Publications by authors named "Qiang Chen"

1,591 Publications

  • Page 1 of 1

Activation of Autophagy Relieves Linoleic Acid-Induced Inflammation in Large Yellow Croaker ().

Front Immunol 2021 30;12:649385. Epub 2021 Jun 30.

Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China.

High levels of soybean oil (SO) in fish diets enriched with linoleic acid (LA, 18:2n-6) could induce strong inflammation. However, the molecular mechanism underlying LA-induced inflammation in the liver of large yellow croaker () has not been elucidated. Based on previous research, autophagy has been considered a new pathway to relieve inflammation. Therefore, the present study was performed to investigate the role of autophagy in regulating LA-induced inflammation in the liver of large yellow croaker and The results of the present study showed that activation of autophagy in liver or hepatocytes could significantly reduce the gene expression of proinflammatory factors, such as tumor necrosis factor α (TNFα) and interleukin 1β (IL1β). The results of the present study also showed that inhibition of autophagy could upregulate the gene expression of proinflammatory factors and downregulate the gene expression of anti-inflammatory factors and . Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression and , while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker and for the first time, which may offer considerable benefits to the aquaculture industry and human health.
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http://dx.doi.org/10.3389/fimmu.2021.649385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279755PMC
June 2021

Regulation and drug modulation of a voltage-gated sodium channel: Pivotal role of the S4-S5 linker in activation and slow inactivation.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;

Voltage-gated sodium (Na) channels control excitable cell functions. While structural investigations have revealed conformation details of different functional states, the mechanisms of both activation and slow inactivation remain unclear. Here, we identify residue T140 in the S4-S5 linker of the bacterial voltage-gated sodium channel NaChBac as critical for channel activation and drug effects on inactivation. Mutations at T140 either attenuate activation or render the channel nonfunctional. Propofol, a clinical anesthetic known to inhibit NaChBac by promoting slow inactivation, binds to a pocket between the S4-S5 linker and S6 helix in a conformation-dependent manner. Using F-NMR to quantify site-specific binding by saturation transfer differences (STDs), we found strong STDs in inactivated, but not activated, NaChBac. Molecular dynamics simulations show a highly dynamic pocket in the activated conformation, limiting STD buildup. In contrast, drug binding to this pocket promotes and stabilizes the inactivated states. Our results provide direct experimental evidence showing distinctly different associations between the S4-S5 linker and S6 helix in activated and inactivated states. Specifically, an exchange occurs between interaction partners T140 and N234 of the same subunit in activation, and T140 and N225 of the domain-swapped subunit in slow inactivation. The drug action on slow inactivation of prokaryotic Na channels seems to have a mechanism similar to the recently proposed "door-wedge" action of the isoleucine-phenylalanine-methionine (IFM) motif on the fast inactivation of eukaryotic Na channels. Elucidating this gating mechanism points to a possible direction for conformation-dependent drug development.
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http://dx.doi.org/10.1073/pnas.2102285118DOI Listing
July 2021

Tracking the dissolution behavior of zinc oxide nanoparticles in skimmed milk powder solutions.

Food Chem 2021 Jul 2;365:130520. Epub 2021 Jul 2.

School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, Zhejiang Province, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Zinc oxide nanoparticles (ZnO NPs) are recently recommended as food additives owing to their outstanding nutritive function. Therefore, understanding their comprehensive information and stability in food samples is highly necessitated. However, the characterization of ZnO NPs in the complex food matrices remains a great challenge, limiting an in-depth understanding of their transformation during food storage. In this study, the hollow fiber flow field-flow fractionation was combined with UV-Vis absorption spectroscopy and inductively coupled plasma optical emission spectroscopy to assess the dissolution behaviors of ZnO NPs in skimmed milk powder solutions by monitoring the changes in the residual ZnO NPs and the amount of dissolved Zn(II) ions. The simultaneous characterization of these two Zn species in skimmed milk powder solutions was achieved without the need for tedious sample pretreatments, and the dissolution of ZnO NPs in skimmed milk powder solutions had time- and temperature-dependent behaviors.
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http://dx.doi.org/10.1016/j.foodchem.2021.130520DOI Listing
July 2021

Recruitment of endoplasmic reticulum-targeted and cytosolic mRNAs into membrane-associated stress granules.

