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.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

血清HMGA2、P-gp与老年进展性脑梗死患者预后相关研究

目的探讨血清高迁移率族蛋白A2(HMGA2)、P-糖蛋白(P-gp)在老年进展性脑梗死患者中的表达水平及其与预后的关系。方法收集2020年2月—2023年2月大连市中心医院神经内科收治老年进展性脑梗死患者67例为进展组,老年非进展性脑梗死患者79例为非进展组;进展组根据治疗后3个月神经功能恢复情况分为预后良好亚组(n=39,mRS评分0~2分)和预后不良亚组(n=28,mRS评分3~6分)。采用酶联免疫吸附法检测血清HMGA2、P-gp水平,Pearson积矩相关分析血清HMGA2、P-gp与NIHSS评分的关系,Logistic回归分析进展性脑梗死患者预后不良的影响因素,受试者工作特征曲线(ROC)评估血清HMGA2、P-gp对预后不良的预测价值。结果进展组血清HMGA2、P-gp水平及NIHSS评分高于非进展组(t/P=13.672/<0.001,8.095/<0.001,8.226/<0.001)。进展性脑梗死患者血清HMGA2、P-gp与NIHSS评分均呈正相关(r/P=0.732/<0.001、0.708/<0.001);预后不良亚组患者年龄大于预后良好亚组,血清HMGA2、P-gp水平及NIHSS评分高于预后良好亚组(t/P=5.092/<0.001、5.103/<0.001、4.449/<0.001、2.357/0.021)。多因素Logistic回归结果显示,高龄和血清HMGA2、P-gp水平及NIHSS评分升高是进展性脑梗死患者预后不良独立危险因素[OR(95%CI)=1.429(1.093~1.869),1.288(1.082~1.533),1.586(1.161~2.165),1.483(1.120~1.963)];血清HMGA2、P-gp及二者联合预测进展性脑梗死患者预后不良的AUC分别为0.738、0.740、0.895,二者联合优于各自单独预测效能(Z/P=2.031/0.002、2.006/0.003)。结论血清HMGA2、P-gp在老年进展性脑梗死患者中异常升高,并与病情严重程度以及预后不良有关,早期联合检测两项指标可预测患者预后不良风险发生。

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.

MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss

Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.

GI.5和GII.4诺如病毒P蛋白的克隆表达及与长牡蛎类HBGAs的结合特性

为明确人诺如病毒(human norovirus,HuNoV)与长牡蛎类组织血型抗原(histo-blood group antigens,HBGAs)的结合特性,本实验运用大肠杆菌表达系统,克隆表达了基因簇I.5(genogroup I.5,GI.5)和GII.4 HuNoV P蛋白,采用酶联免疫吸附测定研究HuNoV P蛋白与唾液HBGAs和长牡蛎类HBGAs的结合特性。结果表明,GII.4 HuNoV与唾液A型、B型、AB型和O型HBGAs均有较好的结合,而GI.5 HuNoV与B型HBGAs结合较弱,与O型HBGAs具有明显的结合优势。GI.5和GII.4 HuNoV在长牡蛎鳃、消化腺和外套膜中均可富集,其中在消化腺中富集最多,二者主要与类A型和H1型HBGAs结合,GII.4HuNoV与类Lea型、Leb型、Lex型和Ley型HBGAs有不同程度的结合,而GI.5 HuNoV与类Leb型HBGAs仅微弱结合,与类H1型HBGAs具有明显结合优势。综上,不同型别HuNoV与HBGAs的结合特性不尽相同,GII.4HuNoV具有广谱结合特性,GI.5HuNoV具有选择结合特性。

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

极大类p群的非线性非忠实不可约特征标个数

利用极大类p群的性质以及有限群的特征标理论探究了极大类p群G的非线性非忠实不可约特征标的个数.证明了p^(n)阶的极大类p群G的非线性非忠实不可约特征标的个数等于p^(n-1)阶的极大类p群G/Z(G)的非线性不可约特征标的个数.特别地,分析了只有3个非线性非忠实不可约特征标的有限p群的性质.

Closed Range Composition Operators on a General Family of Function Spaces

In this paper, necessary and sufficient conditions for a closed range composition operator CФ on the general family of holomorphic function spaces F（p,q,s） and more generally on α-Besov type spaces F（p,αp-2,s） are given. We give a Carleson measure characterization on F （p, αp - 2, s） spaces, then we indicate how Carleson measures can be used to characterize boundedness and compactness of CФ on F（p,q,s） and F（p,αp- 2,s） spaces.

