Publications by authors named "Yue Fu"

172 Publications

miR-181d/RBP2/NF-κB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis.

Front Oncol 2021 25;11:654411. Epub 2021 Mar 25.

Department of Hematology, Qilu Hospital of Shandong University, Jinan, China.

Background: Chronic myeloid leukemia (CML) is a malignant clonal proliferative disease. Once it progresses into the phase of blast crisis (CML-BP), the curative effect is poor, and the fatality rate is extremely high. Therefore, it is urgent to explore the molecular mechanisms of blast crisis and identify new therapeutic targets.

Methods: The expression levels of miR-181d, RBP2 and NF-κB p65 were assessed in 42 newly diagnosed CML-CP patients and 15 CML-BP patients. Quantitative real-time PCR, Western blots, and cell proliferation assay were used to characterize the changes induced by overexpression or inhibition of miR-181d, RBP2 or p65. Luciferase reporter assay and ChIP assay was conducted to establish functional association between miR-181d, RBP2 and p65. Inhibition of miR-181d expression and its consequences in tumor growth was demonstrated models.

Results: We found that miR-181d was overexpressed in CML-BP, which promoted leukemia cell proliferation. Histone demethylase RBP2 was identified as a direct target of miR-181d which downregulated RBP2 expression. Moreover, RBP2 inhibited transcriptional expression of NF-κB subunit, p65 by binding to its promoter and demethylating the tri/dimethylated H3K4 region in the p65 promoter locus. In turn, p65 directly bound to miR-181d promoter and upregulated its expression. Therefore, RBP2 inhibition resulting from miR-181d overexpression led to p65 upregulation which further forwarded miR-181d expression. This miR-181d/RBP2/p65 feedback regulation caused sustained NF-κB activation, which contributed to the development of CML-BP.

Conclusions: Taken together, the miR-181d/RBP2/p65 feedback regulation promoted CML-BP and miR-181d may serve as a potential therapeutic target of CML-BP.
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http://dx.doi.org/10.3389/fonc.2021.654411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027495PMC
March 2021

LASS2 mediates Nrf2-driven progestin resistance in endometrial cancer.

Am J Transl Res 2021 15;13(3):1280-1289. Epub 2021 Mar 15.

Jiangxi Medical College, Nanchang University Nanchang 330000, China.

Progestin administration serves as the optimal conservative treatment method for women with endometrial cancer or precancer lesions who want to preserve fertility. However, there are still at least 30% of patients in which progestin resistance occurs. LASS2 (Ceramide Synthase 2) has been reported to be involved in chemotherapy resistance, whether it also plays a role in progestin resistance is not clear. Here, we explored the detailed mechanism by which Nrf2/LASS2 contributes to progestin resistance and disease progression.

Methods: IHC assays were performed to estimate the expression pattern of Nrf2 and LASS2. Moreover, it bears three antioxidant response elements (ARE) in the promoter region of LASS2 gene, therefore, Luciferase assays were performed to determine if Nrf2 regulates LASS2 by binding with these ARE sequence. Western Blot assays were used to determine the expression of Nrf2 and LASS2 protein among various endometrial cell lines. Relative mRNA expression levels were detected by RT-PCR. Cellular growth was monitored with CCK-8 tests. Apoptosis was determined with Annexin V-PI staining and flow cytometry analysis. siRNA knockdown was performed to investigate the effects of Nrf2 on cell proliferation.

Result: Nrf2/LASS2 is highly expressed in endometrial cancer tissue, as compared to expression levels in normal endometrial tissue. Proliferation assays demonstrated that overexpression of Nrf2/LASS2 resulted in progestin resistance. Conversely, knockdown of LASS2 increased apoptosis and decreased cell viability. In addition, metformin overcame progestin resistance by down-regulating Nrf2/LASS2 expression.

Conclusion: Our findings provide new insight into the mechanism of progestin resistance in type I endometrial cancer. Nrf2/LASS2 may not only be a possible marker for predicting the prognosis of endometrial cancer but also serve as a potential therapeutic target.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014362PMC
March 2021

Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma.

Int J Biol Sci 2021 8;17(3):768-780. Epub 2021 Feb 8.

The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 29 XingLongXiang Road, Changzhou, Jiangsu 213000, P.R. China.

Long noncoding RNAs (LncRNAs) are emerging as crucial regulators in the pathophysiological process of various tumors, including HCC. Here, we identify a novel lncRNA Linc-KILH (KRT19 interacting long noncoding RNA in hepatocellular carcinoma), which is significantly up-regulated in HCC tissues and positively correlated with larger tumor size, severer microvascular invasion, more intrahepatic metastasis and decreased survival of HCC patients. Silence of Linc-KILH remarkably inhibited the proliferation and metastasis abilities of KRT19-positive HCC cells and . Mechanistically, Linc-KILH interacts with KRT19 and then inhibits the phosphorylation of KRT19 on Ser35, thereby, enhancing the translocation of KRT19 from cytoplasm to membrane in KRT19 positive HCC cells. Additionally, we validated that KRT19 interacts with β-catenin but not RAC1 in HCC cells. Linc-KILH enhanced the interaction between β-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of β-catenin in HCC cells. Furthermore, Linc-KILH could enhance the promoting function of KRT19 on Notch1 signaling with the existence of KRT19 in HCC cells. Collectively, we revealed that Linc-KILH exerts a vital function in KRT19 positive HCC progression and may likely be developed into an effective therapeutic target for HCC.
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http://dx.doi.org/10.7150/ijbs.52279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975697PMC
February 2021

Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-β42-Induced Neuroinflammation in Microglia by Regulating the Nrf2/NF-κB Signaling.

