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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng deng dan Yang Lingxi Qing Yifei chen Jilian Zou Meiling Jia Qian wang Runda Jiang Lihua Huang College of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying chen Jiali Pu Baorong Zhang department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NAdPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NAdPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NAdPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NAdPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NAdPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NAdPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NAdPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NAdPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian ding Chun chen Heng Zhao Bin dai Lei Ye Tao Song Shuai Huang Jia wang Tao You department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is w.d.ly expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments show.d.that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2

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Graphene Aerogel Composites with Self‑Organized Nanowires‑Packed Honeycomb Structure for Highly Efficient Electromagnetic wave Absorption

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Nano-Micro Letters 2025年第2期17卷 533-547页

作者： Xiao You Huiying Ouyang Ruixiang deng Qiuqi Zhang Zhenzhong Xing Xiaowu chen Qingliang Shan Jinshan Yang Shaoming dong State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050People’s Republic of China Key Laboratory of Inorganic Coating Materials CAS Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050People’s Republic of China Structural Ceramics and Composites Engineering Research Center Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050People’s Republic of China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049People’s Republic of China School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210People’s Republic of China School of Materials Science and Engineering Zhejiang Sci-Tech UniversityHangzhou 310018People’s Republic of China University of Chinese Academy of Sciences Beijing 100039People’s Republic of China

with vigorous developments in nanotechnology,the elaborate regulation of microstructure shows attractive potential in the design of electromagnetic wave ***,a hierarchical porous structure and composite heterogeneous interface are constructed successfully to optimize the electromagnetic loss *** macro–micro-synergistic graphene aerogel formed by the ice template‑assisted 3d printing strategy is cut by silicon carbide nanowires(SiC_(nws))grown in situ,while boron nitride(BN)interfacial structure is introduced on graphene *** unique composite structure forces multiple scattering of incident EMws,ensuring the combined effects of interfacial polarization,conduction networks,and magnetic-dielectric ***,the as-prepared composites present a minimum reflection loss value of−37.8 dB and a w.d. effective absorption bandw.d.h(EAB)of 9.2 GHz(from 8.8 to 18.0 GHz)at 2.5 ***,relying on the intrinsic high-temperature resistance of SiC_(nws) and BN,the EAB also remains above 5.0 GHz after annealing in air environment at 600℃ for 10 h.

关键词： Hierarchical porous structure Interface High-temperature resistance Graphene aerogel composites Electromagnetic wave absorption

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Cortico-striatal gamma oscillations are modulated by dopamine d3 receptors in dyskinetic rats

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Neural Regeneration Research 2025年第4期20卷 1164-1177页

作者： Pengfei wang Yuewei Bi Min Li Jiazhi chen Zhuyong wang Huantao wen Ming Zhou Minjie Luo wangming Zhang Neurosurgery Center Department of Pediatric NeurosurgeryGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Long-term levodopa administration can lead to the development of levodopa-induced *** oscillations are a w.d.ly recognized hallmark of abnormal neural electrical activity in levodopa-induced ***,studies have reported increased oscillation power in cases of levodopa-induced ***,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced ***,the role of the dopamine d3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is *** found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s ***,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma *** of Pd128907(a selective dopamine d3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum ***,administration of PG01037(a selective dopamine d3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum *** findings suggest that the dopamine d3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

关键词： aperiodic components dopamine d3 receptor dorsolateral striatum functional connectivity gamma oscillations levodopa-induced-dyskinesia local field potentials neuromodulation Parkinson’s disease primary motor cortex

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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen chen Xiaolin Zeng Le wang wenwu Zhang Gang Li Xing cheng Peiqiang Su Yong wan Xiang Li department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Province Key Laboratory of Orthopedics and Traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments show.d.that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments show.d.that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Effect of suction change on water content and total volume of an expansive clay

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2007年第5期8卷 699-706页

作者： ZHAN Liang-tong chen Ping NG C.w.w. ~ department of Civil Engineering Zhejiang University Hangzhou 310027 China department of Civil Engineering Zhejiang Sci- Tech University Hangzhou 310018 China department of Civil Engineering Hong Kong University of Science and Technology Hong Kong China

A laboratory study was carried out on both natural and compacted specimens to investigate the complex soil-water interaction in an unsaturated expansive clay. The laboratory study includes the measurement of soil-water characteristic curves, 1d free swelling tests, measurement of swelling pressure and shrinkage tests. The test results revealed that the air-entry value of the natural specimen was quite low.d.e to cracks and fissures present. The hydraulic hysteresis of the natural specimen was relatively insignificant as compared with the compacted specimen. within a suction range 0 to 500 kPa, a bilinear relationship between free swelling strain (or swelling pressure) and initial soil suction was observed for both the natural and compacted specimens. As a result of over-consolidation and secondary structures such as cementation and cracks, the natural specimens exhibited significant lower swelling (or swelling pressure) than the compacted specimen. The change of matric suction exerts a more significant effect on the water phase than on the soil skeleton for this expansive clay.

关键词： Expansive soil water content Suction Swelling Shrinkage

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Overexpression of low.d.nsity lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang chen Shen Liu Junshan Zhou Hongdong Zhao Ye Hong department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low.d.nsity lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low.d.nsity lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low.d.nsity lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low.d.nsity lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low.d.nsity lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low.d.nsity lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low.d.nsity lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low.d.nsity lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low.d.nsity lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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Effect of Preparation Technique on Microstructure and Hydrogen Storage Properties of LaNi(3.8)Al(1.0)Mn(0.2) Alloys

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Journal of Materials Science & Technology 2016年第12期32卷 1332-1338页

作者： X.B.Han Y.Qian w.Liu d.M.chen K.Yang Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China Institute of Metal Research Chinese Academy of Sdences Shenyang 110016 China

La Ni3.8Al1.0Mn0.2 alloy was prepared by vacuum induction melting and *** effects of different preparation techniques of the as-cast,cast then annealed,as-spun and spun then annealed alloys on the microstructure and hydrogen storage properties were *** results indicated that the non-Ca Cu5 phases in the alloy became tinier and more dispersive after annealing or melt-spinning compared to those of the as-cast *** in the spun then annealed alloy,the non-Ca Cu5 phases disappeared and only a single-phase with Ca Cu5 type structure was *** all the alloys,the cell volume was increased in an order of as-cast 〈 spun then annealed 〈 cast then annealed 〈 as-spun,and the change of plateau pressure show.d.the opposite trend with that of the cell *** plateau could be flattened after melt-spinning or annealing,and the spun then annealed alloy show.d.the minimum plateau *** absorption kinetics of the alloy was promoted after melt-spinning or *** is suggested that the change in cell volume and compositional homogeneity resulting from different preparation techniques contribute to the difference of the hydrogen storage properties of the investigated alloys.

关键词： Annealing Melt-spinning Metal hydride Hydrogen absorption

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Comparative analysis of empirical and deep learning models for ionospheric sporadic E layer prediction

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Earth and Planetary Physics 2025年第1期9卷 10-19页

作者： BingKun Yu PengHao Tian XiangHui Xue Christopher JScott HaiLun Ye JianFei wu wen Yi Tingdi chen XianKang dou Institute of deep Space Sciences Deep Space Exploration LaboratoryHefei 230088China CAS Key Laboratory of Geospace Environment School of Earth and Space SciencesUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China department of Meteorology University of ReadingReading RG66BBUK

Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 *** they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite *** this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde *** deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.

关键词： ionospheric sporadic E layer radio occultation ionosondes numerical model deep learning model artificial intelligence

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