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lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

《医学前沿（英文）》 2023年 第17卷 第2期   页码 317-329 doi: 10.1007/s11684-022-0931-4

摘要： Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.

关键词： lncR-GAS5     miR-193-5p     splicing factor SRSF10     autophagy     atherogenesis    

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Scientific publications on systematic review and meta-analysis from Chinese authors: a 10-year survey

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《医学前沿（英文）》 2012年 第6卷 第1期   页码 94-99 doi: 10.1007/s11684-012-0181-y

摘要：

Systematic reviews and meta-analyses are playing an increasingly important role in clinical research and practice. This study aimed to measure the scientific production of systematic review and meta-analysis from the three major regions of China: the Mainland (ML), Hong Kong (HK), and Taiwan (TW). English articles on systematic review and meta-analysis from ML, HK, and TW from 2001 to 2010 were retrieved from the PubMed database. The total number of articles, impact factors (IF), and articles published in high-impact journals were conducted for quantity and quality comparisons among the three regions. There were 1 587 published articles from ML (1 292), HK (203), and TW (92) during the past ten years. The annual total numbers of articles in the three regions increased significantly from 2001 to 2010 (from 13 to 677). The number of articles from ML has exceeded that from TW since 2001, and surpassed that from HK in 2003. The accumulated IF of articles from ML (3 488.24) was higher than those from HK (493.16) and TW (216.39). HK had the highest average IF of 3.31, followed by ML of 2.90 and TW of 2.85. Researchers from HK published a larger proportion of papers in high-impact journals than those from ML and TW. The Cochrane Database of Systematic Reviews was the most popular journal in China. Chinese authors have been very active to enhance the systematic review and meta-analysis research over the past ten years, especially in ML. The gap between ML and the other two regions has been narrowed. But there is still considerable room for Chinese authors to improve their studies on systematic review and meta-analysis.

关键词： systematic review     meta-analysis     China     Chinese     impact factor    

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Alternative splicing of inner-ear-expressed genes

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 250-257 doi: 10.1007/s11684-016-0454-y

摘要：

Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the α subunit of the Ca2+-activated K+ channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

关键词： alternative splicing     inner ear     hearing loss     hair cells    

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Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive splicing

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 186-195 doi: 10.1007/s11705-015-1540-4

摘要： Increased expression levels of the RNA splicing regulator Transformer2 (abbreviated Tra2 ) have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2 and the highly similar Tra2 protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2 reduces splicing inclusion of a poison exon in the mRNA encoding Tra2 , thereby up-regulating Tra2 protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2 alone. Discovery of this cross-regulation pathway, and its by-pass by joint depletion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 (CHK1) gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing     gene expression     breast cancer     DNA damage     CHK1    

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High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

《医学前沿（英文）》   页码 907-923 doi: 10.1007/s11684-023-1009-7

摘要： The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

关键词： FAK6/7     SRRM4     neuroendocrine neoplasms     pancreas     breast    

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Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

《医学前沿（英文）》 2022年 第16卷 第1期   页码 150-155 doi: 10.1007/s11684-021-0846-5

摘要： Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G>A, p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C>G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C>G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

关键词： cystic fibrosis     CFTR     splicing mutation     minigene    

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PM10 emissions from industrial coal-fired chain-grate boilers

Xinghua Li, Junzan Han, Lei Duan

《环境科学与工程前沿（英文）》 2017年 第11卷 第6期 doi: 10.1007/s11783-017-0966-y

摘要： Industrial coal-fired boiler is an important air pollutant emission source in China. The chain-grate boiler is the most extensively used type of industrial coal-fired boiler. An electrical low-pressure impactor, and a Dekati Low Pressure Impactor were applied to determine mass and number size distributions of PM at the inlet and the outlet of the particulate emission control devices at six coal-fired chain-grate boilers. The mass size distribution of PM generated from coal-fired chain-grate boilers generally displays a bimodal distribution that contains a submicron mode and a coarse mode. The PM in the submicron mode for burning with raw coal contributes to 33%±10 % of PM emissions, much higher than those for pulverized boilers. And the PM in the submicron mode for burning with briquette contributes up to 86 % of PM emissions. Multiclones and scrubbers are not efficient for controlling PM emission. Their average collection efficiencies for sub-micron particle and super-micron particle are 34% and 78%, respectively. Operating conditions of industrial steam boilers have influence on PM generation. Peak of the submicron mode during normal operation period is larger than the start-up period.

关键词： coal-fired chain-grate boiler     PM10     size distribution     particulate emission control devices     size-dependent collection efficiency    

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》   页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10     mice     motile cilia     mutation     primary ciliary dyskinesia    

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年 第16卷 第4期   页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint     Siglec10     kidney renal clear cell carcinoma    

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The most influential “Top 10 Events” in carbon neutrality and climate change in 2022

《能源前沿（英文）》 2023年 第17卷 第1期   页码 1-4 doi: 10.1007/s11708-023-0869-5

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Effect of IL-10 on formation of foam cell induced by ox-LDL

