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Magnetically labeled mesenchymal stem cells after autologous transplantation into acutely injured liver

World Journal of Gastroenterology 2010年第29期16卷 3674-3679页

作者： Xiao-Lei Shi jin-yang gu Bing Han Hai-Yun Xu Liang Fang Yi-Tao Ding Jiangsu Province s Key Medical Center for Hepatobiliary Disease Nanjing 210008 Jiangsu Province China Department of Hepatobiliary Surgery the Af��liated DrumTower Hospital of Nanjing UniversityMedical SchoolNanjing 210008Jiangsu ProvinceChinaJin-Yang GuHai-Yun XuDepartment of Hepatobiliary SurgeryDrumTower Clinical Medical College of Nanjing MedicalUniversityNanjing210008JiangsuProvinceChina

AIM:To evaluate tracking of magnetically labeled mesenchymal stem cells(MSCs) after intraportal transplantation.METHODS:Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifugation,cultured and expanded,after which,they were incubated with super paramagnetic iron oxide(SPIO).Prussian blue staining was performed to highlight intracellular iron.To establish swine models of acute liver injury,0.5 g/kg D-galactosamine was administrated to 10 pigs,six of which were injected via their portal veins with SPIO-labeled MSCs,while the remaining four were injected with unlabeled cells.Magnetic resonance imaging(MRI) was performed with a clinical 1.5T MR scanner immediately before transplantation and 6 h,3 d,7 d and 14 d after transplantation.Prussian blue staining was again performed with the tissue slices at the endpoint.RESULTS:Prussian blue staining of SPIO-labeled MSCs had a labeling efficiency of almost 100%.Signal intensity loss in the liver by SPIO labeling on the FFE(T2*WI) sequence persisted until 14 d after transplantation.Histological analysis by Prussian blue staining confirmed homing of labeled MSCs in the liver after 14 d;primarily distributed in hepatic sinusoids and liver parenchyma.CONCLUSION:MSCs were successfully labeled with SPIO in vitro.MRI can monitor magnetically labeled MSCs transplanted into the liver.

关键词： Magnetic resonance imaging Mesenchymal stem cells Super paramagnetic iron oxide Stem cell transplantation

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Influence of chitosan nanofiber scaffold on porcine endogenous retroviral expression and infectivity in pig hepatocytes

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World Journal of Gastroenterology 2011年第22期17卷 2774-2780页

作者： Bing Han Xiao-Lei Shi Jiang-Qiang Xiao Yue Zhang Xue-Hui Chu jin-yang gu Jia-Jun Tan Zhong-Ze gu Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina Department of Hepatobiliary Surgery Drum Tower Clinical Medical College of Nanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina State Key Laboratory of Bioelectronics Southeast UniversityNanjing 210000Jiangsu ProvinceChina

AIM: To investigate the influence of chitosan nanofiber scaffold on the production and infectivity of porcine endogenous retrovirus (PERV) expressed by porcine hepatocytes. METHODS: Freshly isolated porcine hepatocytes were cultured with or without chitosan nanofiber scaffold (defined as Nano group and Hep group) for 7 d. The daily collection of culture medium was used to detect reverse transcriptase (RT) activity with RT activity assaykits and PERV RNA by reverse transcription-polymerase chain reaction (PCR) and real time PCR with the PERV specific primers. And Western blotting was performed with the lysates of daily retrieved cells to determine the PERV protein gag p30. Besides, the in-vitro infectivity of the supernatant was tested by incubating the human embryo kidney 293 (HEK293) cells. RESULTS: The similar changing trends between two groups were observed in real time PCR, RT activity assay and Western blotting. Two peaks of PERV expression at 10H and Day 2 were found and followed by a regular decline. No significant difference was found between two groups except the significantly high level of PERV RNA at Day 6 and PERV protein at Day 5 in Nano group than that in Hep group. And in the in-vitro infection experiment, no HEK293 cell was infected by the supernatant. CONCLUSION: Chitosan nanofiber scaffold might prolong the PERV secreting time in pig hepatocytes but would not obviously influence its productive amount and infectivity, so it could be applied in the bioartificial liver without the increased risk of the virus transmission.

