Publications by authors named "Qin Yu"

681 Publications

let-7c-5p regulates CyclinD1 in fluoride-mediated osteoblast proliferation and activation.

Toxicol Sci 2021 May 12. Epub 2021 May 12.

School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China.

Endemic fluorosis is caused by the intake of high environmental fluoride levels, which causes dental and skeletal fluorosis. Osteoblast proliferation and activation is closely related to skeletal fluorosis and is tightly regulated by the cell cycle. Several biological processes, including bone metabolism and osteoblast proliferation and activation, are regulated by a type of non-coding RNA called microRNAs (miRNAs). However, the understanding of miRNA functions in skeletal fluorosis is limited. Based on our previous miRNA sequencing results and bioinformatics analysis, we investigated the function of the miRNA let-7c-5p to regulate CyclinD1 in fluoride-induced osteoblast proliferation and activation. We designed population experiments as well as in vitro studies using EdU, flow cytometry, immunofluorescence, dual-luciferase reporters, and chromatin immunoprecipitation. The population-based analysis showed a decrease in let-7c-5p expression as fluoride exposure increased. In addition, let-7c-5p levels were negatively correlated with CyclinD1 and Wnt9a (another let-7c-5p target). We verified in vitro that let-7c-5p participates in the fluoride-induced proliferation and activation of human osteoblasts by directly targeting CyclinD1. Furthermore, we demonstrated that let-7c-5p regulates CyclinD1 expression via the Wnt/β-catenin signaling pathway. This study demonstrated the participation of let-7c-5p in fluoride-induced proliferation and activation of human osteoblasts by regulation of CyclinD1 expression at the post-transcriptional and transcriptional levels. We report for the first time that the Wnt9a/β-catenin/CyclinD1 axis is involved in fluorosis development.
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http://dx.doi.org/10.1093/toxsci/kfab054DOI Listing
May 2021

Multimodal super-resolved q-space deep learning.

Med Image Anal 2021 Apr 21;71:102085. Epub 2021 Apr 21.

School of Information and Electronics, Beijing Institute of Technology, Beijing, China. Electronic address:

Super-resolvedq-space deep learning (SR-q-DL) has been developed to estimate high-resolution (HR) tissue microstructure maps from low-quality diffusion magnetic resonance imaging (dMRI) scans acquired with a reduced number of diffusion gradients and low spatial resolution, where deep networks are designed for the estimation. However, existing methods do not exploit HR information from other modalities, which are generally acquired together with dMRI and could provide additional useful information for HR tissue microstructure estimation. In this work, we extend SR-q-DL and propose multimodal SR-q-DL, where information in low-resolution (LR) dMRI is combined with HR information from another modality for HR tissue microstructure estimation. Because the HR modality may not be as sensitive to tissue microstructure as dMRI, direct concatenation of multimodal information does not necessarily lead to improved estimation performance. Since existing deep networks for HR tissue microstructure estimation are patch-based and use redundant information in the spatial domain to enhance the spatial resolution, the HR information in the other modality could inform the deep networks about what input voxels are relevant for the computation of tissue microstructure. Thus, we propose to incorporate the HR information from the HR modality by designing an attention module that guides the computation of HR tissue microstructure from LR dMRI. Specifically, the attention module is integrated with the patch-based SR-q-DL framework that exploits the sparsity of diffusion signals. The sparse representation of the LR diffusion signals in the input patch is first computed with a network component that unrolls an iterative process for sparse reconstruction. Then, the proposed attention module computes a relevance map from the HR modality with sequential convolutional layers. The relevance map indicates the relevance of the LR sparse representation at each voxel for computing the patch of HR tissue microstructure. The relevance is applied to the LR sparse representation with voxelwise multiplication, and the weighted LR sparse representation is used to compute HR tissue microstructure with another network component that allows resolution enhancement. All weights in the proposed network for multimodal SR-q-DL are jointly learned and the estimation is end-to-end. To evaluate the proposed method, we performed experiments on brain dMRI scans together with images of additional HR modalities. In the experiments, the proposed method was applied to the estimation of tissue microstructure measures for different datasets and advanced biophysical models, where the benefit of incorporating multimodal information using the proposed method is shown.
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http://dx.doi.org/10.1016/j.media.2021.102085DOI Listing
April 2021

Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1.

Front Immunol 2021 23;12:646775. Epub 2021 Apr 23.

Department of Respiratory, The First Hospital of Lanzhou University (The First School of Clinical Medicine), Lanzhou, China.

Intestinal barrier dysfunction is an important contributor to morbidity caused by sepsis. This study investigates the molecular mechanism by which Ghrelin affects intestinal dysfunction in rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture (CLP), revealing that Ghrelin was downregulated when sepsis occurs. Increases in the levels of inflammatory factors tumor necrosis factor α (TNF-α), interleukin-1 (IL-1β), IL-6, gastrin, γ-H2AX and 8-OHdG was also detected in this model system, as was an overall increase in oxidative stress. Introduction of exogenous Ghrelin inhibited these increases in inflammatory response and oxidative stress, leading to a reduction of overall sepsis-induced intestinal dysfunction. Ghrelin was then shown to activate SIRT1 expression , while SIRT1 was found to co-express with KLF4, which in turn was predicted to bind to matrix metalloproteinase 2 (MMP2) promoter. Finally, gain- and loss-of-function experiment demonstrated that SIRT1 upregulated the expression of KLF4 to downregulate MMP2. Collectively, Ghrelin inhibits the oxidative stress and intestinal dysfunction to attenuate sepsis by activating SIRT1 and regulating a KLF4/MMP2 regulatory axis.
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http://dx.doi.org/10.3389/fimmu.2021.646775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102724PMC
April 2021

Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation.

