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Snail acetylation by autophagy-derived acetyl-coenzyme A promotes invasion and metastasis of KRAS-LKB1 co-mutated lung cancer cells

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Cancer Communications 2022年第8期42卷 716-749页

作者： Jang Hee Han Yong Keon Kim Hakhyun Kim Jooyoung Lee Myung Joon Oh Sang Bum Kim Minjee Kim Kook Hwan Kim Hyun Ju Yoon Myung-Shik Lee john d.minna Michael A.White Hyun Seok Kim Severance Biomedical Science Institute Yonsei University College of MedicineSeoul 03722Korea department of Medical Science Yonsei University Graduate SchoolSeoul 03722Korea department of Urology Seoul National University HospitalSeoul 03722Korea Checkmate Therapeutics Inc. Seoul 07207Korea Hamon Center for Therapeutic Oncology Research University of Texas Southwestern Medical CenterDallasTexas 75390USA department of Cell Biology University of Texas Southwestern Medical CenterDallasTexas 75390USA Graduate School of Medical Science Brain Korea 21 ProjectYonsei University College of MedicineSeoul 03722Korea

Background: Autophagy is elevated in metastatic tumors and is often associatedwith active epithelial-to-mesenchymal transition (EMT). However, the extent towhich EMT is dependent on autophagy is largely unknown. This study aimed toidentify the mechanisms by which autophagy facilitates ***: We employed a liquid chromatography-based metabolomic approachwith kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1)gene co-mutated (KL) cells that represent an autophagy/EMT-coactivatedinvasive lung cancer subtype for the identification of metabolites linked to autophagy-driven EMT activation. Molecular mechanisms of autophagy-drivenEMT activation were further investigated by quantitative real-time polymerasechain reaction (qRT-PCR), Western blotting analysis, immunoprecipitation,immunofluorescence staining, and metabolite assays. The effects of chemicaland genetic perturbations on autophagic flux were assessed by two orthogonalapproaches: microtubule-associated protein 1A/1B-light chain 3 (LC3) turnoveranalysis by Western blotting and monomeric red fluorescent protein-greenfluorescent protein (mRFP-GFP)-LC3 tandem fluorescent protein quenchingassay. Transcription factor EB (TFEB) activity was measured by coordinatedlysosomal expression and regulation (CLEAR) motif-driven luciferase reporterassay. Experimental metastasis (tail vein injection) mouse models were used toevaluate the impact of calcium/calmodulin-dependent protein kinase kinase 2(CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVISluciferase imaging ***: We found that autophagy in KL cancer cells increased acetyl-coenzymeA (acetyl-CoA), which facilitated the acetylation and stabilization of theEMT-inducing transcription factor Snail. The autophagy/acetyl-CoA/acetylSnail axis was further validated in tumor tissues and in autophagy-activatedpancreatic cancer cells. TFEB acetylation in KL cancer cells sustained prometastatic autophagy in a mammalian target o

关键词： snail autophagy acetyl-coenzyme A epithelial-to-mesenchymal transition non-small-cell lung cancer CAMKK2 acetyl-snail pancreatic cancer KRAS inhibitor metastasis ACLY

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Pt nanodendrites with a PtIr alloy surface structure exhibit excellent stability toward acidic hydrogen evolution reaction

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Nano Research 2024年第6期17卷 4844-4849页

作者： Chang Liu Zongnan Wei minna Cao Rong Cao State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China University of Chinese Academy of Sciences Beijing 100049China Fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China Fuzhou 350108China

