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Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential

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World Journal of Stem Cells 2024年第5期16卷 512-524页

作者： Hang Zhang ling-zi Wu Zhen-Yu liu zi-Bing Jin Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing 100730China

BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation.

关键词： Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells Transcriptomics Proteomics

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Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1344-1362页

作者： zi-ling Hu Yu-Xuan Wang zi-Yue lin Wen-Shuo Ren Bo liu Hui Zhao Qiong Qin Five Year Program of Ophthalmology and Optometry 2019 Beijing Tong Ren HospitalCapital Medical UniversityBeijing 100054China Four Year Program of Traditional Chinese Pharmacy 2020 School of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Beijing Key Laboratory of TCM Collateral Disease Theory Research Beijing 100069China Five Year Program of Ophthalmology and Optometry 2021 School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Biochemistry&Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual impairment.Increasing evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological role.Nuclear factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes.Its functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been elucidated.Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis.For the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

关键词： Nrf2 upstream regulators retinal pigment epithelia age-related macular degeneration oxidative stress

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Potential use of large language models for mitigating students’problematic social media use:ChatGPT as an example

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World Journal of Psychiatry 2024年第3期14卷 334-341页

作者： Xin-Qiao liu zi-Ru Zhang School of Education Tianjin UniversityTianjin 300350China

The problematic use of social media has numerous negative impacts on individuals'daily lives,interpersonal relationships,physical and mental health,and more.Currently,there are few methods and tools to alleviate problematic social media,and their potential is yet to be fully realized.Emerging large language models(LLMs)are becoming increasingly popular for providing information and assistance to people and are being applied in many aspects of life.In mitigating problematic social media use,LLMs such as ChatGPT can play a positive role by serving as conversational partners and outlets for users,providing personalized information and resources,monitoring and intervening in problematic social media use,and more.In this process,we should recognize both the enormous potential and endless possibilities of LLMs such as ChatGPT,leveraging their advantages to better address problematic social media use,while also acknowledging the limitations and potential pitfalls of ChatGPT technology,such as errors,limitations in issue resolution,privacy and security concerns,and potential overreliance.When we leverage the advantages of LLMs to address issues in social media usage,we must adopt a cautious and ethical approach,being vigilant of the potential adverse effects that LLMs may have in addressing problematic social media use to better harness technology to serve individuals and society.

关键词： Problematic use of social media Social media Large language models ChatGPT Chatbots

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Isolation and culture of human primary osteoblasts:Comparing the effects of differences in method details on osteoblast characteristics

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Genes & Diseases 2024年第2期11卷 546-549页

作者： Fei Chen Yan Zhang Pai Peng Xiao-Ting Huang zi-Han Qiu Bao-Cheng liu Tie-lin Yang Bo Yang Yan Guo Key Laboratory of Biomedical Information Engineering of Ministry of Education Biomedical Informatics & Genomics CenterSchool of Life Science and TechnologyXi'an Jiaotong UniversityXi'anShaanxi 710049China Department of Orthopaedics Shannxi Provincial People's Hospital (The Third Affiliated Hospital of Xi'an Jiaotong University)Xi'anShaanxi 710068China

Osteoblasts are essential in the maintenance of human bone homeostasis.1 The abnormal formation and impaired differentiation ability of osteoblasts are pivotal factors leading to bone-related diseases,suggesting that an indepth study of osteoblasts can provide novel treatment strategies for these diseases.2 Human primary osteoblasts are precious experimental models in bone-related research.3 However,the isolation and culture of human primary osteoblasts still have some difficulties and limitations.Here,we refined a method to isolate and culture human primary osteoblasts by taking cancellous bone through a bone tissue sampler and pre-digesting it with pancreatin,which makes the process easier,cheaper,and more efficient.Furthermore,we compared the effects of the subtle changes in isolation and culture methods on the phenotype of human primary osteoblasts and examined the differences in morphology,proliferation,and differentiation between micro-explants cultured osteoblasts(MECOBs)and explants cultured osteoblasts(EC-OBs).

关键词： impaired culture details

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NUDT5 promotes the growth,metastasis,and Warburg effect of IDH wild-type glioblastoma multiforme cells by upregulating TRIM47

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 82-92页

作者： zi-Fa Zhang Shu-Ming liu Neurosurgery Department Shanxi Bethune HospitalTaiyuanShanxi Province030022China Shanxi Academy of Medical Sciences TaiyuanShanxi province030022China Emergency Department Taiyuan People’s HospitalTaiyuanShanxi Province030021China

Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.

关键词： Glioblastoma multiforme NUDT5 TRIM47 Growth Metastasis Warburg effect

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Global epidemiology of mental disorder in atrial fibrillation between 1998-2021:A systematic review and meta-analysis

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World Journal of Psychiatry 2024年第1期14卷 179-193页

作者： Shuai Zhang Na Zhang liu liu Wang Zheng zi-lin Ma Si-Yu Qiao Ying-Li Zhao Yi-Hong Wei Gang Wu Qiu-Ting Yu Bing Deng lin Shen Department of Cardiology LongHua Hospital Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China