Redox Biol 2021 Apr 30;43:101994. Epub 2021 Apr 30.

Laboratory of Mitochondria and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Anesthesia and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address:

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated. This study was designed to investigate the impact of hypoxic acclimation (HA) on cardiac I/R injury and the antioxidative mechanism(s). Male adult mice were acclimated in a hypoxic chamber (10% oxygen [O]) for 8 h/day for 14 days, and then subjected to cardiac I/R injury by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h or 7 days. Our results showed that HA attenuated oxidative stress and reduced infarct size in the I/R hearts. This cardioprotective effect is coupled with an elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due to inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, resulting in an upregulation of NADPH/NADP and GSH/GSSG couples and enhancement of redox homeostasis in the heart. Pharmacological suppression of O-GlcNAcylation totally abolished the influence of HA on the G6PDH activity, redox balance and post-I/R damage in the hearts and cultured cardiomyocytes, whereby augmentation of O-GlcNAcylation further enhanced the benefits, suggesting a central role of O-GlcNAcylation in HA-initiated antioxidative and cardioprotective effects. These findings, therefore, identified HA as a promising anti-I/R strategy for the heart and proposed O-GlcNAc modification of G6PDH as a therapeutic target in ischemic heart disease.
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http://dx.doi.org/10.1016/j.redox.2021.101994DOI Listing
April 2021

Polycomb group protein Bmi1 is required for the neuronal differentiation of mouse induced pluripotent stem cells.

Exp Ther Med 2021 Jun 14;21(6):619. Epub 2021 Apr 14.

College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zheijiang 310053, P.R. China.

Induced pluripotent stem cells (iPSCs) reprogrammed by somatic cells may be used as a potentially novel treatment regimen in stem cell regenerative medicine, particularly in the central nervous system (CNS). In the present study, iPSCs were generated using mouse embryonic fibroblasts by ectopic overexpression of Sox-2, Oct-3/4, Klf-4 and c-Myc, and cultured under the same conditions as that used for embryonic stem cells. The neuronal differentiation capacity of mouse iPSCs was examined, and the involvement of the formation of embryoid bodies was assessed. The results suggested that after 15 days of neuronal inducement, Nestin, Vimentin and Glast protein expression levels were significantly increased in the mouse iPSC-derived cells. Additionally, Bmi1, which is selectively expressed in differentiated postnatal adult stem cells. such as hematopoietic stem cells and neural stem cells, was required for establishment of the neuronal differentiation of mouse iPSCs. In order to assess the effects of Bmi1 in neuronal differentiation, Bmi1 expression levels were inhibited with the small molecule PTC-209. The results showed that inhibition of Bmi1 expression reduced the expression of neuronal markers, such as Nestin, compared with the controls. These results suggested that mouse iPSCs can be induced to achieve neuronal differentiation. More interestingly, Bmi1 was required during the neuronal differentiation of mouse iPSCs.
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http://dx.doi.org/10.3892/etm.2021.10051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082597PMC
June 2021

Neoantigen: A New Breakthrough in Tumor Immunotherapy.

Front Immunol 2021 16;12:672356. Epub 2021 Apr 16.

Department of Pathology, Xinxiang Medical University, Xinxiang, China.

Cancer immunotherapy works by stimulating and strengthening the body's anti-tumor immune response to eliminate cancer cells. Over the past few decades, immunotherapy has shown remarkable efficacy in the treatment of cancer, particularly the success of immune checkpoint blockade targeting CTLA-4, PD-1 and PDL1, which has led to a breakthrough in tumor immunotherapy. Tumor neoantigens, a new approach to tumor immunotherapy, include antigens produced by tumor viruses integrated into the genome and antigens produced by mutant proteins, which are abundantly expressed only in tumor cells and have strong immunogenicity and tumor heterogeneity. A growing number of studies have highlighted the relationship between neoantigens and T cells' recognition of cancer cells. Vaccines developed against neoantigens are now being used in clinical trials in various solid tumors. In this review, we summarized the latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy. Finally, the application prospects and existing problems of neoantigens were discussed.
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http://dx.doi.org/10.3389/fimmu.2021.672356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085349PMC
April 2021

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

Anal Chem 2021 May 28;93(18):7102-7109. Epub 2021 Apr 28.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.
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http://dx.doi.org/10.1021/acs.analchem.1c00785DOI Listing
May 2021

Anti-stress effects of combined glucocorticoid and mineralocorticoid receptor blockade in the paraventricular nucleus of the hypothalamus.

Br J Pharmacol 2021 Apr 27. Epub 2021 Apr 27.

Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.

Background And Purpose: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are implicated in stress response. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviors.

Experimental Approach: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days corticosterone treatment. Behavioral tests were run on days 22 and 23. Depressive- and anxiety-like behaviors were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by Western-Blot.

Key Results: The rats exposed to corticosterone exhibited depressive- and anxiety-like behaviors. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviors. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN, and improved anxiety-like behaviors. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored the expression of GRs, MRs, and CRF and improved depressive- and anxiety-like behaviors.

Conclusion And Implications: These results suggest that the simultaneous restoration of GRs, MRs, and CRF in the PVN in this rat model of stress might play an important role in the treatment of depression and anxiety.
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http://dx.doi.org/10.1111/bph.15511DOI Listing
April 2021

The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18-59 years: A phase I randomized, double-blinded, controlled trial.

Vaccine 2021 05 9;39(20):2746-2754. Epub 2021 Apr 9.

Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Kunming 650118, China.

Background: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine.

Method: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated.

Results: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine.

Interpretation: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic.

Trial Registration: CTR20200943 and NCT04412538.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040531PMC
May 2021

Long-term multimodal imaging characterization of persistent retinal neovascularization using DL-alpha-aminoadipic acid in pigmented and white rabbits.

Exp Eye Res 2021 Apr 14;207:108577. Epub 2021 Apr 14.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Purpose: Intravitreal (IVT) injection of DL-alpha-aminoadipic acid (AAA) is a new animal model for retinal neovascularization (RNV) reported in rabbits. This study performs longitudinal multimodal imaging for up to 1 year to evaluate DL-AAA RNV in both New Zealand white (NZW) rabbits and Dutch-Belted pigmented (DBP) rabbits.

Method: Detailed characterization and quantification of this model were performed in these two strains in 32 eyes by optical coherence tomography (OCT), fundus photography, and fluorescein angiography (FA) for up to 16 weeks following DL-AAA administration in 32 eyes and up to 52 weeks in 5 eyes. H & E histology was also performed in these two strains 8 weeks after injection of DL-AAA.

Result: RNV was successfully generated using 50 μL 80 mM DL-AAA solution for DBP rabbits and 80 μL 80 mM DL-AAA for NZW rabbits. The incidence of persistent vascular leakage is 100% (15/15) for DBP rabbits and 70.6% (12/17) for NZW rabbits at 16 weeks. Complications with NZW rabbits ultimately decreased the efficiency in NZW rabbits to 58.8% (10/17) of NZW rabbits getting persistent (to 16 weeks) vascular leakage without ocular complications as compared with 100% (15/15) in DBP rabbits. Five eyes (2 DBP and 3 NZW) were selected from those demonstrating RNV at 16 weeks and were monitored for up to 52 weeks. All 5 demonstrated persistent RNV to 52 weeks. Quantification of the mean leakage area (MLA) in DBP rabbits is more accurate than in NZW rabbits since the reduced contrast between the leakage and background in NZW rabbits makes it more challenging to quantify.

Conclusion: DL-AAA can induce persistent and quantifiable RNV in both DBP and NZW rabbits. DBP rabbits have a higher success rate, lower required volume of DL-AAA, and more accurate method for quantification that could be more desirable.
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http://dx.doi.org/10.1016/j.exer.2021.108577DOI Listing
April 2021

Long Non-Coding RNA LOC648987 Promotes Proliferation and Metastasis of Renal Cell Carcinoma by Regulating Epithelial-Mesenchymal Transition.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821997834

Department of General Practice, Ningbo Beilun People's Hospital, Ningbo, Zhejiang, China.

Renal cell carcinoma (RCC) is a type of urinary tumor with a high incidence and is often associated with tumor metastasis. Long non-coding RNA (lncRNA) regulates tumorigenesis, progression, and metastasis. However, the role and the predictive value of lncRNA in RCC progression and metastasis have not been elucidated. The purpose of this study was to evaluate the effect of a newly discovered lncRNA LOC648987 on RCC proliferation and metastasis. LOC648987 was identified by RT-PCR for high expression in human RCC tissues as well as in metastatic RCC tissues. In the cell experiments, we infected the RCC cell lines ACHN and 786-O cells with LOC648987-shRNA and its negative control (shNC). The results showed that the knockdown of LOC648987 inhibited the proliferation of ACHN and 786-O cells and colony formation. The cell cycle and the apoptosis progression of ACHN and 786-O cells were assessed using flow cytometry. The knockdown of LOC648987 significantly inhibited the progression of ACHN and 786-O cells from G0/G1 to S phase and promoted cell apoptosis. The metastasis promoting effects of LOC648987 on ACHN and 786-O cells were verified by transwell migration assays, which depended on vimentin and MMP-9 to regulate the epithelial-mesenchymal transition. Finally, the promotion of LOC648987 on RCC tumorigenesis was evaluated in BALb/c nude mice. These data confirmed that lncRNA LOC648987 promoted RCC cell proliferation and tumor metastasis and regulated the expression of EMT-related proteins in RCC cells.
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http://dx.doi.org/10.1177/1533033821997834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053825PMC
April 2021

