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Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype

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Neural Regeneration Research 2024年第11期19卷 2488-2498页

作者： Yuanyuan Ding Yu Sun hongyan wang Hongqin Zhao Ruihua Yin Meng Zhang Xudong Pan Xiaoyan Zhu Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Qingdao Cadre Health Care Service Center The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of Critical Care Medicine The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

关键词： atherosclerosis inflammation lnc_000048 lncRNA macrophage polarization protein kinase RNA-activated(PKR) STAT1

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New Problems of Boiler Corrosion after Coupling Combustion of Coal and Biomass and Anti-Corrosion Technologies

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Journal of Renewable Materials 2024年第4期12卷 799-814页

作者： Lei wang Ziran Ma Chunlin Zhao Jiali Zhou hongyan wang Ge Li Ningling Zhou National Institute of Clean-and-Low-Carbon Energy Beijing102211China Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education School of Energy&EnvironmentSoutheast UniversityNanjing210096China

This study explores the corrosion issues arising from the coupled combustion of coal and biomass and proposes potential solutions.Biomass,as a renewable energy source,offers advantages in energy-saving and carbon reduction.However,the corrosive effects of alkali metal compounds,sulfur(S)and chlorine(Cl)elements in the ash after combustion cannot be underestimated due to the high volatile content of biomass fuels.We investigate the corrosion mechanisms,as well as the transfer of Cl and alkali metal elements during this process.Comparative corrosion analyses are conducted among coal-fired boilers,pure biomass boilers and boilers with coupled combustion.Various biomass types in co-firing are studied to understand different corrosion outcomes.The main factors influencing corrosion include the physicochemical properties of biomass feedstock,furnace temperature and heating surface materials,with the chemical composition and ash content of biomass playing a dominant role.Currently,the methods used for anti-corrosion include water washing pretreatment of biomass feedstock,application of novel alloys and coatings and the development of additives to inhibit fouling,ash deposition and corrosion.Efficient inhibitors are economical and easy to produce.Additionally,biomass can be converted into biomass gasification gas,although challenges related to tar still need to be addressed.

关键词： Biomass coupled combustion corrosion mechanism anti-corrosion measures

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A mutation in TBXT causes congenital vertebral malformations in humans and mice

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Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei Yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang hongyan wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted Reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well established.Here,we report a family with 15 CVM patients distributed across 4 generations.All affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and phenotype.In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the wild-type.To determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM phenotype.Most heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral deformities.Overall,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway

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Science China Life Sciences 2024年

作者： Ling Li Lei Lu Ziqi Xiao Jingyi Lv Hefeng Huang Bo Wu Tongjin Zhao Chengtao Li Weimin wang hongyan wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering Institute of Reproduction and Development and Children's Hospital Fudan University Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology Fudan University Prenatal Diagnosis Center of Shenzhen Maternity & Child Healthcare Hospital Shanghai Medical College Fudan University Department of Pharmacy College of Life Sciences China Jiliang University

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue homeostasis. SMAD6 encodes a negative regulator of BMP, and rare variants of SMAD6 are recurrently found in individuals with birth defects. However, we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling pathway. We sought to determine whether these SMAD6 variants have common pathogenic mechanisms. Here, we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in deamidation. Mechanistically, increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes, both of which lead to BMP signaling pathway activation. Specifically, two residues, N262 and N404, in SMAD6 were identified as the crucial sites of deamidation, which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2(GFPT2). Additionally, treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling pathway. Conversely,when wild-type SMAD6 was manually simulated to mimic the deamidated state, the reversed function of activating BMP signaling was reproduced. Taken together, these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity, which can be induced by a subset of various SMAD6 variants. Our study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation, which might prevent the off-target effects of gene editing.

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Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of Traditional Chinese Medicine 2024年第3期44卷 515-523页

作者： wang Xiang HUANG Jianping wang Yupeng wang Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing wang hongyan YAN Yonggang Department of Key Laboratory of "Qin Pharmaceutical" Research and Development Shaanxi University of Traditional Chinese Medicine Department of Yupeng Shaanxi Haitian Pharmaceutical Co. Ltd. Department of Acupuncture and Tuina Shaanxi University of Traditional Chinese Medicine

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： Dahuang () Taoren () differential metabolites kernel drug pairs metabolic networks and pathways metabolomics

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An FV-EE model to predict lean blowout limits for gas turbine combustors with different structures and sprays

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Chinese Journal of Aeronautics 2023年第5期36卷 145-156页

作者： Xiwei wang Yong HUANG Yunfeng LIU Yufan WU hongyan wang Collaborative Innovation Center of Advanced Aero-Engine School of Energy and Power EngineeringBeihang UniversityBeijing 102206China National Key Laboratory of Science and Technology School of Energy and Power EngineeringBeihang UniversityBeijing 102206China

The occurrence of Lean Blowout(LBO)is a disadvantage that endangers a stable operation of gas turbines.A determination of LBO limits is essential in the design of gas turbine combustors.A semiempirical model is one of the most widely used methods to predict LBO limits.Among the existing semiempirical models for predicting LBO limits,Lefebvre’s LBO model and the Flame Volume(FV)model are particularly suitable for gas turbine combustors.On the basis of Lefebvre’s and FV models,the concept of effective evaporation efficiency is introduced in this paper,and a Flame Volume-Evaporation Efficiency(FV-EE)model is derived and validated.LBO experiments are carried out in a model combustor with 23 different structures and 10 different sprays.The prediction uncertainty of the FV-EE model is less than±13%for all of these 33 structures and sprays,compared with±50%for the FV model and±60%for Lefebvre’s model.Furthermore,the prediction uncertainty of the FV-EE model is also less than±13%for other combustors from available literature.

