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.

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.

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.

Effect of periodic wide atmospheric pressure change on CO emission in closed goaf

Atmospheric pressure fuctuation is one of the most important factors afecting the climate environment and gas emission in the fre area.To obtain the infuence rule of the surface atmospheric pressure change on the gas sampling and abnormal emission in the mine closed goaf,the No.1 coal mine in Dananhu was taken as the research object.Using Fourier transform and Fisher harmonic analysis and other statistical methods,the infuence of the periodic variation of atmospheric pressure on the gas leakage and outfow in the closed goaf was studied.The results showed that there were three atmospheric pressure periods of 15.2 d,1 d and 182.2 d,and the probability was greater than 95%.The time period with the highest number of atmospheric pressure peaks was 7:00–8:00,which accounted for 20.2%of total occurrence number in a day.And the time periods with the highest number of atmospheric pressure trough were 2:00,15:00 and 16:00,accounting for 27.4%.The peak-to-trough transition time was mainly concentrated around 6 h,and the diurnal variation curve of atmospheric pressure was mainly bimodal.The atmospheric pressure change rate was mostly concentrated in 10–50 Pa/h.It was determined that the distance that the gas sampling pipe was pre-laid into the inner side of the closed wall should be greater than 44.4 m,and the CO concentration and atmospheric pressure in the closed goaf were both periodic and negative with atmospheric pressure.The research results have important guiding signifcance for the monitoring,early warning and environmental protection of the goaf.

Performance analyses of two-phase closed thermosyphons for road embankments in the high-latitude permafrost regions

Two-phase closed thermosyphons(TPCTs)are widely used in infrastructure constructions in permafrost regions.Due to different climatic conditions,the effectiveness of TPCT will also be different,especially in the extremely cold region of the Da Xing'anling Mountains.In this study,a series of three-dimensional finite element TPCT embankment models were established based on the ZhanglingMohe highway TPCT test section in Da Xing'anling Mountains,and the thermal characteristics and the cooling effect of the TPCTs were analyzed.The results indicated that the TPCTs installed in the northeastern high-latitude regions is effective in cooling and stabilizing the embankment.The working cycle of the TPCTs is nearly 7 months,and the cooling range of the TPCTs can reach 3 m in this region.However,due to the extremely low temperature,the TPCT generates a large radial gradient in the permafrost layer.Meanwhile,by changing the climate conditions,the same type of TPCT embankment located in the Da Xing'anling Mountains,the Xiao Xing'anling Mountains,and the Qinghai-Tibet Plateau permafrost regions were simulated.Based on the comparison of the climate differences between the Qinghai-Tibet Plateau and Northeast China,the differences in the effectiveness of TPCTs were studied.Finally,the limitations of using existing TPCTs in high-latitude permafrost regions of China were discussed and the potential improvements of the TPCT in cold regions were presented.

Closed corner divertor with B×▽B away from the divertor:a promising divertor scenario for tokamak power exhaust

A major challenge facing the steady-state operation of tokamak fusion reactors is to develop a viable divertor solution with order-of-magnitude increase in power handling capability as compared with present experience.A recently developed divertor concept for this end has been tested recently on EAST tokamak through combining the effects of a closed divertor corner and E×B drifts.The E×B drifts in the divertor move particles towards the outer divertor corner area in the scrape-off layer for B×▽B directed away from the divertor,which can significantly enhance the particle concentration there,facilitating divertor detachment.In recent EAST experiments,the effects have been demonstrated where the lowest electron temperature at the divertor plate is obtained with strike point located close to the corner in the horizontal target and with B×▽B away from the divertor.These experimental results are in reasonable agreement with SOLPS-ITER simulations including drift effects,suggesting that the new divertor concept potentially provides a promising divertor solution for long-pulse operations of future tokamak fusion reactors with much higher power fluxes.

