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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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Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

《医学前沿（英文）》 2020年 第14卷 第5期   页码 642-650 doi: 10.1007/s11684-019-0719-3

摘要： This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR<30 mg/g, =136, NA), microalbuminuria (UACR at 30–300 mg/g, =132, MA), and clinical albuminuria (UACR>300 mg/g, =122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects ( <0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR ( <0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

关键词： type 2 diabetes mellitus     diabetic kidney disease     miR-154-5p     urinary albumin to creatinine ratio    

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Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis

《医学前沿（英文）》   页码 924-938 doi: 10.1007/s11684-023-1004-z

摘要： Long noncoding RNAs (lncRNAs) play a crucial regulatory role in the development and progression of multiple cancers. However, the potential mechanism by which lncRNAs affect the recurrence and metastasis of ovarian cancer remains unclear. In the current study, the lncRNA LOC646029 was markedly downregulated in metastatic ovarian tumors compared with primary tumors. Gain- and loss-of-function assays demonstrated that LOC646029 inhibits the proliferation, invasiveness, and metastasis of ovarian cancer cells in vivo and in vitro. Moreover, the downregulation of LOC646029 in metastatic ovarian tumors was strongly correlated with poor prognosis. Mechanistically, LOC646029 served as a miR-627-3p sponge to promote the expression of Sprouty-related EVH1 domain-containing protein 1, which is necessary for suppressing tumor metastasis and inhibiting KRAS signaling. Collectively, our results demonstrated that LOC646029 is involved in the progression and metastasis of ovarian cancer, which may be a potential prognostic biomarker.

关键词： ovarian cancer     lncRNA LOC646029     metastasis     microRNA 627-3p     SPRED1    

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RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway

《医学前沿（英文）》 2023年 第17卷 第1期   页码 143-155 doi: 10.1007/s11684-022-0929-y

摘要： Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.

关键词： RGS16     let-7c-5p     glioma     proliferation     migration    

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MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma and exhibit synergistic

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 331-343 doi: 10.1007/s11684-015-0409-8

摘要：

MicroRNAs (miRNAs), an important class of small non-coding RNAs, regulate gene expression at the post-transcriptional level. miRNAs are involved in a wide range of biological processes and implicated in different diseases, including cancers. In this study, miRNA profiling and qRT-PCR validation revealed that miR-142-3p and miR-142-5p were significantly downregulated in hepatocellular carcinoma (HCC) and their expression levels decreased as the disease progressed. The ectopic expression of miR-142 significantly reduced HCC cell migration and invasion. Overexpression of either miR-142-3p or miR-142-5p suppressed HCC cell migration, and overexpression of both synergistically inhibited cell migration, which indicated that miR-142-3p and miR-142-5p may cooperatively regulate cell movement. miR-142-3p and miR-142-5p, which are mature miRNAs derived from the 3′- and 5′-strands of the precursor miR-142, target distinct pools of genes because of their different seed sequences. Pathway enrichment analysis showed a strong association of the putative gene targets of miR-142-3p and miR-142-5p with several cell motility-associated pathways, including those regulating actin cytoskeleton, adherens junctions, and focal adhesion. Importantly, a number of the putative gene targets were also significantly upregulated in human HCC cells. Moreover, overexpression of miR-142 significantly abrogated stress fiber formation in HCC cells and led to cell shrinkage. This study shows that mature miR-142 pairs collaboratively regulate different components of distinct signaling cascades and therefore affects the motility of HCC cells.

关键词： hepatocellular carcinoma     microRNA     metastasis     cytoskeletal reorganization    

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MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 72-80 doi: 10.15302/J-FASE-2016089

摘要： MicroRNAs (miRNAs), small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that miRNAs are important for hair follicle development and growth. In our study, we found by qRT-PCR that miR-148b was significantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148b could activate Wnt/β-catenin pathway and , , and were consistently upregulated accordingly. Furthermore, transcript factor nuclear factor of activated T cells type 5 ( ) and were predicted to be the target of miR-148b and this was substantiated using a Dual-Luciferase reporter system. Subsequently was further identified as the target of miR-148b using western blotting. These results were considered to indicate that miR-148b could activate the Wnt/β-catenin signal pathway by targeting to promote the proliferation of human hair follicle cells.

