33 results on '"Li Shen"'
Search Results
2. Meta‐analysis and transcriptomic analysis reveal that NKRF and ZBTB17 regulate the NF‐κB signaling pathway, contributing to the shared molecular mechanisms of Alzheimer's disease and atherosclerosis.
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Zhang, Di, Chen, Keyan, and Shan, Li Shen
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ALZHEIMER'S disease ,CELLULAR signal transduction ,ZINC-finger proteins ,ATHEROSCLEROSIS ,TRANSCRIPTOMES - Abstract
Introduction: Alzheimer's disease (AD) and atherosclerosis (AS) are widespread diseases predominantly observed in the elderly population. Despite their prevalence, the underlying molecular interconnections between these two conditions are not well understood. Methods: Utilizing meta‐analysis, bioinformatics methodologies, and the GEO database, we systematically analyzed transcriptome data to pinpoint key genes concurrently differentially expressed in AD and AS. Our experimental validations in mouse models highlighted the prominence of two genes, NKRF (NF‐κB‐repressing factor) and ZBTB17 (MYC‐interacting zinc‐finger protein 1). Results: These genes appear to influence the progression of both AD and AS by modulating the NF‐κB signaling pathway, as confirmed through subsequent in vitro and in vivo studies. Conclusions: This research uncovers a novel shared molecular pathway between AD and AS, underscoring the significant roles of NKRF and ZBTB17 in the pathogenesis of these disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Postoperative fibrinogen‐to‐albumin ratio acting as an indicator of futile recanalization in patients with successful thrombectomy.
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Tang, Tao, Li, Di, Fan, Tie‐Ping, Guo, Lin‐Jia, Lan, Xiao‐Yan, Bi, Cong‐Jie, Boltze, Johannes, Thomas, Aline M., Zhao, Xu‐Sheng, Mo, Ming, Zhao, Man‐Hong, Ji, Xun‐Ming, and Li, Shen
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- 2023
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4. Impact of volemia at admission on the effect of collateral status on functional outcomes in patients undergoing endovascular thrombectomy.
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Tang, Tao, Li, Di, Fan, Tie‐Ping, Thomas, Aline M., Zhao, Man‐Hong, and Li, Shen
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ENDOVASCULAR surgery ,FUNCTIONAL status ,LOGISTIC regression analysis ,CEREBRAL hemorrhage ,INTRACRANIAL hemorrhage - Abstract
Background and purpose: Having good collaterals is associated with better clinical outcomes in patients undergoing endovascular thrombectomy. This study aims to evaluate whether the effect of collateral status on functional outcomes is modified by volemia at admission. Methods: This is a single‐center, retrospective analysis of patients who had acute proximal anterior circulation occlusion and underwent endovascular thrombectomy between January 2019 and June 2022. Volemia at admission, evaluated by blood urea nitrogen‐to‐creatinine ratio, was used to dichotomize patients into dehydrated and hydrated groups. The primary outcome was functional independence (90‐day modified Rankin Scale score = 0–2). Secondary outcomes were the rates of successful reperfusion, 24‐h symptomatic intracranial hemorrhage, and 90‐day all‐cause mortality. Multivariable logistic regression analysis was used to assess the interaction between collateral status and volemia at admission on outcomes. Results: A total of 290 patients were enrolled, among whom having good collaterals was associated with functional independence (adjusted odds ratio [OR] = 2.71, 95% confidence interval [CI] = 1.41–5.22, p = 0.003). Having good collaterals benefited dehydrated patients (adjusted OR = 3.33, 95% CI = 1.45–7.63, p = 0.004) but not hydrated patients (adjusted OR = 2.21, 95% CI = 0.73–6.68, p = 0.161). However, an interaction between collaterals and volemia at admission on functional independence was not observed (p = 0.319). The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and all‐cause mortality were similar between those with good and poor collaterals in both dehydrated and hydrated patients. Conclusions: The effect of collateral status on the functional independence of patients undergoing thrombectomy is not modified by volemia at admission. [ABSTRACT FROM AUTHOR]
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- 2023
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5. The effect of intravenous thrombolysis on patients with successful thrombectomy depends on final reperfusion grade: A retrospective study.
