AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

不同强度运动抑制糖尿病大鼠肾脏PI3K/AKT/mTOR信号通路改善自噬的比较

背景:2型糖尿病损害肾功能。研究表明运动干预可以保护肾脏;鸢尾素可以通过抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路恢复自噬,保护糖尿病肾病患者的肾功能。目的:探讨运动能否通过抑制肾脏磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活来恢复自噬,改善肾损伤,以及分析不同方式运动产生影响的差异。方法:将6周龄的SD大鼠随机分为空白对照组(正常大鼠)和糖尿病组,其中糖尿病组大鼠经过高脂高糖喂养加腹腔注射低剂量1%链脲佐菌素(30 mg/kg)建立2型糖尿病模型。造模成功后再将糖尿病组大鼠随机分成糖尿病模型组、中强度持续运动组和高强度间歇运动组。两个运动组大鼠分别进行8周不同强度运动干预。取材后采用葡萄糖氧化酶法检测大鼠空腹血糖,使用试剂盒检测糖化血红蛋白水平,Elisa法检测血清胰岛素浓度,计算胰岛素抵抗指数,RT-PCR检测肾组织磷脂酰肌醇3-激酶、蛋白激酶B、雷帕霉素靶蛋白、Beclin-1、podocin、nephrin的基因表达量,Western Blot检测肾组织雷帕霉素靶蛋白及自噬标记蛋白LC3-1、LC3-2、Beclin-1的蛋白表达量。结果与结论:①2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著性升高,胰岛素抵抗水平显著上升,胰岛素水平显著下降;两种运动均能使2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著下降,胰岛素抵抗水平显著下降,胰岛素水平显著上升;与中强度持续运动组相比,高强度间歇运动组胰岛素水平显著上升。②2型糖尿病大鼠podocin、nephrin基因表达量显著降低;两种不同形式运动均能显著提高其表达;与高强度间歇运动组相比,中等强度持续性运动组足细胞相关蛋白基因表达有进一步上升趋势,但无显著性差异。③2型糖尿病大鼠肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及蛋白的表达量显著增加,自噬标志蛋白Beclin-1、LC3-2表达量以及LC3-2/LC3-1显著降低;两种不同形式运动均能使肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白蛋白的表达量显著降低,自噬标志蛋白Beclin-1、LC3-2以及LC3-2/LC3-1显著升高;与中等强度持续性运动组相比,高强度间歇运动的磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白的蛋白表达量有进一步下降的趋势,Beclin-1、LC3-2以及LC3-2/LC3-1有进一步升高的趋势,但仅Beclin-1有显著性差异。④结果说明2型糖尿病肾脏足细胞损伤,自噬受到抑制,与磷脂酰肌醇3-激酶/蛋白激酶B/mTORC1信号通路被异常激活密切相关。高强度间歇运动和中等强度持续性运动可以保护糖尿病肾脏,减少足细胞损伤,促进自噬恢复,这可能与运动抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活有关。与中等强度持续性运动相比,高强度间歇运动恢复自噬的效果呈更优趋势,但足细胞蛋白表达稍有下降。

二甲双胍抑制PI3K/AKT/mTOR信号通路保护骨关节炎模型大鼠关节软骨

背景:研究表明,二甲双胍具有抗炎、抗肿瘤、抗衰老与血管保护作用,可抑制骨关节炎的进展,但其具体的作用机制仍不明确。目的:探讨二甲双胍对骨关节炎模型大鼠软骨保护的作用机制。方法:取40只雄性SD大鼠,采用随机数字表法分4组(n=10):空白组不进行任何手术,假手术组暴露关节腔,模型组、二甲双胍组采用改良Hulth法建立骨关节炎模型;造模后1 d,二甲双胍组大鼠灌胃给予二甲双胍200 mg/(kg·d),模型组、空白组、假手术组灌胃给予生理盐水,连续给药4周。给药结束后,苏木精-伊红、甲苯胺蓝和番红O-固绿染色观察大鼠膝关节软骨病理形态,免疫组化染色与Western blotting检测大鼠软骨组织中SOX9、Ⅱ型胶原、ADAMTS5、Beclin1、P62、p-PI3K、PI3K、p-AKT、AKT、p-mTOR、mTOR的蛋白表达。结果与结论:①苏木精-伊红、甲苯胺蓝和番红O-固绿染色结果显示,空白组、假手术组大鼠膝关节软骨表面光滑,组织形态正常;模型组大鼠膝关节软骨表面不规则,软骨组织出现缺损,软骨细胞数量减少,软骨基质中蛋白多糖含量减少;相较于模型组,二甲双胍组大鼠膝关节软骨结构损伤有明显改善,软骨表面趋于平整,软骨细胞数量与软骨基质中蛋白多糖含量增加;②免疫组化染色与Western blotting检测结果显示,与空白组、假手术组比较,模型组大鼠软骨组织中SOX9、Ⅱ型胶原、Beclin1蛋白表达降低(P<0.05),ADAMTS5、P62及p-PI3K、p-AKT、p-mTOR蛋白表达升高(P<0.05);与模型组比较,二甲双胍组大鼠软骨组织中SOX9、Ⅱ型胶原、Beclin1蛋白表达升高(P<0.05),ADAMTS5、P62及p-PI3K、p-AKT、p-mTOR蛋白表达降低(P<0.05);③结果表明,二甲双胍可通过抑制PI3K/AKT/mTOR信号通路的活化提高骨关节炎模型大鼠软骨细胞自噬活性、减少软骨基质降解,进而发挥关节软骨保护作用。

