Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
The effects of a magnetic dipole on a nonlinear thermally radiative ferromagnetic liquidflowing over a stretched surface in the presence of Brownian motion and thermophoresis are investigated.By means of a similarity t...The effects of a magnetic dipole on a nonlinear thermally radiative ferromagnetic liquidflowing over a stretched surface in the presence of Brownian motion and thermophoresis are investigated.By means of a similarity transformation,ordinary differential equations are derived and solved afterwards using a numerical(the BVP4C)method.The impact of various parameters,namely the velocity,temperature,concentration,is presented graphically.It is shown that the nanoparticles properties,in conjunction with the magnetic dipole effect,can increase the thermal conductivity of the engineered nanofluid and,consequently,the heat transfer.Comparison with earlier studies indicates high accuracy and effectiveness of the numerical approach.An increase in the Brow-nian motion parameter and thermophoresis parameter enhances the concentration and the related boundary layer.The skin-friction rises when the viscosity parameter is increased.A larger value of the ferromagnetic para-meter results in a higher skin-friction and,vice versa,in a smaller Nusselt number.展开更多
Existing researches on cyber attackdefense analysis have typically adopted stochastic game theory to model the problem for solutions,but the assumption of complete rationality is used in modeling,ignoring the informat...Existing researches on cyber attackdefense analysis have typically adopted stochastic game theory to model the problem for solutions,but the assumption of complete rationality is used in modeling,ignoring the information opacity in practical attack and defense scenarios,and the model and method lack accuracy.To such problem,we investigate network defense policy methods under finite rationality constraints and propose network defense policy selection algorithm based on deep reinforcement learning.Based on graph theoretical methods,we transform the decision-making problem into a path optimization problem,and use a compression method based on service node to map the network state.On this basis,we improve the A3C algorithm and design the DefenseA3C defense policy selection algorithm with online learning capability.The experimental results show that the model and method proposed in this paper can stably converge to a better network state after training,which is faster and more stable than the original A3C algorithm.Compared with the existing typical approaches,Defense-A3C is verified its advancement.展开更多
Lithium sulfur(Li-S)battery is a kind of burgeoning energy storage system with high energy density.However,the electrolyte-soluble intermediate lithium polysulfides(Li PSs)undergo notorious shuttle effect,which seriou...Lithium sulfur(Li-S)battery is a kind of burgeoning energy storage system with high energy density.However,the electrolyte-soluble intermediate lithium polysulfides(Li PSs)undergo notorious shuttle effect,which seriously hinders the commercialization of Li-S batteries.Herein,a unique VSe_(2)/V_(2)C heterostructure with local built-in electric field was rationally engineered from V_(2)C parent via a facile thermal selenization process.It exquisitely synergizes the strong affinity of V_(2)C with the effective electrocatalytic activity of VSe_(2).More importantly,the local built-in electric field at the heterointerface can sufficiently promote the electron/ion transport ability and eventually boost the conversion kinetics of sulfur species.The Li-S battery equipped with VSe_(2)/V_(2)C-CNTs-PP separator achieved an outstanding initial specific capacity of 1439.1 m A h g^(-1)with a high capacity retention of 73%after 100 cycles at0.1 C.More impressively,a wonderful capacity of 571.6 mA h g^(-1)was effectively maintained after 600cycles at 2 C with a capacity decay rate of 0.07%.Even under a sulfur loading of 4.8 mg cm^(-2),areal capacity still can be up to 5.6 m A h cm^(-2).In-situ Raman tests explicitly illustrate the effectiveness of VSe_(2)/V_(2)C-CNTs modifier in restricting Li PSs shuttle.Combined with density functional theory calculations,the underlying mechanism of VSe_(2)/V_(2)C heterostructure for remedying Li PSs shuttling and conversion kinetics was deciphered.The strategy of constructing VSe_(2)/V_(2)C heterocatalyst in this work proposes a universal protocol to design metal selenide-based separator modifier for Li-S battery.Besides,it opens an efficient avenue for the separator engineering of Li-S batteries.展开更多
