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Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani Nicholas W.Markin Kim F.Duncan Michael J.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of natural resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation.Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based interventions.Important considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical practice.We present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical research.Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation.It is imperative to minimize animal loss during procedures that are surgically complex.We present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

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A case study of continental shelf waves in the northwestern South China Sea induced by winter storms in 2021

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Acta Oceanologica Sinica 2024年第1期43卷 59-69页

作者： Junyi Li Chen Zhou Min Li Quanan Zheng Mingming Li Lingling Xie Laboratory of Coastal Ocean Variation and Disaster Prediction College of Ocean and MeteorologyGuangdong Ocean UniversityZhanjiang 524088China Key Laboratory of Climate Resources and Environments in Continent Shelf Sea and Deep OceanDepartment of Education of Guangdong ProvinceZhanjiang 524088China Key Laboratory of Space Ocean Remote Sensing and Application Ministry of Natural ResourcesBeijing 100081China department of Atmospheric and Oceanic Science University of MarylandCollege ParkMaryland 20742USA

This study aims to investigate characteristics of continental shelf wave(CSW)on the northwestern continental shelf of the South China Sea(SCS)induced by winter storms in 2021.Mooring and cruise observations,tidal gauge data at stations Hong Kong,Zhapo and Qinglan and sea surface wind data from January 1 to February 28,2021 are used to examine the relationship between along-shelf wind and sea level fluctuation.Two events of CSWs driven by the along-shelf sea surface wind are detected from wavelet spectra of tidal gauge data.The signals are triply peaked at periods of 56 h,94 h and 180 h,propagating along the coast with phase speed ranging from 6.9 m/s to18.9 m/s.The dispersion relation shows their property of the Kelvin mode of CSW.We develop a simple method to estimate amplitude of sea surface fluctuation by along-shelf wind.The results are comparable with the observation data,suggesting it is effective.The mode 2 CSWs fits very well with the mooring current velocity data.The results from rare current help to understand wave-current interaction in the northwestern SCS.

关键词： continental shelf waves Ekman transport Kelvin mode wavelet analysis northwestern South China Sea

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Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke

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Neuroscience Bulletin 2024年第1期40卷 65-78页

作者： Fangxi Liu Xi Cheng Chuansheng Zhao Xiaoqian Zhang Chang Liu Shanshan Zhong Zhouyang Liu Xinyu Lin Wei Qiu Xiuchun Zhang department of Neurology.The First Affiliated Hospital of China Medical University Shenyang 110001China department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Stroke Center The First Affiliated Hospital of China Medical UniversityShenyang 110001China

Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia.However,con-ventional bulk sequencing makes it challenging to depict this complex immune network.Using single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune cells.Microglia were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal regeneration.Trajectory inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated MDMs.Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying mechanisms.This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

关键词： Ischemic stroke Monocyte-derived macrophage Microglia Neurogenesis Single-cell sequencing

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Distribution of per-and polyfluoroalkyl substances in blood,serum,and urine of patients with liver cancer and associations with liver function biomarkers

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Journal of Environmental Sciences 2024年第5期139卷 418-427页

作者： Cao Dai Lin Peng Yanjie Li Zhendong Li Da Chen Fei Wang Nan Lin department of Hepatobiliary Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China School of Environment Guangdong Key Laboratory of Environmental Pollution and HealthJinan UniversityGuangzhou 510632China State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China South China Institute of Environmental Sciences MEEGuangzhou 510655China

Studies have shown that per-and polyfluoroalkyl substances(PFASs)may be hepatotoxic in animals or humans.However,data on clinical epidemiology are very limited.In this study,21PFASs were determined in patients with liver diseases,with the highest median concentrations detected in the serum sample(26.7 ng/mL),followed by blood(10.7 ng/mL)and urine(5.02 ng/mL).Higher total PFAS concentrations were found in hepatocellular carcinoma(HCC)patients compared to non-HCC patients,with significant discrepancies in serum and blood samples.Besides,significant correlations were also found among PFAS concentrations and age,gender,body mass index(BMI),and liver function biomarkers levels.For example,PFAS concentrations are significantly higher in males than in females;Several serum PFASs concentrations increase with age and BMI,while the serum perfluorohexane sulfonic acid(PFHxS)concentrations are negatively correlated with age.In addition,multiple regression models adjusted for age,gender and BMI found that increased serum perfluorobutane sulfonic acid(PFBS),perfluoroheptane sulfonic acid(PFHpS)and perfluorohexylphosphonic acid(PFHxPA)conentrations are correlated with elevated alkaline phosphatase(ALP),aspartate aminotransferase(AST),and alpha-fetoprotein(AFP)(p<0.05).Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS.

