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Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression

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Genes & Diseases 2024年第2期11卷 952-963页

作者： Zhenhao Zhang Doudou Jing Baijun xuan Zhicai Zhang Wei Wu Zengwu shao Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Orthopedics The Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young adults.However,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than 60.Elderly patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor prognosis.The mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical applications.Senescent cells can accelerate tumor progression by metabolic reprogramming.Recent research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive characteristics.We found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma cells.The expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient aged.Specifically,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT pathways.Moreover,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT phosphorylation.In conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

关键词： Cellular senescence Elderly patients MAFB-NOTCH3axis Methylmalonic acid Osteosarcoma PI3K-AKTpathway

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Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative Medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong shao Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The First Clinical Medical College of Henan University of Traditional Chinese Medicine Zhengzhou450046China Personal Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making.MethodsRandomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results.ResultsA total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively.ConclusionBased on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

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Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu xuan Mo Runhua Wang Xueyan Kong Robin shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

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Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper(Plectropomus leopardus)

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Zoological Research 2024年第2期45卷 329-340页

作者： shao-xuan Wu Qi-Fan Zeng Wen-Tao Han Meng-Ya Wang Hui Ding Ming-xuan Teng Ming-Yi Wang Pei-Yu Li Xin Gao Zhen-Min Bao Bo Wang Jing-Jie Hu MOE Key Laboratory of Marine Genetics and Breeding College of Marine Life Sciences/Key Laboratory of Tropical Aquatic Germplasm of Hainan ProvinceSanya Oceanographic InstitutionOcean University of ChinaQingdaoShandong/SanyaHainan 266100/572025China Hainan Seed Industry Laboratory SanyaHainan 572025China Southern Marine Science and Engineer Guangdong Laboratory GuangzhouGuangdong 511458China

The leopard coral grouper(Plectropomus leopardus)is a species of significant economic importance.Although artificial cultivation of P.leopardus has thrived in recent decades,the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data.In this study,we identified over 8.73 million single nucleotide polymorphisms(SNPs)through whole-genome resequencing of 326 individuals spanning six distinct groups.Furthermore,we categorized 226 individuals with high-coverage sequencing depth(≥14×)into eight clusters based on their genetic profiles and phylogenetic relationships.Notably,four of these clusters exhibited pronounced genetic differentiation compared with the other populations.To identify potentially advantageous loci for P.leopardus,we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity(θπ)and fixation index(FST)in these four clusters.Using these high-coverage resequencing data,we successfully constructed the first haplotype reference panel specific to P.leopardus.This achievement holds promise for enabling high-quality,cost-effectiveimputationmethods.Additionally,we combined low-coverage sequencing data with imputation techniques for a genome-wide association study,aiming to identify candidate SNP loci and genes associated with growth traits.A significant concentration of these genes was observed on chromosome 17,which is primarily involved in skeletal muscle and embryonic development and cell proliferation.Notably,our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs,showing potential for genetic selective breeding efforts.These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P.leopardus.

关键词： Plectropomus leopardus Whole-genome resequencing Growth Haplotype reference panel Single nucleotide polymorphisms

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Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

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World Journal of Gastroenterology 2024年第4期30卷 318-331页

作者： Yu-Zhe Cao Guang-Lei Zheng Tian-Qi Zhang Hong-Yan shao Jia-Yu Pan Zi-Lin Huang Meng-xuan Zuo Department of Minimally Invasive Interventional Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive Interventional Therapy State Key Laboratory of Oncology in South ChinaGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive Interventional Therapy Guangdong Provincial Clinical Research Center for CancerGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

关键词： Unresectable hepatocellular carcinoma Hepatic arterial infusion chemotherapy Angiogenesis inhibitors Programmed cell death protein 1 Programmed death ligand 1

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Corrigendum to"Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression"[Genes&Diseases 11(2024)952-963]

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Genes & Diseases 2024年第3期11卷 491-492页

The authors regret that some data errors were made in"Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression"at Figure 5F for the colony formation of MNNG/HOS cells with si-NOTCH3 and 5G for the tranwell assay of U2OS cells with si-NOCTH3.Correction and supplementation to Figure 5.The author used confusing experimental data and did not notice these errors when submitting the original manuscript.Here,the authors made the latest corrections to the data of the batch of U2OS cells and MNNG/HOS cells transfected with si-NoTCH3.The authors confirm that this correction will not alter the conclusions in the original manuscript.