RNA 2021 Jul 8. Epub 2021 Jul 8.

Duke University Medical Center;

Stress granules (SGs) are membraneless organelles composed of mRNAs and RNA binding proteins which undergo assembly in response to stress-induced inactivation of translation initiation. In general, SG recruitment is limited to a subpopulation of a given mRNA species and RNA-seq analyses of purified SGs revealed that signal sequence-encoding (i.e. endoplasmic reticulum (ER)-targeted) transcripts are significantly under-represented, consistent with prior reports that ER localization can protect mRNAs from SG recruitment. Using translational profiling, cell fractionation, and single molecule mRNA imaging, we examined SG biogenesis following activation of the unfolded protein response (UPR) by 1,4-dithiothreitol (DTT) and report that gene-specific subsets of cytosolic and ER-targeted mRNAs can be recruited into SGs. Furthermore, we demonstrate that SGs form in close proximity to or directly associated with the ER membrane. ER-associated SG assembly was also observed during arsenite stress, suggesting broad roles for the ER in SG biogenesis. Recruitment of a given mRNA into SGs required stress-induced translational repression, though translational inhibition was not solely predictive of an mRNA's propensity for SG recruitment. SG formation was prevented by the transcriptional inhibitors actinomycin D or triptolide, suggesting a functional link between gene transcriptional state and SG biogenesis. Collectively these data demonstrate that ER-targeted and cytosolic mRNAs can be recruited into ER-associated SGs and this recruitment is sensitive to transcriptional inhibition. We propose that newly transcribed mRNAs exported under conditions of suppressed translation initiation are primary SG substrates, with the ER serving as the central subcellular site of SG formation.
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http://dx.doi.org/10.1261/rna.078858.121DOI Listing
July 2021

An Interpretable Computer-Aided Diagnosis Method for Periodontitis From Panoramic Radiographs.

Front Physiol 2021 22;12:655556. Epub 2021 Jun 22.

Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.

Periodontitis is a prevalent and irreversible chronic inflammatory disease both in developed and developing countries, and affects about 20-50% of the global population. The tool for automatically diagnosing periodontitis is highly demanded to screen at-risk people for periodontitis and its early detection could prevent the onset of tooth loss, especially in local communities and health care settings with limited dental professionals. In the medical field, doctors need to understand and trust the decisions made by computational models and developing interpretable models is crucial for disease diagnosis. Based on these considerations, we propose an interpretable method called Deetal-Perio to predict the severity degree of periodontitis in dental panoramic radiographs. In our method, alveolar bone loss (ABL), the clinical hallmark for periodontitis diagnosis, could be interpreted as the key feature. To calculate ABL, we also propose a method for teeth numbering and segmentation. First, Deetal-Perio segments and indexes the individual tooth via Mask R-CNN combined with a novel calibration method. Next, Deetal-Perio segments the contour of the alveolar bone and calculates a ratio for individual tooth to represent ABL. Finally, Deetal-Perio predicts the severity degree of periodontitis given the ratios of all the teeth. The Macro F1-score and accuracy of the periodontitis prediction task in our method reach 0.894 and 0.896, respectively, on data set, and 0.820 and 0.824, respectively on data set. The entire architecture could not only outperform state-of-the-art methods and show robustness on two data sets in both periodontitis prediction, and teeth numbering and segmentation tasks, but also be interpretable for doctors to understand the reason why Deetal-Perio works so well.
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http://dx.doi.org/10.3389/fphys.2021.655556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258157PMC
June 2021

Discovery of a potent and selective inhibitor of histone lysine demethylase KDM4D.