Authors:
Yue Fu Jianping Jia

Front Neurosci 2021 11;15:638772. Epub 2021 Feb 11.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, National Clinical Research Center for Geriatric Diseases, Capital Medical University, Beijing, China.

Background: Neuroinflammation and oxidative stress are two major pathological characteristics of Alzheimer's disease (AD). Amyloid-β oligomers (AβO), a toxic form of Aβ, promote the neuroinflammation and oxidative stress in the development of AD. Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on inflammatory response and oxidative stress.

Objectives: The main purpose of this study is to assess the influence of ISL on inflammatory response and oxidative stress in BV2 cells stimulated with AβO, and to explore the underlying molecular mechanisms.

Methods: 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H- tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) cytotoxicity assays were used to assess the toxic or protective effects of ISL. The expression levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays. Morphological changes in BV2 cells were assessed by immunofluorescence method. Nitric oxide (NO) assay kit was used to determinate the NO production. Western blot, qRT-PCR and immunofluorescence were used to explore the underlying molecular mechanisms.

Results: ISL treatment reduced the production of inflammatory cytokines and NO, and alleviated the morphological changes in BV2 cells induced by AβO. ISL treatment further protected N2a cells from the toxic medium of AβO-stimulated BV2 cells. ISL activated nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and suppressed nuclear factor-κB (NF-κB) signaling in BV2 cells.

Conclusion: ISL suppresses AβO-induced inflammation and oxidative stress in BV2 cells the regulation of Nrf2/NF-κB signaling. Therefore, ISL indirectly protects neurons from the damage of toxic conditioned media.
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http://dx.doi.org/10.3389/fnins.2021.638772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904903PMC
February 2021

[Effect of 4-week electroacupuncture intervention on "Browning" of white fat in rats and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Sep;36(5):471-477

School of Sport Science, Beijing Sport University, Beijing 100084, China.

To investigate the effects of 4-week electroacupuncture intervention on "Browning" of white fat in rats, and to explore its molecular mechanisms. Twenty-four 8-week-old male SD rats were randomly divided into sedentary group (Sed), aerobic exercise group (Exe) and electroacupuncture group (ElA), 8 rats in each group. Exe group used 65% Max oxygen uptake intensity treadmill exercise, 1 h/d,6 d/w, while the ElA group used electric acupuncture to stimulate "zusanli" and "tianshu" points, 20 min/d,6 d/w, and the weight of rats was recorded every week. After 4 weeks of intervention, blood samples were collected from the apex and abdominal aorta. The wet weight of scapular fat and perirenal fat of rats was detected and the body fat and the serum levels of Irisin were determined. What's more, the expressions of adenosine 5'-monophosphate activated protein kinase-α (AMPKα), phosphorylation of adenosine 5'-monophosphate activated protein kinase-α (p-AMPKα), peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α), fibronectin type III domain containing 5 (FNDC5) and uncoupling protein (UCP1) and brown adipose tissue lipid droplets in rats were detected. Compared with the Sed group, the weight gain of rats in the Exe and ElA groups was decreased significantly from the second week. After 4 weeks, the body weight and body fat of the Exe and ElA groups were decreased significantly (<0.01), while there was no significant difference between the Exe and ElA groups (>0.05). ②After 4 weeks of intervention, the white fat wet weight of ElA group and Exe group was significantly was reduced (<0.05 or <0.01). ③The serum levels of Irisin in Exe and ElA groups were significantly increased (<0.05), and the expressions of p-AMPKα/AMPKα, PGC-1α, FNDC5 in the gastrocnemius and the expressions of UCP1 in white fat and brown adipose tissue of Exe and ElA groups were increased (<0.05). ④The area of lipid droplets in white and brown adipose tissue of Exe and ElA groups was significantly reduced (< 0.01). 4 weeks of electroacupuncture intervention can effectively control the weight of rats and induce "browning" of white fat, and its effect was similar to aerobic exercise, which may be release Irisin through the AMPKα-PGC-1α-FNDC5-Irisin signaling pathway, and then "crosstalk" with adipose tissue, up-regulate the expression of UCP1, and induce "browning" of white adipose tissue.
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http://dx.doi.org/10.12047/j.cjap.6005.2020.100DOI Listing
September 2020

Remedial Effect of Intravenous Cyclophosphamide in Corticosteroid-Refractory Patients in the Acute Phase of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis.

Front Neurol 2020 15;11:612097. Epub 2021 Jan 15.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

To investigate the remedial efficacy and safety of intravenous cyclophosphamide (CP) in the acute phase in patients with neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) who are refractory to intravenous methylprednisolone (MP) treatment. This study was a single-center, retrospective, observational case-control cohort study. Thirty-six patients who had acute NMOSD-ON attacks and were refractory to MP treatment were included. Patents were divided into two groups: the remedial CP group, and the MP group. The best-corrected visual acuity (BCVA), mean deviation (MD) of the visual field (VF), visual evoked potential amplitude (VEP-A), visual evoked potential latency (VEP-T), and average thickness of the retinal nerve fiber layer (RNFL) at onset, 1 month (m), 3 m, and 6 m after the attack were analyzed. Routine blood test results, liver and kidney function, routine urinalysis results and general condition were analyzed for safety issues at each follow-up. Fisher's exact test, the Mann-Whitney U test, the Kruskal-Wallis test and the Wilcoxon rank-sum test were used for statistical analysis. The remedial CP group showed significant improvement over 6 m with regard to BCVA and MD ( < 0.05),whereas MP group only showed significant improvement in MD ( < 0.05). Regarding remedial CP intervention time window, the CP ≤ 30 days group showed significant improvement over 6 m with regard to BCVA ( = 0.002), MD ( = 0.003), and VEP-A ( = 0.036), while those CP > 30 days group did not. Both two subgroups showed significantly RNFL thickness reduction, however, BCVA, MD, VEP-A, VEP-T, and RNFL thickness showed no significant differences between the two subgroups at any follow-up point ( > 0.05). CP within 30 days of attack onset is safe and might have a beneficial degree of therapeutic efficacy for acute-phase treatment of NMOSD-ON that is refractory to MP treatment alone.
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http://dx.doi.org/10.3389/fneur.2020.612097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874161PMC
January 2021

