Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
To meet the high-performance requirements of fifth-generation(5G)and sixth-generation(6G)wireless networks,in particular,ultra-reliable and low-latency communication(URLLC)is considered to be one of the most important...To meet the high-performance requirements of fifth-generation(5G)and sixth-generation(6G)wireless networks,in particular,ultra-reliable and low-latency communication(URLLC)is considered to be one of the most important communication scenarios in a wireless network.In this paper,we consider the effects of the Rician fading channel on the performance of cooperative device-to-device(D2D)communication with URLLC.For better performance,we maximize and examine the system’s minimal rate of D2D communication.Due to the interference in D2D communication,the problem of maximizing the minimum rate becomes non-convex and difficult to solve.To solve this problem,a learning-to-optimize-based algorithm is proposed to find the optimal power allocation.The conventional branch and bound(BB)algorithm are used to learn the optimal pruning policy with supervised learning.Ensemble learning is used to train the multiple classifiers.To address the imbalanced problem,we used the supervised undersampling technique.Comparisons are made with the conventional BB algorithm and the heuristic algorithm.The outcome of the simulation demonstrates a notable performance improvement in power consumption.The proposed algorithm has significantly low computational complexity and runs faster as compared to the conventional BB algorithm and a heuristic algorithm.展开更多
The COP9 signalosome(CSN)is a highly conserved protein complex composed of 8 subunits(CSN1 to CSN8).The individual subunits of the CSN play essential roles in cell proliferation,tumorigenesis,cell cycle regulation,DNA...The COP9 signalosome(CSN)is a highly conserved protein complex composed of 8 subunits(CSN1 to CSN8).The individual subunits of the CSN play essential roles in cell proliferation,tumorigenesis,cell cycle regulation,DNA damage repair,angiogenesis,and microenvironmental homeostasis.The CSN complex has an intrinsic metalloprotease that removes the ubiquitin-like activator NEDD8 from cullin-RING ligases(CRLs).Binding of neddylated CRLs to CSN is sensed by CSN4 and communicated to CSN5 with the assistance of CSN6,thus leading to the activation of deneddylase.Therefore,CSN is a crucial regulator at the intersection between neddylation and ubiquitination in cancer progression.Here,we summarize current understanding of the roles of individual CSN subunits in cancer progression.Furthermore,we explain how the CSN affects tumorigenesis through regulating transcription factors and the cell cycle.Finally,we discuss individual CSN subunits as potential therapeutic targets to provide new directions and strategies for cancer therapy.展开更多
Landsat-5 Thematic Mapper(TM) dataset have been used to estimate salinity in the coastal area of Hong Kong. Four adjacent Landsat TM images were used in this study, which was atmospherically corrected using the Second...Landsat-5 Thematic Mapper(TM) dataset have been used to estimate salinity in the coastal area of Hong Kong. Four adjacent Landsat TM images were used in this study, which was atmospherically corrected using the Second Simulation of the Satellite Signal in the Solar Spectrum(6S) radiative transfer code. The atmospherically corrected images were further used to develop models for salinity using Ordinary Least Square(OLS) regression and Geographically Weighted Regression(GWR) based on in situ data of October 2009. Results show that the coefficient of determination(R^2) of 0.42 between the OLS estimated and in situ measured salinity is much lower than that of the GWR model, which is two times higher(R^2 = 0.86). It indicates that the GWR model has more ability than the OLS regression model to predict salinity and show its spatial heterogeneity better. It was observed that the salinity was high in Deep Bay(north-western part of Hong Kong) which might be due to the industrial waste disposal, whereas the salinity was estimated to be constant(32 practical salinity units) towards the open sea.展开更多
High electron mobility transistor(HEMT)based on gallium nitride(GaN)is one of the most promising candidates for the future generation of high frequencies and high-power electronic applications.This research work aims ...High electron mobility transistor(HEMT)based on gallium nitride(GaN)is one of the most promising candidates for the future generation of high frequencies and high-power electronic applications.This research work aims at designing and characterization of enhancement-mode or normally-off GaN HEMT.The impact of variations in gate length,mole concentration,barrier variations and other important design parameters on the performance of normally-off GaN HEMT is thoroughly investigated.An increase in the gate length causes a decrease in the drain current and transconductance,while an increase in drain current and transconductance can be achieved by increasing the concentration of aluminium(Al).For Al mole fractions of 23%,25%,and 27%,within Al gallium nitride(AlGaN)barrier,the GaN HEMT devices provide a maximum drain current of 347,408 and 474 mA/μm and a transconductance of 19,20.2,21.5 mS/μm,respectively.Whereas,for Al mole fraction of 10%and 15%,within AlGaN buffer,these devices are observed to provide a drain current of 329 and 283 mA/μm,respectively.Furthermore,for a gate length of 2.4,3.4,and 4.4μm,the device is observed to exhibit a maximum drain current of 272,235,and 221 mA/μm and the transconductance of 16.2,14,and 12.3 mS/μm,respectively.It is established that a maximum drain current of 997 mA/μm can be achieved with an Al concentration of 23%,and the device exhibits a steady drain current with enhanced transconductance.These observations demonstrate tremendous potential for two-dimensional electron gas(2DEG)for securing of the normally-off mode operation.A suitable setting of gate length and other design parameters is critical in preserving the normally-off mode operation while also enhancing the critical performance parameters at the same time.Due to the normallyon depletion-mode nature of GaN HEMT,it is usually not considered as suitable for high power levels,frequencies,and temperature.In such settings,a negative bias is required to enter the blocking condition;however,in the before-mentioned normally-off devices,the negative bias can be avoided and the channel can be depleted without applying a negative bias.展开更多
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
基金supported in part by the National Natural Science Foundation of China under Grant 61771410in part by the Sichuan Science and Technology Program 2023NSFSC1373in part by Postgraduate Innovation Fund Project of SWUST 23zx7101.
