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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-fei fei Chen Wang Shuang Zhang fei Wang Guan-Min Jiang Hao Wang Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of Clinical Medicine Shandong UniversityJinanChina Core Unit of National Clinical Research Center for Laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of Clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied types.Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted therapeutics.Eventually,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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THE TRUNCATED EM METHOD FOR JUMP-DIFFUSION SDDES WITH SUPER-LINEARLY GROWING DIFFUSION AND JUMP COEFFICIENTS

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Journal of Computational Mathematics 2024年第1期42卷 178-216页

作者： Shounian Deng Chen fei Weiyin fei Xuerong Mao Key Laboratory of Advanced Perception and Intelligent Control of High-end Equipment Ministry of Educationand School of Mathematics-Physics and FinanceAnhui Polytechnic UniversityWuhu 241000China Business School University of Shanghai for Science and TechnologyShanghai 200093China Department of Mathematics and Statistics University of StrathclydeGlasgow G11XHUK

This work is concerned with the convergence and stability of the truncated EulerMaruyama(EM)method for super-linear stochastic differential delay equations(SDDEs)with time-variable delay and Poisson jumps.By constructing appropriate truncated functions to control the super-linear growth of the original coefficients,we present two types of the truncated EM method for such jump-diffusion SDDEs with time-variable delay,which is proposed to be approximated by the value taken at the nearest grid points on the left of the delayed argument.The first type is proved to have a strong convergence order which is arbitrarily close to 1/2 in mean-square sense,under the Khasminskii-type,global monotonicity with U function and polynomial growth conditions.The second type is convergent in q-th(q<2)moment under the local Lipschitz plus generalized Khasminskii-type conditions.In addition,we show that the partially truncated EM method preserves the mean-square and H∞stabilities of the true solutions.Lastly,we carry out some numerical experiments to support the theoretical results.

关键词： SDDEs Truncated EM method Time-variable delay Poisson jumps

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MH-STRALP:A scoring system for prognostication in patients with upper gastrointestinal bleeding

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 790-806页

作者： Jun-Nan Hu fei Xu Ya-Rong Hao Chun-Yan Sun Kai-ming Wu Yong Lin Lan Zhong Xin Zeng Department of Gastroenterology Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Gastroenterology Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China

BACKGROUND Upper gastrointestinal bleeding(UGIB)is a common medical emergency and early assessment of its outcomes is vital for treatment decisions.AIM To develop a new scoring system to predict its prognosis.METHODS In this retrospective study,692 patients with UGIB were enrolled from two cen-ters and divided into a training(n=591)and a validation cohort(n=101).The clinical data were collected to develop new prognostic prediction models.The en-dpoint was compound outcome defined as(1)demand for emergency surgery or vascular intervention,(2)being transferred to the intensive care unit,or(3)death during hos-pitalization.The models’predictive ability was compared with previously esta-blished scores by receiver operating characteristic(ROC)curves.RESULTS Totally 22.2%(131/591)patients in the training cohort and 22.8%(23/101)in the validation cohort presented poor outcomes.Based on the stepwise-forward Lo-gistic regression analysis,eight predictors were integrated to determine a new post-endoscopic prognostic scoring system(MH-STRALP);a nomogram was de-termined to present the model.Compared with the previous scores(GBS,Rock-all,ABC,AIMS65,and PNED score),MH-STRALP showed the best prognostic prediction ability with area under the ROC curves(AUROCs)of 0.899 and 0.826 in the training and validation cohorts,respectively.According to the calibration cur-ve,decision curve analysis,and internal cross-validation,the nomogram showed good calibration ability and net clinical benefit in both cohorts.After removing the endoscopic indicators,the pre-endoscopic model(pre-MH-STRALP score)was conducted.Similarly,the pre-MHSTRALP score showed better predictive value(AUROCs of 0.868 and 0.767 in the training and validation cohorts,respectively)than the other pre-endoscopic scores.CONCLUSION The MH-STRALP score and pre-MH-STRALP score are simple,convenient,and accurate tools for prognosis prediction of UGIB,and may be applied for early decision on its management strategies.

