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Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1593-1601页

作者： Bo Li Yujie Chen Yan Zhou Xuanran Feng Guojun Gu Shuang Han Nianhao Cheng Yawen Sun Yiming Zhang Jiahui Cheng Qi Zhang Wei Zhang Jianhui Liu Department of Radiology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Morphology and Spatial Multi-Omics technology Platform Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghaiChina Department of Anesthesiology Tongji HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Blood Transfusion Huashan HospitalFudan UniversityShanghaiChina

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

关键词： Alzheimer’s disease mitochondrial biogenesis neural stem cell-derived exosome SIRT1-PGC1α regional brain distribution whole brain clearing and imaging

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Aerial target threat assessment based on gated recurrent unit and self-attention mechanism

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Journal of Systems Engineering and Electronics 2024年第2期35卷 361-373页

作者： CHEN Chen QUAN Wei SHAO Zhuang School of Automation Beijing Institute of TechnologyBeijing 100081China State Key Laboratory of Intelligent Control and Decision of Complex Systems Beijing 100081China

Aerial threat assessment is a crucial link in modern air combat, whose result counts a great deal for commanders to make decisions. With the consideration that the existing threat assessment methods have difficulties in dealing with high dimensional time series target data, a threat assessment method based on self-attention mechanism and gated recurrent unit(SAGRU) is proposed. Firstly, a threat feature system including air combat situations and capability features is established. Moreover, a data augmentation process based on fractional Fourier transform(FRFT) is applied to extract more valuable information from time series situation features. Furthermore, aiming to capture key characteristics of battlefield evolution, a bidirectional GRU and SA mechanisms are designed for enhanced features.Subsequently, after the concatenation of the processed air combat situation and capability features, the target threat level will be predicted by fully connected neural layers and the softmax classifier. Finally, in order to validate this model, an air combat dataset generated by a combat simulation system is introduced for model training and testing. The comparison experiments show the proposed model has structural rationality and can perform threat assessment faster and more accurately than the other existing models based on deep learning.

关键词： target threat assessment gated recurrent unit(GRU) self-attention(SA) fractional Fourier transform(FRFT)

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Unraveling the complex roles of macrophages in obese adipose tissue:an overview

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Frontiers of Medicine 2024年第2期18卷 205-236页

作者： Chang Peng Jun Chen Rui Wu Haowen Jiang Jia Li Hangzhou Institute for Advanced Study University of Chinese Academy of SciencesHangzhou310000China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of sciences Beijing100049China Department of Prosthodontics Shanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghai200011China

Macrophages,a heterogeneous population of innate immune cells,exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases.The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects,inducing insulin resistance through increased inflammation,impaired thermogenesis,and adipose tissue fibrosis.Meanwhile,adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis,facilitating the clearance of dead adipocytes,and promoting mitochondrial transfer.Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions.Recently,the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology.In this review,we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity,as well as explore the potential of drug delivery systems targeting macrophages,aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.

关键词： obesity inflammation adipose tissue macrophages adipose tissue homeostasis

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Orbital angular momentum-mediated machine learning for high-accuracy mode-feature encoding

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Light(science & Applications) 2024年第3期13卷 466-477页

作者： Xinyuan Fang Xiaonan Hu Baoli Li Hang Su Ke Cheng Haitao Luan Min Gu Institute of Photonic Chips University of Shanghai for Science and TechnologyShanghai 200093China Centre for Artificial-Intelligence Nanophotonics School of Optical-Electrical and Computer EngineeringUniversity of Shanghai for Science and TechnologyShanghai 200093China

Machine learning with optical neural networks has featured unique advantages of the information processing including high speed,ultrawide bandwidths and low energy consumption because the optical dimensions(time,space,wavelength,and polarization)could be utilized to increase the degree of freedom.However,due to the lack of the capability to extract the information features in the orbital angular momentum(OAM)domain,the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model.Here,we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network(CNN)based on Laguerre-Gaussian(LG)beam modes with diverse diffraction losses.The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction,and deep-learning diffractive layers as a classifier.The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding,leading to an accuracy as high as 97.2%for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes,as well as a resistance to eavesdropping in point-to-point free-space transmission.Moreover,through extending the target encoded modes into multiplexed OAM states,we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%.Our work provides a deep insight to the mechanism of machine learning with spatial modes basis,which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.

