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Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang ting Lei Xiaotong yang Wenqin yang Guo Cheng Huile gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China Laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

Investigating the Absorption and Desorption Behavior of Methylene Chloride in the Poly(aryl ether ketone) Film with Different Crystallinities

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Chinese Journal of Polymer Science 2024年第2期42卷 239-246,I0009页

作者： Hong-Ru yang Jin-Dong Zhang Dong-ting gao Gang Liu Chun-Hai Chen Jia-Nan Yao Center for Advanced Low-Dimension Materials State Key Laboratory for Modification of Chemical Fibers and Polymer MaterialsCollege of Materials Science and EngineeringDonghua UniversityShanghai201620China

Poly(aryl ether keton e)(PAEK) films with different crystallinities were obtained by controlling the cooling rate,which were subjected to the absorption and desorption of methylene chloride(CH_(2)Cl_(2)).We employed attenuated total reflection Fourier transform infrared(ATR-FTIR)spectroscopy analyses to investigate the diffusion behavior of CH_(2)Cl_(2) in PAEK films with different crystallinities.According to the Fickian diffusion model,the calculated diffu sion coefficients of CH_(2)Cl_(2) in PAEK films were observed to decrease with increasing crystallinity.The effect of CH_(2)Cl_(2)absorption and desorption on the mechanical properties of PAEK films with different crystallinity was further analyzed using tensile tests.The tensile tests exhibited that CH_(2)Cl_(2) has two concurrent effects:plasticization and solvent-induced crystallization.Differential scanning calorimetry(DSC) and wide-angle X-ray diffraction(WXRD) techniques further confirmed solvent-induced crystallization behavior.The results would be beneficial to understand the solvent resistance of PAEK materials and consequently provide the practical application conditions of PAEK with a theoretical basis.

关键词： Poly(aryl ether ketone) Diffusion behavior Infrared spectra Solvent-induced crystallization Mechanical properties

Pathogen-induced methylglyoxal negatively regulates rice bacterial blight resistance by inhibiting OsCDR1 protease activity

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Molecular Plant 2024年第2期17卷 325-341页

作者： Zheng-Wei Fu Jian-Hui Li Xiang gao Shi-Jia Wang ting-ting Yuan Ying-Tang Lu State Key Laboratory of Hybrid Rice College of Life SciencesRenmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Biology and Genetic Improvement of OilCrops Ministry of Agriculture and Rural AffairsOilCrops Research Institute of the Chinese Academy of Agricultural SciencesWuhan 430062China

Xanthomonas oryzae pv.oryzae(Xoo)causes bacterial blight(BB),a globally devastating disease of rice(Oryza sativa)that is responsible for significant crop loss.Sugars and sugar metabolites are important for pathogen infection,providing energy and regulating events associated with defense responses;howev-er,the mechanisms by which they regulate such events in BB are unclear.As an inevitable sugar metabolite,methylglyoxal(MG)is involved in plant growth and responses to various abiotic stresses,but the underlying mechanisms remain enigmatic.Whether and how MG functions in plant biotic stress responses is almost completely unknown.Here,we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcrip-tion of OsGLY Il genes by directly binding to their promoters,resulting in overaccumulation of MG.MG negatively regulates rice resistance against Pxo99:osglyll2 mutants with higher MG levels are more sus-ceptible to the pathogen,whereas OsGLYIl2-overexpressing plants with lower MG content show greater resistance than the wild type.Overexpression of OsGLYll2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae pv.oryzicola and the necrotrophic fungal pathogen Rhizoctonia solani,which causes rice sheath blight.Further evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1(OsCDR1).MGmodifies the Arg97 residue of OsCDR1to inhibit its aspartic protease activ-ity,which is essential for OsCDR1-enhanced immunity.Taken together,these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant.

关键词： Oryza sativa bacterial blight OsWRKY62.1 methylglyoxal OsCDR1

Progress on the application of graphene-based composites toward energetic materials:A review

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Defence Technology（防务技术） 2024年第1期31卷 95-116页

作者： ting Zhang Xiaoming gao Jiachen Li Libai Xiao Hongxu gao Fengqi Zhao Haixia Ma College of Chemistry&Chemical Engineering Yan'an UniversityYan'an 716000ShaanxiPR China School of Chemical Engineering Northwest UniversityXi'an 710069ShaanxiPR China Xi'an Modern Chemistry Research Institute Xi'an 710065ShaanxiPR China

Carbon material is an important additive in energetic materials.Graphene is a monolayer carbon material in which carbon atoms are arranged in two-dimensional honeycomb structure,who has special optical,electrical,and mechanical properties.Recently,the application of graphene-based composites in energetic materials has received extensive attention.This review mainly summarizes the applications of graphene and graphene-based nanomaterials in energetic materials.The effects of these materials on the thermal stability,sensitivity,mechanical property,ignition and combustion of energetic materials were discussed.Furthermore,the progress of functionalized modification of graphene has been summarized,including covalent bonding modification and doping modification.These studies show that graphenebased materials exhibit excellent performances and might emerge as promising candidate for energetic materials.

