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Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang xiao-Jiang li xiang-Yu Guo Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

Unconventional Fluorescent and Multi-responsive Polysiloxane:Synthesis,Characterization and Biological Applications

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Chinese Journal of Polymer Science 2024年第5期42卷 579-590,I0006页

作者： xiao-Di li Shu-Sheng li Xu-Bao Jiang xiao-li Zhu xiang Zheng Kong College of Chemistry and Chemical Engineering University of JinanJinan250022China College of Chemical Engineering Tianjin UniversityTianjin300072China Foshan(Southern China)Institute for New Materials Foshan528200China

Owing to their high significance in fundamental study and diverse applications,stimuli-responsive and fluorescent polymers,particularly those with cluster-triggered emission(CTE)featured by non-conjugated chromophores,have drawn tremendous attention in recent years.In this work,fluorescent and multi-responsive polysiloxane(FRPS)was synthesized by hydrolytic condensation polymerization of 3-aminopropyl methyl diethoxysilane(APMS)with 3-(N-isopropyl propionamide)iminopropyl methyl diethoxysilane(APMS-NIP),which was formed in situ through aza-Michael addition between APMS and N-isopropyl acrylamide.FRPS was not only highly sensitive to temperature,pH and CO_(2) in water,but also showed an enhanced and stimuli-adjustable fluorescence emission.The effects of monomer feeding,pH and CO_(2) on its lower critical solution temperature and fluorescent property were investigated.FRPS fluorescence emission was ascribed to CTE mechanism.In addition,FRPS was shown to be highly potential as physiological indicator for cell imaging,and for controlled release and trace detection of doxorubicin.This study provides therefore a type of stimuli-responsive and fluorescent material for potential applications in biomedical fields,and it is also of great significance for understanding of the fluorescence mechanism of polysiloxane-based stimuli-responsive polymers.

关键词： Polysiloxane Multi-responsiveness Cluster-triggered emission Cell imaging Controlled drug release

Unconventional Fluorescent and Multi-responsive Polyethyleneimine with LCST and UCST Behavior:Synthesis,Characterization and Biological Applications

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Chinese Journal of Polymer Science 2024年第6期42卷 826-837页

作者： Feng-Ming Yin li-li Wu Shu-Sheng li xiao-Na Pan xiao-li Zhu Xu-Bao Jiang xiang Zheng Kong College of Chemistry and Chemical Engineering University of JinanJinan250022China Shandong Institute for Product Quality Inspection Jinan250102China College of Chemical Engineering Tianjin UniversityTianjin300072China

Non-aromatic fluorescent and multi-responsive materials,exhibiting inherent fluorescence emission and controlled phase change,have garnered significant attention in recent years.However,the underlying interaction between their fluorescent properties and phase transition remains unclear.In this study,we synthesized a series of catalyst-free aza-Michael addition-based polyethyleneimine(RFPEI)materials by reacting polyethyleneimine(PEI)with N-isopropyl acrylamide(NIPAM).The resulting RFPEI was comprehensively characterized,and demonstrated dual-phase transition behavior(LCST and UCST)in water,which could be finely tuned by adjusting its composition or external factors such as pH.Notably,upon UV irradiation(365 nm),RFPEI exhibited strong fluorescence emission.We further investigated the effects of NIPAM grafting percentage to PEI,polymer concentration,and pH on the LCST/UCST and fluorescent properties of RFPEI aqueous solutions.Moreover,we showcased the great potential of RFPEI as a versatile tool for physiological cell imaging,trace detection,and controlled release of doxorubicin.Our study presents a novel class of stimuli-responsive fluorescent materials with promising applications in the field of biomedicine.

关键词： Polyethyleneimine Multi-responsiveness Intrinsic fluorescence emission Cell imaging Controlled drug release

Development and validation of a nomogram model for predicting the risk of pre-hospital delay in patients with acute myocardial infarction

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World Journal of Cardiology 2024年第2期16卷 80-91页

作者： Jiao-Yu Cao li-xiang Zhang xiao-Juan Zhou Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina

BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium.Timely medical contact is critical for successful AMI treatment,and delays increase the risk of death for patients.Pre-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains difficult.This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment outcomes.AIM To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk.METHODS A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022.The study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio.Independent risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with AMI.The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups.RESULTS Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(Plidation groups,respectively,demonstrating the model's good discriminatory ability.The Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both

关键词： Pre-hospital delay Acute myocardial infarction Risk prediction Nomogram

Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 299-310页

作者： liU xiao-rong li Shuo-fu MEI Wen-ya liU xiang-dan ZHOU Ri-bao College of Pharmacy Hunan University of Chinese MedicineChangsha(410208)China Department of Orthopaedics The First Hospital of Hunan University of Chinese MedicineChangsha(410007)China

Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function.RA-FLS viability,migration,and invasion were evaluated.Moreover,a collagen-induced arthritis(CIA)rat model was established.Rats were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,respectively.Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats.The levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial tissue.Molecular docking was also used to analyze the binding of isorhamnetin to SRC.Results In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(Plity,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial inflammation.Isorhamnetin reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CREB in synovial tissue(P<0.05).Notably,the inhibit

关键词： rheumatoid arthritis isorhamnetin SRC/ERK/CREB matrix metalloproteinase

Sensitivity impacts owing to the variations in the type of zero-range pairing forces on the fission properties using the density functional theory

