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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO YAN TING SU CHI FENG XIN long YIRU PAN RUPEI YE TIAN XIA HANAN long JIANMING WU XIUlI xiao Sichuan Key Medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The Department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The Department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The Department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAl),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAl and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAl’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAl on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAl-induced drug ***ﬁndings reveal that PAl signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAl also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAl’s anti-tumor efﬁcacy.A combination of PAl and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAl and TRA combination emerges as a promising strategy for overcoming PAl-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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Investigating the neutron star physics through observations of several young pulsars in the dipole-field re-emergence scenario

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Science China(Physics,Mechanics & Astronomy) 2024年

作者： Yu-long Yan Quan Cheng xiao-Ping Zheng Institute of Astrophysics Central China Normal University Department of Astronomy Huazhong University of Science and Technology

The observed timing data, magnetic tilt angle χ, and age of young pulsars could be used to probe some important issues about neutron star（NS） physics, e.g., the NS internal magnetic field configuration, and the number of precession cycles ξ. Both quantities are critical in studying the continuous gravitational wave emission from pulsars, and the latter generally characterizes the mutual interactions between superfluid neutrons and other particles in the NS interior. The timing behavior of pulsars can be influenced by the dipole field evolution, which instead of decaying, may increase with time. An increase in the dipole field may result from the re-emergence of the initial dipole field Bd,ithat was buried into the NS interior shortly after the birth of the *** this work, the field re-emergence scenario ξ and the internal field configuration of several young pulsars, as well as their Bd,iare investigated by assuming typical accreted masses △M. Moreover, since the Crab pulsar has an exactly known age and its tilt angle change rate can be inferred from observations, we can set stringent constraints on its ξ, Bd,i, and △M. Although for other young pulsars without exactly known ages and tilt angle change rates, these quantities cannot be accurately determined, we find that their ξ are generally within ～10～4-10～6, and some of them probably have magnetar-strength Bd,i. Our work could be important for investigating the transient emissions associated with NSs, the origin of strong magnetic fields of NSs, pulsar population,continuous gravitational wave emission from pulsars, and accretion under extreme conditions in principle.

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Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1816-1827页

作者： Hou-Shuo li xiao lyu Ao Rong Yan-long Bi Wei Xu Hong-Ping Cui Department of Ophthalmology Tongji HospitalSchool of MedicineTongji UniversityShanghai 200065China Department of Ophthalmology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

AIM:To investigate the role of connective tissue growth factor(CTGF)and vascular endothelial growth factor(VEGF)in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy(PDR)following intravitreal injection of ***:This study included 72 PDR patients and 8 cataract patients as *** patients were divided into 3 groups according to the intervals of 3,5,and 7d between intravitreal conbercept(IVC,0.5 mg/0.05 ml)injection and pars plana vitrectomy(PPV)*** humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay(ElISA).The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the data,and the protein interaction network of 23 differential proteins was ***:Post-IVC,VEGF levels decreased and CTGF levels increased significantly in aqueous humor,with the CTGF/VEGF ratio rising significantly at all *** chromatography tandem mass spectrometry(lC-MS/MS)identified differentially expressed proteins between preand post-IVC *** and KEGG analyses revealed involvement in immune response,stress response,complement and coagulation cascades,ferroptosis,and PPAR signaling *** analysis highlighted key proteins like APOA1,C3,and transferrin(TF).ElISA assay confirmed the differential expression of proteins such as HBA1,SERPINA1,COl1A1,and ACTB,with significant changes in the IVC ***:The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels,thereby modifying the CTGF/VEGF ratio,and IVC significantly alters the protein profile in the aqueous humor of patients with *** analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune respons

关键词： proliferative diabetic retinopathy conbercept vascular endothelial growth factor connective tissue growth factor proteomics

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Casual associations between blood metabolites and colon cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1995-2005页

作者： Ke-Yue Hu Yi-Quan Cheng Zhi-long Shi Fu-Peng Ren Gang-Feng xiao Department of Hematology and Oncology Ningbo No.2 HospitalNingbo 315000Zhejiang ProvinceChina

BACKGROUND limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal *** To investigate causal associations between blood metabolites and colon *** The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal *** primary method of analysis used was the inverse variance weighted *** further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile *** additional analyses were conducted to ensure the reliability and robustness of the *** After rigorous selection for genetic variation,486 blood metabolites were included in the MR *** found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the *** This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk *** other five blood metabolites are protective factors.