关键词：猪内源性逆转录病毒纳米纤维肝细胞壳聚糖感染性 Western印迹法支架 HEK293细胞

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Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

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World Journal of Gastroenterology 2011年第19期17卷 2397-2406页

作者： Xiao-Lei Shi jin-yang gu Yue Zhang Bing Han Jiang-Qiang xiao Xian-Wen Yuan Ning Zhang Yi-Tao Ding Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China Jiangsu Provin- cial Key Medical Center for Hepatobiliary Diseases Nanjing 210008 Jiangsu Province China Jiangsu Key Labora- tory of Molecular Medicine Nanjing 210008 Jiangsu Province Jiangsu Province China Institute of Hepa- tobiliary Surgery Nanjing University Nanjing 210008 Jiangsu Province China Department of Hepatobiliary Surgery Drum Tower Clinical Medical College of Nanjing Medical University Nan- jing 210008 Jiangsu Province China Center for Artificial Liver Therapy Nanjing Sec- ond Hospital Naniing 210008 Jiangsu Province China

AIM:To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-onchronic liver failure (ACLF) patients.METHODS:Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture,respectively.Chemokine profile was also examined for the normal serum and liver failure serum.RESULTS:Hepatocyte growth factor (HGF) and Tumor necrosis factor;tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased.Liver failure serum samples induced a higher detachment rate,lower viability and decreased liver support functions in the homo-hepatocyte culture.Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro.In addition,cocultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.CONCLUSION:ACLF serum does not impair the cell morphology,viability,proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.

关键词：肝细胞生长因子骨髓干细胞 ACLF 体外培养人血清细胞增殖代谢功能保护作用

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Evaluation of a novel hybrid bioartificial liver based on a multi-layer flat-plate bioreactor

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World Journal of Gastroenterology 2012年第28期18卷 3752-3760页

作者： Xiao-Lei Shi Yue Zhang Xue-Hui Chu Bing Han jin-yang gu Jiang-Qiang Xiao Jia-Jun Tan Zhong-Ze gu Hao-Zhen Ren Xian-Wen Yuan Yi-Tao Ding Department of Hepatobiliary Surgery Jiangsu Province's Key Medical Center for Hepatobiliary Disease The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China State Key Laboratory of Bioelectronics Southeast University Nanjing 210008 Jiangsu Province China

AIM: To evaluate the efficacy and safety of a hybrid bioartificial liver (HBAL) system in the treatment of acute liver failure. METHODS: Canine models with acute liver failure were introduced with intravenous administration of D-galactosamine. The animals were divided into: the HBAL treatment group (n = 8), in which the canines received a 3-h treatment of HBAL; the bioartificial liver (BAL) treatment group (n = 8), in which the canines received a 3-h treatment of BAL; the non-bioartificial liver (NBAL) treatment group (n = 8), in which the canines received a 3-h treatment of NBAL; the control group (n = 8), in which the canines received no additional treatment. Biochemical parameters and survival time were determined. Levels of xenoantibodies, RNA of porcine endogenous retrovirus (PERV) and reverse transcriptase (RT) activity in the plasma were detected. RESULTS: Biochemical parameters were significantly decreased in all treatment groups. The TBIL level in the HBAL group was lower than that in other groups (2.19 ± 0.55 mmol/L vs 24.2 ± 6.45 mmol/L, 12.47 ± 3.62 mmol/L, 3.77 ± 1.83 mmol/L, P < 0.05). The prothrombin time (PT) in the BAL and HBAL groups was significantly shorter than the NBAL and control groups (18.47 ± 4.41 s, 15.5 ± 1.56 s vs 28.67 ± 5.71 s, 21.71 ± 3.4 s, P < 0.05), and the PT in the HBAL group was shortest of all the groups. The albumin in the BAL and HBAL groups significantly increased and a significantly higher level was observed in the HBAL group compared with the BAL group (27.7 ± 1.7 g/L vs 25.24 ± 1.93 g/L). In the HBAL group, the ammonia levels significantly decreased from 54.37 ± 6.86 to 37.75 ± 6.09 after treatment (P < 0.05); there were significant difference in ammonia levels between other the groups (P < 0.05). The levels of antibodies were similar before and after treatment. The PERV RNA and the RT activity in the canine plasma were all negative. CONCLUSION: The HBAL showed great efficiency and safety in the treatment of acute liver failure.

关键词：生物人工肝混合型生物反应器评价猪内源性逆转录病毒肝功能衰竭平板基础

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Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review

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Neural Regeneration Research 2024年第6期19卷 1221-1232页

作者： Dandan Chu Xingyue yang jing Wang Yan Zhou jin-Hua gu jin Miao Feng Wu Fei Liu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products Coinnovation Center of Neuroregeneration Nantong University 2. Department of Pharmacology School of Pharmacy Nantong University 3. Department of Biochemistry and Molecular Biology School of Medicine Nantong University 4. Department of Clinical Pharmacy Affiliated Maternity and Child Health Care Hospital of Nantong University Nantong University 5. Laboratory of Animal Center Nantong University Department of Neurochemistry Inge Grundke-Iqbal Research Floor New York State Institute for Basic Research in Developmental Disabilities

Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubuleassociated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease.

关键词： Alzheimer's disease cleavage site diagnosis marker neurofibrillary tangles phosphorylation Tau Tau aggregation therapy truncation

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Layered Structural PBAT Composite Foams for Efficient Electromagnetic Interference Shielding

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Nano-Micro Letters 2024年第2期16卷 273-286页

作者： Jianming yang Hu Wang Yali Zhang Hexin Zhang Junwei gu School of Chemistry and Chemical Engineering Anhui University of TechnologyMa’anshanAnhui 243032People’s Republic of China Shaanxi Key Laboratory of Macromolecular Science and Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072ShaanxiPeople’s Republic of China School of Materials Science and Engineering Jiangsu University of Science and TechnologyZhenjiang 212003JiangsuPeople’s Republic of China

The utilization of eco-friendly,lightweight,high-efficiency and high-absorbing electromagnetic interference(EMI)shielding composites is imperative in light of the worldwide promotion of sustainable manufacturing.In this work,magnetic poly(butyleneadipate-coterephthalate)(PBAT)microspheres were firstly synthesized via phase separation method,then PBAT composite foams with layered structure was constructed through the supercritical carbon dioxide foaming and scraping techniques.The merits of integrating ferroferric oxideloaded multi-walled carbon nanotubes(Fe3O4@MWCNTs)nanoparticles,a microcellular framework,and a highly conductive silver layer have been judiciously orchestrated within this distinctive layered configuration.Microwaves are consumed throughout the process of“absorption-reflection-reabsorption”as much as possible,which greatly declines the secondary radiation pollution.The biodegradable PBAT composite foams achieved an EMI shielding effectiveness of up to 68 dB and an absorptivity of 77%,and authenticated favorable stabilization after the tape adhesion experiment.

关键词： Electromagnetic interference shielding Layered structure Supercritical carbon dioxide foaming Poly(butyleneadipateco-terephthalate) Microcellular

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Automatic velocity picking based on optimal key points tracking algorithm

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Petroleum Science 2024年第2期21卷 903-917页

作者： Yong-Hao Wang Wen-Kai Lu Song-Bai jin yang Li Yu-Xuan Li Xiao-Feng gu The Institute for Artificial Intelligence(THUAI) Tsinghua UniversityBeijing100084China State Key Laboratory of Intelligent Technology and Systems Tsinghua UniversityBeijing100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing100084China The Department of Automation Tsinghua UniversityBeijing100084China

Picking velocities from semblances manually is laborious and necessitates experience. Although various methods for automatic velocity picking have been developed, there remains a challenge in efficiently incorporating information from nearby gathers to ensure picked velocity aligns with seismic horizons while also improving picking accuracy. The conventional method of velocity picking from a semblance volume is computationally demanding, highlighting a need for a more efficient strategy. In this study, we introduce a novel method for automatic velocity picking based on multi-object tracking. This dynamic tracking process across different semblance panels can integrate information from nearby gathers effectively while maintaining computational efficiency. First, we employ accelerated density clustering on the velocity spectrum to discern cluster centers without the requirement for prior knowledge regarding the number of clusters. These cluster centers embody the maximum likelihood velocities of the main subsurface structures. Second, our proposed method tracks key points within the semblance volume. Kalman filter is adopted to adjust the tracking process, followed by interpolation on these tracked points to construct the final velocity model. Our synthetic data example demonstrates that our proposed algorithm can effectively rectify the picking errors of the clustering algorithm. We further compare the performances of the clustering method(CM), the proposed tracking method(TM), and the variational method(VM) on a field dataset from the gulf of Mexico. The results attest that our method offers superior accuracy than CM, achieves comparable accuracy with VM, and benefits from a reduced computational cost.

