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PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu xiaolin Li xiaowei Zhou Wei chen Aidong Wen Minna Liu Yi Ding Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina Department of Pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina Department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κb,NRF2,bCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase b therapeutics

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Phase-field modeling for anisotropic ductile damage of magnesium alloys at finite deformations

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Journal of Magnesium and Alloys 2024年第7期12卷 2967-2984页

作者： C.xie x.K.He x.Liu J.H.Ye J.b.chen Faculty of Mechanical Engineering and Mechanics Ningbo UniversityNingbo 315211PR China Key Laboratory of High Temperature Wear Resistant Materials Preparation Technology of Hunan Province Hunan University of Science and TechnologyXiangtan 411201PR China

The damage anisotropy of an extruded ZK60 Mg alloy is characterized using tensile tests and scanning electronic *** accumulation of anisotropic deformations leads to the great differences of the dimple evolution and strains at fracture along different loading *** introduce the anisotropic deformation information into the damage constitutive relationship,a thermodynamically consistent phase-field model of ductile damage fully coupled with elastoplastic finite deformations is developed in this *** the user-defined constitutive relationship and displacement-temperature coupling element,the finite element simulations are *** results show that:(1)ZK60 Mg alloys presents clear R-value difference in 0°,45°,and 90°tests of intact *** 45°test possesses the greatest R-value(1.50)and the greatest strain at fracture,however,the R-value for 0°is less than 1,indicating the thinning is preferential.(2)The higher ultimate stress leads to a larger average dimension of the dimples,whereas the higher density correlates with a larger elongation ratio at the *** disappearance of the stress-bearing area indicates that the phase-field assumption on stress degradation is completely compatible with the dimple analysis on fractography.(3)The simulation results of the stress-strain relationships and damage paths correlate well with the experimental ductile damage of magnesium alloys at 200◦*** errors are basically attributed to the modeling parameters and finite element iteration *** proposed model presents fine applicability and reliability for the predictions of plastic deformations,ductile damage,and fracture of anisotropic Mg alloys.

关键词： Ductile damage Anisotropy Phase field Constitutive relationship Magnesium

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Specific staining and precise killing of cancer cells through fusion of pharmaceutical chemistry and π-bridge effect design philosophy

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Science China Chemistry 2025年

作者： Qiong Liu Qiyun Deng Changxu Zhu Kongqi chen Lidan chen Zhaohui Sun ben Zhong Tang Zhiming Wang AIE Institute Center for Aggregation-Induced Emission State Key Laboratory of Luminescent Materials and Devices Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province South China University of Technology Department of Laboratory Medicine General Hospital of Southern Theater Command School of Life Sciences The Chinese University of Hong Kong Shenzhen Institute of Aggregate Science and Technology School of Science and Engineering The Chinese University of Hong Kong HKUST-Shenzhen Research Institute

The development of an advanced phototheranostic platform that combines imaging and therapy in a single agent is an appealing yet challenging *** this study,we successfully constructed three novel fluorescent probes by leveraging pharmaceutical chemistry and the design philosophy of theπ-bridge *** a systematic comparative analysis of their fluorescence properties,water solubility,molecular conformation,and electrostatic potential,we revealed the fundamental principles governing the optical behavior and biological selectivity of these ***,the probe TPhIQ-CNTh demonstrated extended fluorescence in the near-infrared region,a significant aggregation-induced emission (AIE) effect,and the ability to distinguish tumor cells from normal ***,it efficiently generated reactive oxygen species (ROS) and specifically labeled lipid droplets,enabling the precise staining and killing of cancer *** study presents a practical strategy for designing precise tumor treatments that integrate efficient imaging-guided photodynamic therapy (PDT) by harnessing the unique properties of AIE materials.

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Room-temperature ferroelectricity in A-site ordered Ruddlesden-Popper Li_(2)CaTa_(2)O_(7) ceramics

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Journal of Materiomics 2020年第3期6卷 593-599页

作者： b.H.Zhang Z.Z.Hu b.H.chen x.Q.Liu x.M.chen Laboratory of Dielectric Materials School of Materials Science and EngineeringZhejiang UniversityNo.38 Zheda RoadHangzhou310027China

In the present work,the crystal structure,ferroelectric and dielectric properties of the dense single-phase Li_(2)CaTa_(2)O_(7) ceramics with A-site ordered double-layer Ruddlesden-Popper structures have been investigated by the experiments and first-principles calculations.A polar Pna21 phase was determined by the Rietveld refinement against the x-ray diffraction pattern at room temperature,and it was confirmed by its lowest calculated energy and rigid phonon *** ferroelectricity was found by observing the ferroelectric hysteresis loop at room temperature,and its remanent polarization was similar to the value calculated from the berry phase and born effective charge *** ferroelectricity is a nonconventional proper one since its polarization is induced from the displacement of oxygen anions instead of tantalum cations based on the individual atomic polarization.A first-order transition from an antiferroelectric to paraelectric phase around 900 K was found by the DSC and variable-temperature dielectric *** the present work,the room-temperature ferroelectricity is experimental confirmed in the present ceramics,inspiring the search for new ferroelectricity in the ceramics with A-site ordered Ruddlesden-Popper structures.

