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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-zhou Sun Chun-xiao Li Hong-Nan Mo Yan-Tong zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 299-310页

作者： LIU xiao-rong LI Shuo-fu MEI Wen-ya LIU Xiang-dan zhou Ri-bao College of Pharmacy Hunan University of Chinese MedicineChangsha(410208)China Department of Orthopaedics The First Hospital of Hunan University of Chinese MedicineChangsha(410007)China

Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS ***-FLS viability,migration,and invasion were ***,a collagen-induced arthritis(CIA)rat model was *** were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,*** index was calculated and synovial tissue inflammation was determined in CIA *** levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial *** docking was also used to analyze the binding of isorhamnetin to *** In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial *** reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CRE

关键词： rheumatoid arthritis isorhamnetin SRC/ERK/CREB matrix metalloproteinase

An improved installation of 2-hydroxy-4-methoxybenzyl(iHmb)method for chemical protein synthesis

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Chinese Chemical Letters 2024年第5期35卷 145-150页

作者： Ying Li Long-Jie Wang Yong-Kang zhou Jun Liang Bin xiao Ji-Shen Zheng The First Affiliated Hospital of USTC MOE Key Laboratory for Membraneless Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Chemistry University of Science and Technology of ChinaHefei 230027China

The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated sidereactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus improving the synthesis of long and challenging peptides and ***,its use is largely precluded by the limited Hmb’s installation *** this report,an improved installation of Hmb(iHmb)method was developed to achieve the flexible installation and the convenient removal of *** iHmb method involves two critical steps:(1)oxidative diazotization of the readily installed 2-hydroxy-4-methoxy-5-amino-benzyl(Hmab)to give 2-hydroxy-4-methoxy-5-diazonium-benzyl(Hmdab)by combining soamyl nitrite(IAN)/HBF_(4),and(2)reductive elimination of Hmdab to give the desired Hmb by 1,2-ethanedithiol(EDT).The iHmb method enables the installation of Hmb at any primary amino acid including the highly sterically hindered amino acids(e.g.,valine and isoleucine).The practicality and utility of the iHmb method was demonstrated by one-shot solid-phase synthesis of a challenging aspartimide-prone peptide,the mirror-image version of a hydrophobic peptide and a long-chain peptide up to ***,the iHmb method can be utilized to facilitate chemical protein ligation,as exemplified by the synthesis of the single-spanning membrane protein *** iHmb method expands the toolkit for peptide synthesis and ligation and facilitates the preparation of peptides/proteins.

关键词： Chemical protein synthesis Solid-phase peptide synthesis Removable backbone modification 2-Hydroxy-4-methoxybenzyl(Hmb)group Aspartimide-prone peptides Difficult peptides Membrane proteins

Composite laminar membranes for electricity generation from water evaporation

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Nano Research 2024年第1期17卷 307-311页

作者： xiao Wang Gang Yuan Han zhou Yu Jiang Shuo Wang Jiaojiao Ma Chongyang Yang Sheng Hu State Key Laboratory of Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials(iChEM)College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China Pen-Tung Sah Institute of Micro-Nano Science and Technology Xiamen UniversityXiamen 361005China

Harvesting clean energy from water evaporation has been extensively investigated due to its *** achieve high efficiency,energy conversion materials should contain multiple features which are difficult to be simultaneously obtained from single-component *** we use composite laminar membranes assembled by nanosheets of graphene oxide and mica,and find a sustained power density induced by water evaporation that is two orders of magnitude larger than that from membranes made by either of the *** power output is attributed to selective proton transport driven by water evaporation through the interlayer nanochannels in the *** process relies on the synergistic effects from negatively charged and hydrophilic mica surfaces that are important for proton selectivity and water transport,and the tunable electrical conductivity of graphene oxide that provides optimized internal *** demonstrated composite membranes offer a strategy of enhancing power generation by combining the advantages from each of their components.