关键词： miR-148b     hair follicle     proliferation     NFAT5     Wnt10b    

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The microRNA, miR-29c, participates in muscle development through targeting the

Weiya ZHANG,Wei WEI,Yuanyuan ZHAO,Shuhong ZHAO,Xinyun LI

《农业科学与工程前沿（英文）》 2015年 第2卷 第4期   页码 311-317 doi: 10.15302/J-FASE-2015075

摘要： Previous studies indicated that miR-29c is important for muscle development in mice and human, but its role in pigs is unknown. In this study, we detected the expression of miR-29c in Meishan longissimus lumborum (LL) muscle. The results showed that miR-29c was gradually upregulated during development of skeletal muscle in pig. Moreover, the expression of and genes, which were confirmed to be targeted by miR-29c in mice, was decreased along with muscle development. Furthermore, the expression level of miR-29c was significantly higher in adult Meishan pigs than Large White pigs, while the expression of and genes was significantly lower in Meishan pigs. These results indicated that the expression pattern of miR-29c was opposite to that of and genes in pigs. Also, the luciferase assay indicated that miR-29s can target the gene in pigs. In addition, we identified a T to C mutation in the primary transcript of miR-29c, which was associated with the postmortem muscle pH in pigs. Based on these results, we concluded that miR-29c is also important in skeletal muscle development of pigs.

关键词： pig     miR-29c     skeletal muscle     expression     SNP    

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Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 456-463 doi: 10.1007/s11684-014-0353-z

摘要：

microRNAs (miRNAs) have played a key role in human tumorigenesis, tumor progression, and metastasis. On the one hand, miRNAs are aberrantly expressed in many types of human cancer; on the other hand, miRNAs can function as tumor suppressors or oncogenes that target many cancer-related genes. This study aimed to investigate the effects of miRNA-200c (miR-200c) on the biological behavior and mechanism of proliferation, migration, and invasion in the prostate cancer cell line Du145. In this study, Du145 cells were transfected with miR-200c mimics or negative control miR-NC by using an X-tremeGENE siRNA transfection reagent. The relative expression of miR-200c was measured by RT-PCR. The proliferation, migration, and invasion abilities of Du145 cells were detected by CCK8 assays, migration assays and invasion assays, respectively. The expressions of ZEB1, E-cadherin, and vimentin were observed by western blot. Results showed that DU145 cells exhibited a high expression of miR-200c compared with immortalized normal prostate epithelial cell RWPE-1. Du145 cells were then transfected with miR-200c mimics and displayed lower abilities of proliferation, migration, and invasion than those transfected with the negative control. The protein levels of ZEB1 and vimentin were expressed at a low extent in Du145 cells, which were transfected with miR-200c mimics; by contrast, E-cadherin was highly expressed. Hence, miR-200c could significantly inhibit the proliferation of the prostate cancer cell line Du145; likewise, miR-200c could inhibit migration and invasion by epithelial-mesenchymal transition.

关键词： miR-200c     proliferation     migration     invasion     prostate cancer     Du145 cell     ZEB1    

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hsa-miR-197在子宫肌瘤中的表达及生物信息学特征分析

徐青,付子毅,吴小莉,皇甫玉爽,凌静

《中国工程科学》 2014年 第16卷 第5期   页码 99-104

摘要： <p style="text-align: justify;">应用实时定量聚合酶链式反应（PCR）技术检测子宫肌瘤组织中的hsa-miR-197 表达水平，并与配对正常子宫肌细胞对比。通过miRbase、UCSC、NCBI等在线数据库获取并分析hsa-miR-197 序列保守性及其基因组特征。选择miRanda、MirTarget2 及TargetScan 三个在线数据库预测hsa-miR-197 的靶基因并取交集以便后续分析。hsa-miR-197 的功能较广泛，参与肿瘤发生的多种生物学过程，提示hsa-miR-197 可能与子宫肌瘤的发病机制密切相关。p>

关键词： 子宫肌瘤     hsa-miR-197     生物信息学     靶基因    

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Overexpressed miR-9 promotes tumor metastasis via targeting E-cadherin in serous ovarian cancer

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 214-222 doi: 10.1007/s11684-017-0518-7