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Tang, Tao, Li, Di, Zhao, Man‐Hong, Thomas, Aline M., Chuang, Chuang, Fan, Tie‐Ping, and Li, Shen
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REPERFUSION ,THROMBECTOMY ,THROMBOLYTIC therapy ,CEREBRAL infarction ,LOGISTIC regression analysis - Abstract
Aims: Although intravenous thrombolysis (IVT) has not shown confirmative effects on the outcomes of patients receiving successful thrombectomy, it might influence the outcomes of a subset of these patients. This study aims to evaluate whether the effects of IVT depend on final reperfusion grade in patients with successful thrombectomy. Methods: This is a single‐center, retrospective analysis of patients with an acute anterior circulation large‐vessel occlusion and a successful thrombectomy between January 2020 and June 2022. Final reperfusion grade was evaluated by the modified Thrombolysis in Cerebral Infarction (mTICI) score, which was dichotomized into incomplete (mTICI 2b) and complete (mTICI 3) reperfusion. The primary outcome was functional independence (90‐day modified Rankin Scale score 0–2). Safety outcomes were 24‐h symptomatic intracranial hemorrhage and 90‐day all‐cause mortality. Multivariable logistic regression analyses were used to assess the interactions between IVT treatment and final reperfusion grade on outcomes. Results: When comparing all 167 patients enrolled in the study, IVT did not influence the extent of functional independence (adjusted OR: 1.38; 95% CI: 0.65–2.95; p = 0.397). The effect of IVT on functional independence depended on final reperfusion grade (p = 0.016). IVT benefited patients with incomplete reperfusion (adjusted OR: 3.70; 95% CI 1.21–11.30; p = 0.022), but not those with complete reperfusion (adjusted OR: 0.48, 95% CI: 0.14–1.59; p = 0.229). IVT was not associated with 24‐h symptomatic intracerebral hemorrhage (p = 0.190) or 90‐day all‐cause mortality (p = 0.545). Conclusions: The effect of IVT on functional independence depended on final reperfusion grade in patients with successful thrombectomy. IVT appeared to benefit patients with incomplete reperfusion, but not those with complete reperfusion. Because reperfusion grade cannot be determined prior to endovascular treatment, this study argues against withholding IVT in IVT‐eligible patients. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Recognizing schizophrenia using facial expressions based on convolutional neural network.
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Zhang, Xiaofei, Li, Tongxin, Wang, Conghui, Tian, Tian, Pang, Haizhu, Pang, Jisong, Su, Chen, Shi, Xiaomei, Li, Jiangong, Ren, Lina, Wang, Jing, Li, Lulu, Ma, Yanyan, Li, Shen, and Wang, Lili
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- 2023
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7. E3 ubiquitin ligase OsPIE3 destabilises the B‐lectin receptor‐like kinase PID2 to control blast disease resistance in rice.
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Wang, Ke, Li, Shen, Chen, Longxin, Tian, Haoran, Chen, Cong, Fu, Yihan, Du, Haitao, Hu, Zheng, Li, Runting, Du, Yanxiu, Li, Junzhou, Zhao, Quanzhi, and Du, Changqing
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RICE blast disease , *UBIQUITIN ligases , *KILLER cell receptors , *MEMBRANE proteins , *BLOOD proteins , *SITE-specific mutagenesis , *PROTEOLYSIS - Abstract
Summary: Previous studies have reported that PID2, which encodes a B‐lectin receptor‐like kinase, is a key gene in the resistance of rice to Magnaporthe oryzae strain ZB15. However, the PID2‐mediated downstream signalling events remain largely unknown.The U‐box E3 ubiquitin ligase OsPIE3 (PID2‐interacting E3) was isolated and confirmed to play key roles in PID2‐mediated rice blast resistance. Yeast two‐hybrid analysis showed that the armadillo repeat region of OsPIE3 is required for its interaction with PID2. Further investigation demonstrated that OsPIE3 can modify the subcellular localisation of PID2, thus promoting its nuclear recruitment from the plasma membrane for protein degradation in the ubiquitin–proteasome system. Site‐directed mutagenesis of a conserved cysteine site (C230S) within the U‐box domain of OsPIE3 reduces PID2 translocation and ubiquitination.Genetic analysis suggested that OsPIE3 loss‐of‐function mutants exhibited enhanced resistance to M. oryzae isolate ZB15, whereas mutants with overexpressed OsPIE3 exhibited reduced resistance. Furthermore, the OsPIE3/PID2‐double mutant displayed a similar blast phenotype to that of the PID2 single mutant, suggesting that OsPIE3 is a negative regulator and functions along with PID2 in blast disease resistance.Our findings confirm that the E3 ubiquitin ligase OsPIE3 is necessary for PID2‐mediated rice blast disease resistance regulation. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Continuous decision‐making for autonomous driving at intersections using deep deterministic policy gradient.
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Li, Guofa, Li, Shenglong, Li, Shen, and Qu, Xingda
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REINFORCEMENT learning ,AUTONOMOUS vehicles ,TRAFFIC safety ,CONVOLUTIONAL neural networks ,DECISION making ,MARKOV processes ,PROBLEM solving - Abstract
Intersections have been identified as the most complex and accident‐prone traffic scenarios on road. Making appropriate decisions at intersections for driving safety, efficiency, and comfort become a challenging task for autonomous vehicles (AVs). The existing research on AV decision‐making at intersections either considers a single scenario only with discrete behaviour outputs or ignores the requirements for driving efficiency and comfort. To address these problems, this study proposed a deep reinforcement learning based continuous decision‐making method to make AVs drive through intersections. The proposed method establishes an end‐to‐end decision‐making framework by using a convolutional neural network to map the relationship between traffic images and vehicle operations. The interaction between the AV and other vehicles was modelled as a Markov decision process (MDP), and a deep deterministic policy gradient algorithm was employed to solve the MDP problem and obtain the optimal driving policy. The top three accident‐prone crossing path crash scenarios at intersections were realized in CARLA to verify the effectiveness of the proposed method. The experimental results demonstrated that the developed method could provide effective policies to ensure driving safety and efficiency while considering driving comfort for autonomous driving at intersections in all the examined scenarios. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Genetically predicted frailty index and risk of stroke and Alzheimer's disease.