关键词： graphene oxide mica water evaporation electrical double layer surface charge ion selectivity

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

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Oncology Research 2024年第5期32卷 943-953页

作者： JIANBO zhou FENG WAN BIN xiao XIN LI CHENG PENG FU PENG Department of Pharmacology West China School of PharmacySichuan UniversityChengduChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduChina Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologySichuan UniversityChengduChina Chengdu No.1 Pharmaceutical Co. Ltd.PengzhouChina Chengdu Push Bio-Technology Co. Ltd.ChengduChina

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,*** the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well *** this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent *** induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in ***,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 *** triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 *** mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

关键词： Metochalcone Breast cancer Lung cancer SASP JAK2/STAT3

Risk factors for cognitive impairment in patients with chronic kidney disease

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World Journal of Psychiatry 2024年第2期14卷 308-314页

作者： xiao-Hui Wang Yong He Huan zhou Ting xiao Ran Du Xin Zhang Department of Nephrology The Fifth Hospital of WuhanWuhan 430050Hubei ProvinceChina Department of Nephrology The Central Hospital of Enshi Tujia and Miao Autonomous PrefectureEnshi 445000Hubei ProvinceChina

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread *** To investigate the risk factors for concurrent cognitive dysfunction in patients with *** This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and *** Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive *** risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married *** The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

关键词： Cognitive impairment Cognitive dysfunction Chronic kidney disease

Research on Quantitative Identification of Three-Dimensional Connectivity of Fractured-Vuggy Reservoirs

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Energy Engineering 2024年第5期121卷 1195-1207页

作者： Xingliang Deng Peng Cao Yintao Zhang Yuhui zhou xiao Luo Liang Wang Exploration and Development Research Institute PetroChina Tarim Oilfield CompanyKorla841000China PetroChina Hangzhou Research Institute of Geology Hangzhou310023China School of Petroleum Engineering Yangtze UniversityWuhan430100China

The fractured-vuggy carbonate oil resources in the western basin of China are extremely *** connectivity of carbonate reservoirs is complex,and there is still a lack of clear understanding of the development and topological structure of the pore space in fractured-vuggy ***,effective prediction of fractured-vuggy reservoirs is *** view of this,this work employs adaptive point cloud technology to reproduce the shape and capture the characteristics of a fractured-vuggy *** identify the complex connectivity among pores,fractures,and vugs,a simplified one-dimensional connectivity model is established by using the meshless connection element method(CEM).Considering that different types of connection units have different flow characteristics,a sequential coupling calculation method that can efficiently calculate reservoir pressure and saturation is *** automatic history matching,the dynamic production data is fitted in real-time,and the characteristic parameters of the connection unit are *** results show that the three-dimensional connectivity model of the fractured-vuggy reservoir built in this work is as close as 90%of the fine grid model,while the dynamic simulation efficiency is much higher with good accuracy.

关键词： Fractured-vuggy reservoir three-dimensional connectivity connection unit dynamic prediction automatic history matching

Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 773-786页

作者： xiao-Cong zhou Fei-Yue Ke Gaurav Dhamija Hao Chen Qiang Wang Department of Colorectal Surgery The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Postgraduate Training Base Alliance of Wenzhou Medical University Wenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina School of International Studies Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Radiology The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various ***,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent *** To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical *** We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic *** anatomical points were carefully marked and measured using advanced 3D modeling *** analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation *** The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue *** demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal *** contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat ***,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal *** The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue *** study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical ***

关键词： Computerized tomography Rectal cancer Three-dimensional reconstruction Pelvimetry Sex differences

SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1890-1907页

作者： xiao-Sheng Jin Lu-Xi Chen Ting-Ting Ji Rong-zhou Li Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical UniversityRuian 325000Zhejiang ProvinceChina

BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human ***,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely *** To investigate the effects of SERPINH1 on CRC cells and its specific *** Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in *** SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein *** SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC *** investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite *** set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle *** findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and *** These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

关键词： Serpin peptidase inhibitor clade H member 1 Colorectal cancer Proliferation Cell cycle Phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin