Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

Real-Time Method for Detecting Harmonic and Reactive Currents of Single-Phase Circuits

According to the characteristics of single-phase circuits and demand of using active filter for real-time detecting harmonic and reactive currents, a detecting method based on Fryze＇s power definition is proposed. The results of theoretical analysis and simula- tion show that the proposed method is effective in realtime detecting of instantaneous harmonic and reactive currents in single-phase circuits. When only detecting the total reactive currents, this method does not need a phase-locked loop circuit, and it also can be used in some special applications to provide different compensations on the ground of different requirements of electric network. Compared with the other methods based on the theory of instantaneous reactive power, this method is simple and easy to realize.

Reactive Current Allocation and Control Strategies Improvement of Low Voltage Ride Though for Doubly Fed Induction Wind Turbine Generation System

为满足风电机组低电压穿越（low voltage ride through,LVRT）的测试要求及其电气模型一致性评估需要,提出考虑向电网注入无功电流的双馈风电机组LVRT的控制策略。在阐述风电机组LVRT测试要求及控制原理的基础上,推导双馈发电机（doubly fed induction generator,DFIG）定子侧及网侧变流器输出无功电流极限表达式,研究电网电压跌落深度和发电机总输出有功功率对其无功电流极限值的影响规律,进而提出DFIG在LVRT期间的无功电流分配算法和改进的有功、无功功率控制策略。最后,以某实际2 MW双馈风电机组为例,分别对风速为5和12 m/s、电网电压对称跌落至20%和50%工况下的LVRT运行性能进行仿真比较和样机测试。与传统LVRT控制方法的对比表明,所提改进控制策略能更好地满足风电机组LVRT的测试要求。样机测试结果进一步证明了改进控制策略和仿真模型的有效性。

Effects of the sputtering power on the crystalline structure and optical properties of the silver oxide films deposited using direct-current reactive magnetron sputtering

This paper reports that a series of silver oxide （AgzO） films are deposited on glass substrates by direct-current reactive magnetron sputtering at a substrate temperature of 250 ℃ and an oxygen flux ratio of 15：18 by modifying the sputtering power （SP）. The AgxO films deposited apparently show a structural evolution from cubic biphased （AgO ＋ Ag20） to cubic single-phased （Ag20）, and to biphased （Ag20 ＋ AgO） structure. Notably, the cubic single-phased Ag20 fihn is deposited at the SP = 105 W and an AgO phase with （220） orientation discerned in the Ag^O films deposited using the SP 〉 105 W. The transmissivity and refiectivity of the AgxO films in transparent region decrease with the increase the SP, whereas the absorptivity inversely increases with the increase of the SP. These results may be due to the structural evolution and the increasing film thickness. A redshift of the films＇ absorption edges determined in terms of Tauc formula clearly occurs from 3.1 eV to 2.73 eV with the increase of the SP.

Formation behaviors of rod-like reactive shaped charge penetrator and their effects on damage capability

Formation behaviors of rod-like reactive shaped charge penetrator(RRSCP)and their effects on damage capability are investigated by experiments and numerical simulations.The pulsed X-ray technology and a spaced aluminum/steel plate with the thicknesses of 5 mm/100 mm are used.Three types of sphericalsegment aluminum-polytetrafluoroethylene-copper(Al-PTFE-Cu)reactive liners with Cu contents of 0%,46.6%,and 66%are fabricated and tested.The experimental results show that the reactive liners can form excellent rod-shaped penetrators with tail skirts under the shaped charge effect,but the tail skirts disappear over time.Moreover,rupturing damage to the aluminum plate and penetration to the steel plate are caused by the RRSCP impact.From simulation analysis,the RRSCP is formed by a mechanically and chemically coupled response with the reactive liner activated by shock in its outer walls and bottom and then backward overturning,forming a leading reactive penetrator and a following chemical energy cluster.The unique formation structure determines the damage modes of the aluminum plate and the steel plate.Further analysis indicates that the formation behaviors and damage capability of Al-PTFE-Cu RRSCP strongly depend on Cu content.With increasing Cu content,the velocity,activation extent,and reaction extent of Al-PTFE-Cu RRSCP decrease,which contribute to elongation and alleviate the negative effects of chemical reactions on elongation,significantly increasing the length-diameter ratio and thus enhancing the capability of steel plate penetration.However,the lower activation extent and energetic density will weaken the RRSCP's capability of causing rupturing damage to the aluminum plate.

Monomeric C-reactive protein:a link between chronic inflammation and neurodegeneration?

Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.

