Publications by authors named "Fan Li"

1,932 Publications

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MRTF-A regulates myoblast commitment to differentiation by targeting PAX7 during muscle regeneration.

J Cell Mol Med 2021 Aug 4. Epub 2021 Aug 4.

Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430081, China.

Myocardin-related transcription factor-A/serum response factor (MRTF-A/SRF), a well-known transcriptional programme, has been proposed to play crucial roles in skeletal muscle development and function. However, whether MRTF-A participates in muscle regeneration and the molecular mechanisms are not completely understood. Here, we show that MRTF-A levels are highly correlated with myogenic genes using a RNA-seq assay, which reveal that MRTF-A knockdown in C2C12 cells significantly reduces PAX7 expression. Subsequent in vitro and in vivo data show that MRTF-A and PAX7 present identical expression patterns during myoblast differentiation and CTX-induced muscle injury and repair. Remarkably, MRTF-A overexpression promotes myoblast proliferation, while inhibiting cell differentiation and the expression of MyoD and MyoG. MRTF-A loss of function produces the opposite effect. Moreover, mice with lentivirus (MRTF-A) injection possesses more PAX7 satellite cells, but less differentiating MyoD and MyoG cells, leading subsequently to diminished muscle regeneration. Our mechanistic results reveal that MRTF-A contributes to PAX7-mediated myoblast self-renewal, proliferation, and differentiation by binding to its distal CArG box. Overall, we propose that MRTF-A functions as a novel PAX7 regulator upon myoblast commitment to differentiation, which could provide pathways for dictating muscle stem cell fate and open new avenues to explore stem cell-based therapy for muscle degenerative diseases.
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http://dx.doi.org/10.1111/jcmm.16820DOI Listing
August 2021

Design of Highly Durable Core-Shell Catalysts by Controlling Shell Distribution Guided by In-Situ Corrosion Study.

Adv Mater 2021 Aug 4:e2101511. Epub 2021 Aug 4.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, P. R. China.

Most degradations in electrocatalysis are caused by corrosion in operation, for example the corrosion of the core in a core-shell electrocatalyst during the oxygen reduction reaction (ORR). Herein, according to the in-situ study on nanoscale corrosion kinetics via liquid cell transmission electron microscopy (LC-TEM) in the authors' previous work, they sequentially designed an optimized nanocube with the protection of more layers on the corners by adjusting the Pt atom distribution on corners and terraces. This modified nanocube (MNC) is much more corrosion resistant in the in-situ observation. Furthermore, in the practical electrochemical stability testing, the MNC catalyst also showed the best stability performance with the 0.37% and 9.01% loss in specific and mass activity after 30 000 cycles accelerated durability test (ADT). This work also demonstrates that how an in-situ study can guide the design of desired materials with improved properties and build a bridge between in-situ study and practical application.
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http://dx.doi.org/10.1002/adma.202101511DOI Listing
August 2021

Integrating electrochemical sensor based on MoO/CoO heterostructure for highly sensitive sensing of nitrite in sausages and water.

Food Chem 2021 Jul 22;367:130666. Epub 2021 Jul 22.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, PR China. Electronic address:

Considering excess nitrites are detrimental to the human body and environment, designing a rapid, sensitive, and real-time quantitative determination for nitrite is of great significance for environmental preservation and public health. In this paper, CoO nanoflowers coupled with ultrafine MoO nanoparticles (MoO/CoO) are obtained via a hybrid electrochemical deposition strategy (HED). The as-designed MoO/CoO/CC integrating electrode exhibits superior electrocatalytic properties towards nitrite oxidation, owing to the synergistic effect between MoO and CoO caused by the heterostructure of MoO/CoO. The electrode achieved a low response time of 2 s, an excellent sensitivity of 1704.1 μA mM cm, and a low limit of detection of 0.075 μM (S/N = 3). Furthermore, the electrode displays promise for nitrite detection in complex food such as water and sausages samples. Our study will provide a significant strategy for the application of bimetallic heterostructure to explore the design of sensing interfaces.
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http://dx.doi.org/10.1016/j.foodchem.2021.130666DOI Listing
July 2021

Analysis of the effect of Color Doppler Ultrasonography in the diagnosis of arteriosclerotic occlusive disease of lower extremities.

Minerva Surg 2021 Aug 3. Epub 2021 Aug 3.

Echo Room, Changzhou No.2 People's Hospital Affiliated to Nanjing Medical University, Changzhou, China -

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http://dx.doi.org/10.23736/S2724-5691.21.09031-6DOI Listing
August 2021

DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway.

Steroids 2021 Jul 30:108898. Epub 2021 Jul 30.

Qiqihaer Medical University, Heilongjiang Qiqihaer 161006, China. Electronic address:

Lung neoplasm has a relatively poor prognosis, and the clinical efficacy of targeted medicine remains unsatisfactory. Therefore, the development of novel efficient anti-lung cancer drugs is urgently needed. In our previous study, we showed that a novel diosgenin derivative 8d (DG-8d), which contained 5-(3-pyridyl)-1,3,4-thiadiazole moiety, had significant cytotoxic activity on human tumor cells, especially the A549 cells. However, the underlying mechanism of DG-8d was unknown. In this study, the pharmacological effect of DG-8d on the A549 cells was inspected.