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Liu, Weishi, Zhang, Luyang, Fang, Hui, Gao, Yuan, Liu, Kai, Li, Shen, Liu, Hongbing, Wang, Xin, Liu, Chen, Song, Bo, Xia, Zongping, and Xu, Yuming
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DISEASE risk factors ,FRAILTY ,INFLAMMATORY bowel diseases ,GENOME-wide association studies ,ALZHEIMER'S disease - Abstract
Background and purpose: Previous studies have reported the association between frailty and stroke or Alzheimer's disease (AD). However, the causality remains unclear. The aim of the present study was to evaluate whether genetically predicted frailty is associated with the risk of stroke or AD by a Mendelian randomization (MR) study. Methods: Genetic variants associated with the frailty index (FI) were obtained from a large genome‐wide association study (GWAS). Summary‐level data for stroke and AD were adopted from the corresponding large GWAS of individuals of European ancestry. The inverse variance weighted method was used for estimating causal effects. Multivariable analysis was performed for further adjustment. Results: The present MR study indicated a suggestive association between genetically predicted FI and a higher risk of any stroke (odds ratio 1.360, 95% confidence interval 1.006–1.838, p = 0.046). Regarding the subtypes of stroke, genetically predicted FI was associated with a higher risk of large artery atherosclerosis stroke (LAS) (odds ratio 2.487, 95% confidence interval 1.282–4.826, p = 0.007). No causal links were identified between genetically predicted FI and any ischaemic stroke, intracranial haemorrhage, cardioembolic stroke, small artery stroke, AD or AD‐by‐proxy. Multivariable MR analysis indicated that the association of genetically predicted FI with LAS was attenuated after adjustment for inflammatory bowel disease (p = 0.114). Conclusions: The MR study suggested that genetically predicted FI may be associated with an increased risk of any stroke. Subgroup analysis indicated a suggestive association between genetically predicted FI and the risk of LAS. The underlying mechanisms need further investigation. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Perioperative stroke: A perspective on challenges and opportunities for experimental treatment and diagnostic strategies.
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Jin, Xia, Li, Peiying, Michalski, Dominik, Li, Shen, Zhang, Yueman, Jolkkonen, Jukka, Cui, Lili, Didwischus, Nadine, Xuan, Wei, and Boltze, Johannes
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STROKE ,MEDICAL research ,ISCHEMIC stroke ,CELLULAR therapy ,DIAGNOSTIC imaging - Abstract
Perioperative stroke is an ischemic or hemorrhagic cerebral event during or up to 30 days after surgery. It is a feared condition due to a relatively high incidence, difficulties in timely detection, and unfavorable outcome compared to spontaneously occurring stroke. Recent preclinical data suggest that specific pathophysiological mechanisms such as aggravated neuroinflammation contribute to the detrimental impact of perioperative stroke. Conventional treatment options are limited in the perioperative setting due to difficult diagnosis and medications affecting coagulation in may cases. On the contrary, the chance to anticipate cerebrovascular events at the time of surgery may pave the way for prevention strategies. This review provides an overview on perioperative stroke incidence, related problems, and underlying pathophysiological mechanisms. Based on this analysis, we assess experimental stroke treatments including neuroprotective approaches, cell therapies, and conditioning medicine strategies regarding their potential use in perioperative stroke. Interestingly, the specific aspects of perioperative stroke might enable a more effective application of experimental treatment strategies such as classical neuroprotection whereas others including cell therapies may be of limited use. We also discuss experimental diagnostic options for perioperative stroke augmenting classical clinical and imaging stroke diagnosis. While some experimental stroke treatments may have specific advantages in perioperative stroke, the paucity of established guidelines or multicenter clinical research initiatives currently limits their thorough investigation. [ABSTRACT FROM AUTHOR]
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- 2022
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11. RAO‐UNet: a residual attention and octave UNet for road crack detection via balance loss.
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Fan, Lili, Zhao, Hongwei, Li, Ying, Li, Shen, Zhou, Rui, and Chu, Wenbo
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CRACKING of pavements ,ROADS ,PROBLEM solving ,COMPUTATIONAL fluid dynamics ,SPEED - Abstract
The acquisition and evaluation of road cracks are essential to ensure the availability of roads and necessary maintenance. However, the road cracks images have been obsessed with the problem of imbalance in the category and the number of categories. Among them, the category imbalance makes the network focus on the background and the detection result will be complete black. The imbalanced number of categories leads to the missed detection of thin cracks. In addition, a large number of images generated in real time put forward higher requirements on memory and calculations. The RAO‐UNet is built which is an efficient and effective network for crack detection in road images using encoder–decoder and residual attention module‐based image frequency relationship. Compared with otheTr methods, RAO‐UNet could learn multiple‐spatial‐frequency features, thus can enhance the differentiation of high‐frequency features while saving the computational cost. Regarding the space optimisation, a novel balance loss function is proposed, which not only solves the balance problem, but also ensures the stability and consistency in the optimisation process. We evaluated RAO‐UNet on public data sets. Compared with state‐of‐the‐art methods, it achieves better performance on processing speed and detection accuracy. Specifically, RAO‐UNet achieves 98.32% / 97.86% Precision, 97.84% / 95.89% Recall, 97.61% / 97.04% F1 score on CFD and AigleRN data sets, respectively. [ABSTRACT FROM AUTHOR]
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- 2022
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12. CRISPR‐based knock‐in mutagenesis of the pioneer transcription factor FOXA1: optimization of strategies for multi‐allelic proteins in cancer cells.
