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| 1 | Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma显示文摘Background:Resistance to ferroptosis,a regulated cell death caused by irondependent excessive accumulation of lipid peroxides,has recently been linked to lung adenocarcinoma(LUAD).Intracellular antioxidant systems are required for protection against ferroptosis.The purpose of the present studywas to investigate whether and how extracellular system desensitizes LUAD cells to ferroptosis.Methods:Established human lung fibroblasts MRC-5,WI38,and human LUAD H1650,PC9,H1975,H358,A549,and H1299 cell lines,tumor and matched normal adjacent tissues of LUAD,and plasma from healthy individuals and LUAD patients were used in this study.Immunohistochemistry and immunoblotting were used to analyze protein expression,and quantitative reverse transcription-PCR was used to analyze mRNA expression.Cell viability,cell death,and the lipid reactive oxygen species generationwere measured to evaluate the responses to ferroptosis.Exosomes were observed using transmission electron microscope.The localization of arachidonic acid(AA)was detected using click chemistry labeling followed by confocal microscopy.Interactions between RNAs and proteins were detected using RNA pull-down,RNA immunoprecipitation and photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation methods.Proteomic analysis was used to investigate RNA-regulated proteins,and metabolomic analysis was performed to analyze metabolites.Cellderived xenograft,patient-derived xenograft,cell-implanted intrapulmonary LUAD mouse models and plasma/tissue specimens from LUAD patients were used to validate the molecular mechanism.Results:Plasma exosome from LUAD patients specifically reduced lipid peroxidation and desensitized LUAD cells to ferroptosis.A potential explanation is that exosomal circRNA_101093(cir93)maintained an elevation in intracellular cir93 in LUAD to modulate AA,a poly-unsaturated fatty acid critical for ferroptosisassociated increased peroxidation in the plasma membrane.Mechanistically,cir93 interacted with and increased fatty acid-binding protein 3(FABP3),which transported AA and facilitated its reaction with taurine.Thus,global AA was reduced,whereas N-arachidonoyl taurine(NAT,the product of AA and taurine)was induced.Notably,the role of NAT in suppressing AA incorporation into the plasma membrane was also revealed.In pre-clinical in vivo models,reducing exosome improved ferroptosis-based treatment.Conclusion:Exosome and cir93 are essential for desensitizing LUAD cells to ferroptosis,and blocking exosome may be helpful for future LUAD treatment. | Xiao Zhang Yunhua Xu Lifang Ma Keke Yu Yongjie Niu Xin Xu Yi Shi Susu Guo Xiangfei Xue Yikun Wang Shiyu Qiu Jiangtao Cui Hong Wang Xiaoting Tian Yayou Miao Fanyu Meng Yongxia Qiao Yongchun Yu Jiayi Wang | 2022 | Cancer Communications2022，42，4： | 10 |
| 2 | Working-in-tandem mechanism of multi-dopants in enhancing electrocatalytic nitrogen reduction reaction performance of carbon- based materials显示文摘Developing carbon-based electrocatalysts with excellent N2 adsorption and activation capability holds the key to achieve highly efficient nitrogen reduction reaction(NRR)for reaching its practical application.Here,we report a highly active electrocatalyst--metal-free pyrrolic-N dominated N,S co-doped carbon(pyrr-NSC)for NRR.Based on theoretical and experimental results,it is confirmed that the N and S-dopants practice a working-in-tandem mechanism on pyrr-NSC,where the N-dopants are utilized to create electropositive C sites for enhancing N2 adsorption and the S-dopants are employed to induce electron backdonation for facilitating N2 activation.The synergistic effect of the pyrrolic-N and S-dopants can also suppress the irritating hydrogen evolution reaction,further boosting the NRR performance.This work gives an indication that the combination of two different dopants on electrocatalyst can enhance NRR performance by working in the two tandem steps-the adsorption and activation of N2 molecules,providing a new strategy for NRR electrocatalyst design. | Wenqing Zhang Keke Mao Jingxiang Low Hengjie Liu Yanan Bo Jun Ma Qiaoxi Liu Yawen Jiang Jiuzhong Yang Yang Pan Zeming Qi Ran Long Li Song Yujie Xiong | 2021 | Nano Research2021，14，9： | 2 |