Method: Cell viability and apoptosis were detected by CCK-8 assays, morphological changes and quantitative analysis of flow cytometry. Levels of gene and protein expression of apoptosis-related and PI3k/Akt pathway were evaluated by qRT-PCR, immunostaining and Western blot analysis.

Result: The findings proved that DG-8d could inhibit cell growth and induce apoptosis. The effect of DG-8d on the proliferation and apoptosis in the A549 cells were improved with LY294002 (PI3K inhibitor). Moreover, the effect of DG-8d on apoptosis was further confirmed by AO-EB dye, mitochondrial depolarization and accrued intracellular ROS. Gene and protein detection showed that DG-8d or DG-8d combined with LY294002 could down-regulate signaling molecules of Bcl-2, PI3k, p-Akt, p-FoxO3a and up-regulate signaling molecules of Bax snd Bim. In addition, nuclear translocation of FoxO3a was observed significantly in the cells.

Conclusion: DG-8d could inhibit the proliferation and induce the apoptosis of the A549 cells, which maybe mainly because of the suppression of the PI3k/Akt pathways. Finally, we believe that DG-8d can be developed as a possible agent for carcinoma therapy.
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http://dx.doi.org/10.1016/j.steroids.2021.108898DOI Listing
July 2021

Construction of Novel lncRNA-miRNA-mRNA Network Associated With Recurrence and Identification of Immune-Related Potential Regulatory Axis in Hepatocellular Carcinoma.

Front Oncol 2021 15;11:626663. Epub 2021 Jul 15.

Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases globally. Despite continuous improvement of treatment methods, high postoperative recurrence rate remains an urgent problem. In order to determine the mechanism underlying recurrence of liver cancer and identify prognostic genes, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were integrated and analyzed. Differentially expressed genes (DEGs) between HCC tissue and normal liver tissue were identified, and a protein-protein interaction network was constructed to find hub genes. Clinical correlation analysis and disease-free survival (DFS) analysis were performed using the R language and GEPIA to identify relapse-related genes. Correlation analysis was used to identify a potential regulatory axis. Dual-luciferase reporter gene assay was used to confirm the reliability of the long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory axis. Immune infiltration analysis was performed using the TIMER database. Correlations between immune gene markers and ASF1B were verified using quantitative real-time polymerase chain reaction (RT-qPCR). In this work, we found that nine lncRNAs and five mRNAs were significantly overexpressed in HCC tissues from patients with recurrence. , , , , , , and were also closely related to HCC grade and stage. Survival analysis showed that these seven DEGs were significantly correlated with poor DFS. Correlation analysis identified -- as a potential regulatory axis. Dual-luciferase reporter gene assay showed that SNHG3 and ASF1B directly bound to miR-214-3p. ASF1B was negatively regulated by miRNA-214-3p, and overexpression of SNHG3 could inhibit the expression of miRNA-214-3p. In addition, was positively correlated with immune infiltration. A reduction in ASF1B could markedly inhibit the expression of CD86, CD8, STAT1, STAT4, CD68, and PD1 in HCC cells. Flow cytometry showed that SNHG3 promoted the PD-1 expression by regulating ASF1B. Meanwhile, elevated predicted poor prognosis of HCC patients in subgroups with decreased B cells, CD8+ T cells, or neutrophils, and those with enriched CD4+ T cells. In conclusion, we found that a novel lncRNA SNHG3/miR-214-3p/ASF1B axis could promote the recurrence of HCC by regulating immune infiltration.
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http://dx.doi.org/10.3389/fonc.2021.626663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320021PMC
July 2021

Clinical observation of macular choroidal thickness in primary chronic angle-closure glaucoma.

Int Ophthalmol 2021 Jul 31. Epub 2021 Jul 31.

Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365 Jianhua Street, Shijiazhuang city, Hebei Province, People's Republic of China.

Purpose: To comparatively analyze differences in macular choroidal thickness and volume in primary chronic angle-closure glaucoma (PACG) eyes.

Methods: Thirty-one PACG patients were sequentially selected for this case-control study. Thirty-one eyes with PACG were included in group A, 31 fellow eyes were included in group B, and group C included 67 normal eyes. Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to measure choroidal thickness and volume.

Results: The choroidal thicknesses and volumes of the central subfield macula (CSM), nasal inner macula (NIM), temporal inner macula (TIM), inferior inner macula (IIM), temporal outer macula (TOM), inferior outer macula (IOM), and mean macula (MM) in group A were all higher than those in group C (P < 0.05). The choroidal thicknesses and volumes of the NIM, superior inner macula (SIM), IIM, nasal outer macula (NOM), and MM in group B were all higher than those in group C (P < 0.05). No statistically significant differences were found between groups A and B (P > 0.05). The choroidal thicknesses of different macular regions in group A were not correlated with the mean defect (MD).

Conclusion: Increased macular choroidal thickness may be a common anatomical characteristic of PACD eyes. Macular choroidal thickness is not a good marker for assessing PACG severity.
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http://dx.doi.org/10.1007/s10792-021-01988-7DOI Listing
July 2021

Unidirectional ion transport in nanoporous carbon membranes with a hierarchical pore architecture.

Nat Commun 2021 Jul 30;12(1):4650. Epub 2021 Jul 30.

Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China.

The transport of fluids in channels with diameter of 1-2 nm exhibits many anomalous features due to the interplay of several genuinely interfacial effects. Quasi-unidirectional ion transport, reminiscent of the behavior of membrane pores in biological cells, is one phenomenon that has attracted a lot of attention in recent years, e.g., for realizing diodes for ion-conduction based electronics. Although ion rectification has been demonstrated in many asymmetric artificial nanopores, it always fails in the high-concentration range, and operates in either acidic or alkaline electrolytes but never over the whole pH range. Here we report a hierarchical pore architecture carbon membrane with a pore size gradient from 60 nm to 1.4 nm, which enables high ionic rectification ratios up to 10 in different environments including high concentration neutral (3 M KCl), acidic (1 M HCl), and alkaline (1 M NaOH) electrolytes, resulting from the asymmetric energy barriers for ions transport in two directions. Additionally, light irradiation as an external energy source can reduce the energy barriers to promote ions transport bidirectionally. The anomalous ion transport together with the robust nanoporous carbon structure may find applications in membrane filtration, water desalination, and fuel cell membranes.
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http://dx.doi.org/10.1038/s41467-021-24947-3DOI Listing
July 2021

Preparation of fluorinated covalent organic polymers at room temperature for removal and detection of perfluorinated compounds.

J Hazard Mater 2021 Jul 16;420:126659. Epub 2021 Jul 16.

Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, China. Electronic address:

Covalent organic polymers (COPs) are promising adsorbents for the removal and detection of various types of pollutants. However, the preparation of COPs that exhibit uniform dispersion and good appearance at room temperature is challenging. Herein, fluorinated covalent organic polymers (F-COPs) with different morphologies were synthesized through the Schiff base reaction of 4,4-diamino-p-terphenyl (DT) and 2,3,5,6-tetrafluoroterephthalaldehyde (TFA). The as-prepared F-COPs could selectively adsorb perfluorinated compounds (PFCs) owing to their fluoro-affinity, hydrophobicity, hydrogen bonding, and electrostatic attraction. The adsorption kinetics and isotherm simulation results showed that the adsorption process conformed to the second-order kinetics and the Langmuir model. The saturated adsorption capacity calculated by the Langmuir model was found to be 323-667 mg/g. The F-COPs were applied to the treatment of simulated fluorine industrial wastewater, and the PFC removal efficiencies of 92.3-100.0% were achieved. Moreover, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) was conducted for the detection of trace-level PFCs using F-COPs as dispersive solid-phase extraction (DSPE) adsorbents. The limits of detection were 0.05-0.13 ng/L and the limits of quantification were 0.17-0.43 ng/L. This study facilitates the synthesis of COPs at room temperature and extends the application of COPs as pretreated materials for environmental remediation and detection.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126659DOI Listing
July 2021

Increased levels of VCAM-1 is associated with higher occurrence of coronary artery disease in adults with moderate to severe obstructive sleep apnea.

Sleep Med 2021 Jul 9;85:131-137. Epub 2021 Jul 9.

Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, China; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China. Electronic address:

Background: Obstructive sleep apnea (OSA) leads to important vascular abnormalities, including the endothelial dysfunction and the production of endothelial cell adhesion molecules. The adhesion molecules play an important role in the process of endothelial dysfunction in the pathogenesis of atherosclerosis. We assess the relationship between the levels of adhesion molecules and the presence of coronary artery disease (CAD) in Chinese adults with moderate to severe OSA.

Methods: The cross-sectional study included a total of 189 Chinese adults: 90 patients with moderate to severe OSA (apnea-hypopnea index≥15 events/h) alone, 40 patients with moderate to severe OSA and CAD, and 59 controls without OSA or with mild OSA and without CAD. We used high-throughput Multiplex Immunobead Assay technology to simultaneously test plasma levels of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The associations between the levels of circulating adhesion molecules and CAD in moderate to severe OSA patients were evaluated by multivariate logistic regression analysis.

Results: The circulating VCAM-1 levels were significantly elevated in patients suffering from moderate to severe OSA combined CAD compared with patients having moderate to severe OSA alone [853.28 (564.26) vs. 416.61 (301.69) ng/mL, P < 0.001]. Furthermore, circulating VCAM-1 levels were independently associated with CAD (odds ration = 2.113, 95%CI 1.400-2.766, P < 0.001) and showed higher discriminatory accuracy in assessing the presence of CAD (AUC: 0.899, 95%CI 0.849-0.950, P < 0.001) in moderate to severe OSA patients. However, no significant association was found between circulating ICAM-1 levels and CAD in moderate to severe OSA patients.

Conclusions: The circulating VCAM-1 levels were significantly correlated with the presence of CAD in Chinese adults with moderate to severe OSA. The circulating VCAM-1 may function as a novel biomarker for monitoring the development and progression of CAD in patients with moderate to severe OSA.
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http://dx.doi.org/10.1016/j.sleep.2021.07.002DOI Listing
July 2021

Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer.

Front Immunol 2021 12;12:702615. Epub 2021 Jul 12.

Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China.

Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan-Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.
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http://dx.doi.org/10.3389/fimmu.2021.702615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311657PMC
July 2021

The / Quorum Sensing System Effects on Pathogenicity in .

Front Microbiol 2021 12;12:679241. Epub 2021 Jul 12.

Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.

is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for healthcare institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion, and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic bases of virulence remains poorly understood. Therefore, the contribution of the / QS system to growth characteristics, morphology, biofilm formation, resistance, motility, and virulence of was studied in detail. RNA sequencing (RNA-seq) analysis indicated that genes involved in various aspects of energy production and conversion; valine, leucine, and isoleucine degradation; and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into the / QS system effects on pathogenicity in . We propose that targeting the acyl homoserine lactone (AHL) synthase enzyme could provide an effective strategy for attenuating virulence. On the contrary, interdicting the AI synthase receptor elicits unpredictable consequences, which may lead to enhanced bacterial virulence.
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http://dx.doi.org/10.3389/fmicb.2021.679241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312687PMC
July 2021

Predictive value of contrast-enhanced ultrasound combined with conventional ultrasound in solid renal parenchymal lesions.

Br J Radiol 2021 Jul 28:20210518. Epub 2021 Jul 28.

Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: This study aimed to develop a model to predict the risk of malignancy in solid renal parenchymal lesions based on the imaging features of combined conventional and contrast-enhanced ultrasound (CEUS).

Methods: A retrospective review was performed among patients with focal solid renal parenchymal lesions on ultrasound images. Ultrasound features were characterized by two experienced radiologists independently. A multiple logistic regression analysis was performed to determine the most relevant features and to estimate the risk of malignancy. Scoring and counting methods were developed based on the most relevant features. The diagnostic performance was evaluated by the sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC).

Results: A total of 519 renal lesions were included in this study. The conventional ultrasound features of diameter, echogenicity, hypoechoic rim and the CEUS feature of heterogeneity were identified as the most relevant features for prediction of malignancy. The sensitivity and specificity for the logistic regression model, the scoring method and the counting method were 95.3 and 93.4%, 93.8 and 87.8%, 88.8 and 93.9%, respectively. The logistic model had the best performance for diagnosing malignant renal lesions with AUC of 0.978, compared with the scoring method and the counting method with AUCs of 0.958 and 0.965.

Conclusion: The combination of contrast-enhanced ultrasound with conventional ultrasound improved the diagnostic performance of solid renal lesions based on the logistic regression model.

Advances In Knowledge: In this study, we revealed that the combination of CEUS and conventional ultrasound provided higher accuracy for diagnosing malignant renal tumors.
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http://dx.doi.org/10.1259/bjr.20210518DOI Listing
July 2021

Suppression of Bta11975, an α-glucosidase, by RNA interference reduces transmission of Tomato chlorosis virus by Bemisia tabaci.

Pest Manag Sci 2021 Jul 26. Epub 2021 Jul 26.

Subcollege of Longping, Graduate School of Hunan University, Changsha, 410125, China.

Background: Tomato chlorosis virus (ToCV) is mainly vectored by Bemisia tabaci (B. tabaci) in China, which has a worldwide distribution, and greatly reduces the yields of tomato and other vegetables. At present, control of ToCV has been focused mainly by the use of insecticides to control whitefly populations. Transcriptome sequencing showed high expression of the B. tabaci Bta11975 gene, an α-glucosidase (AGLU) during ToCV acquisition by whitefly Mediterranean (MED) species. To investigate the role of Bta11975 gene in ToCV acquisition and transmission by B. tabaci MED, we used RNA interference (RNAi) to reduce the expression of Bta11975 gene.

Results: The relative expression of Bta11975 gene was correlated with the ToCV content in B. tabaci. AGLU is highly expressed in primary salivary gland and gut. After Bta11975 gene was silenced, the gene expression of B. tabaci was reduced and B. tabaci mortality was increased. Besides, ToCV acquisition by B. tabaci at 48 and 72-h acquisition access period was reduced, and ToCV transmission was significantly reduced by 25 or 50 of B. tabaci.

Conclusions: These results indicate that suppression of expression of the Bta11975 gene in B. tabaci MED by RNA interference can reduce acquisition and transmission of ToCV by B. tabaci MED. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ps.6572DOI Listing
July 2021

Restoration of H3k27me3 Modification Epigenetically Silences Cry1 Expression and Sensitizes Leptin Signaling to Reduce Obesity-Related Properties.

Adv Sci (Weinh) 2021 07 13;8(14):2004319. Epub 2021 May 13.

Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology, Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai 200011 China.

The trimethylation on histone H3 lysine 27 (H3k27me3), a transcriptionally repressive epigenetic mark of permissive chromatin, can be removed by the histone lysine demethylase 6a (Kdm6a). However, the physiological function of H3k27me3 and Kdm6a on circadian genes remains largely elusive. With the ChIP-Seq and mRNA microarray assays, a critical role is identified for Kdm6a in the regulation of H3k27me3 to impact the expression of Crytochrome 1 (Cry1) in the hypothalamus of diet induced obesity mice. More importantly, both conditional knockout and pharmacological inhibition of reduce body weight and stabilize blood glucose homeostasis. Although a Kdm6a inhibitor fails to decrease body weight in leptin receptor-deficient db/db mice, it significantly decreases Cry1 expression, enhances sensitivity to exogenous leptin administration, and blocks body weight increases in endo-leptin-deficient ob/ob mice. Moreover, gene analysis of the human hypothalamus further reveals a positive correlation between Kdm6a and Cry1. The results show that inhibition of Kdm6a reduces the Cry1 expression and sensitizes leptin signaling to combat obesity-related disease. Therefore, it implicates Kdm6a as an attractive drug target for obesity and metabolic disorders.
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http://dx.doi.org/10.1002/advs.202004319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292908PMC
July 2021

A Meta-Analysis of the Effect of Iodine Excess on the Intellectual Development of Children in Areas with High Iodine Levels in their Drinking Water.

Biol Trace Elem Res 2021 Jul 23. Epub 2021 Jul 23.

National Health commission &Education Bureau of Heilongjiang province, Key laboratory and Etiology and Epidemiology, Key Laboratory of Trace Elements and Human Health, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.

The purpose of this meta-analysis is to comprehensively investigate the effect of iodine excess on children's intellectual development in areas with high iodine levels in their drinking water. We systematically searched the electronic databases and identified 17 publications (16 in Chinese and 1 in English) on the effect of iodine excess on children's intelligence published between January 31, 1985, and January 31, 2020. This meta-analysis included 14,794 children from 28 studies. The results showed that compared with the control group, the intelligence level of children in the high iodine group reduced significantly by 1.64 points (WMD=-1.64; 95% CI (-3.225, -0.049), Z=2.02, P<0.05). Subgroup analyses were performed according to the water iodine concentration, water iodine concentration of the control group, the intelligence test method, and regions of China (i.e., north and south). We noted that when the water iodine concentration was <300μg/L, 301-600μg/L, 600.1-900μg/L, and >900μg/L, the intelligence level of the high iodine groups decreased by varying degrees, although not statistically significant (all P>0.05). The water iodine concentration of the control group was divided into two groups (<150 μg/L and <100 μg/L) and the heterogeneity analysis showed that the heterogeneity of the control group decreased significantly when the concentration of water iodine was <150 μg/L, I = 67.3%, P<0.001, which indicated a potential source of heterogeneity. The analyses by test method showed that among the studies which used the China Joint Raven's test, the intelligence level of children in the high iodine group was 0.86 points lower than in the control group (P>0.05). Conversely, we observed that among the studies which used the China Binet intelligence test and the binaphthalene intelligence test of Tanzhida in Japan to evaluate children's intelligence level, the intelligence level of children in the high iodine groups was significantly lower (3.65 points and 8.0 points, respectively) compared with the control groups (P<0.05). The analysis of the regions of China demonstrated that whereas the reduction in children's intelligence level from excess iodine in the north of China was not statistically significant (WMD=-0.16, 95% CI (-2.18, 1.85), P>0.05), the association was statistically significant in the southern part of China (WMD=-1.86, 95% CI (-3.57, -0.09), P<0.05). This study found that high iodine concentration was statistically significantly associated with a decline in intelligence level in children. Comparatively, the intelligence level of children who were exposed to high iodine concentrations reduced significantly by 1.64 points. These findings have public health implications.
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http://dx.doi.org/10.1007/s12011-021-02801-3DOI Listing
July 2021

Si-Wu-Tang facilitates ovarian function through improving ovarian microenvironment and angiogenesis in a mouse model of premature ovarian failure.

J Ethnopharmacol 2021 Jul 19;280:114431. Epub 2021 Jul 19.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Ethnopharmacological Relevance: Premature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called "the first prescription of gynecology" by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated.

Purpose: This study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice.

Materials And Methods: The main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed.

Results: Treatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group.

Conclusions: Our findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.
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http://dx.doi.org/10.1016/j.jep.2021.114431DOI Listing
July 2021

Covariate adjustment in subgroup analyses of randomized clinical trials: A propensity score approach.

Clin Trials 2021 Jul 16:17407745211028588. Epub 2021 Jul 16.

Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.

Background: Subgroup analyses are frequently conducted in randomized clinical trials to assess evidence of heterogeneous treatment effect across patient subpopulations. Although randomization balances covariates within subgroups in expectation, chance imbalance may be amplified in small subgroups and adversely impact the precision of subgroup analyses. Covariate adjustment in overall analysis of randomized clinical trial is often conducted, via either analysis of covariance or propensity score weighting, but covariate adjustment for subgroup analysis has been rarely discussed. In this article, we develop propensity score weighting methodology for covariate adjustment to improve the precision and power of subgroup analyses in randomized clinical trials.

Methods: We extend the propensity score weighting methodology to subgroup analyses by fitting a logistic regression propensity model with pre-specified covariate-subgroup interactions. We show that, by construction, overlap weighting exactly balances the covariates with interaction terms in each subgroup. Extensive simulations were performed to compare the operating characteristics of unadjusted estimator, different propensity score weighting estimators and the analysis of covariance estimator. We apply these methods to the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial to evaluate the effect of exercise training on 6-min walk test in several pre-specified subgroups.

Results: Standard errors of the adjusted estimators are smaller than those of the unadjusted estimator. The propensity score weighting estimator is as efficient as analysis of covariance, and is often more efficient when subgroup sample size is small (e.g. <125), and/or when outcome model is misspecified. The weighting estimators with full-interaction propensity model consistently outperform the standard main-effect propensity model.

Conclusion: Propensity score weighting is a transparent and objective method to adjust chance imbalance of important covariates in subgroup analyses of randomized clinical trials. It is crucial to include the full covariate-subgroup interactions in the propensity score model.
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http://dx.doi.org/10.1177/17407745211028588DOI Listing
July 2021

Evaluation of Head Injury Criteria for Injury Prediction Effectiveness: Computational Reconstruction of Real-World Vulnerable Road User Impact Accidents.

Front Bioeng Biotechnol 2021 29;9:677982. Epub 2021 Jun 29.

State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body, Hunan University, Changsha, China.

This study evaluates the effectiveness of various widely used head injury criteria (HICs) in predicting vulnerable road user (VRU) head injuries due to road traffic accidents. Thirty-one real-world car-to-VRU impact accident cases with detailed head injury records were collected and replicated through the computational biomechanics method; head injuries observed in the analyzed accidents were reconstructed by using a finite element (FE)-multibody (MB) coupled pedestrian model [including the Total Human Model for Safety (THUMS) head-neck FE model and the remaining body segments of TNO MB pedestrian model], which was developed and validated in our previous study. Various typical HICs were used to predict head injuries in all accident cases. Pearson's correlation coefficient analysis method was adopted to investigate the correlation between head kinematics-based injury criteria and the actual head injury of VRU; the effectiveness of brain deformation-based injury criteria in predicting typical brain injuries [such as diffuse axonal injury diffuse axonal injury (DAI) and contusion] was assessed by using head injury risk curves reported in the literature. Results showed that for head kinematics-based injury criteria, the most widely used HICs and head impact power (HIP) can accurately and effectively predict head injury, whereas for brain deformation-based injury criteria, the maximum principal strain (MPS) behaves better than cumulative strain damage measure (CSDM and CSDM) in predicting the possibility of DAI. In comparison with the dilatation damage measure (DDM), MPS seems to better predict the risk of brain contusion.
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http://dx.doi.org/10.3389/fbioe.2021.677982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275938PMC
June 2021

Recurrent c.459 C>A mutation of the PERP gene results in severe Olmsted syndrome with congenital hypotrichosis, atopic dermatitis, and growth retardation.

J Dermatol 2021 Jul 15. Epub 2021 Jul 15.

Department of Dermatology, West China Hospital of Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1111/1346-8138.16060DOI Listing
July 2021

Nucleic Acid Tests for Clinical Translation.

Chem Rev 2021 Jul 13. Epub 2021 Jul 13.

Institute of Molecular Medicine, Department of Liver Surgery, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.
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http://dx.doi.org/10.1021/acs.chemrev.1c00241DOI Listing
July 2021

Surveillance of West Nile virus infection in Kashgar Region, Xinjiang, China, 2013-2016.

Sci Rep 2021 Jul 7;11(1):14010. Epub 2021 Jul 7.

Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.

West Nile virus (WNV) was first isolated in mainland China from mosquitoes in Jiashi County, Kashgar Region, Xinjiang in 2011, following local outbreaks of viral meningitis and encephalitis caused by WNV. To elaborate the epidemiological characteristics of the WNV, surveillance of WNV infection in Kashgar Region, Xinjiang from 2013 to 2016 were carried out. Blood and CSF samples from surveillance human cases, blood of domestic chicken, cattle, sheep and mosquitoes in Kashgar Region were collected and detected. There were human 65 WNV Immunoglobulin M (IgM) antibody positive cases by ELISA screening, 6 confirmed WNV cases by the plaque reduction neutralization test (PRNT) screening. These cases occurred mainly concentrated in August to September of each year, and most of them were males. WNV-neutralizing antibodies were detected in both chickens and sheep, and the positive rates of neutralizing antibodies were 15.5% and 1.78%, respectively. A total of 15,637 mosquitoes were collected in 2013-2016, with Culex pipiens as the dominant mosquito species. Four and 1 WNV-positive mosquito pools were detected by RT-qPCR in 2013 and 2016 respectively. From these data, we can confirm that Jiashi County may be a natural epidemic foci of WNV disease, the trend highlights the routine virology surveillance in WNV surveillance cases, mosquitoes and avian should be maintained and enhanced to provide to prediction and early warning of outbreak an epidemic of WNV in China.
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http://dx.doi.org/10.1038/s41598-021-93309-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263600PMC
July 2021

Dimeric IgA is a specific biomarker of recent SARS-CoV-2 infection.

medRxiv 2021 Jul 1. Epub 2021 Jul 1.