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Li, Shen, Garay, Joseph P., Tubbs, Colby A., and Franco, Hector L.
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CRISPRS ,MUTAGENESIS ,TRANSCRIPTION factors ,GENOME editing ,CANCER cells ,BREAST cancer ,PROTEINS - Abstract
Precise genome engineering of living cells has been revolutionized by the introduction of the highly specific and easily programmable properties of the clustered regularly interspaced short palindromic repeats (CRISPR) technology. This has greatly accelerated research into human health and has facilitated the discovery of novel therapeutics. CRISPR‐Cas9 is most widely employed for its ability to inactivate or knockout specific genes, but can be also used to introduce subtle site‐specific substitutions of DNA sequences that can lead to changes in the amino acid composition of proteins. Despite the proven success of CRISPR‐based knock‐in strategies of genes in typical diploid cells (i.e., cells containing two sets of chromosomes), precise editing of cancer cells, that typically have unstable genomes and multiple copies of chromosomes, is more challenging and not adequately addressed in the literature. Herein, we detail our methodology for replacing endogenous proteins with intended knock‐in mutants in polyploid cancer cells and discuss our experimental design, screening strategy, and facile allele frequency estimation methodology. As proof of principle, we performed genome editing of specific amino acids within the pioneer transcription factor FOXA1, a critical component of estrogen and androgen receptor signaling, in MCF‐7 breast cancer cells. We confirm mutant FOXA1 protein expression and intended amino acid substitutions via western blotting and mass spectrometry. In addition, we show that mutant allele frequency estimation is easily achieved by topoisomerase‐based cloning combined with allele‐specific PCR, which we later confirmed by next‐generation RNA‐sequencing. Typically, there are 4 ‐ 5 copies (alleles) of FOXA1 in breast cancer cells, making the editing of this protein inherently challenging. As a result, most studies that focus on FOXA1 mutants rely on ectopic overexpression of FOXA1 from a plasmid. Therefore, we provide an optimized methodology for replacing endogenous wild‐type FOXA1 with precise knock‐in mutants to enable the systematic analysis of its molecular mechanisms within the appropriate physiological context. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Altered nitric oxide induced by gutmicrobiota reveals the connection between central precocious puberty and obesity.
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Yinhu Li, Li Shen, Congfu Huang, Xiaoyu Li, Junru Chen, Shuai Cheng Li, and Bairong Shen
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PRECOCIOUS puberty , *NITRIC oxide , *OBESITY , *ANTERIOR pituitary gland , *GUT microbiome , *NITRIC-oxide synthases - Abstract
Received:21December2020 Revised:11January2021 Accepted:14January2021 Publishedonline:25January2021 DOI:10.1002/ctm2.299 LETTER TO EDITOR Alterednitricoxideinducedbygutmicrobiotarevealsthe connectionbetweencentralprecociouspubertyandobesity DearEditor, Central precocious puberty (CPP) is a neuroendocrine disease characterized by the rapid development of genitaliaandthepresenceofsecondarysexualcharacteristics beforeage8ingirlsand9inboys. Notably, the CPP-enriched Gamma-aminobutyric acid-producer Bifidobacterium 6 showed negative associationwiththeHC-enrichedBacteroides(Figure2C),while the correlation was experimentally examined 7 and the neurotransmission-relatedSutterella 5 formedpositivecorrelation with Parabacteroides in CPP patients. Since gut microbiota (GM) associatedwiththehormonesecretionandobesity, 3 itinspires us to detect the mechanism of GM in triggering CPP, and explore their roles for the co-occurrence of obesity andCPP. [Extracted from the article]
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- 2021
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14. MiR-378a-3p as a putative biomarker for hepatocellular carcinoma diagnosis and prognosis: Computational screening with experimental validation.
