Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

The effect of different inflation volumes of laryngeal mask airway on efficacy of closed circuit controlled ventilation in pediatric cancer patients

Objective： The laryngeal mask airway （LMA） is an established way for airway control during spontaneous ventila- tion. Its ability to deliver positive pressure ventilation without leakage especially in low flow states is still controversy. The aim of this study is to test the possibility of using LMA in pediatric closed circuit controlled ventilation, and to find out the optimum cuff volume to perform closed system ventilation. Methods： Twenty children scheduled for elective surgeries were enrolled in a crossover study. Laryngeal mask airway was used. In stage I, the cuff was inflated with the maximum volume of air as rec- ommended by the manufacturers. Adjustment of volume of air inflated into the LMA cuff to the minimum volume to obtain the effective seal was done at stage II. The leak pressure, intracuff pressure and the leak volume were measured in both stages. Results： The cuff filling volume was significantly lower compared to the maximum cuff inflation volume in stage I. Leakage values showed significantly less values in stage II of the study with smaller cuff inflation volumes. The airway leakage pressure was significantly lower in stage fl in comparison to stage I. Cuff inflation pressure in stage I showed marked elevation which dropped significantly after adjustment of cuff volume in stage I1. Conclusion： Laryngeal mask airway is an effective tool to provide closed circuit controlled ventilation in pediatrics. Inflation of the cuff by the minimum volume of air needed to reach the just sealing pressure is suggested to minimize the leakage volume.

Sensing-Communication-Computing-Control Closed Loop for NOMA-UAV Systems

In the areas without terrestrial communication infrastructures,unmanned aerial vehicles(UAVs)can be utilized to serve field robots for mission-critical tasks.For this purpose,UAVs can be equipped with sensing,communication,and computing modules to support various requirements of robots.In the task process,different modules assist the robots to perform tasks in a closed-loop way,which is referred to as a sensing-communication-computing-control(SC3)loop.In this work,we investigate a UAV-aided system containing multiple SC^(3)loops,which leverages non-orthogonal multiple access(NOMA)for efficient resource sharing.We describe and compare three different modelling levels for the SC^(3)loop.Based on the entropy SC^(3)loop model,a sum linear quadratic regulator(LQR)control cost minimization problem is formulated by optimizing the communication power.Further for the assure-to-be-stable case,we show that the original problem can be approximated by a modified user fairness problem,and accordingly gain more insights into the optimal solutions.Simulation results demonstrate the performance gain of using NOMA in such task-oriented systems,as well as the superiority of our proposed closed-loop-oriented design.

Design and Test of Closed Hydraulic Transmission System of 4WD High-clearance Wheeled Sprayer

In conjunction with the working characteristics of the high-clearance wheeled sprayer and the benefits of the closed hydraulic system,a series of reasonable working parameters should be established,and a hydraulic system that fulfills the requisite specifications should be designed.The AMESim software model is employed to construct a closed hydraulic transmission system,and the simulation analysis is then performed according to the data of hydraulic components.According to analysis results,the prototype can be optimized and upgraded,and a verification test is further carried out.The test results demonstrate that the designed closed hydraulic transmission system meets the actual working requirements of the high-clearance wheeled sprayer and provides a stable experimental platform for intelligent control of agricultural machinery.

Simulation Modelling and Techno-Economics of Supercritical Carbon Dioxide Recompression Closed Brayton Cycle

In recent years, there has been global interest in meeting targets relating to energy affordability and security while taking into account greenhouse gas emissions. This has heightened major interest in potential investigations into the use of supercritical carbon dioxide (sCO2) power cycles. Climate change mitigation is the ultimate driver for this increased interest;other relevant issues include the potential for high cycle efficiency and a circular economy. In this study, a 25 MWe recompression closed Brayton cycle (RCBC) has been assessed, and sCO2 has been proposed as the working fluid for the power plant. The methodology used in this research work comprises thermodynamic and techno-economic analysis for the prospective commercialization of this sCO2 power cycle. An evaluated estimation of capital expenditure, operational expenditure, and cost of electricity has been considered in this study. The ASPEN Plus simulation results have been compared with theoretical and mathematical calculations to assess the performance of the compressors, turbine, and heat exchangers. The results thus reveal that the cycle efficiency for this prospective sCO2 recompression closed Brayton cycle increases (39% - 53.6%) as the temperature progressively increases from 550˚C to 900˚C. Data from the Aspen simulation model was used to aid the cost function calculations to estimate the total capital investment cost of the plant. Also, the techno-economic results have shown less cost for purchasing equipment due to fewer components being required for the cycle configuration as compared to the conventional steam power plant.

