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Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： Yuan Yuan Peiyuan li jianghui li qiu Zhao ying Chang Xingxing He Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes.Among these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and cholesterylation.lipid attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing hydrophobicity.Accumulating evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases.Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic strategy.Here,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： lipid ation primarily

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Computed tomography-based radiomics diagnostic approach for differential diagnosis between early-and late-stage pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1256-1267页

作者： Shuai Ren li-Chao Qian ying-ying Cao Marcus J Daniels li-Na Song ying Tian Zhong-qiu Wang Department of Radiology Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Geratology Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing 210022Jiangsu ProvinceChina Department of Radiology NYU Langone HealthNew YorkNY 10016United States

BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.

关键词： Pancreatic ductal adenocarcinoma Radiomics Computed tomography American Joint Committee on Cancer staging

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Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1395-1406页

作者： qiu-Xiao Yu Ping-ying Fu Chi Zhang li li Wen-Ting Huang Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality worldwide.Mesenchymal-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment.MET amplification has been reported in CRC,but data are very limited.Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice.AIM To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy.METHODS A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited.All patients were without RAS/RAF mutation or microsatellite instability-high.MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),respectively.Correlations between MET aberration and pathological features were detected using the chi-squared test.Progression free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank test.The results of MET FISH and IHC were com pared using one-way ANOVA.RESULTS Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not detected.Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(Plified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was detected between patients with different protein lev

关键词： Colorectal cancer MET Amplification Pathological features Prognosis Fluorescence in situ hybridization

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Carbon enhanced nucleophilicity of Na_(3)V_(2)(PO_(4))_(3):A general approach for dendrite-free zinc metal anodes

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Journal of Energy Chemistry 2024年第4期91卷 203-212页

作者： Sijun Wang lingzi Hu Xiaohui li Dan qiu Shunhang qiu Qiancheng Zhou Wenwen Deng Xiaoying Lu Ze Yang Ming qiu ying Yu Institute of Nanoscience and Nanotechnology School of Physical Science and TechnologyCentral China Normal UniversityWuhan 430079HubeiChina School of Material Science and Engineering Suzhou University of Science and TechnologySuzhou 215000JiangsuChina Faculty of Science and Technology Technological and Higher Education Institute of Hong KongHong KongChina

Zincophilic property and high electrical conductivity are both very important parameters to design novel Zn anode for aqueous Zn-ion batteries(AZIBs).However,single material is difficult to exhibit zincophilic property and high electrical conductivity at the same time.Herein,originating from theoretical calculation,a zincophilic particle regulation strategy is proposed to address these limitations and carbon coated Na_(3)V_(2)(PO_(4))_(3)is taken as an example to be a protective layer on zinc metal(NVPC@Zn).Na_(3)V_(2)(PO_(4))_(3)(NVP)is a common cathode material for Zn-ion batteries,which is zincophilic.Carbon materials not only offer an electron pathway to help Zn deposition onto NVPC surface,but also enhance the zinc nucleophilicity of Na_(3)V_(2)(PO_(4))_(3).Hence,this hybrid coating layer can tune zinc deposition and resist side reactions such as hydrogen generation and Zn metal corrosion.Experimentally,a symmetrical battery with NVPC@Zn electrode displays highly reversible plating/stripping behavior with a long cycle lifespan over 1800 h at2 mA cm^(-2),much better than carbon and Na_(3)V_(2)(PO_(4))_(3)solely modified Zn electrodes.When the Na_(3)V_(2)(PO_(4))_(3)is replaced with zincophobic Al2O3or zincophilic V2O3,the stability of the modified zinc anodes is also prolonged.This strategy expands the option of zincophilic materials and provides a general and effective way to stabilize the Zn electrode.

关键词： Zinc-ion batteries Zinc anode Carbon enhanced nucleophilicity Zincophilic particle regulation

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Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2318-2334页

作者： Ya-Kun Jiang Wei li ying-Yang qiu Meng Yue Department of Gastroenterology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Health Management Center Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Yong Loo lin School of Medicine National University of SingaporeSingapore 119077Singapore

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

关键词： Human epidermal growth factor receptor 2 Gastric cancer Targeted therapy Review

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Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1514-1531页

作者： Yong Pan Yi-Ru Zhang ling-Yun Wang li-Na Wu ying-qiu Ma Zhou Fang Shi-Bo li Department of Infectious Disease Zhoushan HospitalWenzhou Medical UniversityZhoushan 316021Zhejiang ProvinceChina State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Infectious Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

关键词： Hepatocellular carcinoma Competitive endogenous RNA Molecular mechanism Prognosis Biomarker

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Synthesis of granulated li_(1.33)Mn_(1.67)O_(4) via two antisolvent methods for lithium adsorption from gas-produced water

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Chinese Journal of Chemical Engineering 2024年第5期69卷 34-46页

作者： Jun qiu Lu-Ri Bao Wei Guo ying Yang Shu-ying Sun National Engineering Research Center for Integrated Utilization of Salt Lake Resource East China University of Science and TechnologyShanghai 200237China

