maintaining adequate system service. However, traditional 2 D image quality metrics are ineffective for evaluating synthetic images as they are not sensitive to geometric distortion. In this paper, we propose a novel no-reference image quality assessment method for synthetic images based on convolutional neural networks, introducing local image saliency as prediction weights. Due to the lack of existing training data, we construct a new DIBR synthetic image dataset as part of our contribution. Experiments were conducted on both the public benchmark IRCCyN/IVC DIBR image dataset and our own dataset. Results demonstrate that our proposed metric outperforms traditional 2 D image quality metrics and state-of-the-art DIBR-related metrics.展开更多
Background:Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease(AD),while how to initiate early cognitive stimulation is unclear.Given that the immature br...Background:Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease(AD),while how to initiate early cognitive stimulation is unclear.Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing,we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period.Methods:After conception,maternal AD transgenic mice(3×Tg AD)were exposed to gestational environment enrichment(GEE)until the day of delivery.The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age.Western blotting,immunohistochemistry,real-time PCR,immunoprecipitation,chromatin immunoprecipitation(ChIP)assay,electrophysiology,Golgi staining,activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring.Results:We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring.The beneficial effects of GEE were accompanied by global histone hyperacetylation,including those at bdnf promoter-binding regions,with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus.GEE increased insulin-like growth factor 1(IGF1)and activated its receptor(IGF1R),which phosphorylates Ca^(2+)/calmodulin-dependent kinase IV(CaMKIV)at tyrosine sites and triggers its nuclear translocation,subsequently upregulating histone acetyltransferase(HAT)and BDNF transcription.The upregulation of IGF1 mimicked the effects of GEE,while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation.Conclusions:These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.展开更多
基金National Natural Science Foundation of China(Grant No.51804318)the China Postdoctoral Science Foundation Founded Project(Grant No.2019M650963)National Key Basic Research and Development Program of China(Grant No.2014CB239203).
文摘Morphology of hydraulic fracture surface has significant effects on oil and gas flow,proppant migration and fracture closure,which plays an important role in oil and gas fracturing stimulation.In this paper,we analyzed the fracture surface characteristics induced by supercritical carbon dioxide(SC-CO_(2))and water in open-hole and perforation completion conditions under triaxial stresses.A simple calculation method was proposed to quantitatively analyze the fracture surface area and roughness in macro-level based on three-dimensional(3D)scanning data.In micro-level,scanning electron micrograph(SEM)was used to analyze the features of fracture surface.The results showed that the surface area of the induced fracture increases with perforation angle for both SC-CO_(2)and water fracturing,and the surface area of SC-CO_(2)-induced fracture is 6.49%e58.57%larger than that of water-induced fracture.The fractal dimension and surface roughness of water-induced fractures increase with the increase in perforation angle,while those of SC-CO_(2)-induced fractures decrease with the increasing perforation angle.A considerable number of microcracks and particle peeling pits can be observed on SC-CO_(2)-induced fracture surface while there are more flat particle surfaces in water-induced fracture surface through SEM images,indicating that fractures tend to propagate along the boundary of the particle for SC-CO_(2)fracturing while water-induced fractures prefer to cut through particles.These findings are of great significance for analyzing fracture mechanism and evaluating fracturing stimulation performance.
基金Supported by the National Key Basic Research Development Program of China(2014CB239200)the National Natural Science Foundation of China(51574173,51705372)+1 种基金the Hubei Provincial Natural Science Foundation(2015CFA154)Jiangsu Provincial Natural Science Foundation of China(No.BK20170411)
文摘A slug flow model considering the dispersed bubbles entrained from the tail of Taylor bubble(TB) and recoalesced with the successive TB was proposed. Experiment was conducted to test the validity of this model by using a high-speed camcorder and particle image velocimetry(PIV). It was found that the model was valid for predicting the characteristics of slug flow in airlift pump within average error of 14%. Moreover, large pipe diameter was found to accelerate the rise velocity of TB and decreases void fraction in liquid slug by a small margin.
基金Financial support for this work,provided by the National Basic Research of China(2014CB239203)the National Natural Science Foundation of China(51474158)+1 种基金also supported by Program for New Century Excellent Talents in University(NCET-12-0424)The authors would like to thank the State Key Laboratory of Coal Mine Disaster Dynamics and Control and Hubei Key Laboratory of Waterjet Theory&New Technology.
