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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU tong qiao yan-fang GU Shu-xiao CHAI xin-lou School of Traditional Chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Digital measuring the ocular morphological parameters of guinea pig eye in vivo with Python

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 239-246页

作者： Yue Di Zhong-Bao qiao Hai-Yun Ye xin-Yue Li wen-Ting Luo Wang-Yi Fang tong qiao Department of Ophthalmology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China

AIM:To quantitatively measure ocular morphological parameters of guinea pig with Python ***:Thirty-six eyeballs of eighteen 3-weekold guinea pigs were measured with keratometer and photographed to obtain the horizontal,coronal,and sagittal planes *** corresponding photo pixels-actual length ratio was acquired by a proportional *** edge coordinates were identified artificially by ginput *** and conic curve fitting were applied to fit the contour of the eyeball in the sagittal,coronal and horizontal *** curvature,curvature radius,eccentricity,tilt angle,corneal diameter,and binocular separation angle were calculated according to the geometric ***,the eyeballs were removed,canny edge detection was applied to identify the contour of eyeball in *** results were compared between in vivo and in ***:Regarding the corneal curvature and curvature radius on the horizontal and sagittal planes,no significant differences were observed among results in vivo,in vitro,and the *** horizontal and vertical binocular separation angles were 130.6°±6.39°and 129.8°±9.58°*** the corneal curvature radius and eccentricity in vivo,significant differences were observed between horizontal and vertical ***:The Graphical interface window of Python makes up the deficiency of edge detection,which requires too much definition in *** are significant differences between guinea pig and human beings,such as exotropic eye position,oblique oval eyeball,and obvious discrepancy of *** study helps evaluate objectively the ocular morphological parameters of small experimental animals in emmetropization research.

关键词： ocular morphological parameters guinea pig digital measurement Python

Optimal proportioning of iron ore in sintering process based on improved multi-objective beluga whale optimisation algorithm

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Journal of Iron and Steel Research International 2024年第7期31卷 1597-1609页

作者： Zong-ping Li Xu-dong Li Xue-tong yan Wu wen Xiao-xin Zeng Rong-jia Zhu Ya-hui Wang Ling-zhi Yi Zhongye Changtian International Engineering Co. Ltd.Changsha 410205HunanChina College of Automation and Electronic Information Xiangtan UniversityXiangtan 411105HunanChina College of Electrical and Information Engineering Hunan UniversityChangsha 410082HunanChina

Proportioning is an important part of sintering,as it affects the cost of sintering and the quality of sintered *** address the problems posed by the complex raw material information and numerous constraints in the sintering process,a multi-objective optimisation model for sintering proportioning was established,which takes the proportioning cost and TFe as the optimisation ***,an improved multi-objective beluga whale optimisation(IMOBWO)algorithm was proposed to solve the nonlinear,multi-constrained multi-objective optimisation *** algorithm uses the con-strained non-dominance criterion to deal with the constraint problem in the ***,the algorithm employs an opposite learning strategy and a population guidance mechanism based on angular competition and two-population competition strategy to enhance convergence and population *** actual proportioning of a steel plant indicates that the IMOBWO algorithm applied to the ore proportioning process has good convergence and obtains the uniformly distributed Pareto ***,compared with the actual proportioning scheme,the proportioning cost is reduced by 4.3361¥/t,and the TFe content in the mixture is increased by 0.0367%in the optimal compromise ***,the proposed method effectively balances the cost and total iron,facilitating the comprehensive utilisation of sintered iron ore resources while ensuring quality assurance.

