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Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao Department of Vascular Surgery.nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary Surgery and Transplantation Surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen Research Institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

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Neural Regeneration Research 2024年第8期19卷 1660-1670页

作者： Li Zhang Zhigang Hu Zhenxing Li Yixing Lin Department of Neurosurgery Jinling HospitalSchool of MedicineNanjing UniversityNanjingJiangsu ProvinceChina

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

关键词： central nervous system injuries death pyroptosis ferroptosis inflammation mitophagy necroptosis programmed cell

One-step quantum dialogue

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Chinese Physics B 2024年第3期33卷 95-104页

作者：朱鹏辉钟伟杜明明李喜云周澜盛宇波 College of Science Nanjing University of Posts and TelecommunicationsNanjing 210023China College of Electronic and Optical Engineering & College of Flexible Electronics (Future Technology) Nanjing University of Posts and TelecommunicationsNanjing 210023China Institute of Quantum Information and Technology Nanjing University of Posts and TelecommunicationsNanjing 210003China

Quantum dialogue(QD)enables two communication parties to directly exchange secret messages simultaneously.In conventional QD protocols,photons need to transmit in the quantum channel for two rounds.In this paper,we propose a one-step QD protocol based on the hyperentanglement.With the help of the non-local hyperentanglement-assisted Bell state measurement(BSM),the photons only need to transmit in the quantum channel once.We prove that our one-step QD protocol is secure in theory and numerically simulate its secret message capacity under practical experimental condition.Compared with previous QD protocols,the one-step QD protocol can effectively simplify the experiment operations and reduce the message loss caused by the photon transmission loss.Meanwhile,the non-local hyperentanglement-assisted BSM has a success probability of 100%and is feasible with linear optical elements.Moreover,combined with the hyperentanglement heralded amplification and purification,our protocol is possible to realize long-distance one-step QD.

关键词： one-step quantum dialogue hyperentanglement hyperentanglement distribution non-local Bell-state measurement

Effective dynamics for a spin-1/2 particle constrained to a curved layer with inhomogeneous thickness

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Chinese Physics B 2024年第2期33卷 78-83页

作者：梁国华尹佩林 School of Science Nanjing University of Posts and TelecommunicationsNanjing 210023China

We derive an effective Hamiltonian for a spin-1/2 particle confined within a curved thin layer with non-uniform thickness using the confining potential approach.Our analysis reveals the presence of a pseudo-magnetic field and effective spin–orbit interaction(SOI)arising from the curvature,as well as an effective scalar potential resulting from variations in thickness.Importantly,we demonstrate that the physical effect of additional SOI from thickness fluctuations vanishes in low-dimensional systems,thus guaranteeing the robustness of spin interference measurements to thickness imperfection.Furthermore,we establish the applicability of the effective Hamiltonian in both symmetric and asymmetric confinement scenarios,which is crucial for its utilization in one-side etching systems.

关键词： curved surface inhomogeneous thickness spin-1/2 particle effective Hamiltonian

Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer

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Chinese Medical Journal 2024年第3期137卷 338-349页

作者： Feng Xu Kun Xu Lingling Fan Xintong Li Yiqiu Liu Fang Yang Chengjun Zhu Xiaoxiang Guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China The Comprehensive Cancer Center of nanjing Drum Tower Hospital Affiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)TNBC.However,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits.This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC tissues.Then,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in TNBC.Chromatin immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of AR.Results:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR positive.We further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative TNBC.Mechanistically,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.Conclusions:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation.Therefore,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

关键词： Androgen receptor Estrogen receptor beta Triple-negative breast cancer NECTIN4 Oncogenic effects Tumor progression

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 343-353页

作者： Li-Xiang Liu Hao Wang Bo Gao Ting-Ting Xu Qing-Gang Yuan Shi-Zhen Zhou Chao Ding Ji Miao Wen-Xian Guan Department of General Surgery Nanjing Drum Tower HospitalNanjing Drum Tower Hospital Clinical CollegeNanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Clinical Nutrition Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower Clinical College of Xuzhou Medical UniversityNanjing 210008Jiangsu ProvinceChina

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

关键词： Controlling nutritional status Colorectal cancer Prognostic marker Sarcopenia Skeletal muscle

Preoperative serum cortisone levels are associated with cognition in preschool‑aged children with tetralogy of Fallot after corrective surgery:new evidence from human populations and mice

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World Journal of Pediatrics 2024年第2期20卷 173-184页