软件定义网络Reactive交换模式IP转发效率研究

现代计算机网络技术发展迅速,SDN具有转发与控制分离、应用灵活多变、适应性强等特点,已逐渐被IT厂商和电信运营商所接纳并采用,但SDN作为一种发展中的技术很多方面还有待完善。本文首先将IP层相关协议的通信过程进行了分析,然后针对SDN的Reactive交换机模式将这些协议的通信效率与以太网进行了对比。实验与分析表明,在地址解析、连通性测试和数据传输等基本网络行为中,SDN的Reactive交换模式效率并不占据优势,需要进一步优化。

Evolution of the structural and optical properties of silver oxide films with different stoichiometries deposited by direct-current magnetron reactive sputtering

Nitrogen doping of silver oxide （AgxO） film is necessary for its application in transparent conductive film and diodes because intrinsic AgxO film is a p-type semiconductor with poor conductivity. In this work, a series of AgxO films is deposited on glass substrates by direct-current magnetron reactive sputtering at different flow ratios （FRs） of nitrogen to 02. Evolutions of the structure, the refiectivity, and the transmissivity of the film are studied by X-ray diffractometry and sphectrophotometry, respectively. The specular transmissivity and the specular refiectivity of the film decreasing with FR increasing can be attributed to the evolution of the phase structure of the film. The nitrogen does not play the role of an acceptor dopant in the film deposition.

On the functions of astrocyte-mediated neuronal slow inward currents

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of astrocytes.These events are significantly slower than the excitatory postsynaptic currents.Parameters of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto rs.Astrocytes are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback loop.Mostly as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological conditions.There is a growing body of evidence on the roles of slow inward currents on a single neuron or local network level.These events often occur in synchro ny on neurons located in the same astrocytic domain.Besides synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic plasticity.In addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory inputs.Of note,there might be important regionspecific differences in the roles and actions triggering slow inward currents.In greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological ones.Slow inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural networks.Slow inward currents are significant contributors to paroxysmal depolarizational shifts/interictal spikes.These events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive functions.Events with features overlapping with slow inward currents(excitatory,N-methyl-Daspartate-receptor mediated currents with astrocytic contribution) as ischemic currents and spreading depolarization also have a well-known pathophysiological role in worsening consequences of stroke,traumatic brain injury,or epilepsy.One might assume that slow inward currents occurring with low frequency under physiological conditions might contribute to synaptic plasticity and memory formation.However,to state this,more experimental evidence from greater neuronal networks or the level of the individual is needed.In this review,I aimed to summarize findings on slow inward currents and to speculate on the potential functions of it.

Enhanced structural damage behavior of liquid-filled tank by reactive material projectile impact

A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.

Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

Lift-Off Effect of Koch and Circular Differential Pickup Eddy Current Probes

A flexible or planar eddy current probe with a differential structure can suppress the lift-off noise during the inspection of defects.However,the extent of the lift-off effect on differential probes,including different coil structures,varies.In this study,two planar eddy current probes with differential pickup structures and the same size,Koch and circular probes,were used to compare lift-off effects.The eddy current distributions of the probes perturbed by 0°and 90°cracks were obtained by finite element analysis.The analysis results show that the 90°crack can impede the eddy current induced by the Koch probe even further at relatively low lift-off distance.The peak-to-peak values of the signal output from the two probes were compared at different lift-off distances using finite element analysis and experimental methods.In addition,the effects of different frequencies on the lift-off were studied experimentally.The results show that the signal peak-to-peak value of the Koch probe for the inspection of cracks in 90°orientation is larger than that of the circular probe when the lift-off distance is smaller than 1.2 mm.In addition,the influence of the lift-off distance on the peak-to-peak signal value of the two probes was studied via normalization.This indicates that the influence becomes more evident with an increase in excitation frequency.This research discloses the lift-off effect of differential planar eddy current probes with different coil shapes and proves the detection merit of the Koch probe for 90°cracks at low lift-off distances.

Reduction Discoloration of Reactive Dyed Cotton Waste and Chemical Recycling via Ionic Liquid

The textile industry generates large volumes of waste throughout its production process.Most of this waste is colored,therefore,discoloration is an important step toward recycling and reusing this waste.This study focused on the chemical reductive discoloration of textile waste composed of cotton dyed with reactive dye.The experimental design demonstrated the significant influence of the concentration of reducing agent and time of reaction on the degree of whiteness of the cotton fibers.The concentration of the alkaline agent was not significant in the process.The optimization of the reaction conditions lead to Berger degree of 50.5±3.5.The discolored cotton was chemically recycled through dissolution in ionic liquid 1-ethyl-3-methylimidazolium chloride and regeneration in film form in water.The microstructure of the regenerated cellulose films was evaluated by Scanning Electron Microscopy(SEM)indicating complete dissolution and uniform regeneration.The discoloration process reduced the polymerization degree and crystallinity index of the cotton fibers but retained the cellulose I structure.The dissolution and cellulose regeneration process results in transparent films with an amorphous structure.The thermal behavior,evaluated by thermogravimetric analysis,indicated that residues and regenerated film presented a main decomposition step.The maximum decomposition rate temperature of the regenerated films was approximately 40℃lower than the cotton fibers,which correlates well with the reduction in polymerization degree and amorphous structure.In general,the study demonstrated that textile cotton waste dyed with reactive dyes can be chemically discolored to form transparent and amorphous films,contributing to the development of sustainable strategies for the textile industry.

