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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

HCN Adsorption on the Fe(100), Fe(111) and Fe(110) Surfaces: a Density Functional Theory Study

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Chinese Journal of Structural Chemistry 2013年第5期32卷 763-773页

作者：辛振东史文静李巧玲 Department of Chemistry College of ScienceNorth University of China The third hospital of shanxi medical University

Twenty kinds of adsorptions of HCN on the Fe（100）, Fe（111） and Fe（110） surfaces at the 1/4 monolayer coverage are found using the density functional theory. For Fe（100）, the adsorption energy of the most stable configuration where the HCN locates at the fourfold site with the C-N bonded to four Fe atoms is 1.928 eV. The most favored adsorption structure for HCN on Fe（111） is f-η3（N）-h-η3（C）, in which the C-N bond is almost parallel to the surface, and the adsorption energy is 1.347 eV. On Fe（110）, the adsorption energy in the most stable configuration in which HCN locates at the two long-bridge sites is 1.777 eV. The adsorption energy of the parallel orientation for HCN is larger than that of the perpendicular configuration. The binding mechanism of HCN on the Fe（100）, Fe（111） and Fe（110） surfaces is also analyzed by Mulliken charge population and the density of states in HCN. The result indicates that the configurations in which the adsorbed HCN becomes the non-linear are beneficial to the formation of the addition reaction for hydrogen. The nature that the introduction of Fe into the catalyst could increase the catalytic activity of the bimetallic catalyst in the addition reaction of hydrogen for nitriles is revealed.

关键词： HCN Fe surfaces adsorption DFT

Sine oculis homeobox homolog family function in gastrointestinal cancer:Progression and comprehensive analysis

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World Journal of Clinical Oncology 2025年第1期16卷 10-24页

作者： Yang-Zheng Lan Zheng Wu Wen-Jia Chen Xin-Ning Yu Hua-Tao Wu Jing Liu Department of The Breast Center Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of General Surgery First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including *** six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX *** or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular *** to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor *** the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic ***,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular *** conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.

关键词： Sine oculis homeobox homolog Gastrointestinal cancer Transcription factor Development Regulation Diagnosis Therapeutics

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

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Neural Regeneration Research 2025年第1期20卷 205-206页

作者： Sarah Fullam Sean O’Dowd Antoinette O’Connor Department of Neurology Tallaght University HospitalDublinIreland Academic Unit of Neurology Trinity College DublinIreland

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of *** evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic *** the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for ***,the expensive and invasive nature of these tests limits their scalability.

关键词： Blood Alzheimer diagnosis

Bridging the translation gap and building the translation platform:translational medicine at Peking Union medical college hospital

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Science China(Life Sciences) 2016年第10期59卷 1048-1050页

作者： Jun Xu Shaojing Liu Xuezhong Yu Peking Union medical college hospital Beijing 100730China

Although there have been progressive advancements in the life sciences since the beginning of the 21st Century, basic medical sciences generally fail to be efficiently translated into clinical research and ultimately into clinical practice. Translational medicine has become a fashionable term de- scribing the inclination of basic science and clinical re- searchers to ultimately help patients through facilitating the incorporation of basic research findings into clinical prac- tice （Zerhouni, 2005）.

关键词：医学科学转化翻译临床实践医院北京平台基础科学

AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union medical college hospital,a General Tertiary hospital in Beijing

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Chinese medical Sciences Journal 2016年第1期31卷 17-22页

作者： Yue-qiu Zhang Sai-nan Bian Xiao-qing Liu Shao-xia Xu Li-fan Zhang Bao-tong Zhou Wei-hong Zhang Yao Zhang Ying-chun Xu Guo-hua Deng Department of Infectious Diseases Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College Clinical Epidemiology Unit Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College Department of Clinical Laboratory Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical College

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union medical college hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

关键词： hepatitis B virus infection positive rate hepatitis B virus serological markers demographic factors

Near-infrared organic photosensitizers with aggregation-induced emission and switchable fluorescence for fungal infection therapy

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Science China Chemistry 2025年

作者： Xinzhe Yang Zixuan Huang Keke Ding Huili Yang Lirong Wang Qing Xia Rong Hu Guang Shi Bingjia Xu Anjun Qin School of Chemistry South China Normal University State Key Laboratory of Luminescent Materials and Devices Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates Center for Aggregation-Induced Emission AIE Institute South China University of Technology Department of Urology The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College) School of Chemistry and Chemical Engineering University of South China

The development of near-infrared (NIR) photosensitizers with aggregation-induced emission (AIE) properties,switchable luminescence colors,and satisfactory photodynamic therapy (PDT) effects on the treatment of fungal infection is of great importance but very ***,two ionic organic luminogens are constructed by employing diphenylamine,diphenylacrylonitrile/1,2-diphenylethene,and methylated quinoline cation as building *** is found that the resulting compounds TCQF and TQF show apparent AIE properties and produce intense fluorescence with high photoluminescence quantum yields of up to 31.2%in the solid *** the meantime,their emission colors can be switched between red and NIR and in the NIR region by mechanical force and solvent vapor,respectively,thereby enabling remarkable and reversible mechanochromism with emission variations of up to 104 *** excitingly,TCQF and TQF can efficiently generate ROS under the illumination of white light and show excellent antimicrobial activities and satisfactory PDT *** by the unique anti-fungus properties,TCQF is employed as a biocompatible NIR photosensitizer for treating wound infection with ***,and apparent PDT effects are *** work provides a new direction for the development of multifunctional NIR materials with AIE properties.

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Pulp health and calcific healing of a complicated crown–root fracture with additional root fracture in a maxillary incisor: A case report

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World Journal of Clinical Cases 2025年第3期13卷 42-49页

作者： Na Li Yue-Yue Ren Ying Tang Qi Yang Tian-Tian Meng Song Li Jing Zhang Stomatological hospital and college Anhui Medical UniversityHefei 230032Anhui ProvinceChina Department of Endodontics The Affiliated Stomatological Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in *** SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical *** the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival ***-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival *** This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.

关键词： Complicated crown-root fracture Multiple root fracture Spontaneous healing Cone-beam computed tomography Long-term follow-up Case report