关键词： Velocity picking Multi-object tracking Density clustering Kalman filter

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A"messenger zone hypothesis"based on the visual three-dimensional spatial distribution of motoneurons innervating deep limb muscles

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Neural Regeneration Research 2024年第7期19卷 1559-1567页

作者： Chen Huang Shen Wang jin Deng Xinyi gu Shuhang guo Xiaofeng Yin MoE Key Laboratory for Trauma Treatment and Nerve Regeneration Peking UniversityBeijingChina Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneuro ns.Howeve r,current research on the spatial location of the spinal motoneurons innervating differe nt muscles is limited.In this study,we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs,which were innervated by the obturator nerve,femoral nerve,inferior gluteal nerve,deep pe roneal nerve,and tibial nerve.Locations were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared o rgans(3DISCO)and 3-D imaging technology based on lightsheet fluorescence microscopy(LSFM).Additionally,we propose the hypothesis that"messenger zones"exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle groups.We hypothesize that these interlaced neurons may participate in muscle coordination as messenger neurons.Analysis revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the mouse.Not only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles,but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

关键词： 3-D imaging motoneurons multiple retrograde tracing muscle coordination skeletal muscle spatial distribution optical tissue clearing

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Comparison of brain functions between healthy participants and methamphetamine users with various addiction histories:Data analysis based on EEG and fNIRS

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Journal of Innovative Optical Health Sciences 2024年第3期17卷 41-55页

作者： Xuelin gu Xiaoou Li Banghua yang College of Medical Instruments Shanghai University of Medicine&Health SciencesShanghai 201318P.R.China School of Mechanical and Electrical Engineering and Automation Shanghai UniversityShanghai 200444P.R.China

The electroencephalogram(EEG)rhythm and functional near-infrared spectroscopy(fNIRS)activation levels have not been compared between a healthy control group(HCG)and methamphetamine user group(MUG)with different addiction histories.This study used 64-electrode EEG and fNIRS to conduct an experiment that analyzed the resting and craving states.The EEG and fNIRS data of 56 participants were collected,including 14 healthy participants,14 methamphetamine users with an addiction history of 0.5–5 years,14 users with an addiction history of 5–10 years,and 14 users with an addiction history of 10–15 years.Isolated effective coherence(iCoh)within the brain network was used to process the EEG data.Statistical analysis was performed to compare differences in iCoh among the delta,theta,alpha,beta,and gamma bands and explore oxyhemoglobin activation levels in the ventrolateral prefrontal cortex,dorsolateral prefrontal cortex,orbitofrontal cortex,and frontopolar prefrontal cortex(FPC)of the control group.Finally,the Kmeans,Gaussian mixed model(GMM),linear discriminant analysis(LDA),support vector machine(SVM),Bayes,and convolutional neural networks(CNN)algorithms were used to classify methamphetamine users based on drug and neutral images.A 3-class accuracy was achieved.Changes in EEG and fNIRS activation levels of HCG and MUG with varied addiction histories were demonstrated.

关键词： Drug addiction history electroencephalogram functional near-infrared spectroscopy isolated effective coherence addiction history classification

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Byzantine Robust Federated Learning Scheme Based on Backdoor Triggers

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Computers, Materials & Continua 2024年第5期79卷 2813-2831页

作者： Zheng yang Ke gu Yiming Zuo School of Computer and Communication Engineering Changsha University of Science and TechnologyChangsha410114China

Federated learning is widely used to solve the problem of data decentralization and can provide privacy protectionfor data owners. However, since multiple participants are required in federated learning, this allows attackers tocompromise. Byzantine attacks pose great threats to federated learning. Byzantine attackers upload maliciouslycreated local models to the server to affect the prediction performance and training speed of the global model. Todefend against Byzantine attacks, we propose a Byzantine robust federated learning scheme based on backdoortriggers. In our scheme, backdoor triggers are embedded into benign data samples, and then malicious localmodels can be identified by the server according to its validation dataset. Furthermore, we calculate the adjustmentfactors of local models according to the parameters of their final layers, which are used to defend against datapoisoning-based Byzantine attacks. To further enhance the robustness of our scheme, each localmodel is weightedand aggregated according to the number of times it is identified as malicious. Relevant experimental data showthat our scheme is effective against Byzantine attacks in both independent identically distributed (IID) and nonindependentidentically distributed (non-IID) scenarios.

关键词： Federated learning Byzantine attacks backdoor triggers

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