文摘Tunnel though coal seam is one of the most difficult tunnels since its risk of coal and gas outburst and the complex geological conditions.According to the directional cutting of water jet and the characteristic of the coal seam and rock mass,this paper presents a new method of tunnelling though coal seam assisted by water jet slotting,which can be divided into improving permeability of coal seam and directional cracking in the rock mass.The mechanism of improving permeability of coal seam was stated,and the crack criterion of rock during blasting was established based on fracture theory.Then,the evolution law of pressure wave and the crack propagation were simulated by FEM software ANSYS/LS-DYNA,the results show that the shape of the crush zone formed by stress wave is different between the normal borehole blasting and the slotted borehole blasting,and the tension is the main factor which let crack propagation.What is more,for normal borehole blasting,the tension concentration occurred along the direction of 45 degrees and let crack expand,while for slotted borehole blasting the tension concentration occurred along the direction of 0 degrees and 90 degrees,and the maximum tension along the direction of 0 degrees is larger than the maximum tension along the direction of 90 degrees,and the main crack expand along the direction of 0 degrees,which prove that the existence of the slot play a good role of orientation for directional cracking.
基金Supported by the National Key Basic Research Development Program of China(2014CB239200)the National Natural Science Foundation of China(51474158)
文摘Experiments were conducted to investigate the flow characteristics in the riser pipe and the suction pipe of airlift pump at a series of air flow rates and submergence ratios by using a high speed camcorder and a Laser Doppler Velocimetvy system (LDV). A modified model was developed to predict the performance of airlift pump operating in gas-liquid two-phase flow, The results show that an unstable flow structure composed by a water falling film, a bubbly mixture, a water ascending film appearing alternately in riser pipe dominates the performance of airlift pump at large air flow rates. The bubbly mixture with a strongest capacity for pumping water first increases to its maximum and then slightly decreases. In suction pipe, the average velocity shows a flat profile and increases with increasing submergence ratio. Moreover, the predicted results of modified model are in good agreement with the experimental data in a margin of ± 12%.
基金supported by the open fund of the Key Laboratory of Deep Earth Science and Engineering(Sichuan University),the Ministry of Education(Grant No.DESEYU202206)the Young Elite Scientists Sponsorship Program by CAST of China(Grant No.2021QNRC001)the Natural Science Foundation of Sichuan Province,China(Grant No.52104143),which are greatly appreciated。
文摘Thermally-induced changes in the fracture properties of geological reservoir rocks can influence their stability,transport characteristics,and performance related to various deep subsurface energy projects.The modified maximum tangential stress(MMTS)criterion is a classical theory for predicting the fracture instability of rocks.However,there is a lack of research on the accuracy of MMTS theory when rocks are subjected to different temperatures.In this study,mechanical theoretical analysis and failure and fracture mechanics experiments of granite under the influence of temperatures ranging from 20℃to 600℃are carried out.The results showed that the theoretical estimated value of MMTS differs significantly from the experimental data at 20℃-600℃.The Keff/KIC ratio is less than the experimental test value due to the critical crack growth radius(rc)estimated by the conventional method being larger than the critical crack growth radius(rce)derived from the experimental data.Varied temperatures affect the fracture process zone size of fine-grained,compact granite,and the MMTS theoretical estimation results.Therefore,it is essential to modify the critical crack growth radius for MMTS theory to accurately predict the fracture characteristics of thermally damaged rocks.In addition,the variation of the rock’s me-chanical properties with temperature and its causes are obtained.Between 20℃and 600℃,the mode-Ⅰ,mode-Ⅱ,and mixed-mode(a-30℃and 45℃)fracture toughness and Brazilian splitting strength of the granite decrease by 80%and 73%,respectively.When the rock is heated above 400℃,its deterioration is mainly caused by a widening of its original cracks.
基金Supported by the National Natural Science Foundation of China(61572058)
文摘Depth discontinuity edge affects the visual quality of synthesized images in 3D image warping.However,it suffers from accuracy degradation when up-sampled from low-resolution depth maps,especially at large scaling factors.To preserve the accuracy of depth discontinuity,a novel joint bilateral depth super-resolution with intensity guidance method is proposed.Particularly,the fast local intensity classification is exploited to estimate depth coefficients in joint bilateral up-sampling for depth maps,so as to eliminate depth discontinuity edge misalignment.Additionally,the proposed method is accelerated on graphic processing units(GPUs)to meet the requirement of realtime application.Experiments demonstrate that our method can preserve the accuracy of depth discontinuity edges after super resolution,leveraging the visual quality of synthesized image in 3D image warping.