Eur J Med Chem 2021 Jun 26;223:113662. Epub 2021 Jun 26.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan, 610041, China. Electronic address:

Histone lysine demethylase 4D (KDM4D) plays an important role in the regulation of tumorigenesis, progression and drug resistance and has been considered a potential target for cancer treatment. However, there is still a lack of potent and selective KDM4D inhibitors. In this investigation, we report a new class of KDM4D inhibitors containing the 2-(aryl(pyrrolidine-1-yl)methyl)phenol scaffold, identified through AlphaLisa-based screening, structural optimization, and structure-activity relationship analyses. Among these inhibitors, 24s was the most potent, with an IC value of 0.023 ± 0.004 μM. This compound exhibited more than 1500-fold selectivity towards KDM4D versus KDM4A as well as other JMJD subfamily members, indicating good selectivity for KDM4D. Kinetic analysis indicated that 24s did not occupy the 2-oxoglutarate binding pocket. In an in vitro assay, 24s significantly suppressed the proliferation and migration of colorectal cancer (CRC) cells. Overall, this study has identified a good tool compound to explore the biological function of KDM4D and a good lead compound for drug discovery targeting KDM4D.
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http://dx.doi.org/10.1016/j.ejmech.2021.113662DOI Listing
June 2021

A Highly Luminescent Nitrogen-Doped Nanographene as an Acid- and Metal-Sensitive Fluorophore for Optical Imaging.

J Am Chem Soc 2021 Jul 5;143(27):10403-10412. Epub 2021 Jul 5.

Max Planck Institute for Polymer Research, Mainz 55128, Germany.

Dibenzo[,]ovalene (DBOV) has excellent photophysical properties, including strong fluorescence and high ambient stability. Moreover, the optical blinking properties of DBOV have enabled optical super-resolution single-molecule localization microscopy with an imaging resolution beyond the diffraction limit. Various organic and inorganic fluorescent probes have been developed for super-resolution imaging, but those sensitive to pH and/or metal ions have remained elusive. Here, we report a diaza-derivative of DBOV (N-DBOV), synthesized in eight steps with a total yield of 15%. Nitrogen (N)-bearing zigzag edges were formed through oxidative cyclization of amino groups in the last step. UV-vis and fluorescence spectroscopy of N-DBOV revealed its promising optical properties comparable to those of the parent DBOV, while cyclic voltammetry and density functional theory calculations highlighted its lower orbital energy levels and potential -type semiconductor character. Notably, in contrast to that of the parent DBOV, the strong luminescence of N-DBOV is dependent on pH and the presence of heavy metal ions, indicating the potential of N-DBOV in sensing applications. N-DBOV also exhibited pH-responsive blinking, which enables pH-sensitive super-resolution imaging. Therefore, N-DBOV appears to be a highly promising candidate for fluorescence sensing in biology and environmental analytics.
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http://dx.doi.org/10.1021/jacs.1c04880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283754PMC
July 2021

Beneficial effects of chlorogenic acid treatment on neuroinflammation after deep hypothermic circulatory arrest may be mediated through CYLD/NF-κB signaling.

Brain Res 2021 Jun 30;1767:147572. Epub 2021 Jun 30.

Department of Cardiac Surgery, Fujian Branch of Shanghai Children's Medical Cente, Fuzhou, China; Fujian Children's Hospital, Fuzhou, China; Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fuzhou, China.

Deep hypothermic circulatory arrest (DHCA) during heart surgery may induce neuroinflammation leading to neurocognitive dysfunction. Chlorogenic acid (CA) is a common phytochemical, which can attenuate neuroinflammation. Nevertheless, the underlying mechanism involved in the anti-inflammatory effect of CA after DHCA is unknown. The present study therefore characterized the anti-inflammatory functions of CA after DHCA using in vivo and in vitro DHCA models. The activation of microglia, inflammatory cytokine levels, and the NF-κB pathway were measured. The results showed that CA treatment ameliorated neurocognitive function and reduced the inflammatory cytokine levels in the brain and circulation. Furthermore, the microglial and NF-κB activations were suppressed after DHCA. CA exerted the same anti-inflammatory effect in hypothermia OGD microglial cells as the in vivo study. Additional studies indicated that the regulation of ubiquitin ligase activity of TRAF6 and RIP1 by CYLD was related to the mechanism involving inhibition of CA in the NF-κB pathway. Together, the results showed that CA may attenuate neuroinflammation after DHCA by modulating the signaling of CYLD/NF-κB.
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http://dx.doi.org/10.1016/j.brainres.2021.147572DOI Listing
June 2021

A facile and rapid route to self-digitization of samples into a high density microwell array for digital bioassays.

