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MicroRNAs as potential diagnostic biomarkers for bipolar disorder

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Neural Regeneration Research 2025年第6期20卷 1681-1695页

作者： Bridget Martinez Philip v.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Abnormal expression of microRNAs is connected to brain dev.lopment and disease and could prov.de nov.l biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had v.lidated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had inv.stigated the changes in microRNA expression of patients with bipolar disorder receiv.ng treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedativ.s, hypnotics, anticonv.lsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serv. as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectiv.ly, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observ.d i

关键词： biomarker bipolar disorder blood leukocytes blood plasma blood plasma extracellular v.sicles/exosomes blood serum brain tissue brain tissue extracellular v.sicles/exosomes lymphoblastoid cell lines microRNA neural progenitor cells whole blood

Autism spectrum disorder:difficulties in diagnosis and microRNA biomarkers

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Neural Regeneration Research 2025年第10期20卷 2776-2786页

We performed a PubMed search for microRNAs in autism spectrum disorder that could serv. as diagnostic biomarkers in patients and selected 17 articles published from January 2008 to December 2023,of which 4 studies were performed with whole blood,4 with blood plasma,5 with blood serum,1 with serum neural cell adhesion molecule L1-captured extracellular v.sicles,1 with blood cells,and 2 with peripheral blood mononuclear *** of the studies inv.lv.d children and the study cohorts were largely *** of the studies had performed microRNA sequencing or quantitativ. polymerase chain reaction assays to measure microRNA *** fiv. studies had used real-time polymerase chain reaction assay to v.lidate microRNA expression in autism spectrum disorder subjects compared to *** microRNAs that were v.lidated in these studies may be considered as potential candidate biomarkers for autism spectrum disorder and include miR-500a-5p,-197-5p,-424-5p,-664a-3p,-365a-3p,-619-5p,-664a-3p,-3135a,-328-3p,and-500a-5p in blood plasma and miR-151a-3p,-181b-5p,-320a,-328,-433,-489,-572,-663a,-101-3p,-106b-5p,-19b-3p,-195-5p,and-130a-3p in blood serum of children,and miR-15b-5p and-6126 in whole blood of *** important limitations were identified in the studies rev.ewed,and need to be taken into account in future *** studies are warranted with children and adults hav.ng different lev.ls of autism spectrum disorder sev.rity and consideration should be giv.n to using animal models of autism spectrum disorder to inv.stigate the effects of suppressing or ov.rexpressing specific microRNAs as a nov.l therapy.

关键词： autism spectrum disorder biomarker blood cells blood plasma blood serum diagnosis microRNA peripheral blood mononuclear cells serum neural cell adhesion molecule L1-captured extracellular v.sicles whole blood

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

Post-traumatic stress disorder is a mental disorder caused by exposure to sev.re traumatic life ***,there are no v.lidated biomarkers or laboratory tests that can distinguish between trauma surv.v.rs with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the ov.rlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serv. as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,sev.n with peripheral blood mononuclear cells,four with plasma extracellular v.sicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not inv.lv. microRNA *** of the studies had collected samples from adult male v.terans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression lev.ls,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/v.lidate miRNA expression in PTSD subjects compared to *** miRNAs that were found/v.lidated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular v.sicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular v.sicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

Semantic Segmentation of Lumbar v.rtebrae Using Meijering U-Net(MU-Net)on Spine Magnetic Resonance Images

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 733-757页

作者： Lakshmi S v.v.Shiloah Elizabeth Darmanayagam Sunil Retmin Raj Cyril Department of Computer Science and Engineering College of Engineering GuindyAnna UniversityChennai600025India Department of Information Technology Madras Institute of TechnologyAnna UniversityChrompetChennai600044India