关键词： Upper gastrointestinal bleeding Prognosis prediction Retrospective study Nomogram Post-endoscopic model Pre-endoscopic model

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Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

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World Journal of Diabetes 2024年第4期15卷 654-663页

作者： Yi Shi Yan-Xin Zhang ming-fei Jiao Xin-Jun Ren Bo-Jie Hu Ai-Hua Liu Xiao-Rong Li Surgical Retina Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Glaucoma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Ocular Trauma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China

BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research.AIM To develop a visual risk profile model to explore factors influencing DR after surgery.METHODS We retrospectively selected 151 patients with DR undergoing PPV.The patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after surgery.Independent risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction curve.RESULTS After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model.The area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,respectively.The AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,respectively.CONCLUSION A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy.This study can help formulate relevant preventive and treatment measures.

关键词： Diabetic retinopathy Retinopathy Neovascular Glaucoma Risk factors Nomogram

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Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty

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Current Medical Science 2024年第3期44卷 561-567页

作者： Xiang-qi WU Long-bo LI Wei YOU Zhi-ming WU Lei ZHAO Zhi-hui WANG Pei-na MENG Bin LIU fei YE Department of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjing210006China Department of Cardiology The Second Hospital of Jilin UniversityJilin130000China

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term follow-up.Methods This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled.The QFR of the entire target vessel was measured offline.The primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had TVF.The QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF group.Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P<0.01].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P<0.01).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P<0.01).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

关键词： percutaneous coronary intervention in-stent restenosis target vessel failure quantitative flow ratio

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NbN quantum dots anchored hollow carbon nanorods as efficient polysulfide immobilizer and lithium stabilizer for Li-S full batteries

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Journal of Energy Chemistry 2024年第1期88卷 260-271,I0007页

作者： fei Ma Zhuo Chen Katam Srinivas Ziheng Zhang Yu Wu Dawei Liu Hesheng Yu Yue Wang Xinsheng Li ming-qiang Zhu Qi Wu Yuanfu Chen School of Integrated Circuit Science and Engineering and State Key Laboratory of Electronic Thin Films and Integrated DevicesUniversity of Electronic Science and TechnologyChengdu 610054SichuanChina College of Science and Institute of Oxygen Supply Center of Tibetan Studies(Everest Research Institute)Tibet UniversityLhasa 850000TibetChina College of Mechanical and Electronic Engineering Northwest A&F UniversityXianyang 712100ShaanxiChina

The shuttle effect of lithium polysulfides(LiPSs)and uncontrollable lithium dendrite growth seriously hinder the practical application of lithium-sulfur(Li-S)batteries.To simultaneously address such issues,monodispersed Nb N quantum dots anchored on nitrogen-doped hollow carbon nanorods(NbN@NHCR)are elaborately developed as efficient Li PSs immobilizer and Li stabilizer for high-performance Li-S full batteries.Density functional theory(DFT)calculations and experimental characterizations demonstrate that the sulfiphilic and lithiophilic NbN@NHCR hybrid can not only efficiently immobilize the soluble Li PSs and facilitate diffusion-conversion kinetics for alleviating the shuttling effect,but also homogenize the distribution of Li+ions and regulate uniform Li deposition for suppressing Li-dendrite growth.As a result,the assembled Li-S full batteries(NbN@NHCR-S||Nb N@NHCR-Li)deliver excellent long-term cycling stability with a low decay rate of 0.031%per cycle over 1000 cycles at high rate of 2 C.Even at a high S loading of 5.8 mg cm^(-2)and a low electrolyte/sulfur ratio of 5.2μL mg^(-1),a large areal capacity of 6.2 mA h cm^(-2)can be achieved in Li-S pouch cell at 0.1 C.This study provides a new perspective via designing a dual-functional sulfiphilic and lithiophilic hybrid to address serious issues of the shuttle effect of S cathode and dendrite growth of Li anode.