Current tests for SARS-CoV-2 antibodies (IgG, IgM, IgA) cannot differentiate recent and past infections. We describe a point of care, lateral flow assay for SARS-CoV-2 dIgA based on the highly selective binding of dIgA to a chimeric form of secretory component (CSC), that distinguishes dIgA from monomeric IgA. Detection of specific dIgA uses a complex of biotinylated SARS-CoV-2 receptor binding domain and streptavidin-colloidal gold. SARS-CoV-2-specific dIgA was measured both in 112 cross-sectional samples and a longitudinal panel of 362 plasma samples from 45 patients with PCR-confirmed SARS-CoV-2 infection, and 193 discrete pre-COVID-19 or PCR-negative patient samples. The assay demonstrated 100% sensitivity from 11 days post-symptom onset, and a specificity of 98.2%. With an estimated half-life of 6.3 days, dIgA provides a unique biomarker for the detection of recent SARS-CoV-2 infections with potential to enhance diagnosis and management of COVID-19 at point-of-care.
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http://dx.doi.org/10.1101/2021.06.28.21259671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259913PMC
July 2021

Serum Hepcidin-25 and Risk of Mortality in Patients on Peritoneal Dialysis.

Front Med (Lausanne) 2021 17;8:684548. Epub 2021 Jun 17.

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Increased serum hepcidin-25 level is associated with excess mortality in hemodialysis patients. However, there is a dearth of published information about its predictive effect for survival in patients on peritoneal dialysis (PD). The purpose of this study is to evaluate the association of serum hepcidin-25 with the risk of mortality in PD patients. Serum hepcidin-25 level was measured using an enzyme-linked immunosorbent assay in a prospective cohort study of PD patients with stored serum samples at baseline. Multivariate linear regression model was used to determine clinical characteristics associated with serum hepcidin-25 concentration. We evaluated the relationship between serum hepcidin-25 and all-cause mortality using a Cox proportional hazards model and the relationship between hepcidin-25 and cardiovascular (CV) and infection-related deaths using competing-risks regression models. In total, 513 PD patients were included in this study. The median serum hepcidin-25 level was 40.9 (17.9-85.9) ng/mL. Body mass index and serum ferritin were positively correlated with serum hepcidin-25 levels. During a median follow-up period of 64.1 months, 122 (24%) patients died, including 61 (50%) CV deaths and 32 (26%) infection-related deaths. In multivariable analysis, patients with the highest tertile of serum hepcidin-25 had a greater risk of all-cause [adjusted hazard ratio (aHR) 1.85, 95% confidence interval (95%CI), 1.14 to 3.00, = 0.013] and infection-related mortality (adjusted subdistribution hazard ratio [aSHR], 2.61; 95%CI, 1.01 to 6.76, = 0.049) when compared with those in the second tertile. However, no significant relationship was observed between serum hepcidin-25 and CV mortality. Higher baseline serum hepcidin-25 level was associated with increased risk for all-cause and infection-related mortality in PD patients.
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http://dx.doi.org/10.3389/fmed.2021.684548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245702PMC
June 2021

Geographic Variation Did Not Affect the Predictive Power of Salivary Microbiota for Caries in Children With Mixed Dentition.

Front Cell Infect Microbiol 2021 18;11:680288. Epub 2021 Jun 18.

School of Stomatology, Qingdao University, Qingdao, China.

Dental caries is one of the most prevalent chronic oral diseases, affecting approximately half of children worldwide. The microbial composition of dental caries may depend on age, oral health, diet, and geography, yet the effect of geography on these microbiomes is largely underexplored. Here, we profiled and compared saliva microbiota from 130 individuals aged 6 to 8 years old, representing both healthy children (H group) and children with caries-affected (C group) from two geographical regions of China: a northern city (Qingdao group) and a southern city (Guangzhou group). First, the saliva microbiota exhibited profound differences in diversity and composition between the C and H groups. The caries microbiota featured a lower alpha diversity and more variable community structure than the healthy microbiota. Furthermore, the relative abundance of several genera (e.g., , and ) was significantly higher in the C group than in the H group (<0.05). Next, geography dominated over disease status in shaping salivary microbiota, and a wide array of salivary bacteria was highly predictive of the individuals' city of origin. Finally, we built a universal diagnostic model based on 14 bacterial species, which can diagnose caries with 87% (AUC=86.00%) and 85% (AUC=91.02%) accuracy within each city and 83% accuracy across cities (AUC=92.17%). Although the detection rate of in populations is not very high, it could be regarded as a single biomarker to diagnose caries with decent accuracy. These findings demonstrated that despite the large effect size of geography, a universal model based on salivary microbiota has the potential to diagnose caries across the Chinese child population.
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http://dx.doi.org/10.3389/fcimb.2021.680288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250437PMC
July 2021

Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes in elderly patients with comorbid coronary heart disease and diabetes mellitus.