The development of effective and stable electrocatalysts for the hydrogen evolution reaction(HER)in acidic electrolytes is a significant *** this work,homogeneous Pt nanodendrites(Pt Nds)with a PtIr shell were successfully synthesized by a two-step wet chemical *** open three-dimensional(3d)dendritic structure exhibited exceptional electrocatalytic characteristics,exposing as many active sites as ***,by alloying Ir with Pt on the surface,catalytic activity was greatly enhanced while ensuring extremely high *** surface-enriched platinum nanodendritic catalysts(Pt@PtIr Nds)outperformed the control samples and the commercial *** acidic HER test,Pt@PtIr Nds had a lower overpotential(22 mV)than Pt Nds(26 mV)and commercial Pt/C(31 mV)at 10 mA/cm^(2),and the activity of Pt@PtIr Nds remained consistent even after undergoing a continuous durability test for at least 168 h,which was much superior to the performance of commercial Pt/C(10 h)under identical test *** study revealed that the application of 3d Pt dendritic metal alloys may offer a chance for the development of enhanced electrocatalysts in acidic HER.

关键词： Pt nanodendrites iridium high stability hydrogen evolution reaction alloy

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MUS Model:A deep Learning-Based Architecture for IoT Intrusion detection

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Computers, Materials & Continua 2024年第7期80卷 875-896页

作者： Yu Yan Yu Yang Shen Fang minna Gao Yiding Chen College of Information Engineering University of Engineering of the Chinese People’s Armed Police Force(PAP)Xi’an710000China College of Missile Engineering Rocket Force Engineering UniversityXi’an710000China

In the face of the effective popularity of the Internet of Things(IoT),but the frequent occurrence of cybersecurity incidents,various cybersecurity protection means have been proposed and *** them,Intrusion detection System(IdS)has been proven to be stable and ***,traditional intrusion detection methods have shortcomings such as lowdetection accuracy and inability to effectively identifymalicious *** address the above problems,this paper fully considers the superiority of deep learning models in processing highdimensional data,and reasonable data type conversion methods can extract deep features and detect classification using advanced computer vision techniques to improve classification *** TransformField(MTF)method is used to convert 1dnetwork traffic data into 2d images,and then the converted 2d images are filtered by UnsharpMasking to enhance the image details by sharpening;to further improve the accuracy of data classification and detection,unlike using the existing high-performance baseline image classification models,a soft-voting integrated model,which integrates three deep learning models,MobileNet,VGGNet and ResNet,to finally obtain an effective IoT intrusion detection architecture:the MUS *** types of experiments are conducted on the publicly available intrusion detection dataset CICIdS2018 and the IoT network traffic dataset N_BaIoT,and the results demonstrate that the accuracy of attack traffic detection is greatly improved,which is not only applicable to the IoT intrusion detection environment,but also to different types of attacks and different network environments,which confirms the effectiveness of the work done.

关键词： Cyberspace security intrusion detection deep learning Markov Transition Fields(MTF) soft voting integration

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Aerodynamics of a Tandem-Bladed Axial Compressor Rotor under Circumferential distortion at different Rotational Speeds

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Journal of Thermal Science 2024年第4期33卷 1340-1356页

作者： Amit KUMAR Jerry T.john A.M.PRAdEEP R.A.dAKKERMANS dragan KOZULOVIC department of Aerospace Engineering Indian Institute of Technology BombayMumbai400076India department of Automotive and Aeronautical Engineering Hamburg University of Applied Sciences20099HamburgGermany Institute of Jet Propulsion Bundeswehr University Munich85577NeubibergGermany

For most aircraft engines,inflow distortion is *** distortion is known to degrade the aerodynamic performance and stable operating limits of a *** rotor configuration is an arrangement that effectively controls the growth of the boundary layer over the suction surface of the ***,a higher total pressure rise can be achieved through this unconventional design approach involving the splitting of the blade into forward and aft *** is expected that the effect of inlet flow distortion would be more severe for a tandem-rotor design due to the greater flow turning inherent in such ***,this aspect needs to be thoroughly *** present study discusses the effect of circumferential distortion on the tandem-rotor at different rotational ***-annulus RANS simulations using ANSYS CFX are used in the present *** performance of the rotor at a particular flow coefficient and different rotational speeds is *** total pressure and efficiency are observed to drop at lower mass flow rates under the influence of circumferential *** loss region in each blade passage is mainly associated with the blade wake,tip leakage vortex,secondary flow,and boundary ***,their contribution varies from passage to passage,particularly in the distorted *** the lower span,the wake width is found to be higher than that at a higher *** to the redistribution of the mass flow,the circumferential extent reduces at a higher *** the undistorted sector,the strength of the tip leakage vortex is significantly higher at the design rotational speed than at lower *** distortion near the tip region promotes an early vortex breakdown even at the design operating *** adversely affects the total pressure,efficiency,and stall *** clean flow conditions,this phenomenon is only observed near the stall *** the design operating condition,the breakdown of the forward rotor tip l