关键词： polarization mode momentum

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Multi-dimensional multiplexing optical secret sharing framework with cascaded liquid crystal holograms

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Opto-Electronic Advances 2024年第1期7卷 28-35页

作者： Keyao Li Yiming Wang Dapu Pi Baoli Li Haitao Luan Xinyuan Fang Peng Chen Yanqing Lu Min Gu Institute of Photonic Chips University of Shanghai for Science and TechnologyShanghai 200093China Centre for Artificial-Intelligence Nanophotonics School of Optical-Electrical and Computer EngineeringUniversity of Shanghai for Science and TechnologyShanghai 200093China National Laboratory of Solid State Microstructures and College of Engineering and Applied SciencesNanjing UniversityNanjing 210093China

Secret sharing is a promising technology for information encryption by splitting the secret information into different shares.However,the traditional scheme suffers from information leakage in decryption process since the amount of available information channels is limited.Herein,we propose and demonstrate an optical secret sharing framework based on the multi-dimensional multiplexing liquid crystal(LC)holograms.The LC holograms are used as spatially separated shares to carry secret images.The polarization of the incident light and the distance between different shares are served as secret keys,which can significantly improve the information security and capacity.Besides,the decryption condition is also restricted by the applied external voltage due to the variant diffraction efficiency,which further increases the information security.In implementation,an artificial neural network(ANN)model is developed to carefully design the phase distribution of each LC hologram.With the advantage of high security,high capacity and simple configuration,our optical secret sharing framework has great potentials in optical encryption and dynamic holographic display.

关键词： holographic encryption optical secret sharing cascaded liquid crystal hologram multi-dimensional multiplexing

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TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1773-1786页

作者： Jia-Hao Chen Li-Yong Zhu Zhi-Wei Cai Xiao Hu Abousalam Abdoulkader Ahmed Jie-Qiong Ge Xiao-Yan Tang Chun-Jing Li Yun-Long Pu Chong-Yi Jiang Department of Hepato-Biliary-Pancreatic Surgery Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China shanghai Key Laboratory of Clinical Geriatric Medicine Fudan UniversityShanghai 200040China Department of Nursing Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

关键词： TRIANGLE operation Pancreatic ductal adenocarcinoma Heidelberg triangle Adjuvant chemotherapy Prognosis Pancreaticoduodenectomy

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of sciences shanghai Huashen Institute of Microbes and Infections College of Life sciences Nanjing Normal University State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key Laboratory of Medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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Deflagration and detonation induced by shock wave focusing at different Mach numbers

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Chinese Journal of Aeronautics 2024年第2期37卷 249-258页

作者： Zezhong YANG Jun CHENG Bo ZHANG School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai 200240China

Shock wave focusing is an effective way to create a hot spot or a high-pressure and hightemperature region at a certain place,showing its unique usage in detonation initiation,which is beneficial for the development of detonation-based engines.The flame propagation behavior after the autoignition induced by shock wave focusing is crucial to the formation and self-sustaining of the detonation wave.In this study,wedge reflectors with two different angles(60°and 90°)and a planar reflector are employed,and the Mach number of incident shock waves ranging from 2.0 to 2.8 is utilized to trigger different flame propagation modes.Dynamic pressure transducers and the high-speed schlieren imaging system are both employed to investigate the shock-shock collision and ignition procedure.The results reveal a total of four flame propagation modes:deflagration,DDT(Deflagration-to-Detonation Transition),unsteady detonation,and direct detonation.The detonation wave formed in the DDT and unsteady detonation mode is only approximately 75%-85%of the Chapman-Jouguet(C-J)speed;meanwhile,the directly induced detonation wave speed is close to the C-J speed.Transverse waves,which are strong evidence for the existence of detonation waves,are discovered in experiments.The usage of wedge reflectors significantly reduces the initial pressure difference ratio needed for direct detonation ignition.We also provide a practical method for differentiating between detonation and deflagration modes,which involves contrasting the speed of the reflected shock wave with the speed of the theoretically nonreactive reflected shock wave.These findings should serve as a reference for the detonation initiation technique in advanced detonation propulsion engines.

