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| 1 | Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response显示文摘Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains elusive.Here,we report that the non-canonical stimulator of interferon genes(STING)-PKR-like ER kinase(PERK)pathway was significantly activated in both human and mice atherosclerotic arteries.Typically,STING activation leads to the activation of interferon regulatory factor 3(IRF3)and nuclear factor-kappa B(NF-κB)/p65,thereby facilitating IFN signals and infammation.In contrast,our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4(BRD4)expression,which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines,thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process.Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation.Mechanistically,this pathway is triggered by leaked mitochondrial DNA(mtDNA)via mitochondrial permeability transition pore(mPTP),formed by voltage-dependent anion channel 1(VDAC1)oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation.Especially,compared to macrophages,endothelial STING activation plays a more pronounced role in atherosclerosis.We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3,NF-κB and BRD4 in inflammatory responses,which provides emerging therapeutic modalities for vascular endothelial dysfunction. | Xuesong Li Xiang Chen Longbin Zheng Minghong Chen Yunjia Zhang Ruigong Zhu Jiajing Chen Jiaming Gu Quanwen Yin Hong Jiang Xuan Wu Xian Ji Xin Tang Mengdie Dong Qingguo Li Yuanqing Gao Hongshan Chen | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 1 |
| 2 | The Effect of Emission Permit Trading with Banking on Firm's Production-inventory Strategies显示文摘 | Shoude Li Mengdi Gu | 2012 | International Journal of Production Economics2012，，137： | 1 |
| 3 | The effect of emission permit trading with banking on firm's production-inventory strategies显示文摘 | Li Shoude Gu Mengdi | 2012 | International Journal of Production Eco- nomics2012，137，2： | 1 |
| 4 | The effect of emission permit trading with banking on firm' s produc- tion - inventory strategies 显示文摘 | Shoude Li Mengdi Gu | 2012 | International Journal of Production Economics2012，137，： | 1 |
| 5 | Constant elasticity of variance model for propor- tional reinsurance and investment strategies显示文摘 | GU Mengdi YANG Yipeng LI Shoude ZHANG Jingyi | 2010 | Insurance: Mathematics and Econmics2010，46，： | 1 |
| 6 | Land use rights, government land supply, and the pattern of redevelopment in Shanghai 显示文摘 | FU Yuming Somerville T GU Mengdi | 1999 | Int Real Estate Review1999，2，1： | 1 |
| 7 | Engineered nitrogen doping on VO_(2)(B)enables fast and reversible zinc-ion storage capability for aqueous zinc-ion batteries显示文摘Vanadium-based compounds with high theoretical capacities and relatively stable crystal structures are potential cathodes for aqueous zinc-ion batteries(AZIBs).Nevertheless,their low electronic conductivity and sluggish zinc-ion diffusion kinetics in the crystal lattice are greatly obstructing their practical application.Herein,a general and simple nitrogen doping strategy is proposed to construct nitrogen-doped VO_(2)(B)nanobelts(denoted as VO_(2)-N)by the ammonia heat treatment.Compared with pure VO_(2)(B),VO_(2)-N shows an expanded lattice,reduced grain size,and disordered structure,which facilitates ion transport,provides additional ion storage sites,and improves structural durability,thus presenting much-enhanced zinc-ion storage performance.Density functional theory calculations demonstrate that nitrogen doping in VO_(2)(B)improves its electronic properties and reduces the zinc-ion diffusion barrier.The optimal VO_(2)-N400 electrode exhibits a high specific capacity of 373.7 mA h g^(-1)after 100 cycles at 0.1 A g^(-1)and stable cycling performance after 2000 cycles at 5 A g^(-1).The zinc-ion storage mechanism of VO_(2)-N is identified as a typical intercalation/de-intercalation process. | Xin Gu Juntao Wang Xiaobin Zhao Xin Jin Yuzhe Jiang Pengcheng Dai Nana Wang Zhongchao Bai Mengdi Zhang Mingbo Wu | 2023 | Journal of Energy Chemistry2023，，10： | 0 |
| 8 | Research on Application of Monte Carlo Simulation in the Income Approach of Asset Valuation A listed Company in China as an Example显示文摘 | Chen Lei Gu Mengdi | 2012 | Journal of Modern Accounting and Auditing2012，8，9： | 0 |