关键词： Sintering process Proportioning Iron ore Multi-objective beluga whale optimisation algorithm Proportioning cost

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening

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Current Medical Science 2024年第4期44卷 748-758页

作者： Shan-shan HU tong-yao WANG Lu NI Fan-xin HU Bo-wen YUE Ying ZHENG Tian-lun WANG Abhishek KUMAR yan-yan WANG Jin-e WANG Zhi-yong ZHOU Third-grade Pharmacological Laboratory of Traditional Chinese Medicine State Administration of Traditional Chinese MedicineChina Three Gorges UniversityYichang 443002China College of Medicine and Health Sciences China Three Gorges UniversityYichang 443002China College of Basic Medical Science China Three Gorges UniversityYichang 443002China

Objective Icariin(ICA)has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging *** dysfunction is associated with brain aging-related neurodegenerative *** opening of the mitochondrial permeability transition pore(mPTP)is a crucial factor in mitochondrial dysfunction and is associated with excessive *** study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose(D-gal)-induced cell injury *** A cell model of neuronal injury was established in rat pheochromocytoma cells(PC12 cells)treated with 200 mmol/L D-gal for 48 *** this cell model,PC12 cells were pre-treated with different concentrations of ICA for 24 *** was used to detect cell *** associatedβ-galactosidase(SA-β-Gal)staining was used to observe cell *** blot analysis was performed to detect the expression levels of a senescence-related protein(p21),autophagy markers(LC3B,p62,Atg7,Atg5 and Beclin 1),mitochondrial fission and fusion-related proteins(Drp1,Mfn2 and Opa1),and mitophagy markers(Pink1 and Parkin).The changes of autophagic flow were detected by using mRFP-GFP-LC3 *** intracellular ultrastructure was observed by transmission electron *** was used to detect mPTP,mitochondrial membrane potential(MMP),mitochondrial reactive oxygen species(mtROS)and ROS *** and apoptosis levels were detected by flow *** D-gal treatment significantly decreased the viability of PC12 cells,and markedly increased the SA-β-Gal positive cells as compared to the control *** the D-gal stimulation,the expression of p21 was significantly ***,D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 ***,autophagosomes and autolysosomes were significantly increased,indicating abnormal activation of autophag

关键词： icariin neuronal injury mitochondrial dysfunction mitochondrial permeability transition pore autophagy

Innovative 3D Microfluidic Intestinal Organoid Model for Assessing Cadmium Bioavailability in Food: Implications for Enhanced Exposure Risk Assessment

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Food Science and Human Wellness 2024年

作者： yan Li wen Sun qiao Wang Wan Shi Yu Chen Zhiyong Gong Xiao Guo xin Liu Yongning Wu Key Laboratory of Animal Biological Products & Genetic Engineering， Ministry of Agriculture and Rural， Sinopharm Animal Health Corporation Ltd. State Key Laboratory of Novel Vaccines for Emerging Infectious Diseases， China National Biotec Group Company Limited Key Laboratory for Deep Processing of Major Grain and Oil (The Chinese Ministry of Education)， College of Food Science and Engineering， Wuhan Polytechnic University Department of Oncology， Xiangya Hospital， Central South University NHC Key Laboratory of Food Safety Risk Assessment， China National Center for Food Safety Risk Assessment

Given the severe toxicity and widespread presence of cadmium (Cd) in staple foods such as rice， accurate dietary exposure assessments are imperative for public health. In vitro bioavailability is commonly used to adjust dietary exposure levels of risk factors; however， traditional planar Transwell models have limitations， such as cell dedifferentiation and lack of key intestinal components， necessitating a more physiologically relevant in vitro platform. This study introduces an innovative three-dimensional (3D) intestinal organoid model using a microfluidic chip to evaluate Cd bioavailability in food. Caco-2 cells were cultured on the chip to mimic small intestinal villi's 3D structure， mucus production， and absorption functions. The model's physiological relevance was thoroughly characterized， demonstrating the formation of a confluent epithelial monolayer with well-developed tight junctions (ZO-1)， high microvilli density (F-actin)， and significant mucus secretion (Alcian blue staining)， closely resembling the physiological intestinal epithelium. Fluorescent particle tracking confirmed its ability to simulate intestinal transport and diffusion. The Cd bioavailability in rice measured by the 3D intestinal organoid model (9.07% ± 0.21%) was comparable to the mouse model (12.82% ± 3.42%) but significantly lower than the Caco-2 monolayer model (26.97% ± 1.11%). This 3D intestinal organoid model provides a novel and reliable strategy for in vitro assessment of heavy metal bioavailability in food， with important implications for food safety and risk assessment.