文摘To meet the high-performance requirements of fifth-generation(5G)and sixth-generation(6G)wireless networks,in particular,ultra-reliable and low-latency communication(URLLC)is considered to be one of the most important communication scenarios in a wireless network.In this paper,we consider the effects of the Rician fading channel on the performance of cooperative device-to-device(D2D)communication with URLLC.For better performance,we maximize and examine the system’s minimal rate of D2D communication.Due to the interference in D2D communication,the problem of maximizing the minimum rate becomes non-convex and difficult to solve.To solve this problem,a learning-to-optimize-based algorithm is proposed to find the optimal power allocation.The conventional branch and bound(BB)algorithm are used to learn the optimal pruning policy with supervised learning.Ensemble learning is used to train the multiple classifiers.To address the imbalanced problem,we used the supervised undersampling technique.Comparisons are made with the conventional BB algorithm and the heuristic algorithm.The outcome of the simulation demonstrates a notable performance improvement in power consumption.The proposed algorithm has significantly low computational complexity and runs faster as compared to the conventional BB algorithm and a heuristic algorithm.
基金This work was supported by the National Natural Science Foundation of China(Grant No.81872080)Jiangsu Provincial Medical Talent(Grant No.ZDRCA 2016055)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘The COP9 signalosome(CSN)is a highly conserved protein complex composed of 8 subunits(CSN1 to CSN8).The individual subunits of the CSN play essential roles in cell proliferation,tumorigenesis,cell cycle regulation,DNA damage repair,angiogenesis,and microenvironmental homeostasis.The CSN complex has an intrinsic metalloprotease that removes the ubiquitin-like activator NEDD8 from cullin-RING ligases(CRLs).Binding of neddylated CRLs to CSN is sensed by CSN4 and communicated to CSN5 with the assistance of CSN6,thus leading to the activation of deneddylase.Therefore,CSN is a crucial regulator at the intersection between neddylation and ubiquitination in cancer progression.Here,we summarize current understanding of the roles of individual CSN subunits in cancer progression.Furthermore,we explain how the CSN affects tumorigenesis through regulating transcription factors and the cell cycle.Finally,we discuss individual CSN subunits as potential therapeutic targets to provide new directions and strategies for cancer therapy.
基金The National Key Research and Development Program of China (No.2016YFC1400901)
文摘Landsat-5 Thematic Mapper(TM) dataset have been used to estimate salinity in the coastal area of Hong Kong. Four adjacent Landsat TM images were used in this study, which was atmospherically corrected using the Second Simulation of the Satellite Signal in the Solar Spectrum(6S) radiative transfer code. The atmospherically corrected images were further used to develop models for salinity using Ordinary Least Square(OLS) regression and Geographically Weighted Regression(GWR) based on in situ data of October 2009. Results show that the coefficient of determination(R^2) of 0.42 between the OLS estimated and in situ measured salinity is much lower than that of the GWR model, which is two times higher(R^2 = 0.86). It indicates that the GWR model has more ability than the OLS regression model to predict salinity and show its spatial heterogeneity better. It was observed that the salinity was high in Deep Bay(north-western part of Hong Kong) which might be due to the industrial waste disposal, whereas the salinity was estimated to be constant(32 practical salinity units) towards the open sea.
文摘High electron mobility transistor(HEMT)based on gallium nitride(GaN)is one of the most promising candidates for the future generation of high frequencies and high-power electronic applications.This research work aims at designing and characterization of enhancement-mode or normally-off GaN HEMT.The impact of variations in gate length,mole concentration,barrier variations and other important design parameters on the performance of normally-off GaN HEMT is thoroughly investigated.An increase in the gate length causes a decrease in the drain current and transconductance,while an increase in drain current and transconductance can be achieved by increasing the concentration of aluminium(Al).For Al mole fractions of 23%,25%,and 27%,within Al gallium nitride(AlGaN)barrier,the GaN HEMT devices provide a maximum drain current of 347,408 and 474 mA/μm and a transconductance of 19,20.2,21.5 mS/μm,respectively.Whereas,for Al mole fraction of 10%and 15%,within AlGaN buffer,these devices are observed to provide a drain current of 329 and 283 mA/μm,respectively.Furthermore,for a gate length of 2.4,3.4,and 4.4μm,the device is observed to exhibit a maximum drain current of 272,235,and 221 mA/μm and the transconductance of 16.2,14,and 12.3 mS/μm,respectively.It is established that a maximum drain current of 997 mA/μm can be achieved with an Al concentration of 23%,and the device exhibits a steady drain current with enhanced transconductance.These observations demonstrate tremendous potential for two-dimensional electron gas(2DEG)for securing of the normally-off mode operation.A suitable setting of gate length and other design parameters is critical in preserving the normally-off mode operation while also enhancing the critical performance parameters at the same time.Due to the normallyon depletion-mode nature of GaN HEMT,it is usually not considered as suitable for high power levels,frequencies,and temperature.In such settings,a negative bias is required to enter the blocking condition;however,in the before-mentioned normally-off devices,the negative bias can be avoided and the channel can be depleted without applying a negative bias.