Meta-analysis of the efficacy of volar plate internal fixation versus closed reduction and external fixation in the treatment of adult distal radius fractures

Objective:To compare the efficacy of open reduction and volar locking plate internal fixation with closed reduction and external fixation in the treatment of distal radius fractures by using meta analysis.Methods:The databases of CNKI,Wanfang,Weipu,Chinese biomedical literature,Pubmed,Embase,and Cochrane Library were retrieved,and the randomized controlled studies that directly compared the efficacy of plate internal fixation and closed reduction external fixation in the treatment of distal radius fractures published publicly from the establishment of the database to April 2023 were collected.The two researchers independently screened the retrieved literature according to the inclusion and exclusion criteria,extracted data,used Cochrane risk bias assessment tool for quality assessment,and used RevMan 5.4 software for meta analysis.Results:A total of 10 randomized controlled trials were included,all of which were in English.There were 1042 patients in total,and 9 of them were rated as low risk.Meta analysis results showed that one year after the treatment of distal radius fracture with volar locking plate internal fixation,DASH score[MD=-5.64,95%CI(-7.21,-4.06),P<0.00001];One year later,PRWE score[MD=-5.90,95%CI(-8.88,-2.92),P=0.001];Palm flexion[MD=5.92,95%CI(1.29,10.55),P=0.01];Pronation[MD=2.48,95%CI(0.59,4.36),P=0.01];Postrotation[MD=4.73,95%CI(2.15,7.31),P=0.0003];Grip strength[MD=0.61,95%CI(0.12,1.10),P=0.02];palmar tilt angle[MD=9.84,95%CI(5.66,14.02),P<0.00001];Radial inclination[MD=4.33,95%CI(2.97,5.69),P<0.00001]was superior to closed reduction plaster or splint external fixation.One year later,the European Five dimensional Health Scale(EQ-5D-5L)score[MD=0.02,95%CI(-0.01,0.05),P=0.27];Back extension[MD=2.22,95%CI(-4.15,8.59),P=0.49];Ulnar deviation[MD=3.49,95%CI(-0.80,7.78),P=0.11];Radial deviation[MD=2.05,95%CI(-2.39,6.50),P=0.37];Ulnar variance[MD=-1.14,95%CI(-3.16,0.88),P=0.27];There was no significant difference in complications[MD=0.77,95%CI(0.54,1.10),P=0.16](P>0.05).Conclusion:Based on the current clinical data,internal fixation with volar locking plate is more conducive to mid-term DASH score and grip strength recovery than closed reduction plaster or splint external fixation,but there is no significant difference in the quality of life and complications of patients.For adult distal radius fractures,surgical indications should be carefully grasped,and non operative treatment should be given priority.

Parameter Design of Current Double Closed Loop for T-Type Three-Level Grid-Connected Inverter

To reduce current harmonics caused by switching frequency,T-type grid-connected inverter topology with LCL filter is adopted.In view of the disadvantages of the slow response speed of the traditional current control and the failure to eliminate the influence of the LCL filter on the grid-connected current by using current PI control alone,a current double closed loop PI current tracking control is proposed.Through the theoretical analysis of the grid-connected inverter control principle,the grid-connected inverter control model is designed,and the transfer functionmodel of each control link is deduced,and the current loop PI regulator is designed at last.The simulation results show that the control strategy is feasible.

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。

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.

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.

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.

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.

SUMMARY OF STUDIES ON CLOSED-POLYCULTURE OF PENAEID SHRIMP WITH FISHES AND MOLUSCANS

Closed polyculture of Chinese penaeid shrimp,Taiwan red tilapia ,and molluscans(constricted tagelus and bay scallop) was studied from 1995 to 1997 with the enclosure experiment method, on a shrimp farm in Haiyang County,Shandong Province. Four structure optimized closed polyculture systems, i.e., the “shrimp tagelus" system, the “shrimp scallop" system,the “shrimp tilapia" system and the “shrimp tilapia tagelus" system,were worked out. All these polyculture systems were superior to shrimp monoculture system in economic and ecological efficiencies. The order of these polyculture systems in efficiencies was “shrimp tilapia tagelus">“shrimp tagelus">“shrimp tilapia">“shrimp scallop". The “shrimp tilapia tagelus" system raised the production by 28% and the utilization efficiency of input nitrogen by 85%.These closed polyculture systems reduced the nitrogen discharge ratio to 6%-8%, instead of 40%-90% in the usual open culture systems. The ecological features of the systems were also investigated and many meaningful results have been obtained. The mechanism enhancing the efficiencies of these systems, the ways to enhance the efficiencies further and those to reuse the sedimented materials are disscussed.