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In-flight Energy Calibration of the GECAM Gamma-ray Detectors

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Research in Astronomy and Astrophysics 2024年第10期24卷 48-57页

作者： Rui qiao Dong-Ya Guo wen-Xi Peng yan-Qiu Zhang Shuo Xiao Shao-Lin Xiong Chao Zheng Chao-yang Li Jia-Cong Liu Wang-Chen Xue Jian-Jian He Zheng-Hua An Da-Li Zhang xin-qiao Li Li-Ming Song Shi-Jie Zheng Ke Gong Ya-Qing Liu xin-Ying Song Xiao-Yun Zhao Xiang-yang wen yan-Bing Xu Xiang Ma Xiao-Bo Li Ping Wang Yue Huang Ce Cai Qi-Bin Yi Yi Zhao Chen-Wei Wang Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China China West Normal University Nanchong 637002China Xiangtan University Xiangtan 411105China Beijing Normal University Beijing 100875China

The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)mission is designed to monitor the Gamma-Ray Bursts(GRBs)associated with gravitational waves and other high-energy transient *** mission consists of two microsatellites which are planned to operate at the opposite sides of the *** GECAM satellite could detect and localize GRBs in about 8 keV-5 MeV with its 25 Gamma-Ray Detectors(GRDs).In this work,we report the in-flight energy calibration of GRDs using the characteristic gamma-ray lines in the background spectra,and show their performance evolution during the commissioning ***,a preliminary cross-calibration of energy response with Fermi GBM data is also presented,validating the energy response of GRDs.

关键词： (stars:)gamma-ray burst:general instrumentation:detectors methods:data analysis

Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation

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Plant Communications 2024年第3期5卷 31-46页

作者： Junfeng Cao Zhiwen Chen Luyao Wang Ning yan Jialing Lin Lipan Hou Yongyan Zhao Chaochen Huang Tingting wen Chenyi Li Saeed ur Rahman Zehui Liu Jun qiao Jianguo Zhao Jie Wang yannan Shi Wei Qin tong Si Yuliang Wang Kexuan Tang Frontiers Science Center for Transformative Molecules Joint International Research Laboratory of Metabolic and Developmental SciencesPlant Biotechnology Research CenterFudan-SJTU Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Engineering Research Center of Coal-based Ecological Carbon Sequestration Technology of the Ministry of Education Key Laboratory of Graphene Forestry Application of National Forest and Grass AdministrationShanxi Datong UniversityDatong 037009China National Key Laboratory of Plant Molecular Genetics Institute of Plant Physiology and Ecology/CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 200032China Hainan Institute Zhejiang UniversityYongyou Industry ParkYazhou Bay Sci-Tech CitySanya 572000China College of Agriculture and Biotechnology Zhejiang UniversityHangzhou 310058China Shandong Provincial Key Laboratory of Dryland Farming Technology College of AgronomyQingdao Agricultural UniversityQingdao 266109China Institute of Millet Crops Hebei Academy of Agriculture&Forestry Sciences/Hebei Branch of China National Sorghum Improvement CenterShijiazhuang 050035China