An ABCC-type transporter endowing glyphosate resistance in plants.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Australian Herbicide Resistance Initiative, School of Agriculture and Environment, University of Western Australia, WA 6009, Australia;

Glyphosate is the most widely used herbicide in world agriculture and for general vegetation control in a wide range of situations. Global and often intensive glyphosate selection of very large weedy plant populations has resulted in widespread glyphosate resistance evolution in populations of many weed species. Here, working with a glyphosate-resistant (GR) population that evolved in a Western Australia agricultural field, we identified an ATP-binding cassette (ABC) transporter () that is consistently up-regulated in GR plants. When expressed in transgenic rice, this transporter endowed glyphosate resistance. Equally, rice, maize, and soybean overexpressing the ortholog genes were made resistant to glyphosate. Conversely, CRISPR/Cas9-mediated knockout of the ortholog gene increased rice susceptibility to glyphosate. Subcellular localization analysis and quantification of glyphosate cellular levels in treated transgenic rice plants and isolated leaf protoplasts as well as structural modeling support that EcABCC8 is likely a plasma membrane-localized transporter extruding cytoplasmic glyphosate to the apoplast, lowering the cellular glyphosate level. This is a report of a membrane transporter effluxing glyphosate in a GR plant species, and its function is likely conserved in crop plant species.
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http://dx.doi.org/10.1073/pnas.2100136118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072331PMC
April 2021

Dinitroaniline Herbicide Resistance and Mechanisms in Weeds.

Front Plant Sci 2021 25;12:634018. Epub 2021 Mar 25.

Australian Herbicide Resistance Initiative (AHRI), School of Agriculture and Environment, University of Western Australia (UWA), Perth, WA, Australia.

Dinitroanilines are microtubule inhibitors, targeting tubulin proteins in plants and protists. Dinitroaniline herbicides, such as trifluralin, pendimethalin and oryzalin, have been used as pre-emergence herbicides for weed control for decades. With widespread resistance to post-emergence herbicides in weeds, the use of pre-emergence herbicides such as dinitroanilines has increased, in part, due to relatively slow evolution of resistance in weeds to these herbicides. Target-site resistance (TSR) to dinitroaniline herbicides due to point mutations in α-tubulin genes has been confirmed in a few weedy plant species (e.g., , , and recently in ). Of particular interest is the resistance mutation Arg-243-Met identified from dinitroaniline-resistant that causes helical growth when plants are homozygous for the mutation. The recessive nature of the TSR, plus possible fitness cost for some resistance mutations, likely slows resistance evolution. Furthermore, non-target-site resistance (NTSR) to dinitroanilines has been rarely reported and only confirmed in due to enhanced herbicide metabolism (metabolic resistance). A cytochrome P450 gene (CYP81A10) has been recently identified in that confers resistance to trifluralin. Moreover, TSR and NTSR have been shown to co-exist in the same weedy species, population, and plant. The implication of knowledge and information on TSR and NTSR in management of dinitroaniline resistance is discussed.
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http://dx.doi.org/10.3389/fpls.2021.634018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027333PMC
March 2021

Viologen-Based Cationic Metal-Organic Framework for Efficient CrO Adsorption and Dye Separation.

Inorg Chem 2021 Apr 7;60(8):5988-5995. Epub 2021 Apr 7.

School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, P. R. China.

A novel cationic metal-organic framework composed of {Cu(COO)} paddle-wheel units and a tetracarboxylic viologen derivative, namely, {[Cu(bdcbp)(HO)]·2NO·2HO} (, HbdcbpCl = 1,1'-bis(3,5-dicarboxyphenyl)-4,4'-bipyridinium dichloride), has been successfully synthesized and structurally characterized. In , the {Cu(COO)} unit and viologen derivative both act as four-connected nodes forming an ssb-type cationic network with 4.8 topology, in which the positive charges are distributed on the organic viologen moieties. Deeper insight of the structure indicates that the 3D architecture of can be seen as packing of a 26-faceted polyhedral cage and two cuboid cages. Notably, displays a highly efficient anion exchange ability for capture and removal of anionic pollutants. UV-vis absorption spectra and digital images demonstrate that is capable of adsorbing the dichromate anion and anionic dyes effectively, such as methyl orange (MO), Congo red (CR), and New Coccine (NC). Meaningfully, anionic dyes (MO, CR, and NC) can be efficiently and selectively removed by in the presence of cationic dye methylene blue (MLB). Such behaviors of anionic pollutant adsorption and dye separation are mainly caused by an ion-exchange process facilitated by the large cavity and decentralized distribution of positive charge in .
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http://dx.doi.org/10.1021/acs.inorgchem.1c00404DOI Listing
April 2021

The effect of coronary slow flow on left atrial structure and function.

Sci Rep 2021 Apr 5;11(1):7511. Epub 2021 Apr 5.

Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, 620061, Liaoning Province, China.

The coronary slow flow phenomenon (CSFP) is common in coronary angiography, however its impact on left atrial (LA) function is still controversial. This study aims to evaluate the LA structure and function of patients with CSFP using two-dimensional speckle tracking echocardiography (2D-STE). Consecutive patients scheduled for coronary angiography from January 2016 to September 2017 were enrolled in this study. Patients' demographic data, clinical histories, laboratory and angiographic findings were collected and recorded. Diagnostic criteria for CSFP is based on Beltrame et al. proposed in 2012. Meanwhile 139 patients who have no significant stenosis (≤ 40%) and normal blood flow were selected as control. All patients received an echocardiographic examination 24 h before coronary angiography. LA structure and function were measured with echocardiography and 2D-STE. Our results showed that among the 1,954 patients who had received coronary angiography, 512 patients were included in the analysis after the exclusion criteria was implemented. Of those, 101 patients met the CSFP criteria (5.5%). CSFP is mainly seen in LAD (~ 70%). There was no statistical difference in baseline characteristics between the CSFP group and control group, except for a higher proportion of smokers in the CSFP group (P = 0.001). The percentage of monocytes is an independent risk factor for the occurrence of CSFP (P = 0.036) after binary logistic regression analysis. The LA global longitudinal strain (LA-GLS, represents reservoir functions) decreased and LA strain rate at late diastole (LA-SRa, represents booster function) increased in patients with CSFP compared to the control group (P < 0.05). Correlation test of continuous variables by Pearson test suggested that LA-GLS was negatively correlated with TIMI frame count (TFC). We concluded that the percentage of monocytes is an independent risk factor for the CSFP; the LA reservoir and booster functions were impaired in patients with CSFP; LA-GLS is negatively correlated with TFC.
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http://dx.doi.org/10.1038/s41598-021-87193-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021584PMC
April 2021

Overexpression of AGAMOUS-like gene PfAG5 promotes early flowering in Polypogon fugax.

Funct Plant Biol 2021 Apr 6. Epub 2021 Apr 6.

Herbicides are the major tool for controlling large populations of yield depleting weeds. However, over-reliance on herbicides has resulted in weed adaptation and herbicide resistance. In recent years, early flowering weed species related to herbicide resistance is emerging, which may cause seed loss before crop harvest, creating a new problem for non-chemical weed management. In this study, a homologue gene of AGAMOUS sub-family (referred to as PfAG5) of the MADS-box family was cloned from plants of an early flowering Polypogon fugax Nees ex Steud. population resistant to the ACCase inhibitor herbicide (clodinafop-propargyl). The PfAG5 gene was functionally characterised in Arabidopsis thaliana L. Overexpression of the PfAG5 gene in Arabidopsis resulted in early flowering, abnormal flowers (e.g. small petals), short plants and reduced seed set, compared with the wild type. The expression of the PfAG5 gene was high in leaves and flowers, but low in pods in transgenic Arabidopsis. The PfAG5 gene was expressed earlier and higher in the resistant (R) than the susceptible (S) P. fugax plants. Furthermore, one protein (FRIGIDA-like) with relevance to flowering time regulation and interacts with PfAG5 in resistant (R) P. fugax was identified by the yeast two-hybrid and pull-down assays. These results suggest that the PfAG5 gene is involved in modulating early flowering in P. fugax.
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http://dx.doi.org/10.1071/FP21047DOI Listing
April 2021

Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting.

Front Cell Infect Microbiol 2021 18;11:650163. Epub 2021 Mar 18.

Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.

Background: The prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.

Methods: 28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.. We analyzed specimen types' effect on these assays' performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.

Results: Sputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB/Xpert and 6/7 of AFB/Xpert cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB or Xpert. However, T-SPOT (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of -specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT. assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB/Xpert patients.

Conclusions: Concurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOT and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB/Xpert patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers' decisions regarding prevention and control of TB in a high burden setting.
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http://dx.doi.org/10.3389/fcimb.2021.650163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012509PMC
March 2021

Molecular epidemiology analysis of early variants of SARS-CoV-2 reveals the potential impact of mutations P504L and Y541C (NSP13) in the clinical COVID-19 outcomes.

Infect Genet Evol 2021 Mar 31;92:104831. Epub 2021 Mar 31.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global pandemic with alarming speed, comprehensively analyzing the mutation and evolution of early SARS-CoV-2 strains contributes to detect and prevent such virus. Here, we explored 1962 high-quality genomes of early SARS-CoV-2 strains obtained from 42 countries before April 2020. The changing trends of genetic variations in SARS-CoV-2 strains over time and country were subsequently identified. In addition, viral genotype mapping and phylogenetic analysis were performed to identify the variation features of SARS-CoV-2. Results showed that 57.89% of genetic variations involved in ORF1ab, most of which (68.85%) were nonsynonymous. Haplotype maps and phylogenetic tree analysis showed that amino acid variations in ORF1ab (p.5828P > L and p.5865Y > C, also NSP13: P504L and NSP13: Y541C) were the important characteristics of such clade. Furthermore, these variants showed more significant aggregation in the United States (P = 2.92E-66, 95%) than in Australia or Canada, especially in strains from Washington State (P = 1.56E-23, 77.65%). Further analysis demonstrated that the report date of the variants was associated with the date of increased infections and the date of recovery and fatality rate change in the United States. More importantly, the fatality rate in Washington State was higher (4.13%) and showed poorer outcomes (P = 4.12E-21 in fatality rate, P = 3.64E-29 in death and recovered cases) than found in other states containing a small proportion of strains with such variants. Using sequence alignment, we found that variations at the 504 and 541 sites had functional effects on NSP13. In this study, we comprehensively analyzed genetic variations in SARS-CoV-2, gaining insights into amino acid variations in ORF1ab and COVID-19 outcomes.
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http://dx.doi.org/10.1016/j.meegid.2021.104831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010360PMC
March 2021

Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.
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http://dx.doi.org/10.1073/pnas.2020215118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040602PMC
April 2021

Effectiveness of cognitive behavior therapy for sleep disturbance and glycemic control in persons with type 2 diabetes mellitus: A community-based randomized controlled trial in China.

World J Diabetes 2021 Mar;12(3):292-305

Department of Control and Prevention of Chronic Non-communicable Diseases, Xuzhou Center for Disease Control and Prevention, Xuzhou 221006, Jiangsu Province, China.

Background: Poor sleep quality is a common clinical feature in patients with type 2 diabetes mellitus (T2DM), and often negatively related with glycemic control. Cognitive behavioral therapy (CBT) may improve sleep quality and reduce blood sugar levels in patients with T2DM. However, it is not entirely clear whether CBT delivered by general practitioners is effective for poor sleep quality in T2DM patients in community settings.

Aim: To test the effect of CBT delivered by general practitioners in improving sleep quality and reducing glycemic levels in patients with T2DM in community.

Methods: A cluster randomized controlled trial was conducted from September 2018 to October 2019 in communities of China. Overall 1033 persons with T2DM and poor sleep quality received CBT plus usual care or usual care. Glycosylated hemoglobin A1c (HbAlc) and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were assessed. Repeated measures analysis of variance and generalized linear mixed effects models were used to estimate the intervention effects on hemoglobin A1c and sleep quality.

Results: The CBT group had 0.64, 0.50, and 0.9 lower PSQI scores than the control group at 2 mo, 6 mo, and 12 mo, respectively. The CBT group showed 0.17 and 0.43 lower HbAlc values than the control group at 6 mo and 12 mo. The intervention on mean ΔHbAlc values was significant at 12 mo ( = 3.68, < 0.01) and that mean ΔPSQI scores were closely related to ΔHbAlc values ( = 7.02, < 0.01). Intention-to-treat analysis for primary and secondary outcomes showed identical results with completed samples. No adverse events were reported.

Conclusion: CBT delivered by general practitioners, as an effective and practical method, could reduce glycemic levels and improve sleep quality for patients with T2DM in community.
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http://dx.doi.org/10.4239/wjd.v12.i3.292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958479PMC
March 2021

CDK1 serves as a novel therapeutic target for endometrioid endometrial cancer.

J Cancer 2021 22;12(8):2206-2215. Epub 2021 Feb 22.

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China, 310006.

Endometrial cancer (EC) is one of the most common and prevalent gynecologic malignancies worldwide. The aim of this study was to identify a novel therapeutic target for endometrioid endometrial cancer. Bioinformatic analysis was performed and CDK1 was screen out as one of the hub genes in the pathogenesis of EC. Immunohistochemistry was used to verify the expression of CDK1 in endometrial cancer tissue. Cell viability and colony formation were used to study the effects of CDK1 on the proliferation and colony formation of endometrial cancer cells . Apoptosis and cell cycle assays were used to elucidate the mechanism of CDK1 affecting cell proliferation. Tumor xenograft transplantation assay was performed to show the effects of CDK1 on the growth of endometrial cancer cells . CDK1 was over expressed in endometrioid endometrial cancer, and accumulation of cytoplasmic CDK1 was associated with histological grade of EC. CDK1 promoted endometrial cancer cell growth and colony formation . The inhibition of CDK1 activity induced cell apoptosis and caused G2/M phase arrest of cell cycle in endometrial cancer cells. The inhibition of CDK1 activity also inhibited endometrial cancer growth in xenograft models. CDK1 was involved in the pathogenesis of endometrioid endometrial cancer and provided a novel therapeutic target for endometrioid endometrial cancer.
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http://dx.doi.org/10.7150/jca.51139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974891PMC
February 2021

The association between daily total physical activity and risk of cardiovascular disease among hypertensive patients: a 10-year prospective cohort study in China.

BMC Public Health 2021 Mar 16;21(1):517. Epub 2021 Mar 16.

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Background: The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention.

Methods: Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004-2008. At baseline, 53,259 participants aged 35-74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs).

Results: During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79-0.97), 0.73 (95%CI: 0.65-0.83) and 0.75 (95%CI: 0.65-0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54-0.74) was observed at 35.4 MET-h/d of total physical activity.

Conclusions: Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.
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http://dx.doi.org/10.1186/s12889-021-10551-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968198PMC
March 2021

Anthraquinone derivative C10 inhibits proliferation and cell cycle progression in colon cancer cells via the Jak2/Stat3 signaling pathway.

Toxicol Appl Pharmacol 2021 05 13;418:115481. Epub 2021 Mar 13.

Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.

Since its discovery, anthraquinone has become very valuable as a lead compound in the development of anti-cancer drugs. Previously, we designed and synthesized a new type of amide anthraquinone derivative (1-nitro-2-acylanthraquinone glycine, C10) with good activity against colon cancer. However, its effect and the underlying mechanism are unclear. In this study, C10 significantly inhibited the proliferation of HCT116 and HT29 colon cancer cells by blocking the cell cycle at the G2/M phase. C10 also plays a role in cell cycle arrest by reducing the protein and gene expression levels of cyclin B1 and its downstream signaling molecule cyclin-dependent kinase (CDK1). In addition, molecular docking studies showed that C10 has high affinity for Jak2, the first target in the cell cycle-related Jak2/Stat3 signaling pathway. Furthermore, C10 downregulated the expression of Jak2/Stat3 signaling pathway-related signaling molecules proteins and genes, and up-regulated the expression of PIAS-3, the upstream signaling molecule of Stat3, thereby down-regulating Stat3 phosphorylation. C10 reversed the expression of Jak2/Stat3 signaling pathway-related molecules activated by IL-6. Overall, our results indicate for the first time that C10 induces cell cycle arrest and inhibits cell proliferation by inhibiting the Jak2/Stat3 signaling pathway. This study provides new insights into the potential role of Jak2/Stat3 in the regulating cell cycle-related signaling pathways that mediate the inhibitory effects of C10 on colon cancer cell proliferation.
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http://dx.doi.org/10.1016/j.taap.2021.115481DOI Listing
May 2021

Ethylene-regulated asymmetric growth of the petal base promotes flower opening in rose (Rosa hybrida).

Plant Cell 2021 Feb 2. Epub 2021 Feb 2.

Department of Ornamental Horticulture, State Key Laboratory of Agrobiotechnology, Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, China Agricultural University, Beijing 100193, China.

Flowers are the core reproductive structures and key distinguishing features of angiosperms. Flower opening to expose stamens and gynoecia is important in cases where pollinators much be attracted to promote cross-pollination, which can enhance reproductive success and species preservation. The floral opening process is accompanied by the coordinated movement of various floral organs, particularly petals. However, the mechanisms underlying petal movement and flower opening are not well understood. Here, we integrated anatomical, physiological, and molecular approaches to determine the petal movement regulatory network using rose (Rosa hybrida) as a model. We found that PETAL MOVEMENT-RELATED PROTEIN1 (RhPMP1), a homeodomain transcription factor (TF) gene, is a direct target of ETHYLENE INSENSITIVE3, a TF that functions downstream of ethylene signaling. RhPMP1 expression was upregulated by ethylene and specifically activated endoreduplication of parenchyma cells on the adaxial side of the petal (ADSP) base by inducing the expression of RhAPC3b, a gene encoding the core subunit of the Anaphase-Promoting Complex. Cell expansion of the parenchyma on the ADSP base was subsequently enhanced, thus resulting in asymmetric growth of the petal base, leading to the typical epinastic movement of petals and flower opening. These findings provide insights into the pathway regulating petal movement and associated flower-opening mechanisms.
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http://dx.doi.org/10.1093/plcell/koab031DOI Listing
February 2021

Identification of a Potentially Functional microRNA-mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis.

Front Cell Dev Biol 2021 18;9:641840. Epub 2021 Feb 18.

The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.

Background: Lung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA-mRNA regulatory network involved in LUAD has not been fully elucidated.

Methods: Differentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA-mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein-protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).

Results: The miRNA-mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.

Conclusion: This study investigated a miRNA-mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.
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http://dx.doi.org/10.3389/fcell.2021.641840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930498PMC
February 2021

Reporting and methodological quality of COVID-19 systematic reviews needs to be improved: an evidence mapping.

J Clin Epidemiol 2021 Feb 28;135:17-28. Epub 2021 Feb 28.

Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China; Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China; WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou University, Lanzhou, China; Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China. Electronic address:

Objectives: To assess the reporting and methodological quality of COVID-19 systematic reviews, and to analyze trends and gaps in the quality, clinical topics, author countries, and populations of the reviews using an evidence mapping approach.

Study Design And Setting: A structured search for systematic reviews concerning COVID-19 was performed using PubMed, Embase, Cochrane Library, Campbell Library, Web of Science, CBM, WanFang Data, CNKI, and CQVIP from inception until June 2020. The quality of each review was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.

Results: In total, 243 systematic reviews met the inclusion criteria, over 50% of which (128, 52.7%) were from 14 developing countries, with China contributing the most reviews (76, 31.3%). In terms of methodological quality of the studies, 30 (12.3%) were of moderate quality, 63 (25.9%) were of low quality, and 150 (61.7%) were of critically low quality. In terms of reporting quality, the median (interquartile range) PRISMA score was 14 (10-18). Regarding the topics of the reviews, 24 (9.9%) focused on the prevalence of COVID-19, 69 (28.4%) focused on the clinical manifestations, 30 (12.3%) focused on etiology, 43 (17.7%) focused on diagnosis, 65 (26.7%) focused on treatment, 104 (42.8%) focused on prognosis, and 25 (10.3%) focused on prevention. These studies mainly focused on general patients with COVID-19 (161, 66.3%), followed by children (22, 9.1%) and pregnant patients (18, 7.4%).

Conclusion: This study systematically evaluated the methodological and reporting quality of systematic reviews of COVID-19, summarizing and analyzing trends in their clinical topics, author countries, and study populations.
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http://dx.doi.org/10.1016/j.jclinepi.2021.02.021DOI Listing
February 2021

pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

Acta Pharm Sin B 2021 Feb 2;11(2):520-533. Epub 2020 Sep 2.

Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NHHCO; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NHHCO accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.
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http://dx.doi.org/10.1016/j.apsb.2020.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893139PMC
February 2021

Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway.

Int J Biol Sci 2021 14;17(2):574-588. Epub 2021 Jan 14.

Integrative Medical Diagnosis Laboratory, Tianjin Nankai Hospital, Tianjin, 300100, China; School of Medical Technology, Tianjin Medical University, Tianjin 300203, China.

CA125/MUC16 is an O-glycosylated protein that is expressed on the surfaces of ovarian epithelial cells. This molecule is a widely used tumor-associated marker for diagnosis of ovarian cancer. Recently, CA125 was shown to be involved in ovarian cancer metastasis. The purpose of this study was to investigate the mechanism of CA125 during ovarian cancer metastasis. We analyzed the Oncomine and CSIOVDB databases to determine the expression levels of DKK1 in ovarian cancer. DKK1 expression levels were upregulated or downregulated and applied with CA125 to Transwell and Western blot assays to ascertain the underlying mechanism by which CA125 stimulates cell migration via the SGK3/FOXO3 pathway. Anti-mesothelin antibodies (anti-MSLN) were used to block CA125 stimulation. Then the expression levels of DKK1were tested by enzyme-linked immunosorbent assay (ELISA) to eliminate the blocking effect of anti-MSLN to CA125 stimulation. Xenograft mouse models were used to detect the effects of CA125 and anti-MSLN on ovarian cancer metastasis . DKK1 levels were downregulated in ovarian tumor tissues according to the analyses of two databases and significantly correlated with FIGO stage, grade and disease-free survival in ovarian cancer patients. DKK1 levels were downregulated by CA125 stimulation . Overexpression of DKK1 reversed the ability of exogenous CA125 to mediate cell migration by activating the SGK3/FOXO3 signaling pathway. Anti-MSLN abrogated the DKK1 reduction and increased the apoptosis of ovarian cancer cells. The use of anti-MSLN in xenograft mouse models significantly reduced tumor growth and metastasis accelerated by CA125. These experiments revealed that the SGK3/FOXO3 pathway was activated, wherein decreased expression of DKK1 was caused by CA125, which fuels ovarian cancer cell migration. Mesothelin is a potential therapeutic target for the treatment of ovarian cancer metastasis.
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http://dx.doi.org/10.7150/ijbs.52097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893585PMC
January 2021

CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial.

Bone Marrow Transplant 2021 Feb 19. Epub 2021 Feb 19.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.
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http://dx.doi.org/10.1038/s41409-021-01226-9DOI Listing
February 2021

Clinical Utility of Circulating Cell-Free DNA Mutations in Anaplastic Thyroid Carcinoma.

Thyroid 2021 Apr 19. Epub 2021 Apr 19.

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid cancer that requires a rapid diagnosis and treatment to achieve disease control. Gene mutation profiling of circulating cell-free DNA (cfDNA) in peripheral blood may help to facilitate early diagnosis and treatment selection. The relatively rapid turnaround time compared with conventional tumor mutation testing is a major advantage. The objectives of this study were to examine the concordance of ATC-related mutations detected in cfDNA with those detected in the corresponding tumor tissue, and to determine the prognostic significance of cfDNA mutations in ATC patients. The ATC patients who were diagnosed and treated at The University of Texas MD Anderson Cancer Center between January 2015 and February 2018 and who had cfDNA testing were included in this study. cfDNA was collected by blood draw and was analyzed by next-generation sequencing (NGS) using the Guardant360-73 gene platform. A total of 87 patients were included in the study. The most frequently mutated genes detected in cfDNA were , and . In 28 treatment naive ATC patients, the concordance rate of detected mutations in , and between cfDNA and matched tissue NGS was 82.1%, 92.9%, and 92.9%, respectively. Patients with a mutation detected on cfDNA had worse overall survival (OS) ( = 0.03). This association was observed across various treatment modalities, including surgery, cytotoxic chemotherapy, radiation, and BRAF inhibitor (BRAFi) therapy. With regard to treatment, BRAFi therapy significantly improved ATC OS ( = 0.003). cfDNA is a valuable tool to evaluate a tumor's molecular profile in ATC patients. We identified high concordance rates between the gene mutations identified via cfDNA analysis and those identified from the NGS of the corresponding tumor tissue sequencing. Identified mutations in cfDNA can potentially provide timely information to guide treatment selection and evaluate the prognosis in patients with ATC.
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http://dx.doi.org/10.1089/thy.2020.0296DOI Listing
April 2021