MUC4 is a novel mediator in infection-related pancreatic cancer.

Oncol Lett 2021 Feb 17;21(2):123. Epub 2020 Dec 17.

Research Center of General Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.

Pancreatic cancer (PC) is a common malignant disease worldwide. Among the potential pathogenic factors, () infection has been associated with the tumorigenesis of PC. The present study aimed to identify the differentially expressed genes (DEGs) of infection-associated PC and to investigate the key factors involved in PC tumorigenesis. Using bioinformatics methods, overlapping DEGs and key gene were identified from -infected gastric mucosa (GM) and infection-associated PC. Survival and tumor stage analyses were performed to assess the clinical associations. In addition, mucin 4 (MUC4) mRNA expression levels were measured in patient blood and tumor samples. According to the correlation analyses of four genes co-expressed, potential biological processes were identified. MUC4 was identified to be associated with infection, and its levels were significantly upregulated in PC samples compared with those in normal samples in TCGA dataset, the PC cell line and patient tissue samples. infection was also associated with MUC4 expression in patients' blood and tissue samples. In conclusion, the results of the present study revealed a potentially pathogenic role of MUC4 in infection-associated PC. Thus, the tumorigenesis and metastasis of PC may be prevented by treating the infection or using MUC4 antagonists.
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http://dx.doi.org/10.3892/ol.2020.12384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798107PMC
February 2021

Complete mitochondrial genome of (Coleoptera: Curculionidae).

Mitochondrial DNA B Resour 2020 Jun 11;5(3):2403-2405. Epub 2020 Jun 11.

College of Biology and Agricultural Resources, Huanggang Normal University, Huanggang, China.

Chao is an important insect pest on many plants which belong to genus The complete mitochondrial genome of was sequenced and analyzed. The phylogenetic relationships between and other 41 species in the family Curculionidae were reconstructed using maximum likelihood (ML) methods based on the concatenated nucleotide sequences, the phylogenetic analysis showed that is closely related to , which is in accordance with the traditional morphological classification.
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http://dx.doi.org/10.1080/23802359.2020.1772683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781971PMC
June 2020

Ab Initio Molecular Dynamics Simulations of the S1/S2 Mechanistic Continuum in Glycosylation Reactions.

J Am Chem Soc 2021 Jan 13;143(3):1577-1589. Epub 2021 Jan 13.

Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.

We report a computational approach to evaluate the reaction mechanisms of glycosylation using molecular dynamics (AIMD) simulations in explicit solvent. The reaction pathways are simulated via free energy calculations based on metadynamics and trajectory simulations using Born-Oppenheimer molecular dynamics. We applied this approach to investigate the mechanisms of the glycosylation of glucosyl α-trichloroacetimidate with three acceptors (EtOH, -PrOH, and -BuOH) in three solvents (ACN, DCM, and MTBE). The reactants and the solvents are treated explicitly using density functional theory. We show that the profile of the free energy surface, the synchronicity of the transition state structure, and the time gap between leaving group dissociation and nucleophile association can be used as three complementary indicators to describe the glycosylation mechanism within the S1/S2 continuum for a given reaction. This approach provides a reliable means to rationalize and predict reaction mechanisms and to estimate lifetimes of oxocarbenium intermediates and their dependence on the glycosyl donor, acceptor, and solvent environment.
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http://dx.doi.org/10.1021/jacs.0c12096DOI Listing
January 2021

Fabrication of Transparent Polymer Optical Device Combined with Selective Visible-Light Transmission and Zero-Birefringence.

Macromol Rapid Commun 2021 Jan 16;42(2):e2000462. Epub 2020 Dec 16.

State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science & Technology, Wuhan, 430074, P. R. China.

The formation of optical products using the traditional molten processing methods is a direct and extensive application of optical fields, and it suffers from intrinsic birefringence and optical distortion due to polymer orientation and residual stress. Here, a unique concept is proposed by assembling photonic crystal nanospheres without orientation in a rubbery state to realize transparent optical devices with zero-birefringence and high transparency. By developing fabrication techniques for transparent zero-birefringence optical devices, certain outstanding performances are realized, including no optical distortion and excellent mechanical properties. Simultaneously, by controlling the particle size of the photonic crystal, one has successfully obtained transparent optical devices with the visible light selective transmission are successfully obtained. The transparent zero-birefringence optical devices are promising candidates for potential applications for fine optical devices. The work opens up an exciting new fabrication route for zero-birefringence and highly transparent polymer devices that have been difficult to create using traditional methods.
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http://dx.doi.org/10.1002/marc.202000462DOI Listing
January 2021

Combining sequence and network information to enhance protein-protein interaction prediction.

BMC Bioinformatics 2020 Dec 16;21(Suppl 16):537. Epub 2020 Dec 16.