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Nuclear Science and Techniques 2024年第3期35卷 198-207页

作者： Yang Su Ze-Yu li li-Le liu Guo-xiang Dong xiao-Bao Wang Yong-Jing Chen China Nuclear Data Center China Institute of Atomic EnergyBeijing 102413China School of Science Huzhou UniversityHuzhou 313000China

Using the Skyrme density functional theory,potential energy surfaces of^(240)Pu with constraints on the axial quadrupole and octupole deformations(q_(20)and q_(30))were calculated.The volume-like and surface-like pairing forces,as well as a combination of these two forces,were used for the Hartree–Fock–Bogoliubov approximation.Variations in the least-energy fission path,fission barrier,pairing energy,total kinetic energy,scission line,and mass distribution of the fission fragments based on the different forms of the pairing forces were analyzed and discussed.The fission dynamics were studied based on the timedependent generator coordinate method plus the Gaussian overlap approximation.The results demonstrated a sensitivity of the mass and charge distributions of the fission fragments on the form of the pairing force.Based on the investigation of the neutron-induced fission of^(239)Pu,among the volume,mixed,and surface pairing forces,the mixed pairing force presented a good reproduction of the experimental data.

关键词： Nuclear fission Density functional theory Pairing force Potential energy surfaces Fission fragment distribution

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

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Cancer Biology & Medicine 2024年第5期21卷 363-381页

作者： Can Xu Pengyu Hou xiang li Menglin xiao Ziqi Zhang Ziru li Jianglong Xu Guoming liu Yanli Tan Chuan Fang School of Clinical Medicine Hebei University Department of Neurosurgery Affiliated Hospital of Hebei University Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma School of Basic Medical Sciences Hebei University Department of Pathology Affiliated Hospital of Hebei University

Among central nervous system-associated malignancies, glioblastoma(GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.

关键词： Glioblastoma characteristic classification mesenchymal transition molecular phenotype

Construction of daily precipitation series and the observational characteristics of extreme precipitation in Tianjin,China during 1888-2022

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Advances in Climate Change Research 2024年第1期15卷 52-61页

作者： Peng SI Qing-xiang li xiao-Yang CHEN Min WANG Chuan-Jun LUO Tianjin Meteorological Information Center Tianjin Meteorological BureauTianjin 300074China Research Centerfor Ecology and Environment of Central Asia Chinese Academy of SciencesWulumuqi 830011China School of Atmospheric Sciences Sun Yat-sen UniversityZhuhai 528478China Key Laboratory of Tropical Amosphere-Ocean System Ministry of EducationZhuhai 528478China Shaoguan Meteorological Service Shaoguan 512028China

Given the difficulties in rescuing and ensuring the quality of long-term climate data,current studies on century-scale climate change are usually limited to annual and monthly data,resulting in the poor detection of extreme climate events and their changes before 1950.In this study,we reconstructed a daily precipitation series for Tianjin from 15 September 1887 to 31 December 2022 on the basis of the most comprehensive daily precipitation records collected from the Tianjin Meteorological Archive,China,and in reference to the precipitation analysis results based on the datasets developed by the Climatic Research Unit Time-Series version 4.06,Global Precipitation Climatology Centre and University of Delaware along with the application of various homogenisation methods for climate series.Our approach provides a complete and reliable century-long daily precipitation series for the study of regional or local extreme weather and climate events.The reconstructed daily dataset reveals that the annual precipitation amount and R95 intensity in Tianjin during 1888-2022 lack significant trends and have values of 0.74±6.99 and-1.84±3.22 mm per decade,respectively.On the annual and seasonal scales,the precipitation amount and R95 intensity,particularly those in autumn,have increased since the latter half of the 20th century relative to those in 1888-1950.However,the increase in precipitation amount and R95 intensity is relatively limited compared with that in atmospheric water vapour content due to surface warming,indicating the highly sensitive response of extreme precipitation events to warming.In addition,the estimates for the return periods of 5,10,20,50 and 100 years covering 1888-2022,1888-1950 and 1951-2022 depict that the intensity of heavy rain and above magnitude was highest in 1888-1950 and decreased in 1951-2022.

关键词： Over a century-long timescale Daily precipitation series Extreme precipitation Return period

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients:a single-centre study

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Chinese Journal of Natural Medicines 2024年第1期22卷 89-96页

作者： xiao Yongjiu li Binbin liU Chang HUANG Xiuyu MA ling QIAN Zhirong ZHANG xiaopeng ZHANG Qian li Dunqing CAI xiaoqing YAN xiangyong LUO Shuping xiang Dawei xiao Kun Emergency Department the 940th Hospital of Jiont Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Scientific Research Center the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China School of Medicine Nankai universityTianjin 300000China Department of Cardiology the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350000China Department of Traditional Chinese Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Geriatric Diseases the Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China Health and Sport Administration Muskingum UniversityOhioanUSA Laboratory of Vaccine and Antibody Engineering Beijing Institute of BiotechnologyBeijing 100071China Department of Pulmonary and Critical Care Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Center of Pulmonary&Critical Care Medicine Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China

As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational study.All patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct treatment.Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed.Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.

关键词： COVID-19 Pneumonia Novel coronavirus Critically ill Traditional Chinese medicine Clinical outcome