On Fuzzy Regularly Closed Filters in Michálek Fuzzy Topological Space

C.L. Chang’s introduction of fuzzy topology in 1981 opened up new avenues for parallel theories in topology. However, Chang’s work appears to focus more on the topology of fuzzy sets rather than fuzzy topology itself. In 1975, Michálek presented a functional definition of ordinary topology and later developed fuzzy topology as a distinct extension of this idea, setting it apart from Chang’s approach. While there has been significant research on Chang’s fuzzy topology, Michálek’s version has not received as much attention. This paper introduces the concept of fuzzy regularly closed filters, or FRCM filters, within Michálek’s fuzzy topological space and explores some properties of FRCM ultrafilters.

OPEN表和CLOSED表的合一

在人工智能传统的搜索方法中,一直是将OPEN表和CLOSED表分开的。这不仅增加了搜索算法的复杂性,久而久之,也许禁锢了人们的思想。文章试图改变这种状况,提出了一种与众不同的新思路,巧妙地将OPEN表和CLOSED表合二为一,减少了一些工作量,在一定程度上降低了算法的复杂性。

Singular Points, Closed Orbits, Stable Manifolds and Unstable Manifolds of Second Order Autonomous Birkhoff Systems

Aim To study singular points, closed orbits, stable manifolds and unstable manifolds of a second order autonomous Birkhoff system. Methods Qualitative methods of ordinary differential equation were used. Results and Conclusion The criteria for singular points, closed orbits and hyperbolic equilibrium points of a second order autonomous Birkhoff system are given. Moreover the stability of equilibria, stable manifolds and unstable manifolds are obtained.

New algorithm of mining frequent closed itemsets

A new algorithm based on an FC-tree （frequent closed pattern tree） and a max-FCIA （maximal frequent closed itemsets algorithm） is presented, which is used to mine the frequent closed itemsets for solving memory and time consuming problems. This algorithm maps the transaction database by using a Hash table,gets the support of all frequent itemsets through operating the Hash table and forms a lexicographic subset tree including the frequent itemsets.Efficient pruning methods are used to get the FC-tree including all the minimum frequent closed itemsets through processing the lexicographic subset tree.Finally,frequent closed itemsets are generated from minimum frequent closed itemsets.The experimental results show that the mapping transaction database is introduced in the algorithm to reduce time consumption and to improve the efficiency of the program.Furthermore,the effective pruning strategy restrains the number of candidates,which saves space.The results show that the algorithm is effective.

Evaluation of Two Cooling Methods for Closed Greenhouses

Special cooling methods are needed for normal growth of crops in closed greenhouses which permit no ventilation, especially during warm seasons. Experi- ments were designed to evaluate two cooling methods （Watergy chimney method and pool method） in a closed greenhouse in Beijing during warm seasons. Prelimi- nary results showed that average temperature at daytime （from 8：00 to 18：00） at 100 cm above ground surface in the closed greenhouse could be reduced by 8 with the Watergy chimney method. Average relative humidity fluctuated between 45% and 75% during daytime at 100 cm above ground surface within the closed greenhouse. With the pool method, average temperature was about 10 ℃ lower than that of the control greenhouse without pool at 50 cm above the ground surface. The peak temperature at 50 cm height was about 32℃ between 11：30 and 15：00 and, close to outside temperature. Temperature in this system satisfied normal growth of most crops, but relative humidity at 50 cm height were above 90% at daytime.

The Predetermined Failure of Murphy＇s Quest for Freedom in Closed Systems--Narritivity Temporality in Murphy

This essay aims at an analysis of Murphy's failure of his quest for freedom from the aspect of narrative temporality whichwill focus on order, duration and frequency. From the perspective of temporal order, the essay will endeavor to probe into the pro-lepsis in the novel to analyse predetermined narrative and its function. Considering with temporal duration, this essay will penetratethe deceleration of narrative—scene and pause in Murphy to explore its thematic meaning. To investigate the temporal frequency,iterative narrative within text will be exemplified to discuss closed systems in the novel. Based on the analysis of the narrativity tem-porality in Murphy, the essay will focuses on that how its narrative strategy well embodies its theme—the predetermined failure ofMurphy's quest for freedom in closed systems.