School of Computer Science, Northwestern Polytechnical University, No.127 West Youyi Road, Xi'an, 710072, China.

Background: Protein-protein interactions (PPIs) are of great importance in cellular systems of organisms, since they are the basis of cellular structure and function and many essential cellular processes are related to that. Most proteins perform their functions by interacting with other proteins, so predicting PPIs accurately is crucial for understanding cell physiology.

Results: Recently, graph convolutional networks (GCNs) have been proposed to capture the graph structure information and generate representations for nodes in the graph. In our paper, we use GCNs to learn the position information of proteins in the PPIs networks graph, which can reflect the properties of proteins to some extent. Combining amino acid sequence information and position information makes a stronger representation for protein, which improves the accuracy of PPIs prediction.

Conclusion: In previous research methods, most of them only used protein amino acid sequence as input information to make predictions, without considering the structural information of PPIs networks graph. We first time combine amino acid sequence information and position information to make representations for proteins. The experimental results indicate that our method has strong competitiveness compared with several sequence-based methods.
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http://dx.doi.org/10.1186/s12859-020-03896-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739453PMC
December 2020

Corynoneura Winnertz (Diptera, Chironomidae, Orthocladiinae) from Zhejiang Province, China.

Zootaxa 2020 Dec 1;4890(1):zootaxa.4890.1.4. Epub 2020 Dec 1.

Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Hubei Zhongke Research Institute of Industrial Technology, Huanggang Normal University, Huanggang City, Hubei, 438000, P.R. China.

The genus Corynoneura Winnertz, 1846 from Zhejiang Province in Oriental China is reviewed. Corynoneura aggeris Fu, sp. n., Corynoneura lateralis Fu, sp. n., Corynoneura petitspectabilis Fu, sp. n., Corynoneura prolata Fu, sp. n., and Corynoneura recta Fu, sp. n. are described and illustrated based on adult males. Corynoneura lobata Edwards, 1924 and Corynoneura tokarapequea Sasa et Suzuki, 1995 are redescribed and illustrated based on newly collected material. A key to known adult males of Corynoneura from Zhejiang Province is given.
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http://dx.doi.org/10.11646/zootaxa.4890.1.4DOI Listing
December 2020

Circ_0075829 facilitates the progression of pancreatic carcinoma by sponging miR-1287-5p and activating LAMTOR3 signalling.

J Cell Mol Med 2020 12 13;24(24):14596-14607. Epub 2020 Nov 13.

Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.

Pancreatic cancer (PC) is a leading cause of cancer-related mortality globally. Though increasing evidence has demonstrated that circular RNAs (circRNAs) are linked to the development and progression of cancers, the biological functions of circRNAs in PC remain largely unexplored so far. Based on previous studies, Hsc_circ_0075829 (circ_0075829) was screened out and then further identified in PC clinical specimens and cell lines by real-time PCR. After the stability tests, a series of in vitro and in vivo functional experiments were performed to investigate the role of circ_0075829 in PC development. Furthermore, fluorescent in situ hybridization (FISH), bioinformatics tools, dual-luciferase assays and rescue experiments were conducted to clarify the regulatory mechanisms of circ_0075829 in SW1990 and BxPC-3 cells. Compared with paracancerous tissues, the expression of circ_0075829 was increased in PC tissues, which was positively correlated with the clinical features of PC. Knockdown of circ_0075829 significantly suppressed the proliferative, migratory and invasive rates of SW1990 and BxPC-3 cells both in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay indicated that circ_0075829 could bind to miR-1287-5p. Mechanism research and rescue experiments demonstrated that circ_0075829 could regulate the LAMTOR3/p-ERK signalling pathway via sponging miR-1287-5p in PC cell lines. Our data reveal that the circ_0075829 could facilitate the proliferation and metastasis of PC through circ_0075829/miR-1287-5p/LAMTOR3 axis.
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http://dx.doi.org/10.1111/jcmm.16089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753824PMC
December 2020

[Comparison of intermittent fasting and exercise on skeletal muscle autophagy activation and fat reduction].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Jul;36(4):289-295

School of Sport Science, Beijing Sport University, Beijing 100084, China.

Objective: To observe the effect of weight control of intermittent fasting in different time course (14 d, 28 d)and explore its effect on skeletal muscle mass and autophagy.

Methods: Sixty SD rats (male) were randomly divided into sedentary group (Sed), intermittent fasting group (InF) and exercise group (Exe), 20 rats of each group, intervention duration is 14 d and 28 d. Animals of InF group were fasted every other day, animals of Exe group underwent aerobic exercise on treadmill, the weight was recorded every week. The body fat mass was recorded by DEXA and then the fat mass index was calculated. The wet weight of bilateral soleus muscle was weighed and wet weight index was calculated. Immunofluorescence was used to detect laminin and light chain 3 (LC3), which reflect muscle fiber cross-sectional area and autophagosome respectively. Transmission electron microscopy was used to observe the number and morphology of autophagosomes. The expression levels of autophagy related proteins Unc-51 like kinase 1 (ULK1), LC3, sequestosome1 protein (p62), AMP activated protein kinase (AMPKα) and p-AMPKα (Thr172) were detected by Western blot.