Talanta 2021 Oct 9;233:122589. Epub 2021 Jun 9.

Key Laboratory of Optoelectronic Technology and Systems, Ministry of Education, Defense Key Disciplines Lab of Novel Micro-Nano Devices and System Technology, Chongqing University, Chongqing, 400044, China. Electronic address:

Digital bioassays are powerful methods to detect rare analytes from complex mixtures and study the temporal processes of individual entities within biological systems. In digital bioassays, a crucial first step is the discretization of samples into a large number of identical independent partitions. Here, we developed a rapid and facile sample partitioning method for versatile digital bioassays. This method is based on a detachable self-digitization (DSD) chip which couples a reversible assembly configuration and a predegassing-based self-pumping mechanism to achieve an easy, fast, and large-scale sample partitioning. The DSD chip consists of a channel layer used for loading the sample and a microwell layer used for holding the sample partitions. Benefitting from its detachability, the chip avoids a lengthy oil flushing process used to remove the excess sample in loading channels and can compartmentalize a sample into more than 100,000 wells of picoliter volume with densities up to 14,000 wells/cm in less than 30 s. We also demonstrated the utility of the proposed method by applying it to digital PCR and digital microbial assays.
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http://dx.doi.org/10.1016/j.talanta.2021.122589DOI Listing
October 2021

Joint Optimization of CycleGAN and CNN Classifier for Detection and Localization of Retinal Pathologies on Color Fundus Photographs.

IEEE J Biomed Health Inform 2021 Jul 1;PP. Epub 2021 Jul 1.

Retinal related diseases are the leading cause of vision loss, and severe retinal lesion causes irreversible damage to vision. Therefore, the automatic methods for retinal diseases detection based on medical images is essential for timely treatment. Considering that manual diagnosis and analysis of medical images require a large number of qualified experts, deep learning can effectively diagnosis and locate critical biomarkers. In this paper, we present a novel model by jointly optimize the cycle genera-tive adversarial network (CycleGAN) and the convolutional neural network (CNN) to detect retinal diseases and localize lesion areas with limited training data. The CycleGAN with cycle consistency can generate more realistic and reliable images. The discriminator and the generator achieve a local optimal solution in an adversarial manner, and the generator and the classifier are in a cooperative manner to distinguish the domain of input images. A novel res-guided sampling block is proposed by combining learn-able residual features and pixel-adaptive convolutions. A res-guided U-Net is constructed as the generator by substituting the traditional convolution with the res-guided sampling blocks. Our model achieve superior classification and localization performance on LAG, Ichallenge-PM and Ichallenge-AMD datasets. With clear localization for lesion areas, the competitive results reveal great potentials of the joint optimization network. The source code is available at https://github.com/jizexuan/JointOptmization.
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http://dx.doi.org/10.1109/JBHI.2021.3092339DOI Listing
July 2021

Transition-metal-like bonding behaviors of a boron atom in a boron-cluster boronyl complex [(η-B)-B-BO].

Chem Sci 2021 May 3;12(23):8157-8164. Epub 2021 May 3.