关键词： Ferroelectricity A-site ordered ruddlesden-popper Dielectric response First-principles calculation

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Mesospheric tide comparisons at low latitudes observed by two collocated meteor radars

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Earth and Planetary Physics 2025年第1期9卷 54-68页

作者： Jian Li Wen Yi xiangHui xue Jie Zeng HaiLun Ye JianYuan Wang JinSong chen Na Li TingDi chen Chinese Academy of Sciences(CAS)Key Laboratory of Geospace Environment Department of Geophysics and Planetary SciencesUniversity of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Comparative Planetology Anhui Mengcheng Geophysics National Observation and Research StationUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230026China Collaborative Innovation Center of Astronautical Science and Technology Harbin 150001China National Key Laboratory of Electromagnetic Environment China Research Institute of Radiowave PropagationQingdao 266107China Yunnan Kunming Electromagnetic Environment National Observation and Research Station Qujing Kunming 655000China

Accurate knowledge of mesospheric winds and waves is essential for studying the dynamics and climate in the mesosphere and lower thermosphere(MLT)*** this study,we conduct a comparative analysis of the mesosphere tidal results obtained from two adjacent meteor radars at low latitudes in Kunming,China,from November 2013 to December *** two radars operate at different frequencies of 37.5 MHz and 53.1 MHz,***,overall good agreement is observed between the two radars in terms of horizontal winds and tide *** results show that the dominant tidal waves of the zonal and meridional winds are diurnal and semidiurnal ***,we conduct an exhaustive statistical analysis to compare the tidal amplitudes and vertical wavelengths recorded by the dual radar systems,which reveals a high degree of alignment in tidal *** investigation includes variances and covariances of tidal amplitudes,which demonstrate remarkable consistency across measurements from both *** finding highlights clear uniformity in the mesospheric tidal patterns observed at low latitudes by the two neighboring meteor *** of the comparative analysis specifically underscore the significant correlation in vertical wavelength measurements,validating the robustness of radar observations for tidal research.

关键词： mesosphere and lower thermosphere region meteor radar mesospheric winds tides

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Improvement of elevated-temperature strength and recrystallization resistance via Mn-containing dispersoid strengthening in Al-Mg-Si 6082 alloys

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Journal of Materials Science & Technology 2020年第4期39卷 135-143页

作者： chen Li Kun Liu x.-Grant chen Department of Applied Science University of Québec at ChicoutimiChicoutimiQC G7H 2B1Canada

The precipitation behavior of Mn-containing dispersoids in Al-Mg-Si 6082 alloys with different Mn contents(0,0.5 and 1.0 wt%)during various heat treatments(300–500℃)was *** effects of dispersoids on elevated-temperature strength and recrystallization resistance during hot-rolling and post-rolling annealing were *** results showed that the dispersoids in the Mn-containing alloys(0.5 and 1.0%)began to precipitate at 350℃and reached the optimum conditions after 2–4 h at 400℃.However,the dispersoids coarsened with increasing holding time at temperatures above450℃.After the peak precipitation treatment at 400℃for 2 h,the yield strength at 300℃increased from 28 MPa(base alloy free of Mn)to 55 MPa(alloy with 0.5%Mn)and 70 MPa(alloy with 1%Mn),respectively,demonstrating a significant dispersoid strengthening effect at elevated *** addition,the dispersoids were thermally stable at 300℃for up to 1000 h holding owing to its relative high precipitation temperature(350–400℃),leading to the superior constant mechanical performance at elevated temperature during the long service *** hot rolling and post-rolling annealing,the presence of a large amount of dispersoids results in the higher Zener drag PZcompared with base alloy and then significantly improved the recrystallization *** alloy containing 0.5%Mn exhibited the highest recrystallization resistance among three experimental alloys studied during the post-rolling process,likely resulted from the lower coarsening rate of dispersoids and the lower dispersoids free zone.

关键词： Al-Mg-Si 6082 alloy Mn addition Dispersoid precipitation Elevated-temperature strength Recrystallization resistance

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Dative b–N bonds weaven toward two-dimensional purely organic materials for single crystals

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Science China Chemistry 2025年第01期 12-14页

作者： Wei-Lei Zhou Siwei Wang Yong chen College of Chemistry and Materials Science Inner Mongolia Key Laboratory of Chemistry for Nature Products and Synthesis for Functional Molecules Innovation Team of Optical Functional Molecular Devices Inner Mongolia Minzu University College of Chemistry Nankai University

Molecular topology is one of the important topics to study and understand the relationship between molecular structure and properties [1]. Particularly, two-dimensional (2D) materials with extremely high surface area and ultra-thin morphology have attracted considerable attention due to their unexpected properties in materials and chemistry [2,3].

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin chen Jinghong xu bin Jiang Lei Li Yawei Li Yuliang Dai bing Wang Department of Spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TbCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory b cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He Zhen Wang Yuchen Wang Mengjie Zhu Zhile Liang Kanghong Zhang Yuge xu Gong chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), Cx43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex Dlx2 gap junction glia-to-neuron conversion neural regeneration NeuroD1 reprogramming

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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang Juan Wang Zongjian Liu xuechai chen beijing International Science and Technology Cooperation base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk b homolog 5(ALKbH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKbH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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