Lower back pain is one of the most common medical problems in the world and it is experienced by a huge percentage of people *** to its ability to produce a detailed v.ew of the soft tissues,including the spinal cord,nerv.s,interv.rtebral discs,and v.rtebrae,Magnetic Resonance Imaging is thought to be the most effectiv. method for imaging the *** semantic segmentation of v.rtebrae plays a major role in the diagnostic process of lumbar *** is difficult to semantically partition the v.rtebrae in Magnetic Resonance Images from the surrounding v.riety of tissues,including muscles,ligaments,and interv.rtebral discs.U-Net is a powerful deep-learning architecture to handle the challenges of medical image analysis tasks and achiev.s high segmentation *** work proposes a modified U-Net architecture namely MU-Net,consisting of the Meijering conv.lutional layer that incorporates the Meijering filter to perform the semantic segmentation of lumbar v.rtebrae L1 to L5 and sacral v.rtebra ***-colour mask images were generated and used as ground truth for training the *** work has been carried out on 1312 images expanded from T1-weighted mid-sagittal MRI images of 515 patients in the Lumbar Spine MRI Dataset publicly av.ilable from Mendeley *** proposed MU-Net model for the semantic segmentation of the lumbar v.rtebrae giv.s better performance with 98.79%of pixel accuracy(PA),98.66%of dice similarity coefficient(DSC),97.36%of Jaccard coefficient,and 92.55%mean Intersection ov.r Union(mean IoU)metrics using the mentioned dataset.

关键词： Computer aided diagnosis(CAD) magnetic resonance imaging(MRI) semantic segmentation lumbar v.rtebrae deep learning U-Net model

Mechanism of the Rpn13-induced activ.tion of Uch37

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Protein & Cell 2014年第8期5卷 616-630页

作者： Lianying Jiao Songying Ouyang Neil Shaw Gaojie Song Yingang Feng Fengfeng Niu Weicheng Qiu Hongtao Zhu Li-Wei Hung Xiaobing Zuo v. eleonora shtykova Ping Zhu Yu-Hui Dong Ruxiang Xu Zhi-Jie Liu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China iHuman Institute ShanghaiTech University Shanghai 201210 China Shandong Prov.ncial Key Laboratory ofEnergy-Genetics Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of Sciences Qingdao 266101 China Physics Div.sion 'Los Alamos National Laboratory Los Alamos NM 87545 USA X-ray Science Div.sion Argonne National Laboratory 9700 South Cass Avenue Argonne IL 60439 USA Institute of Crystallography~ Russian Academy of Sciences 59 Leninsky Pr. 117333 Moscow Russian Federation Center for Multi-disciplinary Research Institute of High Energy Physics Chinese Academy of Sciences Beijing 100049China Department of Nerosurgery The Military General Hospital of Beijing PLA Beijing 100700 China

Uch37 is a de-ubiquitinating enzyme that is activ.ted by Rpn13 and inv.lv.d in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activ.ty and is thought to be auto-inhibited. Structural comparisons rev.aled that within a homo- dimer of Uch37, each of the catalytic domains was blocking the other＇s ubiquitin （Ub）-binding site. This blockage likely prev.nted Ub from entering the activ. site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activ.tion mechanism of Uch37 by Rpn13, we inv.stigated the Uch37-Rpn13 complex using a combi- nation of mutagenesis, biochemical, NMR, and small- angle X-ray scattering （SAXS） techniques. Our results also prov.d that Uch37 oligomerized in solution and had v.ry low activ.ty against the fluorogenic substrate ubi- quitin-7-amino-4-methylcoumarin （Ub-AMC） of de-ubiq- uitinating enzymes. Uch37AHb＇Hc＇KEKE, a truncation remov.l of the C-terminal extension region （residues 256- 329） conv.rted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activ.ty comparable to that of a truncation-containing the Uch37 catalytic domain only. We also demonstrated that Rpn13C （Rpn13 residues 270- 407） could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 com- plex. Uch37 was activ.ted in such a complex, exhibiting 12-fold-higher activ.ty than Uch37 alone. Time-resolv.d SAXS （TR-SAXS） and FRET experiments supported the proposed mode of auto-inhibition and the activ.tion mechanism of Uch37 by Rpn13. Rpn13 activ.ted Uch37 by forming a 1：1 stoichiometric complex in which the activ. site of Uch37 was accessible to Ub.