Department of Chemistry, Brown University Providence Rhode Island 02912 USA

Boron displays many unusual structural and bonding properties due to its electron deficiency. Here we show that a boron atom in a boron monoxide cluster (BO) exhibits transition-metal-like properties. Temperature-dependent photoelectron spectroscopy provided evidence of the existence of two isomers for BO: the main isomer has an adiabatic detachment energy (ADE) of 4.19 eV and a higher energy isomer with an ADE of 3.59 eV. The global minimum of BO is found surprisingly to be an umbrella-like structure ( , A) and its simulated spectrum agrees well with that of the main isomer observed. A low-lying isomer ( , A') consisting of a BO unit bonded to a disk-like B cluster agrees well with the 3.59 eV ADE species. The unexpected umbrella-like global minimum of BO can be viewed as a central boron atom coordinated by a η-B ligand on one side and a BO ligand on the other side, [(η-B)-B-BO]. The central B atom is found to share its valence electrons with the B unit to fulfill double aromaticity, similar to that in half-sandwich [(η-B)-Zn-CO] or [(η-B)-Fe(CO)] transition-metal complexes. The ability of boron to form a half-sandwich complex with an aromatic ligand, a prototypical property of transition metals, brings out new metallomimetic properties of boron.
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http://dx.doi.org/10.1039/d1sc00534kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208299PMC
May 2021

Comparison of the sensitivity of mammography, ultrasound, magnetic resonance imaging and combinations of these imaging modalities for the detection of small (≤2 cm) breast cancer.

Medicine (Baltimore) 2021 Jul;100(26):e26531

Department of Breast Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine.

Abstract: The aim of this study was to compare the sensitivity of mammography (MG), ultrasound (US), magnetic resonance imaging (MRI), and combinations of these imaging modalities for the detection of small (≤2 cm) breast cancer and to evaluate the benefit of preoperative breast MRI after performing conventional imaging techniques for small breast cancer.This was an observational retrospective review of 475 patients with pathologically confirmed breast cancer. We reviewed the medical records; assessed the preoperative reports of MG, US, and MRI; and categorized them as benign features (BI-RADS 1-3) or malignant features (BI-RADS 4 or 5). The criterion standard for detection was the pathologic assessment of the surgical specimen. The sensitivities of the different techniques were compared using the McNemar test.Among the 475 women, the sensitivity of MG was significantly greater in patients with low breast density than in those with high breast density (84.5% vs 65.8%, P < .001). US had higher sensitivity than MG (P < .001), and the combination of MG + US showed better sensitivity than MG or US alone (P < .001). Further addition of MRI to the combination of MG and US statistically contributed to the sensitivity yield (from 93.3% to 98.2%; P < .001) but did not significantly increase the mastectomy rate (from 48.2% to 49.3%; P = .177).MG has limited diagnostic sensitivity in patients with small breast cancer, especially in those with dense breast tissue. US is better than MG at detecting small breast cancer, regardless of breast density. The addition of MRI to MG and US could increase sensitivity without increasing the mastectomy rate. This study suggests performing MRI routinely on the basis of MG and US for small (≤2 cm) breast cancer.
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http://dx.doi.org/10.1097/MD.0000000000026531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257894PMC
July 2021

miR-194-Loaded Gelatin Nanospheres Target MEF2C to Suppress Muscle Atrophy in a Mechanical Unloading Model.

Mol Pharm 2021 Jun 30. Epub 2021 Jun 30.

Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, P. R. China.

Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable , limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00121DOI Listing
June 2021

Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis.

Hum Genomics 2021 Jun 29;15(1):39. Epub 2021 Jun 29.

Department of Gastrointestinal Surgery, the First Affiliated Hospital of Jinan University, No.613 Huangpu Road West, Guangzhou, 510630, China.

Background: Liver cancer is one of the most common cancers and causes of cancer death worldwide. The objective was to elucidate novel hub genes which were benefit for diagnosis, prognosis, and targeted therapy in liver cancer via integrated analysis.

Methods: GSE84402, GSE101685, and GSE112791 were filtered from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified by using the GEO2R. The GO and KEGG pathway of DEGs were analyzed in the DAVID. PPI and TF network of the DEGs were constructed by using the STRING, TRANSFAC, and Harmonizome. The relationship between hub genes and prognoses in liver cancer was analyzed in UALCAN based on The Cancer Genome Atlas (TCGA). The diagnostic value of hub genes was evaluated by ROC. The relationship between hub genes and tumor-infiltrate lymphocytes was analyzed in TIMER. The protein levels of hub genes were verified in HPA. The interaction between the hub genes and the drug were identified in DGIdb.