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Fuliang Qian, Jinghan Wang, Ying Wang, Qian Gao, Wenying Yan, Yuxin Lin, Li Shen, Yufeng Xie, Xiaoqing Jiang, and Bairong Shen
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HEPATOCELLULAR carcinoma ,DIAGNOSIS ,PROGNOSIS ,BIOMARKERS ,CATENINS ,CELL growth - Abstract
Background: Hepatocellular carcinoma (HCC) is a malignant disease with high morbidity and mortality, and the molecular mechanism for the genesis and progression is complex and heterogeneous. Biomarker discovery is crucial for the personalized and precision treatment of HCC. The accumulation of reported microRNA biomarkers makes it possible to combine computational identification with experimental validation to accelerate the discovery of novel biomarker. Results: In the present work, we applied a rational computer-aided biomarker discovery model to screen for the HCC diagnosis biomarker. TwoHCC-associated networks were constructed based on the microRNA and mRNA expression profiles, and the potential microRNA biomarkers were identified based on their unique regulatory and influential power in the network. These putative biomarkers were then experimentally validated. One prominent example among these identified biomarkers is MiR-378a-3p: It was shown to independently regulate several important transcription factors such as PLAGL2 and β-catenin, affecting the β-catenin signaling. Such mechanism may indicate a potential tumor suppressor role of MiR-378a-3p and the impact of its abnormal expression on the cell growth and invasion of HCC. Conclusions: A bioinformatics model with network topological and functional characterization was successfully applied to the identification of HCC biomarkers. The predicted microRNA biomarkers were than validated with experiments using human HCC cell lines, model animal, and clinical specimens. The results confirmed the prediction by our proposed model thatmiR-378a-3pwas a putative biomarker for diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Twist/untwist parameters are promising evaluators of myocardial mechanic changes in heart failure patients with preserved ejection fraction.
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Zhang, Yi, Li, Shen‐Yi, Xie, Juan‐Juan, and Wu, Yuan
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- 2020
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16. Dynamic analysis and current calculation of a permanent magnet spherical motor for point‐to‐point motion.
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Guo, Xiwen, Li, Shen, Wang, Qunjing, Wen, Yan, and Gong, Nengwei
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Point‐to‐point (PTP) motion of the end effector is an essential part for using robot manipulators to perform precision machining task. Traditionally, it is implemented by several motors with complex transmission mechanism, which causes slow responses, low positioning precision and dynamic performance. Therefore, dynamics analysis and modified electrifying method of a permanent magnet spherical motor (PMSM), which can provide up to three degrees‐of‐freedom independently for PTP motion is presented in this study. First, a new inverse kinematics method for solving PMSM's rotation angle using a cross‐product between two points is proposed. Through dynamics analysis, the control torque is designed by using sinusoidal function to plan the PTP motion. Second, a modified electrifying method by combined coils has been proposed based on the current–torque equation, which deduced the calculation burden by reducing the dimensions of characteristic matrix. Finally, the simulations and experimental results show that PTP motion trajectory planning based on sinusoidal function and the modified electrifying control method can not only reduce the torque disturbance and increase the electromagnetic torque, but also has the advantages of relatively simple control and better tracking control performance. [ABSTRACT FROM AUTHOR]
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- 2019
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17. Letter: hepatocellular carcinoma negatively affects sustained virological response of direct‐acting anti‐viral treatment in decompensated cirrhosis.
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He, Caini, Li, Shen, Zhao, Yunyu, and Ji, Fanpu
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HEPATOCELLULAR carcinoma , *CIRRHOSIS of the liver , *LETTERS , *RIBAVIRIN , *ANTIVIRAL agents , *THERAPEUTICS - Abstract
LINKED CONTENT This article is linked to Mecci et al paper. To view this article, visit https://doi.org/10.1111/apt.15296. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Prognostic Utility of Soluble TREM-1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction.
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Yun Kai Wang, Jia Ni Tang, Yun Li Shen, Bo Hu, Chun Yu Zhang, Ming Hui Li, Rui Zhen Chen, Jun Bo Ge, Xue Bo Liu, Wang, Yun Kai, Tang, Jia Ni, Shen, Yun Li, Hu, Bo, Zhang, Chun Yu, Li, Ming Hui, Chen, Rui Zhen, Ge, Jun Bo, and Liu, Xue Bo
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- 2018
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19. Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy.
