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Genes & Diseases 2024年第1期11卷 367-381页

作者： Yunchao Zhang Jiayu Tang Cheng Wang Qinxiu Zhang Anqi Zeng Linjiang Song School of Medical and Life sciences Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China institute of translational Pharmacology and clinical Application Sichuan Academy of Chinese Medical ScienceChengduSichuan 610041China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China

The incidence and mortality rates of cancer are increasing every year worldwide but the survival rate of cancer patients is still ***,it is necessary to further elucidate the molecular mechanisms involved in tumor development and drug resis-tance to improve cancer cure or survival *** recent years,autophagy has become a hot topic in the field of oncology research,which plays a double-edged role in tumorigenesis,pro-gression,and drug ***,long non-coding RNA(lncRNA)has also been shown to regulate autophagy,and the two-sided nature of autophagy determines the dual regulatory role of autophagy-related IncRNAs(ARlncRNAs).Therefore,ARlncRNAs can be effective ther-apeutic targets for various ***,the high abundance and stability of ARlncR-NAs in tumor tissues make them promising *** this review,we summarized the roles and mechanisms of ARlncRNAs in tumor cell proliferation,apoptosis,migration,invasion,drug resistance,angiogenesis,radiation resistance,and immune *** addition,we described the clinical significance of these ARlncRNAs,including as biomarkers/therapeutic targets and their association with clinical drugs.

关键词： Apoptosis Autophagy Biomarker Cancer Drug resistance LncRNA

Integrating spatial transcriptomics and single-nucleus RNA-seq revealed the specific inhibitory effects of TGF-β on intramuscular fat deposition

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Science China Life sciences 2024年

作者： Xiaoyu Wang Chuchu Chen Chenggan Li Xiaochang Chen Rong Xu Meilin Chen Yongpeng Li Yihao Liu Xiaohong Liu Yaosheng Chen Delin Mo State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-Sen University Shaanxi Basic and clinical translational Research Team for Atherosclerotic Cardiovascular Disease Shaanxi Key Laboratory of Ischemic Cardiovascular Disease Institute of Basic and Translational MedicineXi'an Medical University

Intramuscular fat (IMF) is a complex adipose tissue within skeletal muscle, appearing specially tissue heterogeneous, and the factors influencing its formation remain unclear. In conditions such as diabetes, aging, and muscle wasting, IMF was deposited in abnormal locations in skeletal muscle, damaged the normal physiological functions of skeletal muscle. Here, we used Longissimus dorsi muscles from pigs with different IMF contents as samples and adopted a method combining spatial transcriptome (ST) and single-nucleus RNA-seq to identify the spatial heterogeneity of IMF. ST revealed that genes involved in TGF-β signaling pathways were specifically highly enriched in IMF. In lean pigs, IMF autocrine produces more TGF-β2, while in obese pigs, IMF received more endothelial-derived TGF-β1. In vitro experiments have proven that porcine endothelial cells in a simulated high-fat environment released more TGF-β1 than TGF-β2. Moreover,under obesity mice, the addition of TGF-β after muscle injury abolished IMF production and slowed muscle repair, whereas TGF-β inhibition accelerated muscle repair. Our findings demonstrate that the TGF-β pathway specifically regulates these processes, suggesting it as a potential therapeutic target for managing muscle atrophy in obese patients and enhancing muscle repair while reducing IMF deposition.

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Immune cell pair ratio captured by imaging mass cytometry has superior predictive value for prognosis of non-small cell lung cancer than cell fraction and density

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Cancer Communications 2024年第5期44卷 589-592页

作者： Jian-Rong Li Chao Cheng institute for clinical and translational Research Baylor College of MedicineHoustonTexasUSA Section of Epidemiology and Population sciences Department of MedicineBaylor College of MedicineHoustonTexasUSA Dan L Duncan Comprehensive Cancer Center Baylor College of MedicineHoustonTexasUSA

Infiltrating immune cells in the tumor microenvironment(TME)play critical roles in the initiation,progression,and metastasis of cancer[1].Previous studies have reported that the infiltration levels of various immune cell types are significantly associated with patient prognosis in different cancers[2,3].Specifically,in non-small cell lung cancer(NSCLC)the prognostic associations of major immune cell types have been investigated[4–6],however,some of the reported associations are inconsistent and remain debated[7].Limited by technical issues,most studies focused on a few immune cell lineages or relied on inferred immune cell levels from computational *** investigate the prognostic effects of all major immune cell types unbiasedly,more systematic high-quality immune cell profiling data with matched patient survival information are needed.