| 3 | Construction of an artificial intelligence system in dermatology: effectiveness and consideration of Chinese Skin Image Database (CSID)显示文摘After more than 60 years of development,artificial intelligence(AI)has been widely used in various fields.Especially in recent years,with the development of deep learning,AI has made many remarkable achievements in the medical field.Dermatology,as a clinical discipline with morphology as its main feature,is particularly suitable for the development of AI.The rapid development of skin imaging technology has helped dermatologists to assist in the diagnosis of diseases and has greatly improved the accuracy of diagnosis.Skin imaging data have natural big data attributes,which is important for AI research.The establishment of the Chinese Skin Image Database(CSID)has solved many problems such as isolated data islands and inconsistent data quality.Based on the CSID,many pioneering achievements have been made in the research and development of AI-assisted decision-making software,the establishment of expert organizations,personnel training,scientific research,and so on.At present,there are still many problems with AI in the field of dermatology,such as clinical validation,medical device licensing,interdisciplinary,and standard formulation,which urgently need to be solved by joint efforts of all parties. | Chengxu Li Wenmin Fei Yang Han Xiaoli Ning Ziyi Wang Keke Li Ke Xue Jingkai Xu Ruixing Yu Rusong Meng Feng Xu Weimin Ma Yong Cui | 2021 | Intelligent Medicine2021，1，2： | 1 |
| 4 | Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1显示文摘Macrophages in tumors(tumor-associated macrophages,TAMs),a major population within most tumors,play key homeostatic functions by stimulating angiogenesis,enhancing tumor cell growth,and suppressing antitumor immunity.Resetting TAMs by simple,efficacious and safe approach(s)is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy.Previously,we used tumor cell-derived microparticles to package chemotherapeutic drugs(drug-MPs),which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments,implicating that drug-MPs might reset TAMs,considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation.Here,we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-βrelease.Mechanistically,drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases,resulting in superoxide anion formation,which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2.Consequently,lysosomal Ca^(2+)signaling is activated,thus polarizing macrophages towards M1.Meanwhile,the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-βproduction.This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity.These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages.This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade. | Keke Wei Huafeng Zhang Shuaishuai Yang Yuxiao Cui Bingxia Zhang Jincheng Liu Liang Tang Yaoyao Tan Simin Liu Shiqi Chen Wu Yuan Xiao Luo Chen Chen Fei Li Junwei Liu Jie Chen Pingwei Xu Jiadi Lv Ke Tang Yi Zhang Jingwei Ma Bo Huang | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 0 |
| 5 | The RLCK-VND6 module coordinates secondary cell wall formation and adaptive growth in rice显示文摘The orderly deposition of secondary cell wall(SCW)in plants is implicated in various biological programs and is precisely controlled.Although many positive and negative regulators of SCW have been documented,the molecular mechanisms underlying SCW formation coordinated with distinct cellular physiological processes during plant adaptive growth remain largely unclear.Here,we report the identification of Cellulose Synthase co-expressed Kinase1(CSK1),which encodes a receptor-like cytoplasmic kinase,as a negative regulator of SCW formation and its signaling cascade in rice.Transcriptome deep sequencing of developing internodes and genome-wide co-expression assays revealed that CSK1 is co-expressed with cellulose synthase genes and is responsive to various stress stimuli.The increased SCW thickness and vigorous vessel transport in csk1 indicate that CSK1 functions as a negative regulator of SCW biosynthesis.Through observation of green fluorescent protein-tagged CSK1 in rice protoplasts and stable transgenic plants,we found that CSK1 is localized in the nucleus and cytoplasm adjacent to the plasma membrane.Biochemical and molecular assays demonstrated that CSK1 phosphorylates VASCULAR-RELATED NAC-DOMAIN 6(VND6),a master SCW-associated transcription factor,in the nucleus,which reduces the transcription of a suite of SCW-related genes,thereby attenuating SCW accumulation.Consistently,genetic analyses show that CSK1 functions upstream of VND6 in regulating SCW formation.Interestingly,our physiological analyses revealed that CSK1 and VND6 are involved in abscisic acid-mediated regulation of cell growth and SCW deposition.Taken together,these results indicate that the CSK1-VND6 module is an important component of the SCW biosynthesis machinery,which coordinates SCW accumulation and adaptive growth in rice.Our study not only identifies a new regulator of SCW biosynthesis but also reveals a fine-tuned mechanism for precise control of SCW deposition,offering tools for rationally tailoring agronomic traits. | Shaoxue Cao Yan Wang Yihong Gao Rui Xu Jianing Ma Zuopeng Xu Keke Shang-Guan Baocai Zhang Yihua Zhou | 2023 | Molecular Plant2023，16，6： | 0 |