关键词： Graphene Desensitization Thermal decomposition Catalytic combustion Energetic materials

Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells

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World Journal of Clinical Cases 2024年第17期12卷 3019-3026页

作者： Hui-Hui Gan gao yang ting-ting Shen Department of Dermatology Jinshan Hospital of Fudan UniversityShanghai 201508China

BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.METHODS Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group(n=40),which received conventional Western medicine treatment,or an observation group(n=40),which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide.Response and adverse reaction rates,as well as differences in the levels of serum cytokines IFN-γ,IL-2,IL-4,and IL-10 before and after treatment were investigated.RESULTS No difference in overall response rates were found between the observation and control groups(100%vs 90%,respectively;P>0.05);however,the observation group had a higher marked response rate than the control group(87.5%vs 52.5%;P0.05).The observation group exhibited higher post-treatment INF-γand IL-2 but lower IL-4 levels than the control group(P0.05).CONCLUSION Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema.Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels,inhibition of inflammatory reactions,and mitigation of immune imbalance.

关键词： Eczema Acupoint injection T cells Immune imbalance

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 676-685页

作者： ting-ting Feng Xiang gao An-Ran Liang Bo-Wen Zhao Guang-Hui He Song Chen Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye InstituteTianjin Eye HospitalTianjin 300020China Key Laboratory of Ophthalmology Anyang Eye HospitalAnyang 455000Henan ProvinceChina Department of Ophthalmology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of PDR.METHODS:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free technology.Statistically differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were analyzed.RESULTS:A total of 12 samples were analyzed.The proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were down-regulated.We found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept treatment.GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR.In addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural regulation.In addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in PDR.CONCLUSION:Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR.Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

关键词： vitreous proliferative diabetic retinopathy proteome 4D label-free

Wiener Filtration Algorithm of an Ensemble Pulsar Timescale Based on a Power-law Model of Pulsar Power Spectrum

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Research in Astronomy and Astrophysics 2022年第10期22卷 129-140页

作者： ting-gao yang Ming-Lei Tong Yu-Ping gao National Time Service Center Chinese Academy of SciencesXi'an 710600China Key Laboratory of Time and Frequency Primary Standards Chinese Academy of SciencesXi'an 71000China University of Chinese Academy of Sciences Beijing 100049China

An ensemble pulsar timescale derived from the traditional Wiener filtration still contains some high level noise.To improve this situation we developed a Wiener filtration algorithm of the ensemble pulsar timescale based on a power-law model of power spectrum for pulsars.Our algorithm has three strengths:(1)mitigating spectral leakage between frequency bins for Fourier techniques;(2)using a power-law model for power spectrum;(3)signal realization in original residuals of data set by the power-law model.According to improved algorithm we constructed an ensemble pulsar timescale EPT-TAI using timing data with respect to International Atomic Time(TAI)about 16 yr time span of ten pulsars from International Pulsar Timing Array second data release(version A).The results show that EPT-TAI detected correctly the differences TT(BIPM2015)-TAI between terrestrial time TT(BIPM2015)and TAI.Fractional frequency stabilityσzanalysis shows that EPT-TAI does not indicate red noise for 16 yr time interval,and fractional frequency stability for 8 yr and longer time intervals is slightly better than that of TT(BIPM2015)-TAI.Stability for short time intervals of TT(BIPM2015)-TAI is better than that of EPT-TAI,but TT(BIPM2015)-TAI shows red noise for longer time intervals.Using the same algorithm we also derived an ensemble pulsar timescale EPT-TT(BIPM2015)with respect to TT(BIPM2015).The fractional frequency stability curve of EPT-TT(BIPM2015)shows similar characteristics as that of EPT-TAI but with slightly lower values.

关键词： (stars:)pulsars general-time-methods data analysis

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton gao Weiwei Qi Xia yang Ti Zhou Guoquan gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of VIP Medical Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination Center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of Liver Disease Research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of Health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology Research Center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

RNF187 governs the maintenance of mouseGC-2 cell development by facilitating histone H3ubiquitination at K57/80

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Asian Journal of Andrology 2024年第3期26卷 272-281页

作者： Bing-Ya Xu Xiang-Ling Yu Wen-Xin gao ting-ting gao Hao-Yue Hu Tian-Tian Wu Cong Shen Xiao-Yan Huang Bo Zheng Yi-Bo Wu Human Reproductive and Genetic Center Affiliated Hospital of Jiangnan UniversityWuxi 214122China State Key Laboratory of Reproductive Medicine Department ofHistology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Changzhou Maternal and Child Health Care Hospital Changzhou Medical CenterNanjing Medical UniversityChangzhou 213000China State Key Laboratory of Reproductive Medicine Center for Reproduction andGeneticsSuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversitySuzhou 215002China.

RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer cells.However,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells.To investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell line.Our findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 cells.Moreover,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular transcription.This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of genetranscription.These discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.

关键词： GC-2 cell histone H3 RNF187 ubiquitination