关键词： Metabolites Colon cancer Mendelian randomization Genome-wide association studies Casual

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Genetically modified pigs:Emerging animal models for hereditary hearing loss

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Zoological Research 2024年第2期45卷 284-291页

作者： xiao Wang Tian-Xia liu Ying Zhang liang-Wei Xu Shuo-long Yuan A-long Cui Wei-Wei Guo Yan-Fang Wang Shi-Ming Yang Jian-Guo Zhao State Key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Department of Otolaryngology-Head and Neck Surgery Institute of OtolaryngologyChinese PLA General HospitalBeijing 100853China Division of life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230022China State Key laboratory of Animal Biotech Breeding Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

Hereditary hearing loss(HHl),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for *** investigate the underlying causes of HHl and evaluate therapeutic outcomes,appropriate animal models are *** have been extensively used as valuable large animal models in biomedical *** this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing ***,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHl ***,this review provides insights and perspectives for future studies on HHl using porcine models.

关键词： Pigs Animal models Hereditary hearing loss Genetic modification Inner ear

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Ploidy and fruit trait variation in oil-tea Camellia:Implications for ploidy breeding

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Journal of Integrative Agriculture 2024年第8期23卷 2662-2673页

作者： Yanmin li liangjing Yin Xianyu He Cenlong Hu Ronghua Wu Qian long Shixin xiao Deyi Yuan Key laboratory of Cultivation and Protection for Non-Wood Forest Trees of Ministry of Education/Key laboratory of Non-Wood Forest Products of State Forestry Administration Central South University of Forestry and TechnologyChangsha 410004China Qiandongnan Institute of Forestry Qiandongnan Miao and Dong Autonomous Prefecture 556000China Dongfeng Forest Farm of liping County Qiandongnan Miao and Dong Autonomous Prefecture 557300China

Plant polyploidy often occurs in conjunction with higher yield and superior ***,obtaining polyploid germplasms is a significant part of *** oil-tea Camellia tree is an important native woody plant that produces high-quality edible oil and includes many species of Camellia with different ***,whether higher ploidy levels in oil-tea Camellia trees are related to better traits remains *** this study,the ploidy levels of 30 different oil-tea Camellia strains in three different species in the *** were determined by flow cytometry and chromosome preparation,and the phenotypic characteristics and fatty acid compositions of the fruits were examined by field observations and laboratory *** correlations between the ploidy level of oil-tea Camellia and the main traits of the fruit were *** results showed that 10 Camellia lanceoleosa strains were diploid,10 Camellia meiocarpa strains were tetraploid and 10 Camellia oleifera strains were *** *** had larger fruit size and weight,more seeds per fruit,greater seed weight per fruit,higher oil content and greater yield per crown width than tetraploid *** and diploid ***,but their fruit peel thickness and fresh seed rate were significantly lower,and these traits were significantly correlated with ploidy *** addition,in terms of fatty acid composition,hexaploid *** had a higher oleic acid content than tetraploid *** and diploid ***,but their linoleic acid,linolenic acid and arachidonic acid contents were *** contents of palmitic acid,stearic acid and total unsaturated fatty acids were not significantly correlated with ploidy *** conclusion,certain correlations exist between the main characteristics of oil-tea Camellia fruit and the ploidy level,and increasing the ploidy level led to an increase in fruit yield with no effect on oil *** discovery of variations in the m

关键词： oil-tea Camellia ploidy level fruit traits correlation polyploidization

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Metallurgy and Solidification Microstructure Control of Fusion-Based Additive Manufacturing Fabricated Metallic Alloys:A Review