| 6 | Surface polarization enables high charge separation in TiO_(2) nanorod photoanode显示文摘Poor charge separation efficiency of semiconductors often stands in the way of photoelectrochemical (PEC) water splitting realization. In this report, a surface polarized TiO_(2) photoanode is obtained via −OH moiety decoration, which achieves a fundamentally improved charge separation efficiency of about 94% at 1.23 VRHE. Detailed data shows that these hydroxyls with electric dipoles polarize the surface, inducing substantial electric field in the surface region, and elevating band edges so as to form a homojunction within TiO_(2). Such serves as the direct driving force for the photogenerated charge separation and migration. Moreover, these hydroxyls also facilitate water oxidation kinetics. Without typical doping or cocatalyst, surface polarized TiO_(2) photoanode delivers a considerably increased photocurrent density of about 1.41 mA·cm^(−2) at 1.23 VRHE (AM 1.5 G) and a cathodic shift on onset potential over 200 mV. This report highlights new opportunities to modulate charge separation by surface polarization for the construction of robust photoanodes. | Wei Ma Keke Huang Xiaofeng Wu Meng Wang Shouhua Feng | 2021 | Nano Research2021，14，11： | 0 |
| 7 | Generation and metabolomic characterization of functional ductal organoids with biliary tree networks in decellularized liver scaffolds显示文摘Developing functional ductal organoids(FDOs)is essential for liver regenerative medicine.We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds(DLSs)with primary cholangiocytes isolated from mouse bile ducts.The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification.FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers.Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14.The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers.Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylatedα-tubulin.The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems.The metabolomics analysis with 1075 peak pairs showed that serotonin,as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction,was specifically expressed in FDOs during the whole period of culture.Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening,which paves the way for future clinical therapeutic applications. | Jiaxian Chen Shiwen Ma Hui Yang Xi Liang Heng Yao Beibei Guo Deying Chen Jing Jiang Dongyan Shi Jiaojiao Xin Keke Ren Xingping Zhou Yun Li Lei Geng Jun Li | 2023 | Bioactive Materials2023，，8： | 0 |
| 8 | System Evaluation and Meta Analysis of Total Clinical Effective Rate of Acupuncture and Moxibustion in Treating Depression during 2019-2022显示文摘[Objectives]To systematically evaluate the total clinical effective rate of acupuncture treatment of depression,and provide clinical reference for the scheme design and selection of acupuncture treatment of depression.[Methods]By searching CNKI,Wanfang Data,CBM,VIP,Cochrane Library,Cochrane Central,Springer and other databases,randomized controlled experiment(RCT)on acupuncture and moxibustion treatment of depression from January 1,2019 to August 31,2022 was collected,to extract relevant data of total clinical effective rate and conduct methodological quality evaluation.ReviewManager 5.4.1 software was used for Meta analysis.[Results]22 RCTs were included,1602 patients in total.Among them,there were 804 cases in treatment group and 798 cases in control group.Meta analysis results displayed that acupuncture and moxibustion treatment of depression may be better than the control group in improving the total clinical effective rate,and the difference was statistically significant[MD=1.16,95%CI(1.11,1.21)].[Conclusions]Acupuncture and moxibustion can achieve a higher total clinical effective rate in the treatment of depression,which is worthy of clinical application.However,due to fewer studies included in this systematic evaluation,small sample size,and low quality,there was a high possibility of bias.Therefore,the above conclusions needed to be verified by high-quality,large-sample,and multi-center RCTs. | Xiaomeng LUO Xiong CHEN Keke MA Chunqi AI | 2023 | Medicinal Plant2023，14，1： | 0 |
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