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Kyhl, Lars‐Erik Broksoe, Li, Shen, Faerch, Kirstine Ullitz, Soegaard, Birgitte, Larsen, Frank, and Areberg, Johan
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OPIOID receptors , *PHARMACOKINETICS , *PHARMACODYNAMICS , *RADIOIMMUNOASSAY , *LIQUID chromatography-mass spectrometry , *COMPUTER simulation - Abstract
Aims The aims of this study were to develop a population pharmacokinetic (PK) model to describe the PK of nalmefene in healthy subjects and to relate the exposure of nalmefene to the μ-opioid receptor occupancy by simulations in the target population. Methods Data from nine phase I studies (243 subjects) with extensive blood sampling were pooled and used for the population PK model building. Data from four other phase I studies (85 subjects) were pooled and used as an external validation dataset. Eight subjects from an imaging study contributed occupancy data and the pharmacokinetic/pharmacodynamic (PK/PD) relationship was modelled. Combining the population PK model and the PK/PD relationship enabled simulations to predict μ-opioid occupancy. Results A two compartment model with first order absorption best described the nalmefene PK data. The typical subject in the population was estimated to have a systemic clearance of 60.4 l h−1 and a central volume of distribution of 266 l. Absolute oral bioavailability was estimated to 41% without food intake and with food about 53%. Simulation of the μ-opioid receptor occupancy shows that the 95% confidence bound is within or above 60-90% occupancy for up to 22-24 h after a single dose of 20 mg nalmefene. Conclusions A robust population PK model for nalmefene was developed. Based on the concentration-occupancy model the μ-opioid receptor occupancy after a single 20 mg dose of nalmefene is predicted to be above the target therapeutic occupancy for about 24 h in about 95% of the target population. [ABSTRACT FROM AUTHOR]
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- 2016
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20. Drosophila miR-5 suppresses Hedgehog signaling by directly targeting Smoothened
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Wu, Long-Fei, Gao, Lei, Hou, Xiao-Meng, Zhang, Qing-Hai, Li, Shen, Yang, Yong-Fei, and Lin, Xin-Hua
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DROSOPHILA ,MICRORNA ,CANCER invasiveness ,CELLULAR signal transduction ,GENE expression ,DEVELOPMENTAL biology - Abstract
Abstract: Hedgehog (Hh) signaling plays many important roles in developmental processes and cancers. Smoothened (Smo) is an important signal transducer in the Hh pathway, and its expression is tightly regulated by several different post-transcriptional mechanisms. However, whether microRNAs (miRNAs) are involved in Smo regulation is still unclear. Here, we found that miR-5 acts as a suppressor of the Hh pathway by targeting Smo. Through in vivo sensor assay and in vitro luciferase assay, we found that miR-5 downregulates Smo through directly binding to its 3′UTR. Moreover, our data indicated Costal-2 (Cos2) and Fused (Fu) do not play a role in the reduction of Smo mediated by miR-5. Furthermore, we determined that miR-5 not involved in Notch or Dpp signaling pathways by detecting target gene expression. Together, our results indicate that miR-5 can specifically suppress Hh signaling by directly targeting Smo in Drosophila. [Copyright &y& Elsevier]
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- 2012
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21. Participation of Tom1L1 in EGF-stimulated endocytosis of EGF receptor.
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Ning Sheng Liu, Li Shen Loo, Loh, Eva, Li-Fong Seet, and Wanjin Hong
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ENDOCYTOSIS , *PROTEINS , *TYROSINE , *AMINO acids , *CELL physiology - Abstract
Although many proteins have been shown to participate in ligand-stimulated endocytosis of EGF receptor (EGFR), the adaptor protein responsible for interaction of activated EGFR with endocytic machinery remains elusive. We show here that EGF stimulates transient tyrosine phosphorylation of Tom1L1 by the Src family kinases, resulting in transient interaction of Tom1L1 with the activated EGFR bridged by Grb2 and Shc. Cytosolic Tom1L1 is recruited onto the plasma membrane and subsequently redistributes into the early endosome. Mutant forms of Tom1L1 defective in Tyr-phosphorylation or interaction with Grb2 are incapable of interaction with EGFR. These mutants behave as dominant-negative mutants to inhibit endocytosis of EGFR. RNAi-mediated knockdown of Tom1L1 inhibits endocytosis of EGFR. The C-terminal tail of Tom1L1 contains a novel clathrin-interacting motif responsible for interaction with the C-terminal region of clathrin heavy chain, which is important for exogenous Tom1L1 to rescue endocytosis of EGFR in Tom1L1 knocked-down cells. These results suggest that EGF triggers a transient Grb2/Shc-mediated association of EGFR with Tyr-phosphorylated Tom1L1 to engage the endocytic machinery for endocytosis of the ligand–receptor complex. [ABSTRACT FROM AUTHOR]
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- 2009
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22. Dietary Resistant Starch Increases Hypothalamic POMC Expression in Rats.
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Li Shen, Keenan, Michael J., Martin, Roy J., Tulley, Richard T., Raggio, Anne M., McCutcheon, Kathleen L., and Jun Zhou
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STARCH ,GLUCANS ,AMYLOLYSIS ,HYPOTHALAMIC hormones ,HYPOTHALAMUS ,PROOPIOMELANOCORTIN ,PITUITARY hormones - Abstract
Resistant starch (RS) is fermentable dietary fiber. Inclusion of RS in the diet causes decreased body fat accumulation and altered gut hormone profile. This study investigates the effect of feeding RS on the neuropeptide messenger RNA (mRNA) expressions in the arcuate nucleus (ARC) of the hypothalamus and whether vagal afferent nerves are involved. The rats were injected intraperitoneally with capsaicin to destroy unmyelinated small vagal afferent nerve fibers. The cholecystokinin (CCK) food suppression test was performed to validate the effectiveness of the capsaicin treatment. Then, capsaicin-treated rats and vehicle-treated rats were subdivided into a control diet or a RS diet group, and fed the corresponding diet for 65 days. At the end of study, body fat, food intake, plasma peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), and hypothalamic pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AgRP) gene expressions were measured. RS-fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP-1 in both the capsaicin and vehicle-treated rats. Hypothalamic NPY and AgRP gene expressions were not changed by RS or capsaicin. Therefore, destruction of the capsaicin-sensitive afferent nerves did not alter the response to RS in rats. These findings suggest that dietary RS might reduce body fat through increasing the hypothalamic POMC expression and vagal afferent nerves are not involved in this process. This is the first study to show that dietary RS can alter hypothalamic POMC expression.Obesity (2008) 17 1, 40–45. doi:10.1038/oby.2008.483 [ABSTRACT FROM AUTHOR]
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- 2009
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23. Differential regulation of neutrophil chemotaxis to IL-8 and fMLP by GM-CSF: lack of direct effect of oestradiol.