Results: ① From the 7th day of intervention, the body weight of rats in InF and Exe groups was significantly lower than that in Sed group, and the body weight of InF group was significantly lower than that in Exe group (<0.01). After 28 days of intervention, the fat mass index in InF and Exe groups was significantly lower than that in Sed group, the fat mass index of InF group was significantly lower than that in Exe group (<0.05).② After 28 days of intervention, the cross-sectional of muscle fibers in Exe group was significantly larger than that in Sed and InF groups (<0.01). ③The expressions of AMPKα, p-AMPKα (Thr172) and ULK1 in InF and Exe groups were significantly higher than those in Sed group (<0.05). However, at 14 days, only InF group showed the increase of LC3-II/LC3-I ratio and the decrease of p62 level (<0.05). The same indicators of Exe group were only significant changed at 28 d.

Conclusion: ① Intermittent fasting is superior to exercise in controlling the growth of body weight and body fat in rats. ② In terms of skeletal muscle autophagy activation, the length of intervention required for intermittent fasting (14 days) is shorter than aerobic exercise (28 days).
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http://dx.doi.org/10.12047/j.cjap.5942.2020.063DOI Listing
July 2020

Approximate Optimal Tracking Control of Nondifferentiable Signals for a Class of Continuous-Time Nonlinear Systems.

IEEE Trans Cybern 2020 Nov 3;PP. Epub 2020 Nov 3.

In this article, for a class of continuous-time nonlinear nonaffine systems with unknown dynamics, a robust approximate optimal tracking controller (RAOTC) is proposed in the framework of adaptive dynamic programming (ADP). The distinguishing contribution of this article is that a new Lyapunov function is constructed, by using which the derivative information of tracking errors is not required in computing its time derivative along with the solution of the closed-loop system. Thus, the proposed method can make the system states follow nondifferentiable reference signals, which removes the common assumption that the reference signals have to be continuous for tracking control of continuous-time nonlinear systems in the literature. The theoretical analysis, simulation, and application results well illustrate the effectiveness and superiority of the proposed method.
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http://dx.doi.org/10.1109/TCYB.2020.3027344DOI Listing
November 2020

Purification and Enzymatic Properties of a Difunctional Glycoside Hydrolase from HML366.

Indian J Microbiol 2020 Dec 6;60(4):475-484. Epub 2020 Jun 6.

College of Chemistry and Biological Engineering, Hechi University, Yizhou, 546300 China.

In the study, an extracellular enzyme HML CBH1 was purified from the fermentation solution of HML366, and characterized by biological and molecular analysis. Following the culturing of HML366 under the optimized conditions for enzyme production, an enzyme named HML CBH1 with a molecular weight of 48 kDa was purified using 3000 Da cellulose ultrafiltration column and anion exchange chromatography. The specific activity of the purified enzyme was 9.65 U/mg, and the optimum temperature and pH for the enzyme were 50 and 5.0 °C, respectively. The enzyme was stable at temperatures below 60 °C and pH ranging from 3.0 to 10.0. The partial amino acid sequence of HML CBH1 was analyzed by time-of-flight mass spectrometry, and Mascot and Blast analysis showed that the HML CBH1 sequence was identical to the protein gi:22138643, belonging to the glycoside hydrolase family 7, and had exoglucanase and endoglucanase activity.
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http://dx.doi.org/10.1007/s12088-020-00892-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539257PMC
December 2020

One-step purification of two novel thermotolerant β-1,4-glucosidases from a newly isolated strain of Fusarium chlamydosporum HML278 and their characterization.

AMB Express 2020 Oct 8;10(1):182. Epub 2020 Oct 8.

College of Chemistry and Biological Engineering, Hechi University, 546300, Yizhou, China.

A newly identified cellulase-producing Fusarium chlamydosporum HML278 was cultivated under solid-state fermentation of sugarcane bagasse, and two new β-glucosides enzymes (BG FH1, BG FH2) were recovered from fermentation solution by modified non-denaturing active gel electrophoresis and gel filtration chromatography. SDS-PAGE analysis showed that the molecular weight of BG FH1 and BG FH2 was 93 kDa and 52 kDa, respectively, and the enzyme activity was 5.6 U/mg and 11.5 U/mg, respectively. The optimal reaction temperature of the enzymes was 60 ℃, and the enzymes were stable with a temperature lower than 70 ℃. The optimal pH of the purified enzymes was 6.0, and the enzymes were stable between pH 4-10. K and V values ​​were 2.76 mg/mL and 20.6 U/mg for pNPG, respectively. Thin-layer chromatography and high-performance liquid chromatography analysis showed that BG FH1and BG FH2 had hydrolysis activity toward cellobiose and could hydrolyze cellobiose into glucose. In addition, both enzymes exhibited transglycoside activity, which could use glucose to synthesize cellobiose and cellotriose, and preferentially synthesize alcohol. In conclusion, our study demonstrated that F. chlamydosporum HML278 produces heat-resistant β-glucosidases with both hydrolytic activity and transglycosidic activity, and these β-glucosidases have potential application in bioethanol and papermaking industries.
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http://dx.doi.org/10.1186/s13568-020-01116-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544787PMC
October 2020

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Hydroarylation and Hydroalkenylation of Alkenyl Carboxylic Acids*.

Angew Chem Int Ed Engl 2020 12 13;59(51):23306-23312. Epub 2020 Oct 13.

Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.

A nickel-catalyzed regiodivergent hydroarylation and hydroalkenylation of unactivated alkenyl carboxylic acids is reported, whereby the ligand environment around the metal center dictates the regiochemical outcome. Markovnikov hydrofunctionalization products are obtained under mild ligand-free conditions, with up to 99 % yield and >20:1 selectivity. Alternatively, anti-Markovnikov products can be accessed with a novel 4,4-disubstituted Pyrox ligand in excellent yield and >20:1 selectivity. Both electronic and steric effects on the ligand contribute to the high yield and selectivity. Mechanistic studies suggest a change in the turnover-limiting and selectivity-determining step induced by the optimal ligand. DFT calculations reveal that in the anti-Markovnikov pathway, repulsion between the ligand and the alkyl group is minimized (by virtue of it being 1° versus 2°) in the rate- and regioselectivity-determining transmetalation transition state.
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http://dx.doi.org/10.1002/anie.202010840DOI Listing
December 2020

Birefringence- and Optical Distortion-Free Isotropic Polymer Lens Assisted by Photonic Microspheres.