关键词： Dual-functional host NbN quantum dots Shuttle effect Dendrite-free Li anode Li-S full batteries

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Efficacy and safety of Huzhang Granule,a compound Chinese herbal medicine,for acute gouty arthritis:A double-blind,randomized controlled trial

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Journal of Integrative Medicine 2024年第3期22卷 270-278页

作者： Hao Wang Si-ting Chen Xiao-jie Ding Le Kuai Liang Hua Xin Li Yi-fei Wang ming Zhang Bin Li Rui-ping Wang Mi Zhou Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai 201203China Department of Dermatology the Affiliated Hospital of Jiangxi University of Chinese MedicineNanchang 330000Jiangxi ProvinceChina Shanghai Skin Disease Hospital School of MedicineTongji UniversityShanghai 200443China Institute of Dermatology School of MedicineTongji UniversityShanghai 200443China

Background:Acute gouty arthritis(AGA)is an inflammatory joint disease with a high prevalence.Typical medical interventions,including nonsteroidal anti-inflammatory drugs,colchicine and glucocorticoids,can have serious adverse reactions.Huzhang Granule(HZG),a compound Chinese herbal medicine,has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions.However,the efficacy and safety of HZG in AGA patients remains unknown.Objective:The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients.Design,setting,participants and interventions:The current study was conducted as a noninferiority,randomized controlled clinical trial on 180 eligible enrolled participants.Participants were randomly assigned into the HZG and etoricoxib groups.Treatments were administered for 5 d,during which the HZG group received HZG and placebo etoricoxib,while the etoricoxib group received etoricoxib and placebo HZG in the same ratio(1:1).Main outcome measures:The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window.The pain level was measured via a visual analogue scale,ranging from 0 mm to 100 mm.The secondary outcomes comprised joint tenderness and swelling,reduction of inflammatory biomarkers,and the patient’s and investigator’s global evaluations of therapeutic response.Results:The mean reduction in pain was-51.22 mm(95%confidence interval[CI],[-53.42,-49.03]mm)for the HZG and-52.00 mm(95%CI,[-54.06,-49.94]mm)for the etoricoxib groups.The mean difference between the two groups was 0.78 mm(95%CI,[-2.25,3.81]mm).All additional efficacy endpoints,covering decreased inflammation and pain relief,yielded compelling proof of noninferiority.Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group(4.44%vs 13.33%;P≤0.05).Conclusion:HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness

关键词： Acute gouty arthritis Huzhang Granule Randomized controlled trial Blind

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Nanoindentation behavior and creep-induced cracking of long-term crept austenitic steel at 650℃

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Journal of Iron and Steel Research(International) 2024年第2期31卷 464-474页

作者： Zhen Zhang Yu-hang Duan Shuai Wang Jin-shan Chen An-zhe Wang Xiang-yang Mao Yuan-ji Shi Jie Zhang ming Liu Zheng-fei Hu School of Materials Science and Engineering Nanjing Institute of TechnologyNanjing211167JiangsuChina Jiangsu Key Laboratory of Advanced Structural Materials and Application Technology Nanjing211167JiangsuChina Jiangsu Wind Power Engineering Technology Center Nanjing210023JiangsuChina Nanjing Vocational University of Industry Technology Nanjing210023JiangsuChina Baoshan Iron&Steel Co. Ltd.Shanghai201900China Fujian Provincial Key Laboratory of Terahertz Functional Devices and Intelligent Sensing School of Mechanical Engineering and AutomationFuzhou UniversityFuzhou350116FujianChina School of Materials Science and Engineering Tongji UniversityShanghai201804China

The grain boundary(GB)damage of long-term crept HR3C(25Cr–20Ni–Nb–N)austenitic steel with solid solution state was investigated by nanoindentation test accompanied with in-situ electron back-scattered diffraction.The corresponding microstructure was characterized by scanning electron microscopy and transmission electron microscopy.Results show that the increase in nanoindentation hardness at the GBs and triple grain junctions may be related to the dislocation accumulation and carbide growth during the creep.Coarsened M23C6 and dislocations piling-up at the GB accelerate the nucleation and coalescence of creep cavity along the GB.The nanoindentation hardness in grains varies with orientation of the stress axis.The orientation difference of neighbor grains may induce local high geometrically necessary dislocation densities and strain gradients near the GB,consequently causing stress concentration and subsequent crack growth at specific GBs.