| 9 | Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche显示文摘Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches.Precise regulation of these cell types can remodel niches and develop new therapeutics.Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively.However,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell types.Here,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro.Less than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular matrix.Delivery efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was analyzed.The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo.The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of nanocarrier.The overall efficiency into sinusoidal ECswas greatly lower than that into arteriole ECs.All nanocarriers were hard to be delivered into OBs(<1%).Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro.This study provided the methodology for niche-directed nanotherapeutics development. | Huijuan Chen Anzhi Hu Mengdi Xiao Shiyi Hong Jing Liang Quanlong Zhang Yang Xiong Mancang Gu Chaofeng Mu | 2023 | Asian Journal of Pharmaceutical Sciences2023，18，6： | 0 |
| 10 | Laser irradiation constructing all-in-one defective graphenepolyimide separator for effective restraint of lithium dendrites and shuttle effect显示文摘The commercialization of lithium-sulfur(Li-S)batteries faces several bottlenecks,and the major two of which are the shuttle effect of polysulfides and the wild growth of Li dendrites,responsible for fast capacity decay and severe safety issues.As an essential component of Li-S batteries,the structure and properties of the separators are closely related to the above problems,and the exploration of multifunctional separators is highly sought-after.Herein,an integrated separator composited of defective graphene and polyimide(DG-PI)was innovatively fabricated by electrospinning combined with the laser-induced carbonization strategy.The all-in-one compact architecture with well-interconnected channels shows superior mechanical and thermal stability and wettability.More importantly,the PI nanofibers containing N–/O–functional groups can induce the uniform deposition of lithium on the anode surface,while the DG framework with abundant pentagonal/heptagonal rings and vacancies can strongly trap polysulfides and accelerate polysulfide transformation on the cathode side.The strong chemical interaction between the insulative PI layer and the conductive DG layer modulates the surface charge distribution of each other,leading to more prominent contributions to restraining lithium dendrites and shuttle effect.Therefore,the Li-S batteries based on the integrated DG-PI separators afford an excellent performance in protecting lithium anode(stable cycles of 200 h at 5 mA·cm^(−2))and good cycling stability with a low capacity decay of 0.05%per cycle after 700 cycles at 1 C.This work offers a new design concept of multifunctional Li-S battery separators and broadens the application scope of laser micro-nano fabrication technology. | Jiawei Mu Mengdi Zhang Yanan Li Zhiliang Dong Yuanyuan Pan Bei Chen Zhengqiu He Haiqiu Fang Shuoshuo Kong Xin Gu Han Hu Mingbo Wu | 2023 | Nano Research2023，16，10： | 0 |
| 11 | UHRF1/DNMT1—MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer显示文摘As confusion mounts over RNA isoforms involved in phenotypic plasticity,aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity(ITH).Protease serine 3(PRSS3),possessing four splice variants(PRSS3-SVs;PRSS3-V1—V4),is an indispensable trypsin that shows paradoxical effects on cancer development.Here,we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer,exhibiting opposing functions and clinical outcomes,namely,oncogenic PRSS3-V1 and PRSS3-V2 versus tumorsuppressive PRSS3-V3,by targeting different downstream genes.We identified an intragenic CpG island(iCpGI)in PRSS3.Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1(MZF1)to regulate PRSS3 transcription.The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression.Epigenetic silencing of PRSS3-V3 via i CpGI methylation(iCpGIm)in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease.Thus,UHRF1/DNMT1—MZF1 axismodulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs,conferring nongenetic functional ITH,with implications for early detection of lung cancer and targeted therapies. | Shuye Lin Hanli Xu Lin Qin Mengdi Pang Ziyu Wang Meng Gu Lishu Zhang Cong Zhao Xuefeng Hao Zhiyun Zhang Weimin Ding Jianke Ren Jiaqiang Huang | 2023 | Acta Pharmaceutica Sinica B2023，13，5： | 0 |
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