ACS Appl Mater Interfaces 2020 Sep 11;12(39):44172-44179. Epub 2020 Sep 11.

State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Development of low-cost and light polymer optical devices to substitute for inorganic materials is a major trend. Traditional molten processing methods are direct and have been extensively applied in optical product manufacturing. However, the inevitable intrinsic birefringence and optical distortion due to polymer molecular chain anisotropy limit their application in high-end optical devices. Here, we report a novel thermocompression strategy for isotropic polymer lens fabrication, in which a cross-linked photonic crystal (PC) consisting of closely stacked polymer microspheres is used as a precursor and then heated and pressed under the rubbery state. A polymethyl methacrylate microsphere-based PC is used as a demonstration, and the obtained isotropic lenses exhibit superior performance compared to the traditional counterpart, which are birefringence-free (Δ < 1 × 10) and optical distortion-free and have excellent mechanical properties (hardness reaches 0.28 GPa), and the hidden mechanism is carefully studied. These properties enable the isotropic lens to be applied in precision optical components such as the lens of spectacles, microscope, telescope and endoscope, industrial camera, and astronaut helmet, and the proposed general method can extend to various polymers and provide new opportunities for the development of three-dimensional PCs.
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http://dx.doi.org/10.1021/acsami.0c12479DOI Listing
September 2020

Direct thermoforming manufacture of cellulose transparent products employing nanospheres.

Carbohydr Polym 2020 Nov 23;247:116668. Epub 2020 Jun 23.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China.

Cellulose limited by fusibility and solubility is impossible to be directly thermoformed, of which the existing progress crucially relies on larger liquids, making it hard to achieve a direct all-green manufacture. Here, we propose an innovative strategy that the surface molecular chains of cellulose nanospheres are activated at 100 °C and intertwined under 500 MPa because of the high molecular activity on the surface of nanospheres and the reduction of activation energy after ball-milling. It is confirmed that only physical changes are involved, according to infrared spectrum. Results show that applicable mechanical properties (hardness and modulus reach 0.44 and 9.66 GPa, respectively) are successfully obtained. Simultaneously, the optimum optical performance of all-cellulose substrate reaches more than 80 % at visible light. Combined with their intrinsic properties, these cellulose-based products could be potentially utilized as biomass substrates. Therefore, our innovative strategy opens up a door for the direct thermoforming of cellulose.
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http://dx.doi.org/10.1016/j.carbpol.2020.116668DOI Listing
November 2020

Difluorocarbene-Triggered Cyclization: Synthesis of (Hetero)arene-Fused 2,2-Difluoro-2,3-dihydrothiophenes.

Org Lett 2020 09 20;22(17):7047-7051. Epub 2020 Aug 20.

Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.

An efficient method for the synthesis of (hetero)arene-fused 2,2-difluoro-2,3-dihydrothiophene derivatives using readily available sodium chlorodifluoroacetate (ClCFCONa) has been developed. This transformation is achieved through a combination of a thiolate with difluorocarbene, followed by intramolecular nucleophilic addition to a ketone, cyano, or ester functional group.
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http://dx.doi.org/10.1021/acs.orglett.0c02688DOI Listing
September 2020

Decreased LF/HF ratio is associated with worse outcomes in patients who received mechanical thrombectomy under general anesthesia for emergent large vessel occlusion: a retrospective study.

Neurol Sci 2021 Apr 18;42(4):1453-1462. Epub 2020 Aug 18.

Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, China.

Background And Purpose: We aimed to determine whether heart rate variability (HRV) was correlated to long-term outcome in patients who received mechanical thrombectomy (MT) under general anesthesia for emergent large vessel occlusion (ELVO).

Methods: Data from 106 patients receiving MT under general anesthesia to treat ELVO between January 1, 2017 and December 31, 2019 were collected in a multicenter chart review. Univariate analysis, Chi-square test, and bivariate logistic regression were performed to assess the correlations between preoperative risk factors such as HRV and long-term outcome (as indicated by the modified Rankin score [mRS] at 90 days after MT).

Results: Bivariate logistic regression revealed that decreased LF/HF (low frequency/high frequency in HRV) ratio was correlated with unfavorable functional outcome as indicated by mRS ≥ 2 (odds ratio [OR], 0.650; 95% confidence interval [CI], 0.157-0.839; p = 0.018), and functionally dependent outcome as indicated by mRS ≥ 3 (OR, 0.704; 95% CI, 0.360-0.914; p = 0.021). It was also found that ELVO in the right anterior circulation was correlated with lower LF/HF ratio, as compared with ELVO in the contralateral side (p < 0.05).

Conclusion: Our retrospective study demonstrated that worse outcome in patients with ELVO who received MT under general anesthesia induced autonomic changes and that decreased LF/HF ratio.
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http://dx.doi.org/10.1007/s10072-020-04682-1DOI Listing
April 2021

MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells.

Onco Targets Ther 2020 14;13:6873-6884. Epub 2020 Jul 14.

Department of General Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213000, People's Republic of China.