关键词： Deflagration Detonation Hydrogen Ignition Shock wave focusing

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Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 750-760页

作者： Ying-Jie Zhang Meng-Xia Yuan Wu Wen Fan Li Yi Jian Chuan-Ming Zhang Ye Yang Feng-Lin Chen Department of Digestive Diseases Chengdu Second People’s HospitalChengdu 610000Sichuan ProvinceChina Graduate School Chengdu Medical CollegeChengdu 610000Sichuan ProvinceChina

BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled mucosa)surrounding colo-rectal polyps,caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors.CSM-positive colorectal polyps are associated with various diseases;however,their prognosis varies greatly.Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps.Improved imaging is required to diagnose and treat CSM-positive colorectal polyps.METHODS This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy.All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system.Based on the pathological results,patients were classified as non-neoplastic polyps(five juvenile polyps),neoplastic polyps,non-invasive high-grade neoplasia(NHGN),or submucosal invasive carcinoma(SM stage cancer).We analyzed and compared the clinical features,suspected risk factors for malignant transformation of neoplastic polyps,and early infiltration of sub-mucosal carcinoma.RESULTS The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps.Most NHGN polyps had a deeper red mucosal color.On logistic regression analyses,diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps.Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM;type 2 CSM was more common in neoplastic polyps.Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer.Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal ca

关键词： Chicken skin mucosa Colorectal cancer Colorectal polyps Endoscopic resection Malignant transformation White light endoscopy

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Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1

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Chinese Journal of Integrative Medicine 2024年第6期30卷 534-542页

作者： LI Jie CHEN Ya-feng GAO Lei LI Yi-jie FENG Dian-xu Department of General Surgery Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai200062China

Objective To investigate the effect of honokiol(HON)and the role of high-mobility group protein B1(HMGB1)on the pathogenesis of severe acute pancreatitis(SAP).Methods Thirty mice were numbered according to weight,and randomly divided into 5 groups using a random number table,including control,SAP,SAP and normal saline(SAP+NS),SAP and ethyl pyruvate(SAP+EP),or SAP+HON groups,6 mice in each group.Samples of pancreas,intestine,and blood were collected 12 h after SAP model induction for examination of pathologic changes,immune function alterations by enzyme linked immunosorbent assay(ELISA),and Western blot.In vitro experiments,macrophages were divided into 5 groups,the control,lipopolysaccharide(LPS),LPS+DMSO(DMSO),LPS+anti-HMGB1 monoclonal antibody(mAb),and LPS+HON groups.The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled.The location and acetylation of HMGB1 were measured by Western blot.Finally,pyridone 6 and silencing signal transducer and activator of the transcription 1(siSTAT1)combined with honokiol were added to determine whether the Janus kinase(JAK)/STAT1 participated in the regulation of honokiol on HMGB1.The protein expression levels of HMGB1,JAK,and STAT1 were detected using Western blot.Results Mice with SAP had inflammatory injury in the pancreas,bleeding of intestinal tissues,and cells with disrupted histology.Mice in the SAP+HON group had significantly fewer pathological changes.Mice with SAP also had significant increases in the serum levels of amylase,lipase,HMGB1,tumor necrosis factor-α,interleukin-6,diamine oxidase,endotoxin-1,and procalcitonin.Mice in the SAP+HON group did not show these abnormalities(P<0.01).Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability,decreased the levels of junctional adhesion molecule C,and elevated intercellular permeability(P<0.01).HON treatment blocked these effects.Studies of macrophages indicated that LPS led to low nucle

关键词： severe acute pancreatitis intestinal barrier dysfunction honokiol high-mobility group protein B1 Januskinase signal transducerand activatorof transcription1

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