Dynamics of Non-Markovianity, Quantum Correlations and Information Scrambling of Three Qubits Systems Interacting via Rashba Interaction

The behavior of the quantum correlations, information scrambling and the non-Markovianity of three entangling qubits systems via Rashba is discussed. The results showed that, the three physical quantities oscillate between their upper and lower bounds, where the number of oscillations increases as the Rashba interaction strength increases. The exchanging rate of these three quantities depends on the Rashba strength, and whether the entangled state is generated via direct/indirect interaction. Moreover, the coherence parameter can be used as a control parameter to maximize or minimize the three physical quantities.

Interacting topological magnons in a checkerboard ferromagnet

This work is devoted to studying the magnon-magnon interaction effect in a two-dimensional checkerboard ferromagnet with the Dzyaloshinskii-Moriya interaction.Using a first-order Green function method,we analyze the influence of magnon-magnon interaction on the magnon band topology.We find that Chern numbers of two renormalized magnon bands are different above and below the critical temperature,which means that the magnon band gap-closing phenomenon is an indicator for one topological phase transition of the checkerboard ferromagnet.Our results show that the checkerboard ferromagnet possesses two topological phases,and its topological phase can be controlled either via the temperature or the applied magnetic field due to magnon-magnon interactions.Interestingly,it is found that the topological phase transition can occur twice with the increase in the temperature,which is different from the results of the honeycomb ferromagnet.

A new interacting capillary bundle model on the multiphase flow in micropores of tight rocks

Surfactants are widely used in the fracturing fluid to enhance the imbibition and thus the oil recovery rate. However, current numerical models cannot capture the physics behind capillary imbibition during the wettability alteration by surfactants. Although the interacting capillary bundle(ICB) model shows potential in characterizing imbibition rates in different pores during wettability alteration, the existing ICB models neglect the influence of wettability and viscosity ratio on the imbibition behavior, making it difficult to accurately describe the oil-water imbibition behavior within the porous media. In this work,a new ICB mathematical model is established by introducing pressure balance without assuming the position of the leading front to comprehensively describe the imbibition behavior in a porous medium under different conditions, including gas-liquid spontaneous imbibition and oil-water imbibition.When the pore size distribution of a tight rock is known, this new model can predict the changes of water saturation during the displacement process in the tight rock, and also determine the imbibition rate in pores of different sizes. The water saturation profiles obtained from the new model are validated against the waterflooding simulation results from the CMG, while the imbibition rates calculated by the model are validated against the experimental observations of gas-liquid spontaneous imbibition. The good match above indicates the newly proposed model can show the water saturation profile at a macroscopic scale while capture the underlying physics of the multiphase flow in a porous medium at a microscopic scale. Simulation results obtained from this model indicate that both wettability and viscosity ratio can affect the sequence of fluid imbibition into pores of different sizes during the multiphase flow, where less-viscous wetting fluid is preferentially imbibed into larger pores while more-viscous wetting fluid tends to be imbibed into smaller pores. Furthermore, this model provides an avenue to calculate the imbibition rate in pores of different sizes during wettability alteration and capture the non-Darcy effect in micro-and nano-scale pores.