Aim: This study aimed to explore the regulative mechanisms of miR-27a-3p in chemo-resistance of breast cancer cells.

Materials And Methods: qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), colony formation assay, and flow cytometry assay. Moreover, luciferase reporter assay was analyzed to verify the downstream target gene of miR-27a-3p. Further investigation in the correlation between miR-27a-3p and BTG2 was launched by WB, flow cytometry assay, and CCK-8 assay. The expression of Akt and p-Akt was detected by WB.

Key Findings: Significantly higher miR-27a-3p expression was confirmed in MCF-7/ADR as compared with sensitive cell line MCF-7 (<0.05). The down-regulation of miR-27a-3p in MCF-7/ADR enhanced the sensitivity of cancer cells to adriamycin treatment, decreased multidrug resistance gene 1/P-glycoprotein (MDR1/P-gp) expression, enhanced the apoptosis-related proteins expression, increased adriamycin-induced apoptosis, and inhibited cell proliferation as compared to NC groups (<0.05). The up-regulation of miR-27a-3p in MCF-7 showed the opposite results. BTG2 is identified as a direct target of miR-27a-3p and its down-regulation reversed ADR-resistance. BTG2 treatment exhibited inhibitory effect on PI3K/Akt pathway in MCF-7/ADR cells.

Significance: miR-27a-3p might be associated with resistance of breast cancer cells to adriamycin treatments, modulating cell proliferation and apoptosis by targeting BTG2 and promoting the PI3K/Akt pathway in breast cancer cells. miR-27a-3p/BTG2 axis might be a potential therapeutic target for clinical BC resistance.
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http://dx.doi.org/10.2147/OTT.S256153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368588PMC
July 2020

Meta-analysis of the efficacy of Xuebijing combined with hemoperfusion in treating paraquat poisoning.

Ann Palliat Med 2020 Jul 17;9(4):2152-2162. Epub 2020 Jul 17.

Department of Emergency, Foshan First People's Hospital, Foshan, China; The Poison Treatment Centre of Foshan, Foshan, China.

Background: Paraquat (PQ) is a herbicide that is highly toxic to humans and animals. Xuebijing can regulate immune and inflammatory mediators. Blood purification is a conventional treatment for paraquat poisoning. Therefore, this study aimed to investigate the clinical effect of Xuebijing combined with hemoperfusion on acute paraquat poisoning (APQ).

Methods: The PubMed, Cochrane Library, EMbase, CNKI, CBM, and Wanfang databases were searched by computer for randomized controlled trials (RCT) of Xuebijing combined with hemoperfusion in the treatment of APQ. The search time was from the establishment of database to April 2020. The documents were screened and extracted according to the inclusion and exclusion criteria. Meta-analysis and Revman 5.3 were used to evaluate the quality.

Results: The metanalysis included 10 studies, totaling 636 patients. Results showed that the 7-day survival rate of Xuebijing combined with hemoperfusion group was higher than that of the control group [hazard ratio (HR) =1.17, 95% confidence interval (CI): (1.04, 1.32), P<0.008], while 14-day survival rate was higher [HR =1.52, 95% CI: (1.13, 2.06), P<0.006], alanine aminotransferase (ALT) was lower [mean difference (MD) =-32.5, 95% CI: (-52.24, -12.76), P=0.001], creatinine was lower [MD =-60.73, 95% CI: (-103.42, -18.04), P<0.005], oxygen partial pressure (PaO2) was higher [MD =6.21, 95% CI: (1.78, 10.64), P=0.006], and C-reactive protein (CRP) was lower [MD =-6.15, 95% CI: (-7.14, -5.16), P<0.00001]. However, there was no statistical difference in oxygen saturation (SpO2) and carbon dioxide PaO2 between the two groups.

Conclusions: Xuebijing combined with hemoperfusion and conventional treatment can improve the 7-day and 14-day survival rate, oxygenation level, liver and kidney function, and inflammatory response of paraquat poisoning (PQ) patients.
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http://dx.doi.org/10.21037/apm-20-1247DOI Listing
July 2020

Polydatin relieves paraquat-induced human MRC-5 fibroblast injury through inhibiting the activation of the NLRP3 inflammasome.

Ann Transl Med 2020 Jun;8(12):765

Department of Emergency, Foshan First People's Hospital, Foshan, China.

Background: Paraquat (PQ) is a herbicide that is highly toxic to the lungs and kidneys. When it enters the body, it will disrupt the balance of the microenvironment in the body, induce a large number of inflammatory factors and cause cell damage. Polydatin (PD), resveratrol glycoside, has multiple pharmacological effects. However, the protective effect of PD on human embryo lung fibroblast damage caused by PQ poisoning has not been reported. The purpose of this study was to investigate the regulatory effect of PD on human embryo lung fibroblast damage caused by PQ poisoning.

Method: The optimal experimental concentration of PQ for human embryonic lung fibroblast MRC-5 was 100 µmol/L, and then the cells of 100 µmol/L PQ group were treated with different concentrations of PD for 24 h. MTT assay to detect MRC-5 cell viability and flow cytometry to detect apoptosis. The corresponding kit was used to detect the contents of glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and superoxide dismutase (SOD). Enzyme-linked immunosorbent assay (ELISA) to detect the levels of related inflammatory factors tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Western blot detection of NLRP3 inflammatory body activation-related protein expression.

Results: Compared with the PQ group, cell activity, GSH-Px content, and SOD content in PD intervention group were significantly increased, while apoptosis, MDA content, inflammatory factor level, and activation-related proteins of the NLRP3 inflammasome were significantly reduced and were dose-dependent.