关键词： Per-and polyfluoroalkyl substances(PFASs) Liver cancer Serum Blood Urine Liver function biomarkers

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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

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Cancer Biology & Medicine 2024年第1期21卷 83-103页

作者： Yumei Wang Haiyan Wang Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang School of Basic Medical Sciences State Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu University of Traditional Chinese MedicineChengdu 611137China department of Pathology School of MedicineQinghai UniversityXining 810001China Omics Biosciences Inc Beijing 100871China Laboratory of Integrative Medicine Clinical Research Center for BreastState Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China State Key Laboratory of Southwestern Chinese Medicine resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity ResearchMedical Center for Comprehensive Weight ControlThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

关键词： Epigenetic regulators breast cancer regulatory network HTS^(2)

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Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

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Chinese Journal of natural Medicines 2024年第3期22卷 265-272页

作者： XU Shuangyu ZHANG Feng TAO Linlan JIANG Yangming HUANG Tao LI Yanan HU Zhanxing YANG Jue HAO Xiaojiang YUAN Chunmao State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang 550025China natural Products Research Center of Guizhou Province Guiyang 550014China State Key Laboratory of Phytochemistry and Plant resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China

Four new sesquiterpene lactones(SLs)(1–4),along with a biosynthetically related SL(5),have been isolated from the leaves of Magnolia grandiflora.Magrandate A(1)is notable as the first C18 homogemarane type SL,featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core.Compounds 2 and 3,representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products,were also identified.The structures of these isolates were elucidated through a combination of spectroscopic data analysis,electronic circular dichroism calculations,and X-ray single-crystal diffraction analysis.All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells.Notably,3–5 showed a significant inhibitory effect on nitric oxide production,with IC50 values ranging from 0.79 to 4.73μmol·L^(−1).Additionally,4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines,with IC50 values between 3.09 and 11.23μmol·L^(−1).

关键词： Magnolia grandiflora Sesquiterpene lactones Isolation and identification Anti-inflammatory activity

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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching Chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng Leung Chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda department of Chemistry City University of Hong KongHong Kong SARChina iGEM team“VarieCure” City University of Hong KongHong Kong SARChina department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC 16872.Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB.Intriguingly,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic window.Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

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A combined denoising method of empirical mode decomposition and singular spectrum analysis applied to Jason altimeter waveforms: A case of the Caspian Sea

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Geodesy and Geodynamics 2022年第4期13卷 327-342页

作者： Wenguan Jiang Wei You Faculty of Geosciences and Environmental Engineering Southwest Jiaotong UniversityChengdu 611756China third geodetic team of the department of natural resources Chengdu 610100China State-Province Joint Engineering Laboratory of Spatial Information Technology for High-Speed Railway Safety Chengdu 610031China

During the satellite pulse propagation and reception, the altimeter waveform is inevitably affected by noise. To reduce the noise level in Jason altimeter waveforms, we used singular spectrum analysis(SSA),empirical mode decomposition(EMD), and the combination of SSA and EMD to obtain the denoised waveforms. The advantages of the combined method were verified and the accuracy of the mean sea surface height(MSSH) model was improved. Comparing the denoising effect of the three methods, the results show that the signal-to-noise ratio(SNR), correlation coefficient and root-mean-square error are effectively improved by the combination of SSA and EMD. The sea surface heights(SSHs) were remeasured with a 50% threshold retracker of denoised waveforms, and the MSSH model of the Caspian Sea with a grid of 1’× 1’was established from the retracked SSHs of Jason-1/2/3. Taking the mean value of the four models as a control, it is found that the model calculated by the combined denoising method has the highest accuracy. This indicates that using the combined denoising method to reduce the noise level is beneficial to improve the accuracy of the MSSH model.