关键词： tandem rotor circumferential distortion loss tip leakage vortex vortex breakdown diffusion factor aerodynamics of compressor blade

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Challenges and Opportunities in Preserving Key Structural Features of 3d-Printed Metal/Covalent Organic Framework

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Nano-Micro Letters 2024年第8期16卷 362-381页

作者： Ximeng Liu dan Zhao john Wang department of Materials Science and Engineering National University of SingaporeSingapore 117574Singapore department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117585Singapore National University of Singapore(Chongqing)Research Institute Chongqing 401123People’s Republic of China

Metal-organic framework(MOF)and covalent organic framework(COF)are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features,such as large surface area,tunable pore size,and functional surfaces,which have significant values in various application *** emerging 3d printing technology further provides MOF and COFs(M/COFs)with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3d ***,the currently available 3d printing M/COFs strategy faces a major challenge of severe destruction of M/COFs’microstructural features,both during and after 3d *** is envisioned that preserving the microstructure of M/COFs in the 3d-printed monolith will bring a great improvement to the related *** this overview,the 3d-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered *** differences in the properties,applications,and current research states are *** up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3d printing are further discussed for the two types of 3d-printed M/*** the analysis of the current states of 3d-printed M/COFs,the expected future research direction to achieve a highly preserved microstructure in the 3d monolith is proposed.

关键词： Metal-organic frameworks Covalent organic frameworks 3d printing Microstructure Monolith

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Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature

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World Journal of Orthopedics 2024年第9期15卷 870-881页

作者： Christian J Rajkovic Matthew L Merckling Alyssa W Lee Galadu Subah Aryan Malhotra Zachary d Thomas Sabrina L Zeller john V Wainwright Merritt d Kinon department of Neurosurgery Westchester Medical CenterValhallaNY 10595United States

BACKGROUNd Chronic inflammatory pain is associated with increased expression of interleukin(IL)-1,an inflammatory cytokine,and activity on its receptor(IL-1R).In response,the body produces IL-1R antagonist(IL-1Ra)to reduce this *** conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve *** systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal *** To evaluate the use of ACS as a conservative management option for spinal *** A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal *** Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS *** had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(ddd)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(Sd)follow-up was 21.7(4.8)weeks from first ACS *** studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to *** achieved comparable or su-perior results to lumbar epidural steroid *** events were reported in 21 patients(3.1%),with no serious adverse *** ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.

关键词： Spine Autologous conditioned serum Orthokine Regenokine Epidural steroid injection Interleukin-1 Inter-leukin-1 receptor antagonist

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVId-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven d Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall david A dorward Jonathan A Fallowfield Peter C Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUNd Metabolic dysfunction-associated steatotic liver disease(MASLd),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVId-19),while preexisting MASLd increases the risk of LI and the development of COVId-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVId-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLd and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLd were determined in formalin-fixed liver tissue sections across the MASLd pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVId-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLd *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVId-19 COVId-19-associated cholangiopathy

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Endoscopic ultrasound-guided portal pressure gradient identifies patients with previously undiagnosed clinically significant portal hypertension

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Portal Hypertension & Cirrhosis 2024年第2期3卷 67-74页