基金supported by grants from the National Natural Science Foundation of China(31929002,31771114 and 92049107)grant from Innovative Research Groups of the National Natural Science Foundation of China(81721005)the Academic Frontier Youth Team Project(to XW)from Huazhong University of Science and Technology.
文摘Background Methamphetamine(METH)addiction causes a huge burden on society.The prefrontal cortex(PFC),associated with emotion and cognitive behaviours,is also involved in addiction neurocircuitry.Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC,the impact on different cell types remains unknown.Aims To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders.Methods We performed single-nucleus RNA sequencing(snRNA-seq)to examine the transcriptomes of 20465 nuclei isolated from the PFC of chronic METH-treated and control mice.Main cell types and differentially expressed genes(DEGs)were identified and confirmed by RNA fluorescence in situ hybridization(FISH).Results Six main cell types were identified depending on the single-cell nucleus sequencing;of particular interest were the mature oligodendrocytes in the PFC.The DEGs of mature oligodendrocytes were enriched in the myelin sheath,adenosine triphosphate(ATP)metabolic process,mitochondrial function and components,and so on.The messenger RNA levels of Aldoc and Atp5l(FISH)and the protein level of the mitochondrial membrane pore subunit TOM40(immunofluorescence)decreased in the mature oligodendrocytes.Fast blue staining and transmission electron microscopy image indicated myelin damage,and the myelin thickness decreased in METH brains.Conclusions snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment,underscoring potential relationships with psychiatric disorders.
基金supported by the National Natural Science Foundation of China(82230041,91949205,31730035,81721005)the National Key R&D Program of China(2016YFC1305800)the Guangdong Provincial Key S&T Program(018B030336001)。
文摘Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promising for the therapy of these diseases.We have conceptualized a strategy,named dephosphorylation-targeting chimeras(DEPTACs),for specifically hijacking phosphatases to tau to debilitate its hyperphosphorylation.Here,we conducted the step-by-step optimization of each constituent motif to generate DEPTACs with reasonable effectiveness in facilitating the dephosphorylation and subsequent clearance of pathological tau.Specifically,for one of the selected chimeras,D16,we demonstrated its significant efficiency in rescuing the neurodegeneration caused by neurotoxic K18-tau seeds in vitro.Moreover,intravenous administration of D16 also alleviated tau pathologies in the brain and improved memory deficits in AD mice.These results suggested DEPTACs as targeted modulators of tau phosphorylation,which hold therapeutic potential for AD and other tauopathies.
基金supported by the National Natural Science Foundation of China(no.31171176)the Natural Science Foundation of Hunan Province(no.2020JJ4183)the Basic Research Program of Changsha Municipal Science and Technology(no.kq1901028).
文摘Light is a critical environmental cue that regulates a variety of diverse plant developmental processes.Cryptochrome 1(CRY1)is the major photoreceptor that mediates blue light-dependent photomorphogenic responses such as the inhibition of hypocotyl elongation.Gibberellin(GA)participates in the repression of photomorphogenesis and promotes hypocotyl elongation.However,the antagonistic interaction between blue light and GA is not well understood.Here,we report that blue light represses GA-induced degradation of the DELLA proteins(DELLAs),which are key negative regulators in the GA signaling pathway,via CRY1,thereby inhibiting the GA response during hypocotyl elongation.Both in vitro and in vivo biochemical analyses demonstrated that CRY1 physically interacts with GA receptors-GA-INSENSITIVE DWARF 1 proteins(GID1s)-and DELLAs in a blue light-dependent manner.Furthermore,we showed that CRY1 inhibits the association between GID1s and DELLAs.Genetically,CRY1 antagonizes the function of GID1s to repress the expression of cell elongation-related genes and thus hypocotyl elongation.Taken together,our findings demonstrate that CRY1 coordinates blue light and GA signali ng for plant photomorphogenesis by stabilizing DELLAs through the binding and in activation of GID1s,providing new in sights into the mechanism by which blue light antagonizes the function of GA in photomorphogenesis.
基金grants from National Natural Science Foundation of China(31929002,92049107 and 81801077)Innovative Research Groups of the National Natural Science Foundation of China(81721005)+2 种基金Youth Program of Wuhan Municipal Health Commission Foundation(WX18Q41)Technology and Innovation Commission of Shenzhen Municipality(JCYJ20210324141405014)Guangdong Basic and Applied Basic Research Foundation(2020B1515120017)and the Academic Frontier Youth Team Project to Xiaochuan Wang from Huazhong University of Science and Technology.
