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Diabetes mellitus and glymphatic dysfunction:Roles for oxidative stress,mitochondria,circadian rhythm,artificial intelligence,and imaging

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World Journal of Diabetes 2025年第1期16卷 39-48页

作者： Kenneth Maiese national Heart Lungand Blood InstituteNational Institutes of HealthBethesdaMD 20810United States

Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the *** represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately *** cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm *** pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic *** studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.

关键词： Artificial intelligence Circadian rhythm Clock genes Diabetes mellitus magnetic resonance imaging Glymphatic pathway Mitochondria Oxidative stress Programmed cell death Sleep fragmentation

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.Miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA national institutes of health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Continuous R-DA-EDOCH alternated with high-dose Ara-C induces deep remission and overcomes high-risk factors in young patients with newly diagnosed mantle cell lymphoma

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Cancer Biology & Medicine 2025年第02期22卷 177-189页

作者： Yi Wang Yuting Yan Dandan Shan Jiawen Chen Wei Liu Tingyu Wang Gang An Weiwei Sui Wenyang Huang Wenjie Xiong Huimin Liu Qi Sun Huijun Wang Zhijian Xiao Jianxiang Wang Lugui Qiu Dehui Zou Shuhua Yi State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin institutes of health Science

Objective: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma(MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate(CRR) at the end of induction(EOI).Methods: A total of 55 patients were enrolled. The CRR at the EOI was 89.1% [95% confidence interval(CI) 78%±96%], and the overall response rate was 98.1%(95% CI 90%±100%). Most patients with bone marrow involvement quickly attained minimal residual disease(MRD) negative status, with a 95.7% rate at the ***: The 3-year progression-free survival(PFS) and overall survival rates were 66.3% and 83.2%, respectively. No patients discontinued treatment because of adverse events. Univariate analysis identified pathologic morphology and TP53 mutations as risk factors for PFS. However, high tumor proliferative activity and certain cytogenetic abnormalities showed no significant adverse prognostic ***: Intensive therapy based on a high cytarabine dose and continuously administered EDOCH achieved a high MRDnegative rate and provides an optional induction choice for young patients with MCL with high-risk factors.

关键词： Mantle cell lymphoma adverse events high-risk factors immunochemotherapy minimal residual disease

Advancements in proteogenomics for preclinical targeted cancer therapy research

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生物物理学报（英文） 2025年第1期11卷 56-76页

作者： Yuying Suo Yuanli Song Yuqiu Wang Qian Liu Henry Rodriguez Hu Zhou Department of Analytical Chemistry State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China University of Chinese Academy of Sciences Beijing 100049 China Department of Otolaryngology Eye & ENT Hospital Fudan University Shanghai 200031 China Office of Cancer Clinical Proteomics Research National Cancer Institute National Institutes of Health Rockville MD 20850 USA

Advancements in molecular characterization technologies have accelerated targeted cancer therapy research at unprecedented resolution and dimensionality. Integrating comprehensive multi-omic molecular profiling of a tumor, proteogenomics, marks a transformative milestone for preclinical cancer research. In this paper, we initially provided an overview of proteogenomics in cancer research, spanning genomics, transcriptomics, and proteomics. Subsequently, the applications were introduced and examined from different perspectives, including but not limited to genetic alterations, molecular quantifications, single-cell patterns, different post-translational modification levels, subtype signatures, and immune landscape. We also paid attention to the combined multi-omics data analysis and pan-cancer analysis. This paper highlights the crucial role of proteogenomics in preclinical targeted cancer therapy research, including but not limited to elucidating the mechanisms of tumorigenesis, discovering effective therapeutic targets and promising biomarkers, and developing subtype-specific therapies.

关键词： Proteogenomics Targeted cancer therapy Integrated omics analysis

Implement the Guiding Principles of the Third Plenary Session of the 20th CPC Central Committee and Ensure High-Quality Development through High-Level Security

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Contemporary International Relations 2025年第1期35卷 4-27页

作者： Yang Mingjie Chen Xiangyang Chen Qinghong Han Yafeng President of China institutes of Contemporary International Relations(CICIR) Office of the Center for Studies on a Holistic Approach to national Security

As a major principle underlying the Communist Party of China's(CPC)governance in the new era and a core piece of its holistic approach to national security,ensuring both development and security emphasizes comprehensive governance from a long-term perspective and influences the world with its global *** keeps pace with the times by prioritizing innovative areas and is of great theoretical and practical *** the new journey ahead,we must firmly ensure both development and *** importantly,we must ensure both high-quality development and high-level security,safeguarding the former through the *** is an urgent requirement we face in today's world,which has entered a period of turbulence and transformation characterized by increasing *** with the formidable tasks of promoting reform and development while maintaining stability at home and the grave challenges brought about by international turbulence and changes,we must earnestly implement the guiding principles of the 20th CPC national Congress and the third plenary session of the 20th Party Central *** should ensure secure and sustainable development,accelerate efforts to modernize China's national security system and capacity,foster high-level security,and improve the mechanisms for preserving national security in foreign-related *** short,we should strive to achieve a positive interplay between high-quality development and high-level security,so as to effectively safeguard Chinese modernization.

关键词： ensure both development and security high-level security Central Committee new quality combat capabilities third plenary session of the 20th CPC Central Committee

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

LncRNAs:expanding horizons in drug development and disease treatment Author links open overlay panel

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Science Bulletin 2025年第3期70卷 287-289页

作者： Zhizhuo Wang Junfeng Wang Wenfei Wu Chengyu Shi Ying Wang Yu Chen Fangzhou Liu Shanshan Xie Aifu Lin International School of Medicine International Institutes of MedicineThe 4th Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China MOE Laboratory of Biosystem Homeostasis and Protection College of Life SciencesZhejiang UniversityHangzhou 310058China Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Cell Biology Zhejiang University School of MedicineHangzhou 310058China Cancer Center Zhejiang UniversityHangzhou 310058China Key Laboratory for Cell and Gene Engineering of Zhejiang Province Hangzhou 310058China Future health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China Key Laboratory of Cancer Prevention and Intervention China National Ministry of EducationHangzhou 310009China Faculty of health Sciences University of MacaoMacao 999078China

Extensive genome profiling studies have identified thousands of long non-coding RNAs(lncRNAs)associated with human *** are emerging elements through which the complex process of cancer development and progression can be ***,it is crucial to include an examination of lncRNAs when studying human cancer,especially when researching the clinical challenges of relapse and recurrence following targeted therapy[1].

关键词： horizon expanding treatment

Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina institutes of health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells