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Inhibition of EGFR attenuates EGF-induced activation of retinal pigment epithelium cell via EGFR/AKT signaling pathway

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1018-1027页

作者： yu-Sheng Zhu si-Rui Zhou Hui-Hui Zhang Tong Wang Xiao-Dong chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUsiON:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).

关键词： erlotinib epidermal growth factor receptor protein kinase B epithelial-mesenchymal transition retinal pigment epithelium cell

Nature-inspired design of droplet-synthesized polymeric nanoelectrode for photoelectrochemical microRNA sensing within single cells

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Science Bulletin 2024年第2期69卷 159-162页

作者： si-yuan yu Yi-Li Liu Zheng Li Dechen Jiang Jing-Juan Xu Hong-yuan chen Wei-Wei Zhao State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Nanoelectrodes have been shown to be powerful tools for nanoscopic research on single entities,deepening the understanding of heterogeneity and stochastics for single molecules,nanoparticles and cells[1–3].However,despite their importance,current nanoelectrode preparations are highly restrained to flame/electrochemical etching,metal sputtering,electrochemical deposition,etc.[3],resulting in a limited range of materials(mainly gold,platinum and carbon)for potential-resolved detection of redox-active species(Table S1 online).The enrichment of preparation methods to introduce novel materials and mechanisms should prove significant for the development of nanoelectrodes.

关键词： electrode deepening restrained

Boosting thermal stability and crystallization of closed-loop-recyclable biodegradable poly(p-dioxanone) by end-group regulation

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Science China Chemistry 2024年第2期67卷 642-651页

作者： Jin Lei Zhu-Xin Gui Wan-Ting Xiong Gang Wu si-Chong chen yu-Zhong Wang The Collaborative Innovation Center for Eco-Friendly and Fire-Safety Polymeric Materials(MoE) National Engineering Laboratory of Eco-Friendly Polymeric Materials(Sichuan)State Key Laboratory of Polymer Materials EngineeringCollege of ChemistrySichuan UniversityChengdu610064China

A chemically closed-loop-recyclable biodegradable polymer,poly(p-dioxanone)(PPDO),is one of the ideal candidates for single-use plastic products due to its suitability for different application scenarios.Fascinatingly,when PPDO wastes can be collected,its monomer p-dioxanone(PDO) will be obtained through chemical recycling of these wastes;when cannot be collected,the wastes are able to be biodegraded into harmless substances.However,unsatisfied thermal stability and low crystallization rate of PPDO restrict its wider applications.Herein,based on end-group regulation,we simultaneously realized the significant enhancement of thermal stability and crystallization of PPDO through the simple melt processing with tributyl phosphite(TBP) or triphenyl phosphite(TPP).The model reactions were conducted to investigate the reaction mechanism and theoretical products during the preparation of PPDO/phosphite compounds.Two kinds of phosphites were proved to act as the end-capped reagent and chain extender in the melt processing,while TBP presented better reactivity.As a result,the activation energy of thermal decomposition was largely elevated,and the unprecedented T_(5%)(the temperature at a weight loss of 5%) and Tmax(the temperature at a maximum rate of weight loss) of PPDO were obtained,i.e.,T_(5%)of ~330 ℃ and Tmaxof ~385 ℃ in N_(2) atmosphere,T_(5%)of ~240 ℃ and Tmaxof ~317 ℃ in air atmosphere,respectively.Furthermore,the increased crystallization rate,crystallinity,crystalline orderliness,and realizable monomer recovery(yield >90%,purity >99.9%) of PPDO/phosphite compounds were confirmed.

关键词： poly(p-dioxanone) phosphite thermal stability crystallization end-group regulation

Rogue wave solutions and rogue-breather solutions to the focusing nonlinear Schr?dinger equation

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Communications in Theoretical Physics 2024年第3期76卷 33-41页

作者： si-Jia chen Xing Lü College of Science Tianjin University of TechnologyTianjin 300384People's Republic of China Department of Mathematics Beijing Jiaotong UniversityBeijing 100044People's Republic of China Beijing Laboratory of National Economic Security Early-warning Engineering Beijing Jiaotong UniversityBeijing 100044People's Republic of China

Based on the long wave limit method,the general form of the second-order and third-order rogue wave solutions to the focusing nonlinear Schr?dinger equation are given by introducing some arbitrary parameters.The interaction solutions between the first-order rogue wave and one-breather wave are constructed by taking a long wave limit on the two-breather solutions.By applying the same method to the three-breather solutions,two types of interaction solutions are obtained,namely the first-order rogue wave and two breather waves,the second-order rogue wave and one-breather wave,respectively.The influence of the parameters related to the phase on the interaction phenomena is graphically demonstrated.Collisions occur among the rogue waves and breather waves.After the collisions,the shape of them remains unchanged.The abundant interaction phenomena in this paper will contribute to a better understanding of the propagation and control of nonlinear waves.

关键词： nonlinear Schrodinger equation rogue wave solutions interaction solutions

Can serum immunoglobulin G4 levels and age serve as reliable predictors of relapse in autoimmune pancreatitis?

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World Journal of Gastroenterology 2024年第5期30卷 512-515页

作者： Jun-Min Song si-yu Sun Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al.The authors identified higher serum immunoglobulin(Ig)G4 levels and age over 55 years as independent risk factors for disease relapse.Despite notable strengths,it is crucial to address potential biases.Firstly,the cohort study included 189 patients with autoimmune pancreatitis(AIP)type 1(with higher IgG4 seropositivity and higher relapse)and 24 with type 2(with lower IgG4 seropositivity and lower relapse).Consequently,most,if not all,AIP type 2 patients were assigned to the normal group,possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse.Secondly,the authors did not provide sufficient details regarding AIP diagnosis,such as the ratio of definitive vs probable cases and the proportion of biopsies.In cases where histological evidence is unavailable or indeterminate,AIP type 2 may be misdiagnosed as definitive type 1,and type 1 may also be misdiagnosed as probable type 2,particularly in cases with normal or mildly elevated serum IgG4 levels.Lastly,in this retrospective study,approximately one-third of the consecutive patients initially collected were excluded for various reasons.Accordingly,the impact of nonrandom exclusion on relapse outcomes should be carefully considered.In conclusion,the paper by Zhou et al offers plausible,though not entirely compelling,evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse.The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping,heavily dependent on obtaining histological specimens.In this regard,endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process,contributing to mitigating biases in future explorations of the disease.

关键词： Autoimmune pancreatitis Immunoglobulin Endoscopic ultrasound Relapse Age

Rapid Unconscious Acquisition of Conditioned Fear with Low-Spatial-Frequency but Emotionally Neutral Stimuli

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Research 2024年第1期2023卷 753-762页

作者： yujie chen si chen Zhongju Sun Xilei Zhang Xiangyong yuan Liang Wang Yi Jiang State Key Laboratory of Brain and Cognitive Sciences CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100049China Chinese Institute for Brain Research Beijing 102206China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China

It has long been proposed that emotionally“prepared”(i.e.,fear-related)stimuli are privileged in the unconscious acquisition of conditioned fear.However,as fear processing is suggested to highly depend on the coarse,low-spatial-frequency(LSF)components of the fear-related stimuli,it is plausible that LSF may play a unique role in the unconscious fear conditioning even with emotionally neutral stimuli.Here,we provided empirical evidence that,following classical fear conditioning,an invisible,emotionally neutral conditioned stimulus(CS+)with LSF,but not with high spatial frequency(HSF),can rapidly elicit stronger skin conductance responses(SCRs)and larger pupil diameters than its CS−counterpart.In comparison,consciously perceived emotionally neutral CS+with LSF and HSF elicited comparable SCRs.Taken together,these results support that the unconscious fear conditioning does not necessarily entail emotionally prepared stimuli but prioritizes LSF information processing and highlight the crucial distinctions between the unconscious and the conscious fear learning.These findings not only coincide with the postulation that a rapid,spatial-frequency-dependent subcortical route is engaged in unconscious fear processing but also suggest the existence of multiple routes for conscious fear processing.

关键词： neutral necessarily diameters

Demethylase-assisted site-specific detection of N^(1)-methyladenosine in RNA

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Chinese Chemical Letters 2024年第5期35卷 397-401页

作者： Jun Xiong Ke-Ke chen Neng-Bin Xie Wei chen Wen-Xuan Shao Tong-Tong Ji si-yu yu yu-Qi Feng Bi-Feng yuan College of Chemistry and Molecular Sciences Research Center of Public HealthRenmin Hospital of Wuhan UniversitySchool of Public HealthWuhan UniversityWuhan 430071China Department of Laboratory Medicine Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China

The dynamic RNA modifications have been viewed as new posttranscriptional regulator in modulating gene expression as well as in a broad range of physiological processes.N^(1)-methyladenosine(m^(1)A)is one of the most prevalent modifications existing in multiple types of RNAs.In-depth investigation of the functions of m^(1)A requires the site-specific assessment of m^(1)A stoichiometry in RNA.Herein,we established a demethylase-assisted method(DA-m^(1)A)for the site-specific detection and quantification of m^(1)A in RNA.N^(1)-methyl group in m^(1)A could result in the stalling of reverse transcription at m^(1)A site,thus producing the truncated cDNA.E.coli AlkB is a demethylase that can demethylate m^(1)A to produce adenine in RNA,thus generating full-length cDNA from AlkB-treated RNA.Evaluation of the produced amounts of full-length cDNA by quantitative real-time PCR can achieve the site-specific detection and quantification of m^(1)A in RNA.With the DA-m^(1)A method,we examined and successfully confirmed the previously well-characterized m^(1)A sites in various types of RNAs with low false positive rate.In addition,we found that the level of m^(1)A was significantly decreased at the bromodomain containing 2(BRD2)mRNA position 1674 and CST telomere replication complex component 1(CTC1)mRNA position 5643 in human hepatocellular carcinoma tissues.The results suggest that these two m^(1)A sites in mRNA may be involved in liver tumorigenesis.Taken together,the DA-m^(1)A method is simple and enables the rapid,cost-effective,and site-specific detection and quantification of m^(1)A in RNA,which provides a valuable tool to decipher the functions of m^(1)A in human diseases.

关键词： N^(1)-methyladenosine RNA modification AlkB demethylase RNA epigenetics Quantitative real-time PCR Hepatocellular carcinoma

Atomically Dispersed Ruthenium Catalysts with Open Hollow Structure for Lithium-Oxygen Batteries

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Nano-Micro Letters 2024年第2期16卷 154-164页

作者： Xin chen yu Zhang Chang chen Huinan Li yuran Lin Ke yu Caiyun Nan chen chen Beijing Advanced Innovation Center for Materials Genome Engineering Institute of Solid State ChemistryUniversity of Science and Technology BeijingBeijing 100083People’s Republic of China Engineering Research Center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084People’s Republic of China Beijing Key Laboratory of Energy Conversion and Storage Materials Institution College of ChemistryBeijing Normal UniversityBeijing 100875People’s Republic of China

Lithium–oxygen battery with ultrahigh theoretical energy density is considered a highly competitive next-generation energy storage device,but its practical application is severely hindered by issues such as difficult decomposition of discharge products at present.Here,we have developed N-doped carbon anchored atomically dispersed Ru sites cathode catalyst with open hollow structure(h-RuNC)for Lithium–oxygen battery.On one hand,the abundance of atomically dispersed Ru sites can effectively catalyze the formation and decomposition of discharge products,thereby greatly enhancing the redox kinetics.On the other hand,the open hollow structure not only enhances the mass activity of atomically dispersed Ru sites but also improves the diffusion efficiency of catalytic molecules.Therefore,the excellent activity from atomically dispersed Ru sites and the enhanced diffusion from open hollow structure respectively improve the redox kinetics and cycling stability,ultimately achieving a high-performance lithium–oxygen battery.

关键词： Atomically dispersed Open hollow structure Discharge product Lithium Oxygen battery

Hepatocyte growth factor promotes retinal pigment epithelium cell activity through MET/AKT signaling pathway

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 806-814页

作者： si-Rui Zhou yu-Sheng Zhu Wen-Ting yuan Xiao-Yan Pan Tong Wang Xiao-Dong chen Faculty of Life Sciences and Medicine Northwest UniversityXi’an 710069Shaanxi ProvinceChina First Affiliated Hospital of Northwest University Northwest UniversityXi’an 710069Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710002Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Shaanxi Provincial Key Lab of OphthalmologyClinical Research Center for Ophthalmology Diseases of Shaanxi ProvinceXi’an 710002Shaanxi ProvinceChina

AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUsiON:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

关键词： hepatocyte growth factor mesenchymal epithelial transition factor SU11274 retinal pigment epithelial cells