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Acta Metallurgica Sinica(English letters) 2024年第1期37卷 29-53页

作者： Qiang li Xing-Ran li Bai-Xin Dong xiao-long Zhang Shi-li Shu Feng Qiu lai-Chang Zhang Zhi-Hui Zhang Key laboratory of Bionic Engineering(Ministry of Education) and College of Bionic Science and EngineeringJilin UniversityChangchun130022China Institute of Structured and Architected Materials Liaoning Academy of MaterialsShenyang110167China Key laboratory of Automobile Materials Ministry of Education and Department of Materials Science and EngineeringJilin UniversityChangchun130025China School of Mechanical and Aerospace Engineering Jilin UniversityChangchun130025China School of Engineering Edith Cowan University270 Joondalup DriveJoondalupPerthWA6027Australia

The metal-based additive manufacturing(AM),also referred to as metal 3D printing,has drawn particular interest because it enables direct creation,aided by computationally-directed path design,of intricate components with site-specific compositions and geometrical requirements as well as low buy-to-fly *** the last two decades,the objective of this revolutionary technology has been shifting from only“rapid prototyping”to advanced manufacturing of special high-end products or devices,which,in many aspects,outperform conventional manufacturing *** fusion-based AM,significant progress has been achieved in understanding the processing window of macroscopic scales,non-equilibrium metallurgy of mesoscale scales,and grain evolution of microscopic *** the versatile capacity of AM facilitates new avenues for discovering advanced materials and structures,their potential has still not been fully *** the unique non-equilibrium solidification during the AM process,coarse columnar grains with strong textures are usually developed along the build direction,which downgrades the mechanical *** push the limits of this digital manufacturing,this review attempts to provide in-depth and comprehensive overviews of the recent progress in understanding the evolution and control of the as-built microstructure that has been made recently and the challenges encountered during the AM process.

关键词： Additive manufacturing Temperature field Microstructure control Nanoparticles Functionally graded materials

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Enhancing thermoelectric performance of p-type SnTe through manipulating energy band structures and decreasing electronic thermal conductivity

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Rare Metals 2024年第7期43卷 3232-3241页

作者： Xin Qian Hao-Ran Guo Jia-Xin lyu Bang-Fu Ding Xing-Yuan San xiao Zhang Jiang-long Wang Shu-Fang Wang Hebei Key lab of Optic-Electronic Information and Materials College of Physics Science and TechnologyHebei UniversityBaoding 071002China College of Electron and Information Engineering Hebei UniversityBaoding 071002China Research Institute for Frontier Science Beihang UniversityBeijing100191China

SnTe has received considerable attention as an environmentally friendly alternative to the representative thermoelectric material of ***,excessive hole carrier concentration in SnTe results in an extremely low Seebeck coefficient and high thermal conductivity,which makes it exhibit relatively inferior thermoelectric *** this work,the thermoelectric performance of p-type SnTe is enhanced through regulating its energy band structures and reducing its electronic thermal conductivity by combining Bi doping with CdSe ***,the carrier concentration of SnTe is successfully suppressed via Bi doping,which significantly decreases the electronic thermal ***,the convergence and flattening of the valence bands by alloying CdSe effectively improves the effective mass of SnTe while restraining its carrier ***,a maximum figure of merit(ZT) of~ 0.87 at 823 K and an average ZT of~ 0.51 at 300-823 K have been achieved in Sn_(0.96)Bi_(0.04)Te-5%*** results indicate that decreasing the electronic thermal conductivity is an effective means of improving the performance of thermoelectric materials with a high carrier concentration.