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Li Shen, Smith, Jennifer M., Zheng Shen, Hussey, Stephen B., Wira, Charles R., and Fanger, Michael W.
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GRANULOCYTE-macrophage colony-stimulating factor , *ESTRADIOL , *CHEMOTAXIS , *COLONY-stimulating factors (Physiology) , *NEUTROPHILS , *CELLULAR immunity , *IMMUNOREGULATION , *ESTROGEN - Abstract
Neutrophils are a normal constituent of the female reproductive tract and their numbers increase in the late secretory phase of the menstrual cycle prior to menses. Several cytokines are produced in female reproductive tract tissue. In particular granulocyte–macrophage colony-stimulating factor (GM-CSF), a potent activator of neutrophils, is secreted in high concentrations by female reproductive tract epithelia. We previously observed that GM-CSF synergizes strongly with interleukin-8 (IL-8) in enhancing chemotaxis of neutrophils. Thus we investigated whether pretreatment of neutrophils with GM-CSF would prime subsequent chemotaxis to IL-8 in the absence of GM-CSF. Surprisingly, a 3-hr pulse of GM-CSF severely diminished chemotaxis to IL-8, whereas N-formyl-methyl-leucyl-phenylalanine (fMLP)-mediated chemotaxis was retained. Conversely, when cells were incubated without GM-CSF they retained IL-8-mediated migration but lost fMLP chemotaxis. These changes in chemotaxis did not correlate with expression of CXCR1, CXCR2 or formyl peptide receptor. However, IL-8-mediated phosphorylation of p44/42 mitogen-activated protein kinase was greatly reduced in neutrophils that no longer migrated to IL-8, and was diminished in cells that no longer migrated to fMLP. Oestradiol, which is reported by some to exert an anti-inflammatory effect on neutrophils, did not change the effects of GM-CSF. These data suggest that neutrophil function may be altered by cytokines such as GM-CSF through modulation of signalling and independently of surface receptor expression. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
24. A traffic state prediction method based on spatial–temporal data mining of floating car data by using autoformer architecture.
- Author
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Yu, Shuangzhi, Peng, Jiankun, Ge, Yuming, Yu, Xinlian, Ding, Fan, Li, Shen, and Ma, Charlie
- Abstract
Floating car data (FCD), characterized by wide spatiotemporal coverage, low collection cost, and immunity to adverse weather conditions, are one of the key approaches for intelligent transportation systems to obtain real‐time urban road network traffic information. The research aims to utilize GPS data from taxis in Shanghai and vector geographic information data of the road network, with urban expressways as the research focus. Based on the different driving characteristics of expressways and the vehicles on the ramps below, a clustering analysis is employed to determine all floating vehicles traveling on the target road. Furthermore, an adaptive buffer zone consistent with the road orientation is established based on road vector geographic data. This allows for the extraction of FCD within segmented areas, and the average vehicle speed for that road segment is obtained through weighted calculations. This method fully exploits the natural characteristics of taxis in urban areas with a wide spatiotemporal distribution. The data effectiveness and coverage reach 90.2% and 85.7%, respectively, significantly surpassing the traditional grid‐based extraction method for FCD. Additionally, to capture the long‐term spatiotemporal dependencies of road network traffic states, a spatial–temporal autoformer (STAF) network based on spatial–temporal sequence autocorrelation is employed for traffic state prediction. The results indicate that the STAF method demonstrates good performance in medium‐ and long‐term prediction. We believe that the proposed FCD mining method in this paper provides a new approach for efficiently extracting large‐scale road network traffic states and conducting medium‐ to long‐term predictions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Dual-band balun with flexible frequency ratios.
- Author
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Andres Li Shen, Mi Zhou, Bayaner Arigong, Jin Shao, Han Ren, Jun Ding, Rongguo Zhou, and Hualiang Zhang
- Subjects
- *
BALUNS , *COMPUTER simulation , *REFLECTANCE , *PRINTED circuits , *FREQUENCY multipliers - Abstract
A novel dual-band balun is presented. The designed 3-port balun is based on a 4-port structure with the fourth port terminated as an open end. Being a 4-port symmetrical network, even–odd-mode analysis is used to analyse the balun's performance. Based on the derived explicit design equations, a balun is designed to operate at 1.1 and 2 GHz. Numerical simulations show a low reflection coefficient S11, equal magnitude of –3 dB as well as 180° phase difference at the output ports. To validate the theoretical and numerical simulations, the proposed balun is fabricated on the FR4 Isola printed circuit board and measurement results match well with the design theory. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. Dual‐band balun with flexible frequency ratios.