Closed circle DNA algorithm of change positive-weighted Hamilton circuit problem

Chain length of closed circle DNA is equal. The same closed circle DNA＇s position corresponds to different recognition sequence, and the same recognition sequence corresponds to different foreign DNA segment, so closed circle DNA computing model is generalized. For change positive-weighted Hamilton circuit problem, closed circle DNA algorithm is put forward. First, three groups of DNA encoding are encoded for all arcs, and deck groups are designed for all vertices. All possible solutions are composed. Then, the feasible solutions are filtered out by using group detect experiment, and the optimization solutions are obtained by using group insert experiment and electrophoresis experiment. Finally, all optimization solutions are found by using detect experiment. Complexity of algorithm is concluded and validity of DNA algorithm is explained by an example. Three dominances of the closed circle DNA algorithm are analyzed, and characteristics and dominances of group delete experiment are discussed.

Finite-time stability with respect to a closed invariant set for a class of discontinuous systems

This paper discusses the problem of finite-time stability with respect to a closed, but not necessarily compact, invariant set for a class of nonlinear systems with discontinuous right-hand sides in the sense of the Filippov solutions. When the Lyapunov function is Lipschitz continuous and regular, the Lyapunov theorem on finite-time stability with respect to a closed invariant set is presented.

Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

BACKGROUND： Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE： To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN： A randomized controlled animal experiment. SETTING： Training Division of the Medical College of Chinese People＇s Armed Police Force. MATERIALS： Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris （Sigma, USA）; WCX-2 （Ciphergen, USA）. Ultra-high speed hypothermia centrifuger （Bechman, USA）; Rotary tissue microtome （Keuca, Germany）; Biochip processor and PBS II-C protein chip reader （Ciphergen, USA）. METHODS： The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People＇s Armed Police Force from June 2005 to March 2006. ① Grouping and treatment： The experiments were completed in molecular pathological institute, central laboratory and pathological department. ② The rats were randomly divided into control group （n =12） and brain injury group （n =60）. Marmarou＇s weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were killed at 4, 8, 12, 24 and 48 hours after model establishment. ③ Pathological observation： Longitudinal section was made on cerebral cortex, and sections of 5 μm were prepared, then stained with hematoxylin and eosin （HE）. ④Protein chip analysis： 100 mg cerebral cortex was collected from each rat, and the protein content in sample was detected with Bradford method, meanwhile, WCX-2 protein chip was used to analyze the protein spectrum. The data were automatically collected with Ciphergen proteinchip 3.0 software, and the results were analyzed using Biomarker Wizard software to compare the differences of protein spectrum in rat cortex between the groups. MAIN OUTCOME MEASURES： Results of the pathological observation of cerebral cortex and the protein spectrum analysis. RESULTS：①Pathological changes of cerebral cortex： In the control group, no necrosis and edema was observed. In the brain injury group, injures of different severity occurred at different time points; After 4 hours, focal or scattered red nerve cells could be observed, the size of some cells was increased, cytoplasm was lightly stained, and only nuclear fragments were seen; After 8 hours, the necrotic nerve cells were increased, and the number of nerve cells was reduced, astrocytes （neuronophagia） could be seen in partial cytoplasm; there was small vascular dilatation, and endothelial cell proliferation; interstitial edema, regional rarefaction lightly stained. After 12- 48 hours, the necrotic nerve cells were reduced, and astrocytes proliferated. ② Results of protein spectrum analysis： The WCX-2 experiment found that the expressions of 5 639, 3 212 and 7 536 u proteins in cerebral cortex changed after injury in the brain injury group. The peak intensity of 5 639 u protein in the brain injury group at 8 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 3 212 u protein in the brain injury group at 48 hours after injury was higher than that in the control group （P 〈 0.05）; The peak intensity of 7 536 u protein at 24 hours after injury was higher than that in the control group （P 〈 0.05）. CONCLUSION： Brain injury can cause the changes of protein expression spectrum in cerebral cortex, it is suggested that brain injury can induce the expression of protein.