关键词： Thermoelectric materials SnTe Energy band structure Electronic thermal conductivity ZT value

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Micro defects formation and dynamic response analysis of steel plate of quasi-cracking area subjected to explosive load

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Defence Technology（防务技术） 2024年第1期31卷 580-593页

作者： Zheng-qing Zhou Ze-chen Du xiao Wang Hui-ling Jiang Qiang Zhou Yu-long Zhang Yu-zhe liu Pei-ze Zhang Research Institute of Macro-Safety Science University of Science and TechnologyBeijing100083China School of Civil and Resource Engineering University of Science and Technology BeijingBeijing100083China School of Mechanical Engineering Nantong UniversityNantong226019China China North Industry Advanced Technology Generalization Institute Beijing100089China China Academy of Ordnance Science China

As the protective component,steel plate had attracted extensive attention because of frequently threats of explosive *** this paper,the evolution of microstructure and the mechanism of damage in the quasi-cracking area of steel plate subjected to explosive load were discussed and the relationships between micro defects and dynamic mechanical response were *** the explosion experiment,five observation points were selected equidistant from the quasi-cracking area of the section of the steel plate along the thickness direction,and the characteristics of micro defects at the observation points were analyzed by optical microscope(OM),scanning electron microscope(SEM) and electron backscattered diffraction(EBSD).The observation result shows that many slip bands(SBs) appeared,and the grain orientation changed obviously in the steel plate,the two were the main damage types of micro *** addition,cracks,peeling pits,grooves and other lager micro defects were appeared in the lower area of the *** stress parameters of the observation points were obtained through an effective numerical *** mechanism of damage generation and crack propagation in the quasicracking area were clarified by comparing the specific impulse of each observation point with the corresponding micro *** result shows that the generation and expansion of micro defects are related to the stress area(*** upper compression area,the neutral plane area,and the lower tension area).The micro defects gather and expand at the grain boundary,and will become macroscopic damage under the continuous action of tensile ***,the micro defects at the midpoint of the section of the steel plate in the direction away from the explosion center(*** horizontal direction) were also *** was found that the specific impulse at these positions were much smaller than that in the thickness direction,the micro defects were only SBs and a few micro cracks,and the those decrea

关键词： Explosive load Quasi-cracking area Micro defects Steel plate Dynamic response Numerical simulation

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Dual template-induced construction of three-dimensional porous SiO2/NC/Co-CNTs heterostructure with highly dispersed active sites for efficient oxygen evolution reaction

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Tungsten 2024年第3期6卷 585-595页

作者： Hai-Qi Zhang xiao-Jun Zeng Qing-Qing Zhang Zu-liang Zhang Chu-long Jin Rong-Hai Yu School of Materials Science and Engineering Jingdezhen Ceramic University School of Materials Science and Engineering Beihang University

The development and exploration of efficient and economical electrocatalysts for oxygen evolution reaction（OER） represents the main bottleneck to unlocking a sustainable energy scenario based on elec trocataly tic water *** scale integration of three-dimensional（3D） porous heterostructure with highly dispersed active sites and good structural stability is ***,a dual template route is developed to construct the 3D porous SiO2/nitrogen-doped carbon（NC）/Co-carbon nano tubes（CNTs） hetero ***,the hard template（SiO2nano spheres） contributes to 3D porous structure,increases the specific surface area,and promotes the contact area of the *** the same time,the soft template（basic zinc carbonate） can control the growth of 1D CNTs and facilitate the exposure of the active ***,3D porous SiO2/NC/Co-CNTs hetero structure inherits highly dispersed Co nanoparticles coated by *** conductive channels and abundant N hetero atoms doping are reasonably constructed by a dual template ***,SiO2/NC/Co-CNTs catalyst provides an extraordinary activity for the OER in alkaline media,with a low overpotential of 298 mV at a current density of 10 mA·***,SiO2/NC/Co-CNTs hetero structure enables excellent long-term durability with a 10 mV decay in overpotential after 3000 cyclic voltammetry cycles,and 97% remain in current density over 20 *** is believed that this dual template strategy can provide a new and simple way to construct a highly dispersed active site in electrocatalysts.

关键词： Dual template High dispersion Porous heterostructure Conductive channels Oxygen evolution reaction

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