Conclusions: PD can relieve PQ-induced human MRC-5 fibroblasts injury by reducing the inflammatory response, improving the antioxidant stress capacity, and inhibiting the activation of the NLRP3 inflammasome.
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http://dx.doi.org/10.21037/atm-20-4570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333108PMC
June 2020

The Protection Effect of Resveratrol Against Radiation-Induced Inflammatory Bowel Disease via NLRP-3 Inflammasome Repression in Mice.

Dose Response 2020 Apr-Jun;18(2):1559325820931292. Epub 2020 Jun 26.

Laboratory of Radiation Medicine and radiation injury effects, Tianjin Institute of Radiology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China.

With the extensive application of radiotherapy in various cancers, its side effects in tissues adjacent to cancers are garnering much attention. Intestines are sensitive to irradiation due to its rapid proliferation, and irradiation-induced enteric inflammation is common in patients with pelvic peritoneal tumors. Sirt1, class III protein deacetylase, could lead to transcriptional repression of various inflammation-associated genes, and our previous study has proved its relationship with interleukin (IL)-1β. Here we show that resveratrol, the activator of Sirt1, could alleviate the bowel inflammation induced by irradiation and the expression of Sirt1 is consistent with the inflammation level. We further identified in vivo that Sirt1 repress the expression of IL-1β by the repression of NLR Family, Pyrin Domain Containing protein 3 (NLRP3) expression. In conclusion, this study confirms resveratrol acts against radiation-induced inflammatory bowel disease via NLRP-3 inflammasome repression in mice and supports Sirt1 as a potential biomarker and therapy target in intestinal radiation protection.
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http://dx.doi.org/10.1177/1559325820931292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323307PMC
June 2020

Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol.

Nat Commun 2020 07 7;11(1):3387. Epub 2020 Jul 7.

Novartis Institutes for BioMedical Research, Novartis Pharma AG, Forum 1 Novartis Campus, CH-4056, Basel, Switzerland.

Biosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and is essential for the integrity of the fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. The compound targets the catalytic subunit Spt14 (also referred to as Gpi3) of the fungal UDP-glycosyltransferase, the first step in GPI biosynthesis, with good selectivity over the human functional homolog PIG-A. Jawsamycin displays antifungal activity in vitro against several pathogenic fungi including Mucorales, and in vivo in a mouse model of invasive pulmonary mucormycosis due to Rhyzopus delemar infection. Our results provide a starting point for the development of Spt14 inhibitors for treatment of invasive fungal infections.
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http://dx.doi.org/10.1038/s41467-020-17221-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341893PMC
July 2020

Three-Dimensional Photonic Crystal Bulks with Outstanding Mechanical Performance Assembled by Thermoforming-Etching Cross-linked Polymer Microspheres.

ACS Appl Mater Interfaces 2020 Aug 21;12(31):35311-35317. Epub 2020 Jul 21.

State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

Traditional self-assembly methods for photonic crystals (PCs) limited by poor mechanical performance and microstructure defects make it hard to be directly applied to optical devices, whose performance strongly rely on mechanical performance and microstructure of PCs. Here, a thermoforming-etching strategy combining both traditional processing and nanofabrication is reported to develop cross-linked polystyrene microsphere-based PC bulks with outstanding mechanical performance. It illustrates scientific principles, where surface molecular chains of PS microspheres were activated and entangled with each other under thermoforming conditions (200 °C; 220 MPa), resulting in applicable mechanical strength (hardness and modulus reach 0.12 and 4.12 GPa, respectively). The optimum optical reflectivity of the PS microsphere-based (180 nm) PC bulk is 49.4% at 381 nm. Furthermore, these PC bulks have been successfully written in anti-counterfeiting and realized colorful pattern printing. The innovative method opens a new route for the rapid and simple fabrication of the nanoparticle structure which can be used as various functional devices and directly promotes the industrialization of bulk PC devices, such as optical and display devices, and so forth.
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http://dx.doi.org/10.1021/acsami.0c04723DOI Listing
August 2020

Screening and identification of key biomarkers in alimentary tract cancers: A bioinformatic analysis.

Cancer Biomark 2020 ;29(2):221-233

Center of Gastrointestinal Disease, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.

Background: Alimentary tract cancers (ATCs) are the most malignant cancers in the world. Numerous studies have revealed the tumorigenesis, diagnosis and treatment of ATCs, but many mechanisms remain to be explored.

Methods: To identify the key genes of ATCs, microarray datasets of oesophageal cancer, gastric cancer and colorectal cancer were obtained from the Gene Expression Omnibus (GEO) database. In total, 207 differentially expressed genes (DEGs) were screened. KEGG and GO function enrichment analyses were conducted, and a protein-protein interaction (PPI) network was generated and gene modules analysis was performed using STRING and Cytoscape.

Results: Five hub genes were screened, and the associated biological processes indicated that these genes were mainly enriched in cellular processes, protein binding and metabolic processes. Clinical survival analysis showed that COL10A1 and KIF14 may be significantly associated with the tumorigenesis or pathology grade of ATCs. In addition, relative human ATC cell lines along with blood samples and tumour tissues of ATC patients were obtained. The data proved that high expression of COL10A1 and KIF14 was associated with tumorigenesis and could be detected in blood.

Conclusion: In conclusion, the identification of hub genes in the present study helped us to elucidate the molecular mechanisms of tumorigenesis and identify potential diagnostic indicators and targeted treatment for ATCs.
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http://dx.doi.org/10.3233/CBM-201580DOI Listing
January 2020