关键词： Austenitic steel Creep Nanoindentation Grain orientation Creep-induced cracking

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Three cancers in the renal pelvis,bladder,and colon:A case report

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World Journal of Clinical Cases 2024年第2期12卷 392-398页

作者： Jing Chen Hua-Yan Huang Hui-Chun Zhou Lin-Xiao Liu Chuang-Fan Kong Quan Zhou Jian-ming fei Yuan-ming Zhu Hu Liu Ye-Chen Tang Cheng-Zhong Zhou Department of General Surgery The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina Department of Pathology The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina Department of Medical Imaging The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina Department of Urology The Second Affiliated Hospital of Jiaxing UniversityJiaxing 31400Zhejiang ProvinceChina

BACKGROUND Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development.It is particularly rare for an individual to have more than two primary cancers.In this report,we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis,bladder,and colon.CASE SUMMARY On December 30,2014,a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week.A computed tomography(CT)scan revealed wall thickening in the left ureter’s upper segment,while a CT urography revealed a left renal pelvis tumor.A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015.The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis.The final pathological tumor stage was pT1N0M0.After surgery,this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin,as well as bladder infusion therapy with gemcitabine.On December 18,2017,the patient was admitted once again to our hospital with a one-day history of painless gross hematuria.A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder.Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29,2017.The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder(maximum size 3.7 cm×2.6 cm).The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery.The pathological tumor stage was pT1N0M1.The patient refused chemotherapy after surgery.After another six years,the patient returned on February 28,2023,complaining of periumbilical pain that had lasted six days.This time,a CT scan of the abdomen showed a tumor in the ascending colon,but a subsequent colonoscopy examinat

关键词： Metachronous primary carcinoma Renal pelvis carcinoma Bladder carcinoma Colon carcinoma Case report

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Efficient micrometer-scale thick-film perovskite solar cells with superior stability

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Rare Metals 2024年第4期43卷 1647-1657页

作者： Jian-fei Hu Gang Chen Shun-Zhang Yu Yue-Xin Lin Kai-Yu Wang Zong-Wei Li Guo-Dong Zhang Teng-fei Pan Ya-Jing Li ming-Jie Li Ying-Dong Xia Yi-Fan Lv Yong-Hua Chen Key Laboratory of Flexible Electronics (KLoFE) and Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies)Nanjing Tech University (NanjingTech) Department of Applied Physics The Hong Kong Polytechnic University Shenzhen Research Institute The Hong Kong Polytechnic University Optics Valley Laboratory

It is essential to enhance the thickness of the absorber layer for perovskite solar cells(PSCs) to improve device performance and reduce industry refinement.However,thick perovskite films(> 1 μm) are difficult to be fabricated by employing traditional solvents,such as N,N-dimethylformamide(DMF),dimethyl sulfoxide(DMSO).Besides,it is a challenge to fabricate thick-film perovskite owing to the deteriorated surface morphology and serious defect density.Herein,a simple method was reported to deposit uniform pinhole-free perovskite films with a thickness of more than 2 μm utilizing the methylamine acetate(MAAc) ionic liquid as the solvent.Combined with methylammonium chloride(MACl) as an additive,thick-film perovskite with～ 2μm in grain size and few grain boundaries(GBs) was prepared,which dramatically improved the perovskite crystal quality and enhanced carrier transport performance.The final PSCs exhibited a power conversion efficiency(PCE) of 20.16%.The device showed improved stability with 95% of its initial efficiency in a nitrogen environment over 5000 h.This work provides an alternative strategy to produce extremely efficient and stable thick-film PSCs.It can be believed that this device has great potential in the application of large areas and laminated PSCs.

关键词： Perovskite solar cells Thick-film Stability Ionic liquid

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