关键词： PI3K/AKT osteosarcoma submit

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Demethylase-assisted site-specific detection of N^(1)-methyladenosine in RNA

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Chinese Chemical Letters 2024年第5期35卷 397-401页

作者： Jun Xiong Ke-Ke Chen Neng-Bin Xie Wei Chen Wen-xuan shao Tong-Tong Ji Si-Yu Yu Yu-Qi Feng Bi-Feng Yuan College of Chemistry and Molecular Sciences Research Center of Public HealthRenmin Hospital of Wuhan UniversitySchool of Public HealthWuhan UniversityWuhan 430071China Department of Laboratory Medicine Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China

The dynamic RNA modifications have been viewed as new posttranscriptional regulator in modulating gene expression as well as in a broad range of physiological processes.N^(1)-methyladenosine(m^(1)A)is one of the most prevalent modifications existing in multiple types of RNAs.In-depth investigation of the functions of m^(1)A requires the site-specific assessment of m^(1)A stoichiometry in RNA.Herein,we established a demethylase-assisted method(DA-m^(1)A)for the site-specific detection and quantification of m^(1)A in RNA.N^(1)-methyl group in m^(1)A could result in the stalling of reverse transcription at m^(1)A site,thus producing the truncated cDNA.E.coli AlkB is a demethylase that can demethylate m^(1)A to produce adenine in RNA,thus generating full-length cDNA from AlkB-treated RNA.Evaluation of the produced amounts of full-length cDNA by quantitative real-time PCR can achieve the site-specific detection and quantification of m^(1)A in RNA.With the DA-m^(1)A method,we examined and successfully confirmed the previously well-characterized m^(1)A sites in various types of RNAs with low false positive rate.In addition,we found that the level of m^(1)A was significantly decreased at the bromodomain containing 2(BRD2)mRNA position 1674 and CST telomere replication complex component 1(CTC1)mRNA position 5643 in human hepatocellular carcinoma tissues.The results suggest that these two m^(1)A sites in mRNA may be involved in liver tumorigenesis.Taken together,the DA-m^(1)A method is simple and enables the rapid,cost-effective,and site-specific detection and quantification of m^(1)A in RNA,which provides a valuable tool to decipher the functions of m^(1)A in human diseases.

关键词： N^(1)-methyladenosine RNA modification AlkB demethylase RNA epigenetics Quantitative real-time PCR Hepatocellular carcinoma

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Placental Development and Pregnancy-Associated Diseases

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Maternal-Fetal Medicine 2022年第1期4卷 36-51页

作者： Xin Yu Hongyu Wu Yun Yang Feiyang Wang Yan-Ling Wang xuan shao State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyInstitute for Stem Cell and RegenerationChinese Academy of SciencesBeijing 100101China University of the Chinese Academy of Sciences Beijing 101408China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China

Serving as the interface between the fetal and maternal environments during gestation,the placenta plays critical roles in the protection of the developing fetus and the maintenance of maternal health.The placenta is primarily derived from the embryonic trophectoderm which differentiates into various subtypes of trophoblast cells through villous and extravillous pathways.The interactions among trophoblasts and multiple decidual cells and immune cells at the maternal-fetal interface fundamentally form the functional units of the placenta,which are responsible for blood perfusion and maternal-fetal material exchange,immune tolerance,and the regulation of pregnancy adaptation.Defects in placental development and functional maintenance are in tight association with adverse pregnancy outcomes such as preeclampsia.In this article,we review recent advances on human trophoblast cell differentiation and the construction of placental functional units and discuss the placental and maternal factors that may contribute to the occurrence of preeclampsia.