Gas-produced water is an accompanying wastewater in the natural gas extraction process,and it is a potential liquid lithium resource that contains a considerable amount of lithium.This study investigated the feasibility of using manganese-based ion sieves to adsorb and extract lithium from gas-produced water.And we focused on the applicability of two different granulation methods,extrusion and droplet,in gas-produced water systems.Two types of H_(1.33)Mn_(1.67)O_(4) particles were prepared by the extrusion method(EHMO)and the droplet method(DHMO).The porosity of DHMO was much higher than that of EHMO,and the adsorption performance of DHMO increased with the decrease of binder concentration.DHMO prepared with a binder concentration of 0.14 g·ml^(-1)exhibited the best adsorption performance in gas-produced water,and the li^(+)adsorption capacity could reach 25.14 mg·g^(-1).In gas-produced water,the adsorption equilibrium of DHMO only took 9 h,and the adsorption process conformed to the Langmuir model and pseudo-second-order kinetic model.The pore diffusion model(PDM)could well describe its adsorption process.Besides,DHMO showed a great selectivity to li^(+),and the selectivity order of DHMO in gas-produced water was li^(+)>Ba^(2+)>>Mg^(2+),Ca^(2+),Sr^(2+)>>Na^(+)>>K^(+).After 20 cycles,the li^(+)adsorption capacity was still higher than 17.30 mg·g^(-1),and the rate of manganese dissolution was less than 1%.

关键词： Gas-produced water Granulation li_(1.33)Mn_(1.67)O_(4)

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Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

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World Journal of Clinical Cases 2024年第12期12卷 2040-2049页

作者： Mei-Hua Sun liu-Sheng Wu ying-Yang qiu Jun Yan Xiao-Qiang li Department of Thoracic Surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina School of Medicine Tsinghua UniversityBeijing 100084China Yong Loo lin School of Medicine National University of SingaporeSingapore 119077Singapore

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

关键词： Enhanced recovery after surgery Non-small cell lung cancer Perioperative care Propensity score Video-assisted thoracic surgery

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Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/m TOR Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 251-259页

作者： YAO Jun-peng FENG Xiu-mei WANG Lu li Yan-qiu ZHU Zi-yue YAN Xiang-yun YANG Yu-qing li ying ZHANG Wei Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Rehabilitation Medicine Guanghan People’s HospitalGuanghanSichuan Province618399China Academic Affairs Office Chengdu University of Traditional Chinese MedicineChengdu611137China

Objective:To explore the mechanism of electroacupuncture(EA) in promoting recovery of the facial function with the involvement of autophagy,glial cell line-derived neurotrophic factor(GDNF),and phosphatidylinositol-3-kinase(PI3K)/mammalian target of rapamycin(mTOR) signaling pathway.Methods:Seventy-two male Sprague-Dawley rats were randomly allocated into the control,sham-operated,facial nerve injury(FNI),EA,EA+3-methyladenine(3-MA),and EA+GDNF antagonist groups using a random number table,with 12 rats in each group.An FNI rat model was established with facial nerve crushing method.EA intervention was conducted at Dicang(ST 4),Jiache(ST 6),Yifeng(SJ 17),and Hegu(li 4) acupoints for 2 weeks.The Simone’s 10-Point Scale was utilized to monitor the recovery of facial function.The histopathological evaluation of facial nerves was performed using hematoxylin-eosin(HE) staining.The levels of Beclin-1,light chain 3(LC3),and P62 were detected by immunohistochemistry(IHC),immunofluorescence,and reverse transcriptionpolymerase chain reaction,respectively.Additionally,IHC was also used to detect the levels of GDNF,Rai,PI3K,and mTOR.Results:The facial functional scores were significantly increased in the EA group than the FNI group(Plin sheaths,which were destroyed immediately after the injury,were recovered with EA treatment.The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats(P<0.01);however,EA treatment reversed these abnormal changes(P<0.01).Meanwhile,EA stimulation significantly increased the levels of GDNF,Rai,PI3K,and mTOR(P<0.01).After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist,the repair effect of EA on facial function was attenuated(P<0.05 or P<0.01).Conclusions:EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI.EA may exert this neuroreparative effect through mediating the release of GDNF,activating the PI3

关键词： electroacupuncture facial nerve injury autophagy glial cell line-derived neurotrophic factor phosphatidylinositol-3-kinase/mammalian target of rapamycin Chinese medicine

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One-pot and One-step Cu(0)-mediated Reversible-Deactivation Radical Polymerization of N-Isopropylacrylamide(NIPAM) in Water

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Chinese Journal of Polymer Science 2024年第1期42卷 1-6,I0004页

作者： Zi-Shan li Jing Lyu Bei qiu ying-Hao li Ruth Foley Ri-Jian Song Melissa Johnson Qiang Geng Wen-Xin Wang Institute of Precision Medicine(AUST-IPM) Anhui University of Science and TechnologyHuainan 232001China Charles Institute of Dermatology School of MedicineUniversity College DublinDublin D04 V1W8Ireland

Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.

关键词： Cu(0)-mediated RDRP N-isopropylacrylamide Propagation Deactivation Reaction parameters

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