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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen ye-xiong li Zhenkun Lou Min Deng State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of General Surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Department of General Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Dermatology University of California San DiegoSan DiegoCA 92093USA Department of Oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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C_(Ar)-Br bond cleavage via cooperative EnT/NHC catalysis: mild access to indolines

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Science China Chemistry 2024年第3期67卷 922-927页

作者： Yi-xiong Dong Cao-Bo li Ming-Lei Jin Zhong-Hua Gao Song ye Beijing National Laboratory for Molecular Sciences CAS Key Laboratory of Molecular Recognition and FunctionCAS Research/Education Center for Excellence in Molecular SciencesInstitute of ChemistryChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

The cooperative visible-light mediated and NHC-catalyzed dearomative arylation-acylation of N-(2-bromobenzoyl)indoles with aldehydes was developed, affording the corresponding highly functionalized polycyclic indolines in moderate to good yields with exclusive diastereoselectivities. Mechanism investigations support the activation of CAr-Br bond via visible-light mediated energy transfer(EnT) and the following single-electron-transfer(SET) with Breslow intermediate under NHC catalysis to give key aryl radical and ketyl radical. This protocol demonstrates the cleavage of CAr-Br bond under mild cooperative EnT/NHC catalysis.

关键词： energy transfer N-heterocyclic carbenes photocatalysis aryl radicals indolines

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In-situ polymerized PEO-based solid electrolytes contribute better li metal batteries:Challenges,strategies,and perspectives

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Journal of Energy Chemistry 2024年第5期92卷 548-571页

作者： Zhihui Jia Yong liu Haoming li Yi xiong Yingjie Miao Zhongxiu liu Fengzhang Ren School of Materials Science and Engineering Henan Key Laboratory of Non-Ferrous Materials Science&Processing TechnologyHenan University of Science and TechnologyLuoyang 471023HenanChina Provincial and Ministerial Co-construction of Collaborative Innovation Center for Non-ferrous Metal new Materials and Advanced Processing Technology Henan University of Science and TechnologyLuoyang 471023HenanChina

Polyethylene oxide(PEO)-based solid polymer electrolytes(SPEs)with good electrochemical stability and excellent li salt solubility are considered as one of the most promising SPEs for solid-state lithium metal batteries(SSLMBs).However,PEO-based SPEs suffer from low ionic conductivity at room temperature and high interfacial resistance with the electrodes due to poor interfacial contact,seriously hindering their practical applications.As an emerging technology,in-situ polymerization process has been widely used in PEO-based SPEs because it can effectively increase li-ion transport at the interface and improve the interfacial contact between the electrolyte and electrodes.Herein,we review recent advances in design and fabrication of in-situ polymerized PEO-based SPEs to realize enhanced performance in LMBs.The merits and current challenges of various SPEs,as well as their stabilizing strategies are presented.Furthermore,various in-situ polymerization methods(such as free radical polymerization,cationic polymerization,anionic polymerization)for the preparation of PEO-based SPEs are summarized.In addition,the application of in-situ polymerization technology in PEO-based SPEs for adjustment of the functional units and addition of different functional filler materials was systematically discussed to explore the design concepts,methods and working mechanisms.Finally,the challenges and future prospects of in-situ polymerized PEO-based SPEs for SSLMBs are also proposed.

关键词： In-situ polymerization Polyethylene oxide Solid polymer electrolytes lithium metal anodes

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Long non-coding RNAs with essential roles in neurodegenerative disorders

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Neural Regeneration Research 2024年第6期19卷 1212-1220页

作者： Wandi xiong lin Lu Jiali li Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology the Chinese Academy of Sciences Tsinghua-Peking Center for life Sciences National Institute on Drug Dependence Peking University PKU/McGovern Institute for Brain Research Peking University Institute of Mental Health National Clinical Research Center for Mental Disorders Key Laboratory of Mental Health and Peking University Sixth Hospital Peking University

Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number of long non-coding RNAs(lncRNAs) have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns, across different neurodegenerative diseases. However, the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood. This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles, regulatory mechanisms, and research status of lncRNAs in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Finally, this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases, hoping to provide broader implications for developing effective treatments.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis biomarker Huntington’s disease long non-coding RNAs neurodegenerative diseases Parkinson’s disease therapy transcriptional regulation translational regulation

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Efficient NO_x abatement by passive adsorption over a Pd-SAPO-34 catalyst prepared by solid-state ion exchange

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Chinese Chemical Letters 2024年第4期35卷 210-213页

作者： linhui liu Wuwan xiong Mingli Fu Junliang Wu Zhenguo li Daiqi ye Peirong Chen National Engineering Laboratory for VOCs Pollution Control Technology and Equipment Guangdong Provincial Key Laboratory of Atmospheric Environment and Pollution ControlSchool of Environment and EnergySouth China University of TechnologyGuangzhou 510006China National Engineering Laboratory for Mobile Source Emission Control Technology China Automotive Technology&Research Center Co.Ltd.Tianjin 300300China

Palladium-exchanged chabazite(Pd-CHA) zeolites as passive NO_x adsorbers(PNAs) enable efficient purification of nitrogen oxides(NO_x) in cold-start diesel exhausts. Their commercial application, however,is limited by the lack of facile preparation method. Here, high-performance CHA-type Pd-SAPO-34 zeolite was synthesized by a modified solid-state ion exchange(SSIE) method using PdO as Pd precursor,and demonstrated superior PNA performance as compared to Pd-SAPO-34 prepared by conventional wetchemistry strategies. Structural characterization using Raman spectroscopy and X-ray diffraction revealed that the SSIE method avoided water-induced damage to the zeolite framework during Pd loading. Mechanistic investigations on the SSIE process by in situ infrared spectroscopy and X-ray photoelectron spectroscopy disclosed that, while PdO precursor was mainly converted to Pd^(2+) cations coordinated to the zeolite framework by consuming the-OH groups of the zeolite, a portion of PdO could also undergo thermal decomposition to form highly dispersed Pd~0 clusters in the pore channels. This simplified and scalable SSIE method paves a new way for the cost-effective synthesis of defect-free high-performance Pd-SAPO-34 zeolites as PNA catalysts.

关键词： Pd-SAPO-34 Passive NO_x adsorber Pd loading Solid-state ion exchange Pd transformation

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Effects of microenvironment and biological behavior on the paracrine function of stem cells

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Genes & Diseases 2024年第1期11卷 135-147页

作者： Zhixin Xue Yunjun liao ye li The Department of Plastic and Cosmetic Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Mesenchymal stem cells(MSCs),the most well-studied cell type in the field of stem cell therapy,have multi-lineage differentiation and self-renewal potential.MsC-based thera-pies have been used to treat diverse diseases because of their ability to potently repair tissue and locally restore function.An increasing body of evidence demonstrates that paracrine func-tion is central to the effects of MsC-based therapy.Growth factors,cytokines,chemokines,extracellular matrix components,and extracellular vehicles all contribute to the beneficial ef-fects of MSCs on tissue regeneration and repair.The paracrine substances secreted by MSCs change depending on the tissue microenvironment and biological behavior.In this review,we discuss the bioactive substances secreted by MsCs depending on the microenvironment and biological behavior and their regulatory mechanisms,which explain their potential to treat human diseases,to provide new ideas for further research and clinical cell-free therapy.

关键词： Bioactive behavior Mesenchymal stem cells Microenvironment Paracrine Secretome

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Character of Convective Systems Producing Short-Term Heavy Precipitation in Central China Revealed by Kilometer and Minute Interval Observations

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Journal of Meteorological Research 2024年第3期38卷 530-541页

作者： Zitong CHEN Yunying li Zhiwei ZHANG Jing SUN Chengzhi ye Anyuan xiong College of Meteorology and Oceanography National University of Defense Technology High Impact Weather Key Laboratory of China Meteorological Administration Unit No.92192 of Chinese People's liberation Army Hubei Key Research Laboratory for Heavy Rain Monitoring and Warning Institute of Heavy RainChina Meteorological Administration Institute of Meteorological Sciences of Hunan Province Hunan Meteorological Bureau National Meteorological Information Centre China Meteorological Administration

Accurate forecasting of heavy precipitation in central China is still a challenge, within which a key issue is our still incomplete understanding of the convective systems（CSs） responsible for such events. In this study, through use of an iterative rain-cell tracking algorithm, the macroscale characteristics（scale, intensity, duration, etc.） of the CSs that produced 595 short-term heavy precipitation events in Hunan Province, central China, are quantitatively analyzed,based on radar reflectivity, echo top, and rainfall observations at 1-km and 6-min intervals in April–September of2016–2018. The results show that CSs present significant seasonal and diurnal features. Spring CSs usually cover a larger echo area with stronger convective cores and thus generate more precipitation than summer CSs, though summer CSs develop more vigorously and frequently. CSs initiated at 1400–1600 local time are characterized by the strongest convection and a smaller spatiotemporal scale, causing violent and transient showers with typical areal precipitation of 0.5–1mm km-2, but less total precipitation. Further analyses of the relationships among the scale, intensity, duration, and total precipitation of CSs reveal that the convective intensity is linearly correlated to the spatiotemporal scale of CSs, with the duration increasing on average by 0.0372 h dBZ-1; the echo area is significantly correlated to the total precipitation, and the duration and rainfall amount are connected with the area expansion rate（AER）of CSs: when the AER exceeds 50%, CSs expand rapidly with increasing total precipitation, but the duration is shorter.These findings provide a helpful reference for the forecasting of short-term heavy precipitation induced by CSs in central China.

关键词： convective system radar reflectivity factor total precipitation iterative rain-cell tracking

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Investigations of Water Flow Behaviors Induced by Local Temperature Variations through a Single Rough Fracture for the Enhanced Geothermal Systems

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Journal of Thermal Science 2024年第3期33卷 1055-1064页

作者： li Jiawei ye lin Department of Energy and Power Engineering Tsinghua UniversityBeijing100084China School of Power and Energy Northwestern Polytechnical UniversityXi’an710072China

In recent years,Enhanced Geothermal System(EGS)technologies have been applied to the geothermal resources production in the Hot Dry Rock(HDR).The core of EGS technologies is to adopt hydraulic fracturing in the reservoir to create a connected network of discrete fractures with the consideration of water as a working fluid for hydraulic fracturing and heat production.This paper investigates the characteristics of water flow behaviors through a single rough fracture under different temperature and pressure conditions.A single fracture model with rough fracture surfaces is constructed and then characterized,and influences of the anisotropic factor on the average tortuosity and frictional resistance coefficient of water flow through a single fracture with rough surfaces have been compared and analyzed.With consideration of other impacting factors(temperature,pressure,fracture roughness),the impact of mass flow rate has also been presented.Numerical simulation results present that changes of average tortuosity for water flow through a single rough facture are mainly affected by temperature.It can be observed that higher temperature leads to larger average tortuosity but the frictional resistance coefficient shows an opposite trend.As for pressure conditions,it is found that effects of pressure on average tortuosity and frictional resistance coefficient is very small,which can be neglected under high pressure conditions.Furthermore,the average tortuosity shows a progressively linear relationship with the mass flow rate.On the contrary,the frictional resistance coefficient has a negative relationship with the mass flow rate.It is revealed that when the mass flow rate reaches a critical point,the influences of temperature on the frictional resistance coefficient will be negligible.Comparisons of single rough fractures with different anisotropic factors show that values of average tortuosity and frictional resistance coefficient have positive relationships with the increase of anisotropic factors.

关键词： single rough fracture tortuosity frictional resistance enhanced geothermal system

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Multi-Objective Multi-Variable Large-Size Fan Aerodynamic Optimization by Using Multi-Model Ensemble Optimization Algorithm

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Journal of Thermal Science 2024年第3期33卷 914-930页

作者： xiong Jin GUO Penghua li Jingyin School of Energy and Power Engineering Xi’an Jiaotong UniversityXi’an710049China

The constrained multi-objective multi-variable optimization of fans usually needs a great deal of computational fluid dynamics(CFD)calculations and is time-consuming.In this study,a new multi-model ensemble optimization algorithm is proposed to tackle such an expensive optimization problem.The multi-variable and multi-objective optimization are conducted with a new flexible multi-objective infill criterion.In addition,the search direction is determined by the multi-model ensemble assisted evolutionary algorithm and the feature extraction by the principal component analysis is used to reduce the dimension of optimization variables.First,the proposed algorithm and other two optimization algorithms which prevail in fan optimizations were compared by using test functions.With the same number of objective function evaluations,the proposed algorithm shows a fast convergency rate on finding the optimal objective function values.Then,this algorithm was used to optimize the rotor and stator blades of a large axial fan,with the efficiencies as the objectives at three flow rates,the high,the design and the low flow rate.Forty-two variables were included in the optimization process.The results show that compared with the prototype fan,the total pressure efficiencies of the optimized fan at the high,the design and the low flow rate were increased by 3.35%,3.07%and 2.89%,respectively,after CFD simulations for 500 fan candidates with the constraint for the design pressure.The optimization results validate the effectiveness and feasibility of the proposed algorithm.

关键词： multi-objective optimization surrogate-assisted evolutionary algorithm axial fan computational fluid dynamics aerodynamic optimization

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Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1339-1345页

作者： De-Kui Gao Xiang-lin ye Zhen Duan Hong-Yang Zhang Tao xiong Zheng-Hong li Hai-Feng Pei Department of Cardiology Jiangyou Second People's HospitalJiangyou 621701Sichuan ProvinceChina Department of Cardiology The General Hospital of Western Theater CommandChengdu 610083Sichuan ProvinceChina Department of Clinical Medicine Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Special Inspection Jiangyou Second People's HospitalJiangyou 621701Sichuan ProvinceChina

BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.

关键词： Bradycardia cardiomyopathy Heart rate Atrial fibrillation Cardiac dilatation Case report

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