WANG Fei, DAI Yalei, XU Ting, XU Bo, WANG Kaifeng

《医学前沿（英文）》 2008年 第2卷 第3期   页码 298-302 doi: 10.1007/s11684-008-0057-3

摘要： Atherosclerosis is a chronic disease that causes various cardiovascular complications. It has been realized that cellular and humoral immunity plays crucial roles in atherogenic lesion formation. In this study the effects of lipopolysaccharide (LPS) and interleukin-10 (IL-10) on the formation of foam cells during the early stages of atherosclerosis have been investigated. Macrophage was induced by phorbol myristate acetate (PMA) treatment on THP-1 cells. The cells were further stimulated by ox-LDL, ox-LDL plus LPS, ox-LDL plus IL-10 and LPS. By using an oil red O staining technique, the formation of foam cells was evaluated by lipid granules formation in the cells. The ratio of foam cell formation was increased from (9.77 ± 1.70)% to (16.27 ± 2.27)% after 24 h stimulation with ox-LDL, and the increase was observed with incubating time. The foam cells were significantly increased in the presence of LPS in a dose-dependent manner. The maximum increase of about 40% was observed. However, the significant elevation by LPS was abrogated when IL-10 was added. These results indicated that IL-10 can effectively prevent the formation of foam cells induced by ox-LDL with or without LPS. This study demonstrates that ox-LDL can cause foam cell formation from macrophages . LPS can significantly accelerate this event. IL-10, an anti-inflammatory cytokine, can inhibit the effect of ox-LDL and LPS. These results indicate that inflammatory effects in blood vessels can speed up foam cell formation. The inhibitive effect of IL-10 is an important factor for delaying atherosclerosis processes.

关键词： inflammatory     presence     interleukin-10     dose-dependent     ox-LDL    

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Preface of special issue of the 10 th International Conference on CO 2 Utilization

Changjun LIU,

《化学科学与工程前沿（英文）》 2010年 第4卷 第2期   页码 109-109 doi: 10.1007/s11705-009-0258-6

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Cross-sectional prevalence and pattern of non-anaemia severe malaria among 2–10 year olds in Sokoto in

《医学前沿（英文）》 2022年 第16卷 第6期   页码 969-974 doi: 10.1007/s11684-021-0912-z

摘要： Malaria is highly prevalent in Nigeria and accounts for approximately 40% of global malaria mortality. However, most reports on severe malaria in Nigeria are from hospital-based studies without accurate information from communities; thus, malaria-related deaths in the community are left untracked. This study aimed to describe the prevalence and pattern of severe malaria in a community in Northwestern Nigeria. A cross-sectional study was conducted among 2–10-year-old children in Sokoto, in August and December 2016, to determine the endemicity of malaria based on Plasmodium falciparum prevalence rate (PfPR2-10) and to describe the disease pattern. Severe malaria was diagnosed according to the World Health Organisation criteria. Data were described using Stata version 15. The prevalence of non-anaemia severe malaria was higher than expected (2.6%), considering the endemicity pattern which was mesoendemic based on a PfPR2-10 of 34.8%. The mean age of children with severe malaria was 3.73 years, and the male–female ratio was 2:1. However, 54.0% of the patients had hyperparasitaemia. A relatively high prevalence of non-anaemia severe malaria was found in Wamakko. This finding suggests the need to identify and treat cases in the community using modifications of current strategies, particularly seasonal malaria chemoprophylaxis.

关键词： severe malaria     nigeria     malaria mortality     PfPR2-10     intermediate malaria transmission    

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GENOME EDITING: A GROUND BREAKING RESEARCH HAS BEEN RANKED TOP 10 ENGINEERING FRONTS FROM 2017 TO 2021

《农业科学与工程前沿（英文）》 2022年 第9卷 第2期   页码 309-311 doi: 10.15302/J-FASE-2022440

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Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 24-32 doi: 10.1007/s11684-014-0312-8

摘要：

In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivoinvestigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

关键词： osteopontin (OPN)     hepatocellular carcinoma     metastasis     prognosis     therapeutic target     biomarker     genetic polymorphism    

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标题 作者 时间 类型 操作

lncR-GAS5 upregulates the splicing factor to impair endothelial autophagy, leading to atherogenesis

期刊论文

Scientific publications on systematic review and meta-analysis from Chinese authors: a 10-year survey

null

期刊论文

Alternative splicing of inner-ear-expressed genes

null

期刊论文

Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive splicing

Andrew Best,Katherine James,Gerald Hysenaj,Alison Tyson-Capper,David J. Elliott

期刊论文

High frequency of alternative splicing variants of the oncogene in neuroendocrine tumors of the pancreas

期刊论文

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

期刊论文

PM10 emissions from industrial coal-fired chain-grate boilers

Xinghua Li, Junzan Han, Lei Duan

期刊论文

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

期刊论文

The most influential “Top 10 Events” in carbon neutrality and climate change in 2022

期刊论文

Effect of IL-10 on formation of foam cell induced by ox-LDL

WANG Fei, DAI Yalei, XU Ting, XU Bo, WANG Kaifeng

期刊论文

Preface of special issue of the 10 th International Conference on CO 2 Utilization

Changjun LIU,

期刊论文

Cross-sectional prevalence and pattern of non-anaemia severe malaria among 2–10 year olds in Sokoto in

期刊论文

GENOME EDITING: A GROUND BREAKING RESEARCH HAS BEEN RANKED TOP 10 ENGINEERING FRONTS FROM 2017 TO 2021

期刊论文

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

期刊论文