关键词： Atomization characteristic Evaporation efficiency Gas turbine combustors Lean blowout limit Semiempirical correlation

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Improvement of reservoir quality of ultra-deep tight sandstones by tectonism and fluid:A case study of Keshen gas field in Tarim Basin,western China

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Petroleum 2023年第1期9卷 124-134页

作者： Junpeng wang hongyan wang Ronghu Zhang Li Dong Ke wang Zhiyuan Zhang China University of Petroleum BeijingChina PetroChina Hangzhou Research Institute of Geology ZhejiangChina Research Institute of Petroleum Exploration&Development CNPCBeijingChina Petroleum Exploration and Production Research Institute SINOPECBeijingChina

The Keshen gas field is one of the most important natural gas supply sources in the Tarim basin,western China.The main gas producing interval there is the Lower Cretaceous Bashijiqike Formation(K1bs),it is an ultra-deep tight reservoir whose buried depth exceeds 6000 m,and it shows a low matrix porosity(<10%)and extremely low matrix permeability(<0.1mD).However,this reservoir can supply extremely high and stable gas production due to improvement of reservoir quality by tectonism and fluid.Based on tectonic evolution analysis by plenty of lab data of core plugs or thin sections,the enhancement models of tectonism and fluid are built,evidence suggests both tectonism and fluid improve the reservoir quality greatly.Tectonic evolution produces lots of natural fractures in 3stages which promote the ultra-deep tight reservoir permeability 10–200 times,then,testing results of new boreholes without fracturing show reservoir permeability underground can reach 20 mD.Furthermore,fluid dissolution increases reservoir porosity 1–2 times,the main dissolved mineral is feldspar,all fluid dissolution came from the unconformity controlling the dissolution distance.Tectonism and fluid interact on each other:Tectonism controls fracture distribution and types of diagenic fluid in reservoir,but fluids influence fracture cements and dissolution.Both tectonic folding and the fluid flow control the sweet point reservoir located in upper 150 m formation.

关键词： Reservoir quality Fluid interaction Tectonism Diagenesis Deep gas

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The critical role of Zr in controlling the activity of Pd/Beta on the hydrogenation of phenol to cyclohexanone

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Chinese Journal of Chemical Engineering 2023年第5期57卷 79-87页

作者： Bin Gao Junwen Chen Qi Zuo hongyan wang Wenlin Li College of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan 030024China State Key Laboratory of Catalytic Material and Reaction Engineering Research Institute of Petroleum ProcessingSinopecBeijing 100083China

The promoting effect of zirconium addition on Pd/Beta catalysts has been investigated in the selective hydrogenation of phenol to cyclohexanone in the aqueous phase. The activity of the catalyst in the reaction was greatly improved by introducing Zr atoms into the framework of H-Beta zeolite. An important synergy between the Zr species and Pd, affecting the Pd dispersion state on the support, has been observed. The modification of the support with Zr^(4+) improves the Lewis/Brφnsted acid ratio of the catalyst, suppressing the further transformation of cyclohexanone. The kinetics of Pd/Zr-Beta catalyst showed high selectivity to cyclohexanone. The catalytic results showed that the Pd/Zr-Beta had the best catalytic performance at the desired temperature of 80℃ for 5 h.

关键词： Palladium Phenol hydrogenation Cyclohexanone Zirconium Zeolite

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Downregulated nuclear lncRNA NRON inhibits SHP2/Wnt/β-catenin signaling and cardiomyocyte differentiation during the development of Tetralogy of Fallot

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Genes & Diseases 2023年第3期10卷 750-752页

作者： Hui Zhang Lei Lu Chao Li Hongdou Li Jie Tian hongyan wang Zhang Zhongjing School of Chinese Medicine Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for ImmunoregulationNanyang Institute of TechnologyNanyangHenan 473004China Department of Cardiology Heart CentreMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Pediatrics China International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200011China Obstetrics and Gynecology Hospital NHC Key Laboratory of Reproduction RegulationShanghai Institute of Planned Parenthood ResearchState Key Laboratory of Genetic Engineering at School of Life SciencesChildren's HospitalFudan UniversityShanghai 200438China

Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart disease and the incidence of late cardiac death in long-term survivors continues to increase.1 So,there is an urgent need to explore the etiology and pathogenesis of TOF.The precise cause of TOF is currently unclear,and exploration of the pathogenesis has focused increasingly in recent years on the roles of noncoding gene products,especially long noncoding RNAs(lncRNAs).

关键词： pathogenesis cardiac congenital

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Demonstration of a diode-pumped dual-wavelength metastable krypton laser

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High Power Laser Science and Engineering 2023年第6期11卷 223-228页

作者： Qingshan Liu Rui wang Zining Yang Jianyong Sun Weiqiang Yang hongyan wang Xiaojun Xu College of Advanced Interdisciplinary Studies National University of Defense TechnologyChangshaChina Nanhu Laser Laboratory National University of Defense TechnologyChangshaChina Hunan Provincial Key Laboratory of High Energy Laser Technology National University of Defense TechnologyChangshaChina

Diode-pumped rare gas lasers are potential candidates for high-energy and high-beam quality laser systems.Currently,most investigations are focused on metastable Ar lasers.The Kr system has the unique advantages of higher quantum efficiency and lower discharge requirements for comparison.In this paper,a diode-pumped metastable Kr laser was demonstrated for the first time.Using a repetitively pulsed discharge at a Kr/He pressure of up to approximately1500 Torr,metastable Kr atoms of more than 10^(13)cm^(-3)were generated.Under diode pumping,the laser realized a dual-wavelength output with an average output power of approximately 100 mW and an optical conversion efficiency of approximately 10% with respect to the absorbed pump power.A kinetics study involving population distribution and evolution was conducted to analyze the laser performance.

关键词： diode pump krypton metastable rare gas laser

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