- Author
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Li Shen, Andres, Zhou, Mi, Arigong, Bayaner, Shao, Jin, Ren, Han, Ding, Jun, Zhou, Rongguo, and Zhang, Hualiang
- Abstract
A novel dual‐band balun is presented. The designed 3‐port balun is based on a 4‐port structure with the fourth port terminated as an open end. Being a 4‐port symmetrical network, even–odd‐mode analysis is used to analyse the balun's performance. Based on the derived explicit design equations, a balun is designed to operate at 1.1 and 2 GHz. Numerical simulations show a low reflection coefficient S11, equal magnitude of −3 dB as well as 180° phase difference at the output ports. To validate the theoretical and numerical simulations, the proposed balun is fabricated on the FR4 Isola printed circuit board and measurement results match well with the design theory. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
27. Rhetorical Implications of Linguistic Relativity: Theory and Application to Chinese and Tawanese Interlanguages.
- Author
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Douglas, Dan and Li Shen
- Subjects
LANGUAGE & languages ,NONFICTION - Abstract
Reviews the book "Rhetorical Implications of Linguistic Relativity: Theory and Application to Chinese and Taiwanese Interlanguages," by Kristopher H. Kowal.
- Published
- 2000
28. On Second Language Writing.
- Author
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Vann, Roberta J. and Li Shen
- Subjects
SECOND language acquisition ,NONFICTION - Abstract
Reviews the book "On Second Language Writing," edited by Tony Silva and Paul Kei Matsuda.
- Published
- 2002
29. 2-Methyl-12H-benzimidazo[2,1-b][1,3]benzothia-zin-12-one.
- Author
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Wang Z, Yu B, Li S, Zou C, and Sun X
- Abstract
In the title compound, C(15)H(10)N(2)OS, prepared by the reaction of 2-iodo-5-methyl-benzoyl chloride with 2-mercaptobenzimidazole, the four-membered fused-ring system is essentially planar [maximum deviation from the least-squares plane = 0.137 (6) Å]. The crystal packing is stabilized by weak inter-molecular π-π inter-actions [minimum ring centroid separation = 3.536 (4) Å] and weak C-H⋯π inter-actions.
- Published
- 2011
- Full Text
- View/download PDF
30. 3-(3,4-Dichloro-phen-yl)-1-(2-naphth-yl)prop-2-en-1-one.
- Author
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Lu ZK, Feng Y, Li S, and Diao HL
- Abstract
The asymmetric unit of the title compound, C(19)H(12)Cl(2)O, contains four independent mol-ecules, which can be divided into two pairs of mol-ecules with close values of the C-C(=O)-C=C torsion angles in each pair, viz. 165.12 (16) and 165.68 (15)° in one pair, and -164.66 (15) and -164.81 (15)° in the other pair. The crystal packing exhibits short inter-molecular Cl⋯Cl contacts of 3.362 (1) Å.
- Published
- 2009
- Full Text
- View/download PDF
31. Bis(2,3-dimethyl-butane-2,3-diamine)nickel(II) dinitrate monohydrate.
- Author
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Li SX, Zou LK, Xie B, Wang J, and Li JZ
- Abstract
In the title compound, [Ni(C(6)H(16)N(2))(2)](NO(3))(2)·H(2)O, the bis-(2,3-dimethyl-butane-2,3-diamine)nickel(II) complex cation possesses a relatively undistorted square-planar geometry about the Ni atom, which lies on an inversion centre and is coordinated by four N atoms from two symmetry-related 2,3-diamino-2,3-dimethyl-butane (tmen) ligands. The amine groups are N-H⋯O hydrogen bonded to the nitrate anions, which are, in turn, linked by inter-stitial water mol-ecules lying on a twofold axis. The infinite zigzag chains thus formed along [001] are further connected to each other by N-H⋯O hydrogen bonds towards the water mol-ecules, forming layers of two-dimensional hydrogen-bonded arrays.
- Published
- 2009
- Full Text
- View/download PDF
32. 1-[5-(3,4-Dichlorophenyl)-3-(2-naphthyl)-4,5-dihydropyrazol-1-yl]ethanone.
- Author
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Lu ZK, Li S, and Feng Y
- Abstract
In the title compound, C(21)H(16)Cl(2)N(2)O, the central pyrazoline ring makes dihedral angles of 90.1 (3) and 7.8 (3)°, with the pendant benzene ring and naphthalene ring system, respectively. In the crystal structure, weak C-H⋯O inter-actions lead to chains of mol-ecules.
- Published
- 2008
- Full Text
- View/download PDF
33. 1-[3-(2-Naphth-yl)-5-(3,4,5-trimethoxy-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone.
- Author
-
Lu ZK, Diao HL, Li S, and He B
- Abstract
In the title compound, C(24)H(24)N(2)O(4), the pendant benzene and naphthalene ring systems make dihedral angles of 87.9 (3) and 19.2 (3)°, respectively, with the central pyrazoline ring. In the crystal structure, weak C-H⋯O inter-actions help to establish the packing.
- Published
- 2008
- Full Text
- View/download PDF
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