摘要：

MicroRNAs (miRNAs) play critical roles in the development and progression in various cancers. Dysfunctional miR-9 expression remains ambiguous, and no consensus on the metastatic progression of ovarian cancer has been reached. In this study, results from the bioinformatics analysis show that the 3′-UTR of the E-cadherin mRNA was directly regulated by miR-9. Luciferase reporter assay results confirmed that miR-9 could directly target this 3′-UTR. miR-9 and E-cadherin expression in ovarian cancer tissue was quantified by qRT-PCR. Migration and invasion were detected by wound healing and Transwell system assay in SKOV3 and A2780. qRT-PCR and Western blot were performed to detect the epithelial?mesenchymal transition-associated mRNA and proteins. Immunofluorescence technique was used to analyze the expression and subcellular localization of E-cadherin, N-cadherin, and vimentin. The results showed that miR-9 was frequently upregulated in metastatic serous ovarian cancer tissue compared with paired primary ones. Upregulation of miR-9 could downregulate the expression of E-cadherin but upregulate the expression of mesenchymal markers (N-cadherin and vimentin). Overexpression of miR-9 could promote the cell migration and invasion in ovarian cancer, and these processes could be effectively inhibited via miR-9 inhibitor. Thus, our study demonstrates that miR-9 may promote ovarian cancer metastasis via targeting E-cadherin and a novel potential therapeutic approach to control metastasis of ovarian cancer.

关键词： ovarian cancer     metastasis     miR-9     E-cadherin    

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-Derived miR162a Functions on Osteoporosis Through Directly Promoting Osteoblast Formation

Chunyan Gu,Xichao Yu,Xiaozhu Tang,Leilei Gong,Jingquan Tan,Yuanjiao Zhang,Huili Zheng,Ze Wang,Chenqian Zhang,Yejin Zhu,Zuojian Zhou,Heming Yu,Kai Xu,Jinao Duan,Xiaosong Gu,Ye Yang,

《工程（英文）》 doi: 10.1016/j.eng.2023.09.007

摘要： Traditional Chinese medicine (TCM) can help prevent or treat diseases; however, there are few studies on the active substances of TCM. For example, Lycium barbarum L. has been proven to be effective in treating osteoporosis for thousands of years, but its active substance remains to be unknown. Prompted by the efforts to modernize TCM, the present study focused on the novel active substance of Lycium barbarum L. to reinforce kidney essence to produce bone marrow. Illumina deep sequencing analysis and stem-loop polymerase chain reaction (PCR) assay revealed that miR162a, a Lycium barbarum L.-derived microRNA, can pass through the gastrointestinal tract to target the bone marrow in mice. Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1 (SIDT1) in the stomach. Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor (NcoR). Alizarin red staining and micro-computed tomography (microCT) confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells, zebrafish, and a mouse model of osteoporosis. In addition, transgenic Nicotiana benthamiana (N. benthamiana) leaves overexpressing miR162a were developed by agrobacterium infiltration method. microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N. benthamiana leaves effectively protected against osteoporosis in mice. Our study mechanistically explains how Lycium barbarum L. improves osteoporosis and supports that Lycium barbarum L. reinforces kidney essence, thereby strengthening the bone. miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.

关键词： Traditional Chinese medicine     Lycium barbarum     L     miR162a     Osteoporosis     Nuclear receptor corepressor     Transgenic plants    

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促进肝癌致癌活性和细胞代谢的新型介质——miR-516a-3p

芮韬, 张学优, 冯时, 黄海涛, 詹少伟, 谢海洋, 周琳, 郑树森, 凌琪

《工程（英文）》 2022年 第16卷 第9期   页码 162-175 doi: 10.1016/j.eng.2021.07.020

摘要： 目前的研究旨在探讨miR-516a-3p 在HCC 中的作用。miR-516a-3p 是一种由C19MC 4 个致癌前体miRNA（即mir-516a-1、mir-516a-2、mir-516b-1 和mir-516b-2）所共同剪接而成的相同的成熟体miRNA。在肝癌队列中，与瘤旁组织相比，miR-516a-3p 在肝癌组织中显著高表达。肿瘤miR-516a-3p 的高表达与肝癌高肿瘤负荷相关，可以区分高HCC复发率和死亡率，并独立预测肝癌的不良预后。进一步通过体外实验发现miR-516a-3p 增强了肝癌细胞的增殖、迁移和侵袭性，并通过体内实验验证miR-516a-3p 促进了肿瘤的增殖和远处转移能力。总之，本研究发现，miR-516a-3p 可以通过调节细胞代谢和外泌体递送系统
影响相邻细胞，促进肝癌细胞的肿瘤恶性进展。因此，miR-516a-3p可作为肝癌治疗的新分子靶点。

关键词： 肝细胞肝癌     miRNA簇     外泌体     多组学    

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Estimation of flexible pavement structural capacity using machine learning techniques

Nader KARBALLAEEZADEH, Hosein GHASEMZADEH TEHRANI, Danial MOHAMMADZADEH SHADMEHRI, Shahaboddin SHAMSHIRBAND

《结构与土木工程前沿（英文）》 2020年 第14卷 第5期   页码 1083-1096 doi: 10.1007/s11709-020-0654-z

摘要： The most common index for representing structural condition of the pavement is the structural number. The current procedure for determining structural numbers involves utilizing falling weight deflectometer and ground-penetrating radar tests, recording pavement surface deflections, and analyzing recorded deflections by back-calculation manners. This procedure has two drawbacks: falling weight deflectometer and ground-penetrating radar are expensive tests; back-calculation ways has some inherent shortcomings compared to exact methods as they adopt a trial and error approach. In this study, three machine learning methods entitled Gaussian process regression, M5P model tree, and random forest used for the prediction of structural numbers in flexible pavements. Dataset of this paper is related to 759 flexible pavement sections at Semnan and Khuzestan provinces in Iran and includes “structural number” as output and “surface deflections and surface temperature” as inputs. The accuracy of results was examined based on three criteria of , , and . Among the methods employed in this paper, random forest is the most accurate as it yields the best values for above criteria ( =0.841, =0.592, and =0.760). The proposed method does not require to use ground penetrating radar test, which in turn reduce costs and work difficulty. Using machine learning methods instead of back-calculation improves the calculation process quality and accuracy.

关键词： transportation infrastructure     flexible pavement     structural number prediction     Gaussian process regression     M5P model tree     random forest    

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Preparation of P

Wenjiang LI, Fei XIE, Dongxu HUA, Chunli ZHANG, Chen DAI, Zhenyun YU, Meizhou QI, Shaojun YU

《化学科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 314-317 doi: 10.1007/s11705-010-0573-y

摘要： Silica hollow microspheres containing phosphorous have been prepared by a sol-gel/emulsion method which uses tetraethoxysilane (TEOS) as the precursor for the SiO and phosphoric acid (H PO ) as the precursor for P O . The hollow structure forms an emulsion system which is composed of an oil phase (kerosene, sorbitan monooleate (Span 80)) and an aqueous phase (a viscous sol solution of ethanol, TEOS and H PO ). Some of the phosphorous remains in the final silica shell structure even after calcination at 650°C. The hollow structure of the P O -SiO (silicophosphate) was characterized by X-ray diffraction (XRD), polarized optical microscopy (POM), scanning electron microscopy (SEM), nitrogen adsorption measurement and Fourier transform infrared spectroscopy (FTIR).

关键词： P2O5-SiO2     hollow microspheres     sol-gel/emulsion     phosphoric acid    

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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

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes

Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, Qiuyue Wang

期刊论文

Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis

期刊论文

RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway

期刊论文

MicroRNA-142-3p and microRNA-142-5p are downregulated in hepatocellular carcinoma and exhibit synergistic

null

期刊论文

MicroRNA-148b promotes proliferation of hair follicle cells by targeting

Wanbao YANG,Qinqun LI,Bo SU,Mei YU

期刊论文

The microRNA, miR-29c, participates in muscle development through targeting the

Weiya ZHANG,Wei WEI,Yuanyuan ZHAO,Shuhong ZHAO,Xinyun LI

期刊论文

Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and

null

期刊论文

hsa-miR-197在子宫肌瘤中的表达及生物信息学特征分析

徐青,付子毅,吴小莉,皇甫玉爽,凌静

期刊论文

Overexpressed miR-9 promotes tumor metastasis via targeting E-cadherin in serous ovarian cancer

null

期刊论文

-Derived miR162a Functions on Osteoporosis Through Directly Promoting Osteoblast Formation

Chunyan Gu,Xichao Yu,Xiaozhu Tang,Leilei Gong,Jingquan Tan,Yuanjiao Zhang,Huili Zheng,Ze Wang,Chenqian Zhang,Yejin Zhu,Zuojian Zhou,Heming Yu,Kai Xu,Jinao Duan,Xiaosong Gu,Ye Yang,

期刊论文

促进肝癌致癌活性和细胞代谢的新型介质——miR-516a-3p

芮韬, 张学优, 冯时, 黄海涛, 詹少伟, 谢海洋, 周琳, 郑树森, 凌琪

期刊论文

Estimation of flexible pavement structural capacity using machine learning techniques

Nader KARBALLAEEZADEH, Hosein GHASEMZADEH TEHRANI, Danial MOHAMMADZADEH SHADMEHRI, Shahaboddin SHAMSHIRBAND

期刊论文

Preparation of P

Wenjiang LI, Fei XIE, Dongxu HUA, Chunli ZHANG, Chen DAI, Zhenyun YU, Meizhou QI, Shaojun YU

期刊论文

construction integration technology in Brazil’s superlarge deep-water offshore oil and gas unit project (FPSO P67/P70)

期刊论文