关键词： Placenta Human placenta Trophoblast cell differentiation Functional units Preeclampsia

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型钢开口肋-UHPC轻型组合桥面新结构静力与疲劳性能

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中国公路学报 2024年第4期37卷 252-262页

作者：孙璇邵旭东邹德强湖南大学土木工程学院湖南长沙410082 湖南大学风工程与桥梁工程湖南省重点实验室湖南长沙410082 中国建筑第五工程局有限公司市政设计院湖南长沙410004

为解决传统正交异性钢桥面疲劳开裂、铺装层破损难题,研究团队于2010年研发成功钢-UHPC轻型组合桥面体系,并在中国的钢桥上获得了规模化的应用。鉴于UHPC层大幅度提高了钢面板的局部刚度,为简化施工和降低造价,可对传统正交异性钢桥面... 详细信息

为解决传统正交异性钢桥面疲劳开裂、铺装层破损难题,研究团队于2010年研发成功钢-UHPC轻型组合桥面体系,并在中国的钢桥上获得了规模化的应用。鉴于UHPC层大幅度提高了钢面板的局部刚度,为简化施工和降低造价,可对传统正交异性钢桥面进一步优化。为此,提出了型钢开口肋-UHPC轻型组合桥面结构,首次应用在某大跨度拱桥主梁结构中,以实桥为背景展开了桥面方案比选和有限元计算。在此基础上,进行了型钢组合桥面关键部位负弯矩条带静力试验,对UHPC裂缝进行观测和宽度验算;对型钢组合桥面抗疲劳性能做了计算与分析,并针对桥面纵横肋重要连接焊缝开展了负弯矩条带疲劳试验。研究结果表明:负弯矩区UHPC表现出优良的受弯拉韧性,抗拉强度是实桥应力的1.4倍;型钢组合桥面通过新型的纵横肋连接构造,将所有连接焊缝均置于低应力区,将非焊接型钢母材置于高应力区,以达到提高桥面抗疲劳能力目的,型钢组合桥面包含10个钢结构疲劳细节,所有疲劳细节计算应力幅均在常幅疲劳极限以下;型钢组合桥面纵横肋新型连接焊缝在设计疲劳应力幅下等效加载4840万次才发生疲劳破坏,疲劳强度满足实桥应用需求。综上表明,型钢组合桥面具有优良的静力与疲劳性能,加工制造简便,建设成本低,是一种具有竞争力的新型桥面方案。

关键词：桥梁工程型钢-UHPC轻型组合桥面条带模型试验静力与疲劳性能正交异性钢桥面

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Deciphering the placental abnormalities associated with somatic cell nuclear transfer at single-nucleus resolution

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Protein & Cell 2023年第12期14卷 924-928页

作者： Liyuan Jiang Xin Wang Leyun Wang Sinan Ma Yali Ding Chao Liu Siqi Wang xuan shao Ying Zhang Zhikun Li Wei Li Guihai Feng Qi Zhou College of Life Sciences Northeast Agricultural UniversityHarbin 150030China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China

Dear Editor,The placenta connecting the fetus to the matermal uterus provides material exchange and an immune-tolerant environment for the embryo in all eutherian mammals(shao et al.,2022).The representative mouse placenta displays a multilayered structure with distinct characteristics and functions,including the matermal decidua,junctional zone,and labyrinth layer(Marsh and Blelloch,2020).The decidua,which is thought to be derived from the matermal endometrium(and further undergoes decidualization),provides an anchor for fetal trophoblast invasion.The junctional zone predominantly contains spongiotrophoblasts(SpT),glycogen trophoblasts(GlyT),and trophoblast giant cells(TGCs).The labyrinth is the innermost two-layer structure,which mainly consists of syncytiotrophoblast cells(SynTI and SynTII),sinusoidal TGCs(S-TGCs),and fetal endothelial cells(Simmons and Cross,2005).

关键词： fetal invasion fetus

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