作者： Jerome C.Edelson Scott F.d.Edelson john G.Quiles Cyrus V.Edelson Eric M.Montminy Christian L.Horn john P.Magulick don C.Rockey department of Gastroenterology and Hepatology Brooke Army Medical CenterFort Sam HoustonTexasUSA department of Medicine Uniformed Services University of the Health SciencesBethesdaMarylandUSA department of Medicine Brooke Army Medical CenterFort Sam HoustonTexasUSA john H.Stroger Jr.Hospital of Cook County ChicagoIllinoisUSA digestive disease Research Center Medical University of South CarolinaCharlestonSouth CarolinaUSA

Aims:Portal hypertension(PH)is a complication of cirrhosis that leads to hepatic *** the portal pressure gradient(PPG)provides valuable information for disease assessment,staging,and *** this study,we aimed to report the utilization of endoscopic ultrasound(EUS)-guided PPG(EUS-PPG)measurements in a real-world ***:This retrospective analysis included patients at a tertiary care center who underwent EUS-PPG between February 2021 and May *** most common indication was to establish or exclude the diagnosis of cirrhosis,followed by an assessment of surgical risk in the setting of suspected *** demographic and clinical data were collected,and statistical analysis was performed using the Student's t ***:Eighteen patients underwent *** success was achieved in 17 of the 18 *** complications were *** mean scores of Child-Pugh,Model for End-Stage Liver disease-Sodium,and Fibrosis-4 scores were 5.1±0.5,9.0±3.0,and 3.7±4.5,*** the 18 patients,two presented with esophageal varices and six with portal hypertensive *** mean PPG was 5.8±4.5 mmHg,and five patients exhibited clinically significant PH(CSPH).Of the 18 patients,15 underwent concurrent EUS-liver biopsy,which was 100%successful and provided diagnostic histology for all *** PPG data led to changes in the clinical management of 17 ***:EUS-PPG is safe and technically *** Child-Pugh score did not correlate well with the presence of CSPH;however,PPG measurements resulted in changes in the management of almost all *** studies correlating EUS-PPG with other assessments of liver diseases are required.

关键词： EUS portal hypertension portal pressure gradient

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damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 597-615页

作者： Xin Yu Yuye Tan Weidong Song john Kemeny Shengwen Qi Bowen Zheng Songfeng Guo Key Laboratory of Shale Gas and Geoengineering Institute of Geology and GeophysicsChinese Academy of SciencesBeijing100089China Innovation Academy for Earth Science Chinese Academy of SciencesBeijing100089China University of Chinese Academy of Sciences Beijing100049China School of Civil and Resources Engineering University of Science and Technology BeijingBeijing100083China Key Laboratory of High-Efficient Mining and Safety of Metal Mines(Ministry of Education of China) University of Science and Technology BeijingBeijing100083China department of Mining and Geological Engineering University of ArizonaTucsonAZ86721USA

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping *** understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3d fracture *** results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill *** important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases ***,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction *** finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture *** transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa *** the findings have important practical implications on t

关键词： Rock and backfill Triaxial cyclic loading Volume fraction damage evolution 3d visualization

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development and characterization of 3d-printed electroconductive pHEMA-co-MAA NP-laden hydrogels for tissue engineering

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Bio-design and Manufacturing 2024年第3期7卷 262-276页

作者： Sara de Nitto Aleksandra Serafin Alexandra Karadimou Achim Schmalenberger john J.EMulvihill Maurice N.Collins dIBRIS Polytechnic Inter-School Section University of Genoa16126 GenoaItaly School of Engineering Bernal InstituteUniversity of LimerickLimerick V94 T9PXIreland School of Natural Sciences Department of Biological SciencesUniversity of LimerickLimerick V94 T9PXIreland Health Research Institute University of LimerickLimerick V94 T9PXIreland AMBER University of LimerickLimerick V94 T9PXIreland

Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEdOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3d)*** presence of the NPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3d *** were 3d printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various TE strategies.

关键词： Conductive nanoparticles Hydroxyethyl methacrylate(HEMA) Ultraviolet(UV)polymerization 3d printing

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