Generation and regulation of electromagnetic pulses generated by femtosecond lasers interacting with multitargets

Ultrashort and powerful laser interactions with a target generate intense wideband electromagnetic pulses(EMPs).In this study,we report EMPs generated by the interactions between petawatt(30 fs,1.4×10^(20) W/cm^(2))femtosecond(fs)lasers with metal flat,plastic flat,and plastic nanowire-array(NWA)targets.Detailed analyses are conducted on the EMPs in terms of their spatial distribution,time and frequency domains,radiation energy,and protection.The results indicate that EMPs from metal targets exhibit larger amplitudes at varying angles than those generated by other types of targets and are enhanced significantly for NWA targets.Using a plastic target holder and increasing the laser focal spot can significantly decrease the radiation energy of the EMPs.Moreover,the composite shielding materials indicate an effective shielding effect against EMPs.The simulation results show that the NWA targets exert a collimating effect on thermal electrons,which directly affects the distribution of EMPs.This study provides guidance for regulating EMPs by controlling the laser focal spot,target parameters,and target rod material and is beneficial for electromagnetic-shielding design.

The DUF579 proteins GhIRX15s regulate cotton fiber development by interacting with proteins involved in xylan synthesis

Cotton provides the most abundant natural fiber for the textile industry.The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and lignin.To dissect the roles of hemicellulosic polysaccharides during fiber development,four IRREGULAR XYLEM 15(IRX15)genes,GhIRX15-1/-2/-3/-4,were functionally characterized in cotton.These genes encode DUF579 domain-containing proteins,which are homologs of AtIRX15 involved in xylan biosynthesis.The four GhIRX15 genes were predominantly expressed during fiber secondary wall thickening,and the encoded proteins were localized to the Golgi apparatus.Each GhIRX15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double mutant.Silencing of GhIRX15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild type.Intriguingly,GhIRX15-2 and GhIRX15-4 formed homodimers and heterodimers.In addition,the GhIRX15s showed physical interaction with glycosyltransferases GhGT43C,GhGT47A and GhGT47B,which are responsible for synthesis of the xylan backbone and reducing end sequence.Moreover,the GhIRX15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis,such as GhGUX1/2,GhGXM1/2 and GhTBL1.These findings suggest that GhIRX15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes.

PRKCQ-AS1通过Akt信号促进气道平滑肌细胞增殖的研究

目的探讨PRKCQ-AS1在气道平滑肌细胞(airway smooth muscle cells,ASMCs)的作用。方法首先通过转录组测序技术(RNA-seq)检测哮喘儿童肺泡灌洗液中的差异表达基因(differentially expressed genes,DEGs)。随后,分别构建PRKCQ-AS1慢病毒敲低和过表达载体并转染ASMCs。qRT-PCR方法检测了ASMCs中PRKCQ-AS1的表达;用CCK-8和流式细胞术分别检测ASMCs的增殖和凋亡;酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测ASMCs培养上清液中TNF-α和IL-1β的含量;lncRNA芯片检测PRKCQ-AS1敲低后的DEGs并进行KEGG通路富集;Western blot检测p-Akt和Akt的水平。结果RNA-seq结果显示,PRKCQ-AS1是上调最明显的DEGs之一。PRKCQ-AS1过表达促进了ASMCs的增殖和迁移并抑制了其凋亡,同时,PRKCQ-AS1过表达使上清液中炎性因子TNF-α和IL-1β的水平升高,而PRKCQ-AS1敲低则呈现相反的结果。对PRKCQ-AS1敲低后得到的606个DEGs进行KEGG信号通路富集分析,结果显示PI3K-Akt信号被明显富集。Western blot结果表明,PRKCQ-AS1敲低抑制了Akt的活化;相反,PRKCQ-AS1过表达则促进了Akt的水平。结论PRKCQ-AS1可能通过增强Akt信号促进ASMCs炎症反应,进而加剧了ASMCs的增殖和迁移,最终导致哮喘的发展。

Studies on the temporal,structural,and interacting features of the clubroot resistance gene Rcr1 using CRISPR/Cas9-based systems

Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most important strategy for managing the disease.However,studies on the CR gene functions are quite limited.In this study,we have conducted investigations into the temporal,structural,and interacting features of a newly cloned CR gene,Rcr1,using CRISPR/Cas9 technology.For temporal functionality,we developed a novel CRISPR/Cas9-based binary vector,pHHIGR-Hsp18.2,to deliver Rcr1 into a susceptible canola line(DH12075)and observed that early expression of Rcr1 is critical for conferring resistance.For structural functionality,several independent mutations in specific domains of Rcr1 resulted in loss-offunction,highlighting their importance for CR phenotype.In the study of the interacting features of Rcr1,a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein,resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1.These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response.This study,the first of its kind,provides valuable insights into the functionality of Rcr1.Further,the new vector p HHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits,which should be useful for functional genomics and other similar research in brassica crops.

Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer

BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.