关键词： prognosis cancer lung

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

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Neural Regeneration Research 2024年第7期19卷 1423-1424页

作者： Jessica Moretti Jennifer Rodger Experimental and Regenerative Neurosciences School of Biological SciencesUniversity of Western AustraliaCrawleyWAAustralia Brain Plasticity Lab Perron Institute for Neurological and Translational ScienceNedlandsWAAustralia

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying *** rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

关键词： stimulation transcranial treatment

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun Cancer institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

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Science China(Life sciences) 2024年第7期67卷 1427-1440页

作者： Hongfeng Guo Qihang Sun Xiaoli Huang Xiaohao Wang Feng Zhang Wenzheng Qu Jinling Liu Xuejun Cheng Qiang Zhu Wen Yi Qiang Shu Xuekun Li The Children’s Hospital National Clinical Research Center for Child HealthSchool of MedicineZhejiang UniversityHangzhou 310052China The institute of translational Medicine School of MedicineZhejiang UniversityHangzhou 310029China College of Life sciences Zhejiang UniversityHangzhou 310058China Binjiang institute of Zhejiang University Hangzhou 310053China Zhejiang University Cancer Center Zhejiang UniversityHangzhou 310029China

Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy ***,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains *** have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain ***8 depletion reduces the proliferation of a NSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,***,Fut8 deficiency impairs learning and memory in ***,Fut8 directly interacts with integrinα6(Itga6),an upstream regulator of the PI3kAkt signaling pathway,and catalyzes core fucosylation of *** of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to *** levels of Itga6 inhibit the activity of the PI3K/Akt signaling ***,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 *** summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

关键词： Fut8 adult neural stem/progenitor cells neurogenesis Itga6 PI3K/Akt

Exocrine pancreatic insufficiency: more compromise than precision

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 523-526页

作者： Matteo Tacelli Paolo Giorgio Arcidiacono Gabriele Capurso Pancreato-Biliary Endoscopy and Endosonography Division Pancreas Translational and Clinical Research CenterSan Raffaele Scientific Institute IRCCSMilanItaly Vita-Salute San Raffaele University MilanItaly

Exocrine pancreatic insufficiency(EPI)can be defined as a reduction in the secretion or intraluminal activity of pancreatic enzymes at a level that does not allow the normal digestion of nutrients contained in *** condition is difficult to diagnose and treat and has long been misunderstood,underestimated,and overlooked to some extent.

关键词： Exocrine pancreatic insufficiency(EPI) fecal elastase-1(FE-1) chronic pancreatitis pancreaticoduodenectomy(PD) pancreatic enzyme replacement therapy(PERT)

Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer institute Beijing 100191China institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

“Treat-all”Strategy for Patients with Chronic Hepatitis B Virus Infection in China:Are We There Yet?

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Journal of clinical and translational Hepatology 2024年第6期12卷 589-593页

作者： Mengyang Zhang Yuanyuan Kong Xiaoqian Xu Yameng Sun Jidong Jia Hong You Liver Research Center Beijing Friendship HospitalCapital Medical UniversityBeijing Key Laboratory of Translational Medicine on Liver CirrhosisNational Clinical Research Center of Digestive DiseasesState Key Lab of Digestive HealthBeijingChina clinical Epidemiology and EBM Unit Beijing Friendship HospitalCapital Medical UniversityBeijing Clinical Research InstituteBeijingChina

Chronic hepatitis B remains the primary cause of liver-related events in *** World Health Organization set a goal to eliminate viral hepatitis as a public health threat by ***,achieving this goal appears challenging due to the current low rates of diagnosis and ***“Treat-all”strategy,which proposes treating all patients with detectable hepatitis B virus(HBV)DNA or even all patients with positive HBsAg,has been suggested to simplify anti-HBV *** 2022,the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China,expanding antiviral indications and simplifying the treatment *** to this latest guideline,nearly 95%of patients with detectable HBV DNA are eligible for antiviral *** review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B(version 2022)and to identify gaps in achieving the“Treat-all”strategy in China.

关键词： Chronic hepatitis B Antiviral therapy Treatment indication Expanding treatment Treatment rate “Treat-all”strategy