J Geriatr Cardiol 2021 Jun;18(6):440-448

Chinese PLA Medical School, Chinese PLA General Hospital, Beijing, China.

Objective: To investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular outcomes in elderly Chinese patients with comorbid coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM).

Methods: A retrospective cohort study was conducted on 501 elderly inpatients (≥ 60 years) with comorbid CHD/T2DM in Department of Cardiovascular Medicine and Endocrinology, Chinese PLA General Hospital from January 2018 to December 2019. These patients were divided into two groups according to the administration of SGLT2i. All the demographic characteristics and clinical data were collected. Cardiovascular outcomes, including all-cause mortality, major adverse cardiovascular events (MACE), and hospitalization for heart failure (HHF), were followed up.

Results: In the cohort, there were 167 patients in the SGLT2i group and 334 patients in the control group. In the efficacy analyses, the incidence of MACE was lower in the SGLT2i group than in the control group: 3.6% . 9.3% ( = 0.022). A lower risk of MACE was observed in the SGLT2i group [hazard ratio (HR) = 0.40, 95% CI: 0.17-0.95]. There was no significant difference in the incidence of all-cause mortality or HHF between the two groups. No significant difference of HR was observed for all-cause mortality (HR = 0.41, 95% CI: 0.12-1.41) or HHF (HR = 0.58, 95% CI: 0.12-2.81).

Conclusions: SGLT2i treatment exhibited benefits for elderly patients with comorbid CHD/T2DM with a lower risk for MACE.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220386PMC
June 2021

[Stable isotope ratio characteristics and origin tracing of ].

Ying Yong Sheng Tai Xue Bao 2021 Jun;32(6):2021-2027

Shandong Marine Resource and Environment Research Institute, Yantai 264006, Shandong, China.

A method for geographical discrimination of was explored to provide technical support for the protection of geographical indication products and for tracing the origin of seafood. were collected from three major production areas, including the Yellow Sea, the Bohai Sea, and the East China Sea. The variations of carbon and nitrogen stable isotope values of origins and the correlation of stable isotope ratios in different tissues were analyzed. The results showed that there were significant differences in carbon and nitrogen stable isotope ratio among different origins. Significant isotope fractionation effects were observed among different tissues. The discriminant model was developed and the origin discriminant analysis was performed by the stable isotope ratios of different tissues in The correct rate of origin diffe-rentiationf using carbon and nitrogen stable isotopes in muscle and gills (>95%) was significantly higher than that of hepatopancreas and gonad, indicating that stable isotope ratios of muscle and gills could effectively differentiate in different sea areas. This study filled the gap of stable isotope tracing technology for .
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http://dx.doi.org/10.13287/j.1001-9332.202106.025DOI Listing
June 2021

Efficient continuous-wave eye-safe Nd:YVO self-Raman laser at 1.5  µm.

Opt Lett 2021 Jul;46(13):3183-3186

Due to a high Raman threshold and serious thermal effect, a challenge is to achieve efficient continuous-wave (CW) operation of a crystalline Raman laser at 1.5 µm. Based on effective thermal management and the self-Raman effect, we demonstrate, to our knowledge, the first efficient CW operation of a : Raman laser at 1.5 µm. We achieve 685 mW of CW eye-safe emission at 1524.5 nm by the use of a 20-mm-long composite : and 300-µm pump beam radius, with a diode-to-Stokes conversion efficiency of 4.8%. Lasers operating at ∼1.5µ have found many important applications in various areas such as optical communication, laser radar, laser ranging, remote sensing, and spectral research.
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http://dx.doi.org/10.1364/OL.429982DOI Listing
July 2021

Role of Exosomal Non-coding RNAs in Gastric Cancer: Biological Functions and Potential Clinical Applications.

Front Oncol 2021 14;11:700168. Epub 2021 Jun 14.

Department of Gastroenterology, The First Hospital of Jilin University, Changchun, China.

Gastric cancer (GC) is one of the most common fatal cancers worldwide. The communication between GC and other cells in the GC microenvironment directly affects GC progression. Recently, exosomes have been revealed as new players in intercellular communication. They play an important role in human health and diseases, including cancer, owing to their ability to carry various bioactive molecules, including non-coding RNAs (ncRNAs). NcRNAs, including micro RNAs, long non-coding RNAs, and circular RNAs, play a significant role in various pathophysiological processes, especially cancer. Increasing evidence has shown that exosomal ncRNAs are involved in the regulation of tumor proliferation, invasion, metastasis, angiogenesis, immune regulation, and treatment resistance in GC. In addition, exosomal ncRNAs have promising potential as diagnostic and prognostic markers for GC. Considering the biocompatibility of exosomes, they can also be used as biological carriers for targeted therapy. This review summarizes the current research progress on exosomal ncRNAs in gastric cancer, focusing on their biological role in GC and their potential as new biomarkers for GC and therapeutics. Our review provides insight into the mechanisms involved in GC progression, which may provide a new point cut for the discovery of new diagnostic markers and therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2021.700168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238120PMC
June 2021
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