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

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Neural Regeneration Research 2025年第8期20卷 2420-2432页

作者： lin Yin Yalan xu Jie Mu Yu Leng lei Ma Yu Zheng Ruizhi li Yin Wang Peifeng li Hai Zhu Dong Wang Jing li Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina College of life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina Department of Urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

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 *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** 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 ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

Advances in the Development of Gradient Scaffolds Made of Nano-Micromaterials for Musculoskeletal Tissue Regeneration

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NANO-MICRO LETTERS 2025年第1期17卷 1-46页

作者： Fang, lei lin, xiaoqi xu, Ruian liu, Lu Zhang, Yu Tian, Feng li, Jiao Jiao xue, Jiajia Beijing Univ Chem Technol Beijing Lab Biomed Mat Beijing 100029 Peoples R China Beijing Univ Chem Technol State Key Lab Organ Inorgan Composites Beijing 100029 Peoples R China Univ Technol Sydney Fac Engn & IT Sch Biomed Engn Sydney NSW 2007 Australia

This review highlights the gradient variations in the structural composition of musculoskeletal tissues and comprehensively examines recent progress in the fabrication and application of biomimetic gradient scaffolds for musculoskeletal *** challenges and prospects of gradient scaffolds for clinical application are discussed. The intricate hierarchical structure of musculoskeletal tissues, including bone and interface tissues, necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes. This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes. Building on the anatomical characteristics of bone and interfacial tissues, this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues, specifically focusing on methods used to construct compositional and structural gradients within the scaffolds. The latest applications of gradient scaffolds for the regeneration of bone, osteochondral, and tendon-to-bone interfaces are presented. Furthermore, the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed, as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.

关键词： Gradient scaffolds Musculoskeletal tissues Advanced manufacturing Biomaterials Tissue regeneration

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： xihang Chen zhifeng Chen menghua li Weiwei Guo Shuolong Yuan liangwei xu Chang lin xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

An experiment evaluating how the tiny mass eccentricities in spinstabilized projectiles affect the position of impact points

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Defence Technology（防务技术） 2021年第3期17卷 948-960页

作者： Chuan-lin Chen hui xu Chen-lei Huang Zhong-xin li zhi-lin Wu School of Mechanical Engineering Nanjing University of Science and TechnologyNanjingJiangsu210094China

This study investigates and quantifies some possible sources affecting the position of impact points of small caliber spin-stabilized projectiles(such as 12.7 mm bullets).A comparative experiment utilizing the control variable method was designed to figure out the influence of tiny eccentric centroids on the *** study critically analyzes data obtained from characteristic parameter measurements and precision *** also combines Sobol’s algorithm with an artificial intelligence algorithmdAdaptive Neuro-Fuzzy Inference Systems(ANFIS)ein order to conduct global sensitivity analysis and determine which parameters were most *** results indicate that the impact points of projectiles with an entry angle of 0°deflected to the left to that of projectiles with an entry angle of 90°.The difference of the mean coordinates of impact points was about 12.61 cm at a target range of 200 *** analysis indicated that the entry *** initial position of mass eccentricityehad a notable *** global sensitivity analysis,the significance of the effect of mass eccentricity was confirmed again and the most influential factors were determined to be the axial moment and transverse moment of inertia(Izz Iyy),the mass of a projectile(m),the distance between nose and center of mass along the symmetry axis for a projectile(Lm),and the eccentric distance of the centroid(Lr).The results imply that the control scheme by means of modifying mass center(moving mass or mass eccentricity)is promising for designing small-caliber spin-stabilized projectiles.

关键词： Tiny mass eccentricity Small-caliber projectile Bullet Artificial intelligence algorithm Global sensitivity analyses Precision trials ANFIS Sobol’s algorithm

Anefficient parallel and distributed solution to nonconvex penalized linear SVMs

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Frontiers of Information Technology & Electronic Engineering 2020年第4期21卷 587-603页

作者： lei GUAN Tao SUN lin-bo QIAO zhi-hui YANG Dong-sheng li Ke-shi GE xi-cheng LU College of Computer National University of Defense TechnologyChangsha 410073China School of Computer Science Fudan UniversityShanghai 201203China Shanghai Key Laboratory of Data Science Shanghai 201203China

Support vector machines(SVMs)have been recognized as a powerful tool to perform linear *** combined with the sparsity-inducing nonconvex penalty,SVMs can perform classification and variable selection ***,the nonconvex penalized SVMs in general cannot be solved globally and efficiently due to their nondifferentiability,nonconvexity,and *** solutions to the nonconvex penalized SVMs typically solve this problem in a serial fashion,which are unable to fully use the parallel computing power of modern multi-core *** the other hand,the fact that many real-world data are stored in a distributed manner urgently calls for a parallel and distributed solution to the nonconvex penalized *** circumvent this challenge,we propose an efficient alternating direction method of multipliers(ADMM)based algorithm that solves the nonconvex penalized SVMs in a parallel and distributed *** design many useful techniques to decrease the computation and synchronization cost of the proposed parallel *** time complexity analysis demonstrates the low time complexity of the proposed parallel ***,the convergence of the parallel algorithm is *** evaluations on four liBSVM benchmark datasets demonstrate the efficiency of the proposed parallel algorithm.