Close Coupled Showerhead Reactors for the Growth of Group Ⅲ Nitrides

The group Ⅲ nitrides are an important class of materials with aplications in UV and visible optoelectronics,high temperature electronics,cold cathodes and solar blind detectors.In recent years,with the realisation of nitride based LEDs,the use of GaN IED has the potential to compete with 1raditional filament and discharge lamps,for the provision of white lighting,and there has been an explosion of interest in the MOCVD growth of GaN based materials with an increasing focus on large area multiwafer reactors and wafer uniforrmity.This paper will review the design philosophy and characteristics of close-coupled showerhead reactors,relating these to the requirements of group Ⅲ-nitride growth,and will present a selection of data resulting from the operation of such equipment.These results suggest that the close coupled showerhead style of reactor is very suitable for the growth of GaN based structures in both research and production environments.

c-正规性对有限群p-可解性的影响

利用c-正规性给出了有限群是p-幂零群的充要条件,并通过分析Sylow子群及其极大子群在G中的c-正规性,给出了有限群G是p-超可解群的2个充分条件.

SS-拟正规子群对有限群p-超可解性的影响

设G为有限群,若存在B≤G使得G=HB,且对任意p∈π(B),P∈Sy1_( p)(B),都有HP=PH,则称子群H在G中SS-拟正规.利用极小阶反例法,讨论某些p-子群SS-拟正规的有限群结构,得到p-超可解群的若干充分条件,推广了p-超可解性的部分结果.

p-超可解群的新判定

设p是有限群G的一个素因子,P是G的p-子群且t是正整数满足|P|>p^(t).通过P的任意pt阶子群和4阶循环子群(P为非交换2-群且t=1)在G中c-正规或者Φ-可补,得到p-超可解群的一些新判定方法.

具有指数p的子群的双循环群

研究了当有限群G是具有指数p的子群(即极大子群)的双循环群时的另一种结构,利用群G的2阶子群对循环子群的共轭作用导出了24阶双循环群的结构。

间隔p Virasoro代数的导子代数和自同构群

Virasoro代数作为圆上的多项式向量场的复李代数的泛中心扩张在二维共形量子场论中起到奠基性作用,间隔p Virasoro代数是一类与无心的Heisenberg-Virasoro代数密切相关的无限维李代数.本文研究了间隔p Virasoro代数的导子代数和自同构群.特别地,本文给出间隔p Virasoro代数到它自身的一阶同调群和所有的外导子.

机械臂的P型闭环时变滑模迭代学习控制

针对周期运动的机械臂轨迹跟踪控制问题,在任意迭代初始值背景下,提出一种P型闭环滑模迭代学习控制算法。结合滑模控制原理,提出一种带遗忘因子的P型闭环滑模迭代学习控制策略,使处于任意初始位置的状态变量先迭代收敛到滑模面内,再在滑模面内收敛到期望位置,有效解决了任意迭代初始值的控制问题。从理论上证明了P型闭环滑模迭代学习控制算法的收敛性,给出了迭代收敛的条件。机械臂轨迹跟踪控制的仿真结果表明,当迭代初始值远离期望初始值时,机械臂的实际位置能精确跟踪期望位置,大的外部干扰不影响机械臂的轨迹跟踪性能。

非正规子群共轭类数为4的有限p群的分类

利用非正规子群的共轭类研究有限p群的结构是有限p群领域的前沿问题之一,其中,p表示一个素数。当p>2时,非正规子群的共轭类不超过2p的有限p群已被分类,然而,当p=2时,非正规子群共轭类数为4的有限2群至今未被分类。本文与p>2的分类方法不同,采用中心积和中心扩张的方法对非正规子群共轭类数为4的有限2群进行了研究,分导群的阶为2,4和8三种情况讨论:对于导群的阶为2的群,将其转化为内交换p群的中心积,通过对内交换p群共轭类的讨论,将大部分群转化为内交换p群与循环群的直积;对于导群的阶为4的群,将其商群转化为内交换p群,利用内交换p群的中心扩张进一步转化为一些具体的群;导群的阶为8的群属于广义四元数群。最后通过进一步的讨论,并结合Magma软件的计算,给出了非正规子群共轭类数为4的有限2群的完全分类。

A series solution for surface motion amplification due to underground group cavities:Incident P waves

A series solution for surface motion amplification due to underground group cavities for incident plane P waves is derived by Fourier-Bessel series expansion method. It is shown that underground group cavities significantly am-plify the surface ground motion nearby. It is suggested that the effect of subways on ground motion should be con-sidered when the subways are planned and designed.

中国拉祜族PP1PK血型频率调查

目的 了解中国拉祜族人群中P1PK血型和GLOB血型表现频率,掌握拉祜族人群遗传现状。掌握该类血型表现型频率可为患者临床输血安全提供数据支撑,为孕妇提供妊娠建议及用血指导。方法 随机抽取中国拉祜族人群无关个体,进行P1PK、P血型血清学鉴定及基因测序分析,分析P1PK血型和GLOB血型表现频率。结果 从300名拉祜族人群中检出6例抗-PP1Pk(原抗-Tja,以下均称抗-PP1Pk)反应阴性血型,鉴定为罕见的P1-PK-P-血型(原称Tja-血型或p血型,以下均称为p血型)。拉祜族人群P1PK、GLOB血型系统中p血型表型频率为2.0%(6/300)。结论 拉祜族人群p血型表型频率明显高于欧州(5.8人/每百万人)和中国香港地区(1人/每百万人),存在显蓍的民族特异性和地域种族差异性。