文摘Accumulation of impaired mitochondria and energy metabolism disorders are non-negligible features of both aging and age-related neurodegeneration,including Alzheimer’s disease(AD).A growing number of studies suggest that mitophagy disorders play an important role in AD occurrence and development.The interaction between mitophagy deficits and Aβor Tau pathology may form a vicious cycle and cause neuronal damage and death.Elucidating the molecular mechanism of mitophagy and its role in AD may provide insights into the etiology and mechanisms of AD.Defective mitophagy is a potential target for AD prevention and treatment.
基金This study was supported by the National Natural Science Foundation of China(81471482).We thank the patient and his parents for their cooperation。
文摘Accumulating evidence indicates that RIPK1 is associated with inflammation and apoptotic.RIPK1 deficiency leads to proinflammatory signaling impaired.However,only few patients with homozygous loss-of-function mutation in RIPK1 gene had been reported until now.Here,we report a Chinese combined immunodeficiency patient.He had recurrent infection,diarrhea after 3 months old.Immune function indicated that T,B and NK cells decreased significantly but immunoglobulins approximately remained normal.Whole-exome sequencing indicated that he had novel compound heterozygous mutations(c.998 C>A from his mother and c.1934 C>T from his father)in RIPK1 gene,which were confirmed by Sanger sequencing.Our study reports novel mutations in RIPK1 gene and new phenotype of patient with RIPK1 deficiency.
基金This research highlight article was supported by grants from the National Natural Science Foundation of China(92049107 and 31771114)Innovative Research Groups of the National Natural Science Foundation of China(81721005)the Ministry of Science and Technology of China(2016YFC1305800)。
文摘As a major public health problem in modern society,Alzheimer’s disease(AD)is currently the most widely prevalent neurodegenerative disease,which will indubitably increase dramatically in the coming years,unless drugs that can prevent or cure the disease become available.Because AD is characterized histopathologically by extracellular deposition of amyloid beta(Aβ)surrounded by dystrophic neuritis forming senile plaques(SPs).
基金sponsored by the National Key R&D Program of China (No. 2017YFB1002702)the National Natural Science Foundation of China (Nos. 61572058, 61472363)
文摘Depth-image-based rendering(DIBR) is widely used in 3 DTV, free-viewpoint video, and interactive 3 D graphics applications. Typically, synthetic images generated by DIBR-based systems incorporate various distortions, particularly geometric distortions induced by object dis-occlusion. Ensuring the quality of synthetic images is critical to maintaining adequate system service. However, traditional 2 D image quality metrics are ineffective for evaluating synthetic images as they are not sensitive to geometric distortion. In this paper, we propose a novel no-reference image quality assessment method for synthetic images based on convolutional neural networks, introducing local image saliency as prediction weights. Due to the lack of existing training data, we construct a new DIBR synthetic image dataset as part of our contribution. Experiments were conducted on both the public benchmark IRCCyN/IVC DIBR image dataset and our own dataset. Results demonstrate that our proposed metric outperforms traditional 2 D image quality metrics and state-of-the-art DIBR-related metrics.
基金This work was supported in part by grants from the NSFC(91632305,91632111,31730035 and 81721005)by the Ministry of Science and Technology of China(2016YFC1305800).
文摘Background:Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer’s disease(AD),while how to initiate early cognitive stimulation is unclear.Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing,we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period.Methods:After conception,maternal AD transgenic mice(3×Tg AD)were exposed to gestational environment enrichment(GEE)until the day of delivery.The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age.Western blotting,immunohistochemistry,real-time PCR,immunoprecipitation,chromatin immunoprecipitation(ChIP)assay,electrophysiology,Golgi staining,activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring.Results:We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring.The beneficial effects of GEE were accompanied by global histone hyperacetylation,including those at bdnf promoter-binding regions,with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus.GEE increased insulin-like growth factor 1(IGF1)and activated its receptor(IGF1R),which phosphorylates Ca^(2+)/calmodulin-dependent kinase IV(CaMKIV)at tyrosine sites and triggers its nuclear translocation,subsequently upregulating histone acetyltransferase(HAT)and BDNF transcription.The upregulation of IGF1 mimicked the effects of GEE,while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation.Conclusions:These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.