Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squ...Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.展开更多
BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an a...BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an anti-ulcer drug.It was reported that geraniol might participate in lipid metabolism through a variety of pathways.The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia.METHODS In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,respectively.At baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were tested.RESULTS After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant difference.CONCLUSIONS The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia.This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.展开更多
看点key feature科技探索之旅THE JOURNEY OF SCIENTIFIC AND TECHNOLOGICAL EXPLORATION无数的“窗”COUNTLESS"WINDOWS"“数字文明”“自然”“生活模式”"DIGITAL CIVILIZATION","NATURE","LIFES...看点key feature科技探索之旅THE JOURNEY OF SCIENTIFIC AND TECHNOLOGICAL EXPLORATION无数的“窗”COUNTLESS"WINDOWS"“数字文明”“自然”“生活模式”"DIGITAL CIVILIZATION","NATURE","LIFESTYLE"由Lenovo联想集团与UCCA Lab打造的「从未来到未来—数字文明艺术展」,通过“未来序曲”“奔腾时代”“数字新生”“瞬息万物”“遇见未来”5个篇章,为人们呈现了一场科技探索之旅。展开更多
旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样...旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样,采用荧光定量PCR分析VGLL2基因和其反义链转录本VGLL2-AS的表达谱;采用双向转录试验和核酸酶保护试验检测VGLL2和VGLL2-AS是否可以双向转录且两者之间关系;体外分离培养原代成肌细胞(11胚龄固始鸡胚),然后用2μg·mL^(-1)的放线菌素D处理成肌细胞(对照组不做处理),收取处理不同时间点细胞(0~8 h,每组各个时间点各做3个重复),检测VGLL2-AS与VGLL2的半衰期;分离鸡成肌细胞的细胞核和细胞质,通过RT-qPCR方法确定两者的细胞定位;利用PCR扩增及测序对VGLL2的转录本进行验证;最后利用RT-qPCR检测它们在固始蛋鸡胸肌组织(1日龄、6周龄、16周龄、22周龄、30周龄每个周龄各6只)中的时空表达规律和相关性。结果表明,VGLL2-AS在鸡的转录组中真实存在;VGLL2与VGLL2-AS均在肌肉中特异高表达(P<0.05);VGLL2-AS与VGLL2可以进行双向转录且二者之间可以形成双链RNA;VGLL2-AS半衰期较VGLL2长;在成肌细胞中,VGLL2-AS和VGLL2主要定位于细胞质中(P<0.001);VGLL2只存在VGLL2-mRNA、VGLL2-X2和VGLL2-X3转录本;VGLL2-mRNA和VGLL2-X3与VGLL2-AS表达趋势一致,且VGLL2-mRNA、X3和VGLL2-AS的表达呈现极强的正相关(r分别为0.943和0.935,P<0.01)。综上所述,VGLL2-AS作为VGLL2的反义链编码的lncRNA定位于细胞质中,可能通过与VGLL2形成的双链RNA之间的相互作用,然后参与调节VGLL2的表达并维持其稳定性,最终在鸡的早期肌肉发育中发挥重要作用。本研究的结果扩展了鸡中关于NATs的研究,并为鸡VGLL2基因与其天然反义链转录本VGLL2-AS在鸡骨骼肌发育中的生物学功能的研究奠定了基础,对于提高禽类的生长发育具有一定的意义。展开更多
Millions of hibernating bats across North America have died from white-nose syndrome(WNS),an emerging disease caused by a psychrophilic(cold-loving)fungus,Pseudogymnoascus destructans,that invades their skin.Mechanism...Millions of hibernating bats across North America have died from white-nose syndrome(WNS),an emerging disease caused by a psychrophilic(cold-loving)fungus,Pseudogymnoascus destructans,that invades their skin.Mechanisms of P.destructans invasion of bat epidermis remain obscure.Guided by our in vivo observations,we modeled hibernation with a newly generated little brown bat(Myotis lucifugus)keratinocyte cell line.展开更多
基金supported by the National Natural Science Foundation of China(82173362 and 81872409)the Guangdong Basic and Applied Basic Research Foundation(2019A1515110110)。
文摘Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.