关键词： linear classification Support vector machine(SVM) Nonconvex penalty Alternating direction method of multipliers(ADMM) Parallel algorithm

Effect of thermal aging on the fatigue crack growth behavior of cast duplex stainless steels

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International Journal of Minerals,Metallurgy and Materials 2015年第11期22卷 1163-1170页

作者： xu-ming Lü Shi-lei li Hai-long Zhang Yan-li Wang xi-tao Wang State Key Laboratory for Advanced Metals and Materials University of Science and Technology Beijing Collaborative Innovation Center of Steel Technology University of Science and Technology Beijing

The effect of thermal aging on the fatigue crack growth（FCG） behavior of Z3CN20？09M cast duplex stainless steel with low ferrite content was investigated in this study. The crack surfaces and crack growth paths were analyzed to clarify the FCG mechanisms. The microstructure and micromechanical properties before and after thermal aging were also studied. Spinodal decomposition in the aged ferrite phase led to an increase in the hardness and a decrease in the plastic deformation capacity, whereas the hardness and plastic deformation capacity of the austenite phase were almost unchanged after thermal aging. The aged material exhibited a better FCG resistance than the unaged material in the near-threshold regime because of the increased roughness-induced crack closure associated with the tortuous crack path and rougher fracture surface; however, the tendency was reversed in the Paris regime because of the cleavage fracture in the aged ferrite phases.

关键词： stainless steels fatigue crack growth thermal aging embrittlement fracture morphology

New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第2期22卷 161-170页

作者： SUN Zeshi lin Shan WU zhi-li DONG Hong-Yuan xu xi-Ke li hui-liang WANG Jinxin School of Pharmacy Second Military Medical UniversityShanghai 200433China State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 201203China

Our continued works on the chemical constituents of Ginkgo biloba(***)leaves has led to the isolation of two novel phenylbutenoids(1,2),along with five previously unidentified terpene glycosides(3−7).Among them,compounds 1 and 2 represent unique(Z)-phenylbutenoids,3−6 are megastigmane glycosides,and 7 is identified as a rare bilobanone glycoside(Fig.1).This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from *** chemical structures of these compounds were elucidated through extensive spectroscopic analysis,including HR-ESI-MS and various 1D and 2D NMR ***,the absolute configurations of these molecules were determined using Mosher’s method,ECD experiments,and Cu-KαX-ray crystallographic analyses.

关键词： Ginkgo biloba Phenylbutenoid Megastigmane glycoside Bilobanone glycoside

PEN/BADCy Interlayer Dielectric Films with Tunable Microstructures via an Assist of Temperature for Enhanced Frequency Stability

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Chinese Journal of Polymer Science 2020年第11期38卷 1258-1266,I0009页

作者： xi-Ting lei li-Fen Tong ming-Zhen xu Yong You xiao-Bo liu School of Materials and Energy University of Electronic Science and Technology of ChinaChengdu 610054China

Low dielectric in terlayer films have become an important element to ensure the development of the microelectr onics industry.A kind of flexible interlayer dielectrics,polyarylene ether nitrile/bisphenol A cyanate ester(PEN/BADCy)film,with good thermal stability and low frequency dependence,has been developed by solution casting ***,materials were designed to incorporate bisphenol A cyanate ester as a part of blend,contributing to the frequency stability and structural *** morphological study combined with electron microscopy revealed the uniform and flexible microstructure information with controllable morphology through self-polymerization of cyanate esters with different prepolymerization time and curing *** dielectric films could present high thermal stability with Tg>180℃.Significant improvement in the dielectric properties was achieved for the dielectric constant and loss was much stabler than neat PEN over the frequency range from 100 Hz to 5 *** the prepolymerization time was 3h and final curing temperature reached 230℃,the dielectric constant and dielectric loss of the films were 3.36 and 0.013 at 100 kHz,*** dimensional stability(CTE=53.67×10^-6 K^-1)was confirmed and con sidered beneficial to use as an in terlayer dielectrics.

关键词： Polyarylene ether nitrile Bisphenol A cyanate ester Interlayer dielectrics Tunable microstructures

Vasectomy reversal in China during the recent decade:insights from a multicenter retrospective investigation

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Asian Journal of Andrology 2023年第3期25卷 416-420页

作者： li-Juan Ren Rui-zhi xue Zi-Qiang Wu Er-lei zhi Wei li liang Huang xu-Yu xiang Dao-Yuan li xue-ming lin Department of Urology First Hospital of Shanxi Medical UniversityTaiyuan 030000China Department of Urology Xiangya Hospital of Central South UniversityChangsha 410000China Department of Urology Shanghai General HospitalShanghai 200000China Department of Urology Second Hospital of Tianjin Medical UniversityTianjin 300000China Department of Urology Zhujiang Hospital of Southern Medical UniversityGuangzhou 510000China Department of Urology First Affiliated Hospital of Nanchang UniversityNanchang 330000China Department of Urology Hainan General HospitalHaikou 570100China

To date,there is little information about the demography of vasectomy reversal(VR)patients or the factors currently influencing VR effectiveness in China,especially after the universal two-child policy was released in *** this research,demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of ***,a telephone survey of the patients was conducted to collect follow-up ***,448 VR cases from the past 13 years were *** results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy *** statistical methods were used,and all of the protocols were approved by the Ethics Committees of the institutes in this *** results showed that the annual operation volume of VR quadrupled after the two-child policy was *** and a long duration of vasectomy were significantly associated with a lower patency rate.A follow-up survey showed that the general postoperative pregnancy rate was 27.2%.For female partners over the age of 35 years,the postoperative pregnancy rate showed a more severe decline,but only 35.5%of them had been given a fertility examination before their husbands’VR *** work revealed that more patients in China have been demanding VR in recent ***-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by *** andrologists should perform a preoperative fertility evaluation of the patients’female partners.

关键词： demography microsurgery multicenter vasectomy reversal