RETRACTED: Nuclear Structure Study of Odd-Odd Yttrium Nuclei within Interacting-Boson Fermi-Fermion Model (IBFFM)

Short Retraction NoticeThe paper does not meet the standards of "Journal of Applied Mathematics and Physics". This article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. The aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused.Editor guiding this retraction: Prof. Wen-Xiu Ma (EiC of JAMP)The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

Tailoring Light–Matter Interactions in Overcoupled Resonator for Biomolecule Recognition and Detection

Plasmonic nanoantennas provide unique opportunities for precise control of light–matter coupling in surface-enhanced infrared absorption(SEIRA)spectroscopy,but most of the resonant systems realized so far suffer from the obstacles of low sensitivity,narrow bandwidth,and asymmetric Fano resonance perturbations.Here,we demonstrated an overcoupled resonator with a high plasmon-molecule coupling coefficient(μ)(OC-Hμresonator)by precisely controlling the radiation loss channel,the resonator-oscillator coupling channel,and the frequency detuning channel.We observed a strong dependence of the sensing performance on the coupling state,and demonstrated that OC-Hμresonator has excellent sensing properties of ultra-sensitive(7.25%nm^(−1)),ultra-broadband(3–10μm),and immune asymmetric Fano lineshapes.These characteristics represent a breakthrough in SEIRA technology and lay the foundation for specific recognition of biomolecules,trace detection,and protein secondary structure analysis using a single array(array size is 100×100μm^(2)).In addition,with the assistance of machine learning,mixture classification,concentration prediction and spectral reconstruction were achieved with the highest accuracy of 100%.Finally,we demonstrated the potential of OC-Hμresonator for SARS-CoV-2 detection.These findings will promote the wider application of SEIRA technology,while providing new ideas for other enhanced spectroscopy technologies,quantum photonics and studying light–matter interactions.

Catalyst–Support Interaction in Polyaniline‑Supported Ni_(3)Fe Oxide to Boost Oxygen Evolution Activities for Rechargeable Zn‑Air Batteries

Catalyst–support interaction plays a crucial role in improving the catalytic activity of oxygen evolution reaction(OER).Here we modulate the catalyst–support interaction in polyaniline-supported Ni_(3)Fe oxide(Ni_(3)Fe oxide/PANI)with a robust hetero-interface,which significantly improves oxygen evolution activities with an overpotential of 270 mV at 10 mA cm^(-2)and specific activity of 2.08 mA cm_(ECSA)^(-2)at overpotential of 300 mV,3.84-fold that of Ni_(3)Fe oxide.It is revealed that the catalyst–support interaction between Ni_(3)Fe oxide and PANI support enhances the Ni–O covalency via the interfacial Ni–N bond,thus promoting the charge and mass transfer on Ni_(3)Fe oxide.Considering the excellent activity and stability,rechargeable Zn-air batteries with optimum Ni_(3)Fe oxide/PANI are assembled,delivering a low charge voltage of 1.95 V to cycle for 400 h at 10 mA cm^(-2).The regulation of the effect of catalyst–support interaction on catalytic activity provides new possibilities for the future design of highly efficient OER catalysts.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

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.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Dynamic Interaction Analysis of Coupled Axial-Torsional-Lateral Mechanical Vibrations in Rotary Drilling Systems

Maintaining the integrity and longevity of structures is essential in many industries,such as aerospace,nuclear,and petroleum.To achieve the cost-effectiveness of large-scale systems in petroleum drilling,a strong emphasis on structural durability and monitoring is required.This study focuses on the mechanical vibrations that occur in rotary drilling systems,which have a substantial impact on the structural integrity of drilling equipment.The study specifically investigates axial,torsional,and lateral vibrations,which might lead to negative consequences such as bit-bounce,chaotic whirling,and high-frequency stick-slip.These events not only hinder the efficiency of drilling but also lead to exhaustion and harm to the system’s components since they are difficult to be detected and controlled in real time.The study investigates the dynamic interactions of these vibrations,specifically in their high-frequency modes,usingfield data obtained from measurement while drilling.Thefindings have demonstrated the effect of strong coupling between the high-frequency modes of these vibrations on drilling sys-tem performance.The obtained results highlight the importance of considering the interconnected impacts of these vibrations when designing and implementing robust control systems.Therefore,integrating these compo-nents can increase the durability of drill bits and drill strings,as well as improve the ability to monitor and detect damage.Moreover,by exploiting thesefindings,the assessment of structural resilience in rotary drilling systems can be enhanced.Furthermore,the study demonstrates the capacity of structural health monitoring to improve the quality,dependability,and efficiency of rotary drilling systems in the petroleum industry.

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.