作者： Si-Yu Ma Yu-Ting Liu Yue-Shuang Cun Qiang Wang Ming-Cui Fu Ke-De Wu Xin-Yu Cai Shu-Ting Cheng Nishant Patel Min Da Liang Hu Zhuoga Deqin Xue-Jun Kang Ming Yang Xu-Ming Mo Department of Cardiothoracic Surgery Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Department of Radiology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing 210008China Key Laboratory of Child Development and Learning Science Research Center For Learning ScienceSchool of Biological Sciences&Medical EngineeringMinistry of EducationSoutheast UniversityNanjing 210096China Medical School of nanjing university Nanjing 210093China

Background Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart disease.Children with TOF would be confronted with neurological impairment across their lifetime.Our study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with TOF.Methods We used mass spectrometry(MS)technology to assess the levels of serum metabolites,Wechsler preschool and primary scale of intelligence-Fourth edition(WPPSI-Ⅳ)index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging(MRI)to detect cortical morphological changes.Results Multiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal index.Meanwhile,preoperative SpO_(2) was negatively correlated with levels of serum cortisone after adjusting for all covariates.Furthermore,after intervening levels of cortisone in chronic hypoxic model mice,total brain volumes were reduced at both postnatal(P)11.5 and P30 days.Conclusions Our results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with TOF.Our study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

关键词： Cognition Cortisone MRI Neurodevelopment Tetralogy of Fallot

Occurrence and risk assessment of azole fungicides during the urban water cycle:A year-long study along the Yangtze River,China

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Journal of Environmental Sciences 2024年第7期141卷 16-25页

作者： Yangyang Zhang Xinjie Gu Xiuwen Li Qiuyun Zhao Xiaodong Hu Rui Huang Jixiong Xu Zilong Yin Qing Zhou Aimin Li Peng Shi State Key Laboratory of Pollution Control and Resource Reuse School of the EnvironmentNanjing UniversityNanjing 210023China Jiangsu Province Hydraulic Research Institute Nanjing 210023China

Azole fungicides(AFs)play an important role in the prevention and treatment of fungal diseases in agricultural crops.However,limited studies are addressing the fate and ecological risk of AFs in the urban water cycle at a large watershed scale.To address this gap,we investigated the spatiotemporal distribution and ecological risk of twenty AFs in the lower reaches of the Yangtze River across four seasons.Carbendazim(CBA),tebuconazole(TBA),tricyclazole(TCA),and propiconazole(PPA)were found to be the dominant compounds.Their highest concentrations were measured in January(188.3 ng/L),and November(2197.1 ng/L),July(162.0 ng/L),and November(1801.9 ng/L),respectively.The comparison between wastewater treatment plants(WWTPs)effluents and surface water suggested that industrial WWTPs are major sources of AFs in the Yangtze River.In particular,TBA and PPA were found to be the most recalcitrant AFs in industrial WWTPs,while difenoconazole(DFA)was found to be the most potent pollutant in municipal WWTPs,with an average removal rate of less than60%.The average risk quotient(RQ)for the entire AFs was 6.45 in the fall,which was higher than in January(0.98),April(0.61),and July(0.40).This indicates that AFs in surface water posed higher environmental risks during the dry season.Additionally,the exposure risk of AFs via drinking water for sensitive populations deserves more attention.This study provides benchmark data on the occurrence of AFs in the lower reaches of the Yangtze River,and offers suggestions for better reduction of AFs.

关键词： Azole fungicides Spatiotemporal distribution Ecological risk Urban water cycle the Yangtze River

Generation of orbital angular momentum hologram using a modified U-net

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Chinese Physics B 2024年第3期33卷 401-407页

作者：郑志刚韩菲菲王乐赵生妹 Institute of Signal Processing and Transmission Nanjing University of Posts and TelecommunicationsNanjing 210003China Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education) Nanjing University of Posts and TelecommunicationsNanjing 210003China National Laboratory of Solid State Microstructures Nanjing UniversityNanjing 210093China

Orbital angular momentum(OAM)holography has become a promising technique in information encryption,data storage and opto-electronic computing,owing to the infinite topological charge of one single OAM mode and the orthogonality of different OAM modes.In this paper,we propose a novel OAM hologram generation method based on a densely connected U-net(DCU),where the densely connected convolution blocks(DCB)replace the convolution blocks of the U-net.Importantly,the reconstruction process of the OAM hologram is integrated into DCU as its output layer,so as to eliminate the requirement to prepare training data for the OAM hologram,which is required by conventional neural networks through an iterative algorithm.The experimental and simulation results show that the OAM hologram can rapidly be generated with the well-trained DCU,and the reconstructed image's quality from the generated OAM hologram is significantly improved in comparison with those from the Gerchberg-Saxton generation method,the Gerchberg-Saxton based generation method and the U-net method.In addition,a 10-bit OAM multiplexing hologram scheme is numerically demonstrated to have a high capacity with OAM hologram.

关键词： orbital angular momentum(OAM) holography OAM holography deep learning