Fabrication and Properties of a New Reactive Diluent for Cationic UV Curing

The reactive diluent prepared by siloxane modified Trimethylene oxide can improve the performance of the UV curing system.Therefore,1,7-bis[(3-ethyl-3-methoxyoxacylobutane)propyl]octadecylosiloxane(BEMOPOMTS)was synthesized from diethyl carbonate,trimethylopropanes,allyl bromide,and 1,1,3,3,5,5,7,7-octadecylosiloxane as the main raw materials.BEMOPOMTS can be used as reactive diluents in the field of cationic UV curing.It has good thermal stability,and the addition of BEMOPOMTS significantly improves the tensile strength and elongation at break of epoxy resin.Compared with the pure epoxy resin,adding 20%BEMOPOMTS increased the elastic modulus by 25%to 677 MPa.

Evidence of guide field magnetic reconnection in flapping current sheets

Based on current sheet flapping motion on 27 August 2018 in the dusk flank magnetotail,as recorded by instruments aboard Magnetospheric Multiscale(MMS)spacecraft,we present the first study of guide field reconnection observed in the flux rope embedded in kink-like flapping current sheets near the dusk-side flank of the magnetotail.Unlike more common magnetotail reconnections,which are symmetric,these asymmetric small-scale(λ_(i)~650 km)reconnections were found in the highly twisted current sheet when the direction normal to the sheet changes from the Z direction into the Y direction.The unique feature of this unusual reconnection is that the reconnection jets are along the Z direction-different from outflow in the X direction,which is the more usual situation.This vertical reconnection jet is parallel or antiparallel to the up-and-down motion of the tail’s current sheet.The normalized reconnection rate R is estimated to be~0.1.Our results indicate that such asymmetric reconnections can significantly enlarge current sheet flapping,with large oscillation amplitudes.This letter presents direct evidence of guide field reconnection in a highly twisted current sheet,characterized by enlarged current sheet flapping as a consequence of the reconnection outflow.

Responses of serum inflammatory factor high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in elderly males with cerebral infarction Non-randomized concurrent control

BACKGROUND： Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE： To detect the levels of high-sensitivity C-reactive protein （hs-CRP）, interleukin-6 （IL-6）, and tumor necrosis factor- a （TNF- α ） in elderly males with cerebral infarction. DESIGN： Non-randomized current control study. SETTING： Cadre Medical Department, Guizhou Provincial People＇s Hospital. PARTICIPANTS： Forty elderly males （65-89 years old） with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People＇s Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients （65-87 years old） without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group （P 〉 0.05）, and this suggested that the baseline data of both groups were comparable. METHODS： Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF- α in the serum. MAIN OUTCOME MEASURES： The levels of hs-CRP, 1L-6, and TNF- α in the serum in both groups. RESULTS： Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss. Levels of hs-CRP, IL-6, and TNF-α in the cerebral infarction group were significantly higher than those in the control group （P 〈 0.01 ）. CONCLUSION： Levels of serum inflammatory reactive factors are increased in elderly males with cerebral infarction.

Adaptive optimisation of explosive reactive armour for protection against kinetic energy and shaped charge threats

We evaluate an adaptive optimisation methodology,Bayesian optimisation(BO),for designing a minimum weight explosive reactive armour(ERA)for protection against a surrogate medium calibre kinetic energy(KE)long rod projectile and surrogate shaped charge(SC)warhead.We perform the optimisation using a conventional BO methodology and compare it with a conventional trial-and-error approach from a human expert.A third approach,utilising a novel human-machine teaming framework for BO is also evaluated.Data for the optimisation is generated using numerical simulations that are demonstrated to provide reasonable qualitative agreement with reference experiments.The human-machine teaming methodology is shown to identify the optimum ERA design in the fewest number of evaluations,outperforming both the stand-alone human and stand-alone BO methodologies.From a design space of almost 1800 configurations the human-machine teaming approach identifies the minimum weight ERA design in 10 samples.

Double-ring high-frequency common-mode switching oscillation current sensor for inverter-fed machine winding insulation monitoring

Insulation failure significantly contributes to the unpredictable shutdown of power equipment.Compared to the partial discharge and high-frequency(HF)injection methods,the HF common-mode(CM)leakage current method offers a non-intrusive and highly sensitive alternative.However,the detection of HF CM currents is susceptible to interference from differential-mode(DM)currents,which exhibit high-amplitude and multifrequency components during normal operation.To address this challenge,this paper proposes a double-ring current sensor based on the principle of magnetic shielding for inverter-fed machine winding insulation monitoring.The inner ring harnesses the magnetic aggregation effect to isolate the DM current magnetic field,whereas the outer ring serves as the magnetic core of the Rogowski current sensor,enabling HF CM current monitoring.First,the magnetic field distributions of the CM and DM currents were analyzed.Then,a correlation between the sensor parameters and signal-to-noise ratio of the target HF CM current was established.Finally,an experimental study was conducted on a 3-kW PMSM for verification.The results indicate that the proposed double-ring HF CM sensor can effectively mitigate DM current interference.Compared to a single-ring sensor,a reduction of approximately 40%in the DM component was achieved,which significantly enhanced the precision of online insulation monitoring.