[Objective]This paper was to investigate the action targets and pathways of tea polyphenols in alleviating heat stress-induced injury by using network pharmacological analysis and an H9C2 cell model.[Method]First,the ...[Objective]This paper was to investigate the action targets and pathways of tea polyphenols in alleviating heat stress-induced injury by using network pharmacological analysis and an H9C2 cell model.[Method]First,the corresponding targets of tea polyphenols were obtained from the PubChem database.Then,the core targets were screened based on topological parameters.The relevant metabolism pathways of tea polyphenols related to diseases were identified through GO functional annotation and KECG signaling pathway enrichment.Moreover,common targets for thermal injury and targets of tea polyphenols were obtained.Then,GO functional annotation was performed to explore the pathway of tea polyphenols in alleviating heat stress damage.H9C2 cells were cultured at 42℃ to construct the heat stress model,and the cells were treated with 10μg/mL tea polyphenols.The key genes were confirmed using RT-PCR technology.[Result]The study yielded 364 targets corresponding to tea polyphenols,including 68 core targets.These targets are related to various biological processes such as involve oxidative stress,cancer,lipopolysaccharide-mediated signaling pathways,antiviral responses,regulation of cellular response to heat,apoptosis,and cellular lipid metabolic metabolism.Tea polyphe nols alleviate thermal damage by targeting BCL2,HSP90AA1,HSPA1A,JUN,MAPK1,NFKB1,NFKBIA,NOS3,and TP53.Moreover,10 mg/L tea polyphenols were found to upregulate the transcription levels of Hsp70,HO-1,NQ-O1,Nrf2,and MAPKI,and the transcription levels of Bax/Bcl2,p38,and JNK were downregulated to alleviate the heat stress-induced injury.[Conclusion]Tea polyphenols may enhance the antioxidant ability of H9C2 cells and inhibit cell apoptosis,thereby reducing heat stress injury.展开更多
BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking ...BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.展开更多
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
文摘The effects of a magnetic dipole on a nonlinear thermally radiative ferromagnetic liquidflowing over a stretched surface in the presence of Brownian motion and thermophoresis are investigated.By means of a similarity transformation,ordinary differential equations are derived and solved afterwards using a numerical(the BVP4C)method.The impact of various parameters,namely the velocity,temperature,concentration,is presented graphically.It is shown that the nanoparticles properties,in conjunction with the magnetic dipole effect,can increase the thermal conductivity of the engineered nanofluid and,consequently,the heat transfer.Comparison with earlier studies indicates high accuracy and effectiveness of the numerical approach.An increase in the Brow-nian motion parameter and thermophoresis parameter enhances the concentration and the related boundary layer.The skin-friction rises when the viscosity parameter is increased.A larger value of the ferromagnetic para-meter results in a higher skin-friction and,vice versa,in a smaller Nusselt number.
基金supported by the Major Science and Technology Programs in Henan Province(No.241100210100)The Project of Science and Technology in Henan Province(No.242102211068,No.232102210078)+2 种基金The Key Field Special Project of Guangdong Province(No.2021ZDZX1098)The China University Research Innovation Fund(No.2021FNB3001,No.2022IT020)Shenzhen Science and Technology Innovation Commission Stable Support Plan(No.20231128083944001)。
文摘Existing researches on cyber attackdefense analysis have typically adopted stochastic game theory to model the problem for solutions,but the assumption of complete rationality is used in modeling,ignoring the information opacity in practical attack and defense scenarios,and the model and method lack accuracy.To such problem,we investigate network defense policy methods under finite rationality constraints and propose network defense policy selection algorithm based on deep reinforcement learning.Based on graph theoretical methods,we transform the decision-making problem into a path optimization problem,and use a compression method based on service node to map the network state.On this basis,we improve the A3C algorithm and design the DefenseA3C defense policy selection algorithm with online learning capability.The experimental results show that the model and method proposed in this paper can stably converge to a better network state after training,which is faster and more stable than the original A3C algorithm.Compared with the existing typical approaches,Defense-A3C is verified its advancement.