Novel therapeutic approaches for hepatitis B virus covalently closed circular DNA

Hepatitis B virus(HBV) infection is a major global health problem. Although current therapies, such as the use of nucleos(t)ide analogs, inhibit HBV replication efficiently, they do not eliminate covalently closed circular DNA(ccc DNA), which persists in hepatocyte nuclei. As HBV ccc DNA is a viral transcription template, novel therapeutic approaches to directly target HBV ccc DNA are necessary to completely eradicate persistent HBV infections. HBV ccc DNA levels in HBV-infected human liver cells are extremely low; thus, more reliable and simple measurement methods are needed to correctly monitor their levels during therapeutic treatment. Although reverse transcription-polymerase chain reaction or Southern blot procedures are currently used in research studies, these methods are not completely reliable and are also time-consuming and labor-intensive. Genome editing technologies, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9(CRISPR/Cas9) system, which are designed to target specific DNA sequences, represent highly promising potential therapeutic tools. In particular, the CRISPR/Cas9 system is an easily customizable sequencespecific nuclease with high flexibility and may be the most feasible approach to target HBV ccc DNA. Further research to develop easier, safer, and more effective protocols should be pursued.

Closed form solutions for free vibrations of rectangular Mindlin plates

A new two-eigenfunctions theory, using the amplitude deflection and the generalized curvature as two fundamental eigenfunctions, is proposed for the free vibration solutions of a rectangular Mindlin plate. The three classical eigenvalue differential equations of a Mindlin plate are reformulated to arrive at two new eigenvalue differential equations for the proposed theory. The closed form eigensolutions, which are solved from the two differential equations by means of the method of separation of variables are identical with those via Kirchhoff plate theory for thin plate, and can be employed to predict frequencies for any combinations of simply supported and clamped edge conditions. The free edges can also be dealt with if the other pair of opposite edges are simply supported. Some of the solutions were not available before. The frequency parameters agree closely with the available ones through pb-2 Rayleigh-Ritz method for different aspect ratios and relative thickness of plate.

Effects of antiviral agents and HBV genotypes on intrahepaticcovalently closed circular DNA in HBeAg-positive chronichepatitis B patients

AIM： To evaluate the effects of antiviral agents and HBV genotypes on intrahepatic covalently closed circular DNA （ccc DNA） in HBeAg-positive chronic hepatitis B patients.METHODS： Seventy-one patients received lamivudine （n = 35）, or sequential therapy with lamivudine- interferon alpha 2b （IFN-α 2b, n = 24） for 48 wk, or IFN-α 2b （n = 12） for 24 wk. All subjects were followed up for 24 wk. Intrahepatic ccc DNA was measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.RESULTS： Sequential lamivudine- INF-α therapy, lamivudine and INF-α monotherapy reduced ccc DNA of 1.7 log, 1.4 log and 0.8 log, respectively （P 〈 0.05）. Seventeen out of the 71 patieots developed HBeAg seroconversion, the reduction of ccc DNA in the HBeAg seroconversion patients was more significant than that in the HBeAg positive patients （3.0 log vs 1.6 log, P = 0.0407）. Twenty-four weeks after antiviral therapy withdrawal, 16 patients had a sustained virological response, the baseline intrahepatic ccc DNA in the patients with a sustained virological response was significantly lower than that in the patients with virological rebound （4.6 log vs 5.4 log, P = 0.0472）. HBV genotype C accounted for 85.9% （n = 61）, and genotype B for 14.1% （n = 10）, respectively, in the 71 patients. There was no significant difference in the change of ccc DNA level between HBV genotypes C and B （2.1 log vs 1.9 log）.CONCLUSION： Forty-eight week sequential lamivudine- INF-α therapy and lamivudine monotherapy reduce ccc DNA more significantly than 24-wk INF-α monotherapy. Low baseline intrahepatic ccc DNA level may predict the long-term efficacy of antiviral treatment. HBV genotypes C and B have no obvious influence on ccc DNA load.

Mechanical model for controlling floor heave in deep roadways with U-shaped steel closed support

Open U-shaped steel arch supports are commonly used in large-section static-pressure roadways in coal mines that are more than 900 m deep;however,it is very difficult to control floor heave of roadways.In this paper,a U-shaped steel closed support with an inverted U-shaped steel arch in the floor is proposed as a method for improving the support effect of the surrounding rock during the process of floor heaving.This research established a mechanical model for the U-shaped steel closed support,and determined the reaction forces at the connection of a camber angle.Using the limit load method calculated the critical buckling load of the inverted U-shaped steel arch,and use of a strength check method tested the strength of the U-shaped steel material.A numerical simulation was conducted using the finite difference software FLAC3 D.The simulation results show that the U-shaped steel closed support is able to control the floor heave of roadways,which is successfully used in the West 11-2 development roadway of the Zhuji Mine in the Huainan mining area in China.The cumulative floor heave over two years was less than50 mm.

Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B

250 million people worldwide continue to be chronically infected with the virus.While patients may be treated with nucleoside/nucleotide analogues,this only suppresses HBV titre to sub-detection levels without eliminating the persistent HBV covalently closed circular DNA(cccDNA)genome.As a result,HBV infection cannot be cured,and the virus reactivates when conditions are favorable.Interferons(IFNs)are cytokines known to induce powerful antiviral mechanisms that clear viruses from infected cells.They have been shown to induce cccDNA clearance,but their use in the treatment of HBV infection is limited as HBVtargeting immune cells are exhausted and HBV has evolved multiple mechanisms to evade and suppress IFN signalling.Thus,to fully utilize IFN-mediated intracellular mechanisms to effectively eliminate HBV,instead of direct IFN administration,novel strategies to sustain IFN-mediated anti-cccDNA and antiviral mechanisms need to be developed.This review will consolidate what is known about how IFNs act to achieve its intracellular antiviral effects and highlight the critical interferon-stimulated gene targets and effector mechanisms with potent anti-cccDNA functions.These include cccDNA degradation by APOBECs and cccDNA silencing and transcription repression by epigenetic modifications.In addition,the mechanisms that HBV employs to disrupt IFN signalling will be discussed.Drugs that have been developed or are in the pipeline for components of the IFN signalling pathway and HBV targets that detract IFN signalling mechanisms will also be identified and discussed for utility in the treatment of HBV infections.Together,these will provide useful insights into design strategies that specifically target cccDNA for the eradication of HBV.

GENERALIZATIONS AND CARTESIAN CLOSED SUBCATEGORIES OF SEMICONTINUOUS LATTICES

In this article, the authors mainly study how to obtain new semicontinuous lattices from the given semicontinuous lattices and discuss the conditions under which the image of a semicontinuous projection operator is also semicontinuous. Moreover, the authors investigate the relation between semicontinuous lattices and completely distributive lattices. Finally, it is proved that the strongly semicontinuous lattice category is a Cartesian closed category.

SPALLATION ANALYSIS WITH A CLOSED TRANS-SCALE FORMULATION OF DAMAGE EVOLUTION

A closed,trans-scale formulation of damage evolution based on the statistical mi- crodamage mechanics is summarized in this paper.The dynamic function of damage bridges the mesoscopic and macroscopic evolution of damage.The spallation in an aluminium plate is studied with this formulation.It is found that the damage evolution is governed by several dimensionless parameters, i.e.,imposed Deborah numbers De~* and De,Mach number M and damage number S.In particular, the most critical mode of the macroscopic damage evolution,i.e.,the damage localization,is deter- mined by Deborah number De~*.Deborah number De~* reflects the coupling and competition between the macroscopic loading and the microdamage growth.Therefore,our results reveal the multi-scale nature of spallation.In fact,the damage localization results from the nonlinearity of the microdamage growth.In addition,the dependence of the damage rate on imposed Deborah numbers De~* and De, Mach number M and damage number S is discussed.

Accuracy Compensation Technology of Closed⁃Loop Feedback of Industrial Robot Joints

The existing kinematic parameter calibration method cannot further improve the absolute positioning accuracy of the robot due to the uncertainty of positioning error caused by robot joint backlash.In view of this problem,a closed‑loop feedback accuracy compensation method for robot joints was proposed.Firstly,a Chebyshev polynomial error estimation model was established which took geometric error and non‑geometric error into account.In addition,the absolute linear grating scale was installed at each joint of the robot and the positioning error of the robot end was mapped to the joint angle.And the joint angle corrected value was obtained.Furthermore,the closed‑loop feedback of robot joints was established to realize the online correction of the positioning error.Finally,an experiment on the KUKA KR210 industrial robot was conducted to demonstrate the effectiveness of the method.The result shows that the maximum absolute positioning error of the robot is reduced by 75%from 0.76 mm to 0.19 mm.This method can compensate the robot joint backlash effectively and further improve the absolute positioning accuracy of the robot.