关键词： Altimetry waveforms Jason-1/2/3 Combined method Waveform retracking Mean sea surface height

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Large-scale interplant exchange of macromolecules between soybean and dodder under nutrient stresses

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Plant Diversity 2024年第1期46卷 116-125页

作者： Jingxiong Zhang Shalan Li Wenxing Li Zerui Feng Shuhan Zhang Xijie Zheng Yuxing Xu Guojing Shen Man Zhao Guoyan Cao Xuna Wu Jianqiang Wu department of Economic Plants and Biotechnology Yunnan Key Laboratory for Wild Plant ResourcesKunming Institute of BotanyChinese Academy of SciencesKunming 650201China CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan and Center for Life Science School of Life SciencesYunnan UniversityKunming 650500China

Parasitic plants and their hosts communicate through haustorial connections.Nutrient deficiency is a common stress for plants,yet little is known about whether and how host plants and parasites communicate during adaptation to such nutrient stresses.In this study,we used transcriptomics and proteomics to analyze how soybean(Glycine max)and its parasitizing dodder(Cuscuta australis)respond to nitrate and phosphate deficiency(-N and-P).After-N and-P treatment,the soybean and dodder plants exhibited substantial changes of transcriptome and proteome,although soybean plants showed very few transcriptional responses to-P and dodder did not show any transcriptional changes to either-N or-P.Importantly,large-scale interplant transport of mRNAs and proteins was detected.Although the mobile mRNAs only comprised at most 0.2%of the transcriptomes,the foreign mobile proteins could reach 6.8%of the total proteins,suggesting that proteins may be the major forms of interplant communications.Furthermore,the interplant mobility of macromolecules was specifically affected by the nutrient regimes and the transport of these macromolecules was very likely independently regulated.This study provides new insight into the communication between host plants and parasites under stress conditions.

关键词： Cuscuta Mobile molecules Nutrient deficiency Host plant-parasitic plant interaction Interplant transport Systemic signaling

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Divergent responses of growth rate and antioxidative system of ten Bacillus strains to acid stresses

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Soil Ecology Letters 2024年第1期6卷 107-118页

作者： Xiaoran Shan Jiayi Chen Jiaen Zhang Ziqiang Liu Shufang Chen Hui Wei Key Laboratory of Agro-Environment in the Tropics of Ministry of Agriculture and Rural Affairs Guangdong Laboratory for Lingnan Modern AgricultureCollege of Natural Resources and EnvironmentSouth China Agricultural UniversityGuangzhou 510642China Guangdong Engineering Research Center for Modern Eco-agriculture and Circular Agriculture South China Agricultural UniversityGuangzhou 510642China

Response of growth rate and antioxidative system of ten Bacillus strains to acid stresses was assayed.Strong acid treatment significantly decreased the growth rate of the strains.Acid stresses increased the GPX activity and GSSG content of the tested strains.Divergent changes occurred in ROS and antioxidative system(SOD,CAT,GR,MDA and GSH).Environmental changes including soil acidification exert obvi-ous stresses on soil ecosystems and influence soil microor-ganisms.In this study,ten microbial strains were incubated under different acid treatments to investigate responses of microbial growth and antioxidative system to acid stress.All the strains belong to Bacillus genus,but exhibit distinct ecological functions.We observed that these microbial strains had obviously different pH tolerance threshold,in spite of the close phylogenetic classification among strains.Acid stresses exerted significant effects on microbial antiox-idative system,including superoxide dismutase(SOD),cata-lase(CAT)and glutathione transferring enzymes(GPX and GR)and reactants(GSH and GSSH),but the effects were strain specific.Furthermore,we found acid stress effects on total variances of the investigated microbial antioxidative system along the first two principal components(PCs).Activities of CAT and SOD contributed substantially to PC1 that reflected obvious acid effects on NC7 and ZC4,and closely related to intracellular malondialdehyde content.The GSSG activities and GSH/GSSG contributed greatly to PC2 that unveiled acid stress effects on most of the microbial strains.Our results highlight substantially heterogeneous responses of microbial strains to acid stress and support that phylogenetic closeness does not imply functional similarity of soil microorganisms under environmental changes.

关键词： soil acidification microbial strain acid tolerance capacity microbial growth oxidative stress antioxidative system

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