基金supported by the State Key Program of National Natural Science Foundation of China(No.82330014)the Youth Program of the National Natural Science Foundation of China(No.81900374&No.82100455)+2 种基金the Postdoctoral Science Foundation of Heilongjiang Province(LBH-Z20175)the Key Research and Development Plan of Heilongjiang Province(2022ZX06C23&JD2023SJ44)the Outstanding Youth Science Foundation in the First Affiliated Hospital of Harbin Medical University(HYD2020YQ0002&HYD2024YQ16)。
文摘BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an anti-ulcer drug.It was reported that geraniol might participate in lipid metabolism through a variety of pathways.The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia.METHODS In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,respectively.At baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were tested.RESULTS After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant difference.CONCLUSIONS The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia.This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.
文摘看点key feature科技探索之旅THE JOURNEY OF SCIENTIFIC AND TECHNOLOGICAL EXPLORATION无数的“窗”COUNTLESS"WINDOWS"“数字文明”“自然”“生活模式”"DIGITAL CIVILIZATION","NATURE","LIFESTYLE"由Lenovo联想集团与UCCA Lab打造的「从未来到未来—数字文明艺术展」,通过“未来序曲”“奔腾时代”“数字新生”“瞬息万物”“遇见未来”5个篇章,为人们呈现了一场科技探索之旅。
文摘旨在探究鸡骨骼肌中VGLL2基因天然反义链转录本VGLL2 AS lncRNA(VGLL2-AS)与VGLL2的关系。本研究首先采用PCR和测序技术验证VGLL2-AS是否存在;之后分别采集不同周龄固始蛋鸡(1日龄、6周龄、16周龄、22周龄、30周龄,每个周龄各6只)组织样,采用荧光定量PCR分析VGLL2基因和其反义链转录本VGLL2-AS的表达谱;采用双向转录试验和核酸酶保护试验检测VGLL2和VGLL2-AS是否可以双向转录且两者之间关系;体外分离培养原代成肌细胞(11胚龄固始鸡胚),然后用2μg·mL^(-1)的放线菌素D处理成肌细胞(对照组不做处理),收取处理不同时间点细胞(0~8 h,每组各个时间点各做3个重复),检测VGLL2-AS与VGLL2的半衰期;分离鸡成肌细胞的细胞核和细胞质,通过RT-qPCR方法确定两者的细胞定位;利用PCR扩增及测序对VGLL2的转录本进行验证;最后利用RT-qPCR检测它们在固始蛋鸡胸肌组织(1日龄、6周龄、16周龄、22周龄、30周龄每个周龄各6只)中的时空表达规律和相关性。结果表明,VGLL2-AS在鸡的转录组中真实存在;VGLL2与VGLL2-AS均在肌肉中特异高表达(P<0.05);VGLL2-AS与VGLL2可以进行双向转录且二者之间可以形成双链RNA;VGLL2-AS半衰期较VGLL2长;在成肌细胞中,VGLL2-AS和VGLL2主要定位于细胞质中(P<0.001);VGLL2只存在VGLL2-mRNA、VGLL2-X2和VGLL2-X3转录本;VGLL2-mRNA和VGLL2-X3与VGLL2-AS表达趋势一致,且VGLL2-mRNA、X3和VGLL2-AS的表达呈现极强的正相关(r分别为0.943和0.935,P<0.01)。综上所述,VGLL2-AS作为VGLL2的反义链编码的lncRNA定位于细胞质中,可能通过与VGLL2形成的双链RNA之间的相互作用,然后参与调节VGLL2的表达并维持其稳定性,最终在鸡的早期肌肉发育中发挥重要作用。本研究的结果扩展了鸡中关于NATs的研究,并为鸡VGLL2基因与其天然反义链转录本VGLL2-AS在鸡骨骼肌发育中的生物学功能的研究奠定了基础,对于提高禽类的生长发育具有一定的意义。
文摘Millions of hibernating bats across North America have died from white-nose syndrome(WNS),an emerging disease caused by a psychrophilic(cold-loving)fungus,Pseudogymnoascus destructans,that invades their skin.Mechanisms of P.destructans invasion of bat epidermis remain obscure.Guided by our in vivo observations,we modeled hibernation with a newly generated little brown bat(Myotis lucifugus)keratinocyte cell line.