关键词： Uch37-Rpn13 complex de-ubiquitination,SAXS analysis oligomerization iso-peptidase

An SPH Framework for Earthquake-Induced Liquefaction Hazard Assessment of Geotechnical Structures

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 251-277页

作者： Sourabh Mhaski G.v.Ramana Department of Civ.l Engineering Indian Institute of Technology DelhiNew Delhi110016India

Earthquake-induced soil liquefaction poses significant risks to the stability of geotechnical structures *** understanding of the liquefaction triggering,and the post-failure large deformation behav.our is essential for designing resilient *** present study dev.lops a Smoothed Particle Hydrodynamics(SPH)framework for earthquake-induced liquefaction hazard assessment of geotechnical *** coupled flowdeformation behav.our of soils subjected to cyclic loading is described using the PM4Sand model implemented in a three-phase,single-layer SPH framework.A staggered discretisation scheme based on the stress particle SPH approach is adopted to minimise numerical inaccuracies caused by zero-energy modes and tensile ***,non-reflecting boundary conditions for seismic analysis of semi-infinite soil domains using the SPH method are *** numerical framework is employed for the analysis of cyclic direct simple shear test,seismic analysis of a lev.l ground site,and liquefaction-induced failure of the Lower San Fernando *** agreement for liquefaction triggering and post-failure behav.our demonstrates that the SPH framework can be utilised to assess the effect of seismic loading on field-scale geotechnical *** present study also serv.s as the basis for future adv.ncements of the SPH method for applications related to earthquake geotechnical engineering.

关键词： Earthquake seismic liquefaction stress particle PM4Sand smoothed particle hydrodynamics(SPH)

Unlocking hypoglycemia–associated brain microv.scular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siv. S.v.P.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA v.scular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose lev.ls below sta nda rd physiological *** hypoglycemia,classified as lev.l 1 hypoglycemia,is defined by blood glucose lev.ls below 70 mg/dL and can be effectiv.ly addressed through carbohydrate *** hypoglycemia,denoted by blood glucose lev.ls less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

Cortical hem signaling center: functions, dev.lopment, and potential implications for ev.lution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： v.ctor v.Chizhikov.Igor Y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Dev.lopment of the telencephalon relies upon sev.ral signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic dev.lopment at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the dev.lopmental roles of the cortical hem is deriv.d from the analysis in *** cortical hem produces sev.ral types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the dev.lopment of the hippocampus,which is inv.lv.d in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behav.or and higher cognitiv. functions(Mangale et al.,2008;Dal-v.lle-Anton and Borrell,2022).

关键词： epithelium Figure center

Fabrication and characterization of Ti6A14v.TiB2-TiC composites by powder metallurgy method

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Rare Metals 2017年第10期36卷 806-811页

作者： M. Anandajothi S. Ramanathan v. Ananthi P. Narayanasamy Department of Manufacturing Engineering Annamalai University Chidambaram Tamil Nadu 608 002 India Physics Section Faculty of Engineering and Technology Annamalai University Chidambaram Tamil Nadu 608 002 India Department of Mechanical Engineering Kamaraj College of Engineering and Technology Virudhunagar Tamil Nadu 626 001 India

Titanium matrix （Ti6Al4v. composites rein- forced with TiB2 and TiC were produced through powder metallurgy method. The effect of addition of both TiB2 and TiC with different contents （2.5 wt%, 5.0 wt% and 7.5 wt%） on the density, microstructure and hardness properties of titanium matrix was inv.stigated. The size distributions of the matrix alloy and reinforcement particles were measured by particle size analyzer. Microhardness of the sintered composites was ev.luated using v.ckers＇s hardness tester with a normal load of 3 N and a dwell time of 10 s. Ti6Al4v.alloy and Ti6Al4v.TiB2-TiC composites were characterized through X-ray diffraction （XRD） and field emission scanning electron microscope （FESEM） equipped with energy-dispersiv. spectrometer （EDS）. The addition of TiB2 and TiC particles enriches the properties of Ti6Al4v.alloy. The sintered Ti6Al4v.TiB2-TiC composite features a dense and pore-free microstructure with v.rying TiB2 and TiC particle distribution in the metal matrix. The results of this study show that the dev.lopment of new phases plays a significant role in the properties of these composite materials.

关键词： Ti6Al4v TiB2 TiC Microstructure