We investigated the effects of graphene on the model herb Artemisia annua,which is renowned for produc-ing artemisinin,a widely used pharmacological *** growth and biomass were promoted when *** was cultivated with low concentrations of graphene,an effect which was attributed to a 1.4-fold increase in nitrogen uptake,a 15%–22%increase in chlorophyllfluorescence,and greater abun-dance of carbon cycling–related *** to 10 or 20 mg/L graphene resulted in a�60%increase in H2O2,and graphene could act as a catalyst accelerator,leading to a 9-fold increase in catalase(CAT)ac-tivity in vitro and thereby maintaining reactive oxygen species(ROS)***,graphene exposure led to an 80%increase in the density of glandular secreting trichomes(GSTs),in which artemisinin is biosynthesized and *** contributed to a 5%increase in artemisinin content inmature ***-estingly,expression of miR828 was reduced by both graphene and H2O2 treatments,resulting in induction of its target gene AaMYB17,a positive regulator of GST *** molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA(miRNA)biogenesis through Dicers and regulates the miR828–AaMYB17 module,thus affecting GST *** results suggest that graphene may contribute to yield improvement in *** via dynamic physiological processes together with miRNA regulation,and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

关键词： Artemisia annua artemisinin glandular secreting trichomes GSTs miRNA graphene

Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population

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Journal of Geriatric Cardiology 2024年第6期21卷 642-650页

作者： xin-Yu WANG Chao-Ying MIAO Xiao-Fei YE wen-Yuan-Yue WANG Jia-Bo ZHU Yi ZHOU yan LI Ji-Guang WANG School of Public Health Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Cardiovascular Medicine Centre for Epidemiological Studies and Clinical TrialsThe Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese *** The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry ***)and the composition of fatty acids(poly-unsaturated ***-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum *** The 1186 study participants had a mean age of 70.9±5.4 *** mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,*** proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,*** before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose *** similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and *** This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to sev

关键词： cooking elderly unsaturated

Observation of spectral lines in the exceptional GRB 221009A

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Science China(Physics,Mechanics & Astronomy) 2024年第8期67卷 187-206页

作者： yan-Qiu Zhang Shao-Lin Xiong Ji-Rong Mao Shuang-Nan Zhang Wang-Chen Xue Chao Zheng Jia-Cong Liu Zhen Zhang Xi-Lu Wang Ming-Yu Ge Shu-Xu Yi Li-Ming Song Zheng-Hua An Ce Cai xin-qiao Li wen-Xi Peng wen-Jun Tan Chen-Wei Wang Xiang-yang wen Yue Wang Shuo Xiao Fan Zhang Peng Zhang Shi-Jie Zheng Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China Yunnan Observatories Chinese Academy of SciencesKunming 650011China Center for Astronomical Mega-Science Chinese Academy of SciencesBeijing 100012China Key Laboratory for the Structure and Evolution of Celestial Objects Chinese Academy of SciencesKunming 650216China College of Physics and Hebei Key Laboratory of Photophysics Research and Application Hebei Normal UniversityShijiazhuang 050024China Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guizhou Normal UniversityGuiyang 550001China College of Electronic and Information Engineering Tongji UniversityShanghai 201804China

As the brightest gamma-ray burst ever observed,GRB 221009A provided a precious opportunity to explore spectral line *** this article,we performed a comprehensive spectroscopy analysis of GRB 221009A jointly with GECAM-C and Fermi/GBM data to search for emission and absorption *** the first time we investigated the line feature throughout this GRB including the most bright part where many instruments suffered problems,and identified prominent emission lines in multiple time *** central energy of the Gaussian emission line evolves from about 37 to 6 MeV,with a nearly constant ratio(about 10%)between the line width and central ***,we find that both the central energy and the energy flux of the emission line evolve with time as a power law decay with power law index of–1 and–2,*** suggest that the observed emission lines most likely origin from the blue-shifted electron positron pair annihilation 511 ke V *** find that a standard high latitude emission scenario cannot fully interpret the observation,thus we propose that the emission line comes from some dense clumps with electron positron pairs traveling together with the *** this scenario,we can use the emission line to directly,for the first time,measure the bulk Lorentz factor of the jet(Γ)and reveal its time evolution(i.e.,Γ~t^(-1))during the prompt ***,we find that the flux of the annihilation line in the co-moving frame keeps *** discoveries of the spectral line features shed new and important lights on the physics of GRB and relativistic jet.

关键词： GRB GRB 221009A emission line