基金supported by the National Natural Science Foundation of China(No.52072099)the Joint Guidance Project of the Natural Science Foundation of Heilongjiang Province,China(No.LH2022E093)the Team Program of the Natural Science Foundation of Heilongjiang Province,China(No.TD2021E005)。
文摘Lithium sulfur(Li-S)battery is a kind of burgeoning energy storage system with high energy density.However,the electrolyte-soluble intermediate lithium polysulfides(Li PSs)undergo notorious shuttle effect,which seriously hinders the commercialization of Li-S batteries.Herein,a unique VSe_(2)/V_(2)C heterostructure with local built-in electric field was rationally engineered from V_(2)C parent via a facile thermal selenization process.It exquisitely synergizes the strong affinity of V_(2)C with the effective electrocatalytic activity of VSe_(2).More importantly,the local built-in electric field at the heterointerface can sufficiently promote the electron/ion transport ability and eventually boost the conversion kinetics of sulfur species.The Li-S battery equipped with VSe_(2)/V_(2)C-CNTs-PP separator achieved an outstanding initial specific capacity of 1439.1 m A h g^(-1)with a high capacity retention of 73%after 100 cycles at0.1 C.More impressively,a wonderful capacity of 571.6 mA h g^(-1)was effectively maintained after 600cycles at 2 C with a capacity decay rate of 0.07%.Even under a sulfur loading of 4.8 mg cm^(-2),areal capacity still can be up to 5.6 m A h cm^(-2).In-situ Raman tests explicitly illustrate the effectiveness of VSe_(2)/V_(2)C-CNTs modifier in restricting Li PSs shuttle.Combined with density functional theory calculations,the underlying mechanism of VSe_(2)/V_(2)C heterostructure for remedying Li PSs shuttling and conversion kinetics was deciphered.The strategy of constructing VSe_(2)/V_(2)C heterocatalyst in this work proposes a universal protocol to design metal selenide-based separator modifier for Li-S battery.Besides,it opens an efficient avenue for the separator engineering of Li-S batteries.
基金Supported by National Natural Science Foundation of China(32302919,32302918)Taishan Industrial Experts Program(tscx202306046)+1 种基金Key R&D Program Rural Revitalization Project of Shandong Province(2023TZXD083)Science and Technology Cooperation Project of Shandong and Chongqing(2022LYXZ030)。
文摘[Objective]This paper was to investigate the action targets and pathways of tea polyphenols in alleviating heat stress-induced injury by using network pharmacological analysis and an H9C2 cell model.[Method]First,the corresponding targets of tea polyphenols were obtained from the PubChem database.Then,the core targets were screened based on topological parameters.The relevant metabolism pathways of tea polyphenols related to diseases were identified through GO functional annotation and KECG signaling pathway enrichment.Moreover,common targets for thermal injury and targets of tea polyphenols were obtained.Then,GO functional annotation was performed to explore the pathway of tea polyphenols in alleviating heat stress damage.H9C2 cells were cultured at 42℃ to construct the heat stress model,and the cells were treated with 10μg/mL tea polyphenols.The key genes were confirmed using RT-PCR technology.[Result]The study yielded 364 targets corresponding to tea polyphenols,including 68 core targets.These targets are related to various biological processes such as involve oxidative stress,cancer,lipopolysaccharide-mediated signaling pathways,antiviral responses,regulation of cellular response to heat,apoptosis,and cellular lipid metabolic metabolism.Tea polyphe nols alleviate thermal damage by targeting BCL2,HSP90AA1,HSPA1A,JUN,MAPK1,NFKB1,NFKBIA,NOS3,and TP53.Moreover,10 mg/L tea polyphenols were found to upregulate the transcription levels of Hsp70,HO-1,NQ-O1,Nrf2,and MAPKI,and the transcription levels of Bax/Bcl2,p38,and JNK were downregulated to alleviate the heat stress-induced injury.[Conclusion]Tea polyphenols may enhance the antioxidant ability of H9C2 cells and inhibit cell apoptosis,thereby reducing heat stress injury.
基金Supported by the Academic Leaders Training Program of Pudong Health Bureau of Shanghai,No.PWRd2023-03Clinical Research Fund of Shanghai Municipal Commission of Health,No.202040136+1 种基金National Natural Science Foundation of China,No.82070842Jiangxi Health Commission Science and Technology Plan Project,No.202212838 and No.202212852.
文摘BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.