BACKGROUND As the burden of mental disorders among patients with atrial fibrillation(AF)increases,researchers are beginning to pay close attention to the risk and prevalence of these comorbidities.Although studies have independently analyzed the risk of comorbidity with depression and anxiety in patients with AF,no study has systematically focused on the global epidemiology of these two mental disorders.AIM To explore the prevalence of depression and anxiety in patients with AF.METHODS Five databases were searched from their date of establishment until January 2023.Observational studies reporting the comorbidity of AF with depression and anxiety,were included in this study.Basic information,such as the first author/publication year,study year,study type,and prevalence of depression and anxiety,were extracted.STATA SE 15.1 was used to analyze the data.Subgroup,meta-regression,and sensitivity analyses were performed to estimate study heterogeneity.RESULTS After a thorough search,26 studies were identified and included in this metaanalysis.The prevalence rates of depression and anxiety in adults with AF were 24.3%and 14.5%,respectively.Among adult males with AF,the prevalence was 11.7%and 8.7%,respectively,whereas in females it was 19.8%and 10.1%,respectively.In older adults with AF,the prevalence rates of depression and anxiety were 40.3%and 33.6%,respectively.The highest regional prevalence of depression and anxiety was observed in European(30.2%)and North American(19.8%)patients with AF.CONCLUSION In this study,we found that the prevalence of depression and anxiety among patients with AF varies with sex,region,and evaluation scales,suggesting the need for psychological interventions for patients with AF in clinical practice.

关键词： Atrial fibrillation Depression Anxiety Prevalence

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Predictive value of red blood cell distribution width and hematocrit for short-term outcomes and prognosis in colorectal cancer patients undergoing radical surgery

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World Journal of Gastroenterology 2024年第12期30卷 1714-1726页

作者： Dong Peng zi-Wei Li Fei liu Xu-Rui liu Chun-Yi Wang Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preopera

关键词： Colorectal cancer Red blood cell distribution width Survival Short-term outcomes

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NFXL1 functions as a transcriptional activator required for thermotolerance at reproductive stage in Arabidopsis

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Journal of Integrative Plant Biology 2024年第1期66卷 54-65页

作者： Qiao‐Yun Zhu lin‐lin Zhang Jian‐Xiang liu State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejiang UniversityHangzhou 310027China

Plants are highly susceptible to abiotic stresses,particularly heat stress during the reproductive stage.However,the specific molecular mechanisms underlying this sensitivity remain largely unknown.In the current study,we demonstrate that the Nuclear Transcription Factor,X-box Binding Protein 1-Like 1(NFXL1),directly regulates the expression of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A(DREB2A),which is crucial for reproductive thermotolerance in Arabidopsis.NFXL1 is upregulated by heat stress,and its mutation leads to a reduction in silique length(seed number)under heat stress conditions.RNA-Seq analysis reveals that NFXL1 has a global impact on the expression of heat stress responsive genes,including DREB2A,Heat Shock Factor A3(HSFA3)and Heat Shock Protein 17.6(HSP17.6)in flower buds.Interestingly,NFXL1 is enriched in the promoter region of DREB2A,but not of either HSFA3 or HSP17.6.Further experiments using electrophoretic mobility shift assay have confirmed that NFXL1 directly binds to the DNA fragment derived from the DREB2A promoter.Moreover,effector-reporter assays have shown that NFXL1 activates the DREB2A promoter.The DREB2A mutants are also heat stress sensitive at the reproductive stage,and DEREB2A is epistatic to NFXL1 in regulating thermotolerance in flower buds.It is known that HSFA3,a direct target of DREB2A,regulates the expression of heat shock proteins genes under heat stress conditions.Thus,our findings establish NFXL1 as a critical upstream regulator of DREB2A in the transcriptional cassette responsible for heat stress responses required for reproductive thermotolerance in Arabidopsis.

关键词： Arabidopsis DREB2A heat stress NFXL1 reproductive thermotolerance

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Dynamical switchable quantum nonreciprocity induced by off-resonant chiral two-photon driving

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 31-37页

作者： Da-Wei liu zi-Hao Li Shi-Lei Chao Ying Wu liu-Gang Si School of Physics and Institute for Quantum Science and Engineering Huazhong University of Science and TechnologyWuhan 430074China

Optical nonreciprocity,which refers to the direction-dependent emission,scattering and absorption of photons,plays a very important role in quantum engineering and quantum information processing.Here,we propose an all-optical approach to achieve the optical dynamical switchable quantum nonreciprocity by an off-resonant chiral two-photon driving in a single microring cavity,which differs from the conventional nonreciprocal schemes.It is shown that the optical field with time-dependent statistical properties can be generated and the nonreciprocity flips periodically,with switchable photon blockade and photon-induced tunneling effects.We find that the dynamical system is robust and immune to the parameter variations,which loosens the parameter range of system.Meanwhile,the time window for one-way quantum information is sufficiently wide and tunable.Our work opens a new idea for the current quantum nonreciprocal research,which can facilitate a memory functionality and be used for future inmemory superconducting quantum compute.The other nonreciprocal quantum devices,i.e.,dynamical switchable nonreciprocal squeezing and entanglement,may be inspired by our method,which is expected to have important applications in future quantum technology.

关键词： dynamical switchable nonreciprocity single-photon source chiral two-photon driving

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Broadband angular spectrum analog processors based on all-dielectric metasurfaces

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 188-190页

作者： lin Deng Yongmin liu Department of Electrical and Computer Engineering Northeastern UniversityBoston 02115USA Department of Mechanical and Industrial Engineering Northeastern UniversityBoston 02115USA

Digital signal processors are extensively used to execute mathematical operations and advanced computational tasks on digital data.However,they suffer from several inherent limitations,including low speed,high energy consumption,and large memory requirements,because of the hardware bottleneck and the imperative conversion between digital and analogue signals.

关键词： dielectric spectrum hardware

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