Results: In total, 108 upregulated and 60 downregulated DEGs were enriched in 148 GO terms and 20 KEGG pathways. The mRNA levels and protein levels of CDK1, HMMR, PTTG1, and TTK were higher in liver cancer tissues compared to normal tissues, which showed excellent diagnostic and prognostic value. CDK1, HMMR, PTTG1, and TTK were positively correlated with tumor-infiltrate lymphocytes, which might involve tumor immune response. The CDK1, HMMR, and TTK had close interaction with anticancer agents.

Conclusions: The CDK1, HMMR, PTTG1, and TTK were hub genes in liver cancer; hence, they might be potential biomarkers for diagnosis, prognosis, and targeted therapy of liver cancer.
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http://dx.doi.org/10.1186/s40246-021-00341-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243535PMC
June 2021

Tough, Transparent, and Anti-Freezing Nanocomposite Organohydrogels with Photochromic Properties.

ACS Appl Mater Interfaces 2021 Jul 27;13(26):31180-31192. Epub 2021 Jun 27.

Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 352001, China.

Poor mechanical properties and freezing at low temperatures of traditional photochromic hydrogels limit their applications. Here, a novel type of photochromic nanocomposite organohydrogels (NC OGHs) by adding tungsten oxide nanoparticles was prepared by a simple one-pot method. The photochromic NC OGHs demonstrated excellent integrated properties, including high transparency, high mechanical properties, low-temperature resistance, anti-dehydration, rewrite capability, and UV blocking ability. In addition, the degree of coloration of NC OGHs could be precisely controlled by UV irradiation, and the bleaching process could be controlled by the temperature and atmosphere. Besides flexible optical information storage devices and optical filters, these photochromic NC OGHs were also used for smart windows in both room temperature and cold environments. The work provides a new insight into photochromic organohydrogels.
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http://dx.doi.org/10.1021/acsami.1c07563DOI Listing
July 2021

MicroRNAs as Important Regulators Mediate the Multiple Differentiation of Mesenchymal Stromal Cells.

Front Cell Dev Biol 2021 7;9:619842. Epub 2021 Jun 7.

Stem Cells and Regenerative Medicine Research Center, Sichuan Stem Cell Bank/Sichuan Neo-Life Stem Cell Biotech Inc., Chengdu, China.

MicroRNAs (miRNAs) are endogenous short non-encoding RNAs which play a critical role on the output of the proteins, and influence multiple biological characteristics of the cells and physiological processes in the body. Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells and characterized by self-renewal and multidifferentiation and have been widely used for disease treatment and regenerative medicine. Meanwhile, MSCs play a critical role in maintaining homeostasis in the body, and dysfunction of MSC differentiation leads to many diseases. The differentiation of MSCs is a complex physiological process and is the result of programmed expression of a series of genes. It has been extensively proven that the differentiation process or programmed gene expression is also regulated accurately by miRNAs. The differentiation of MSCs regulated by miRNAs is also a complex, interdependent, and dynamic process, and a full understanding of the role of miRNAs will provide clues on the appropriate upregulation or downregulation of corresponding miRNAs to mediate the differentiation efficiency. This review summarizes the roles and associated signaling pathways of miRNAs in adipogenesis, chondrogenesis, and osteogenesis of MSCs, which may provide new hints on MSCs or miRNAs as therapeutic strategies for regenerative medicine and biotherapy for related diseases.
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http://dx.doi.org/10.3389/fcell.2021.619842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215576PMC
June 2021

Perforated extensible 3-D hyperbolic secant lens antenna for directive antenna applications using additive manufacturing.

Opt Express 2021 Jun;29(12):18932-18949

In this paper, a novel three-dimensional (3-D) generalized hyperbolic secant (H-S) lens is first introduced using perforated dielectric material. The attractiveness of this new lens is its unique intrinsic flat shape characteristic and extensibility for different configuration scenarios, which provide a potential alternative design for a planar Luneburg and half Maxwell fish-eye lens based on a complex conformal mapping method. A high gain and wideband printed antipodal fermi antenna as a feeding source is employed in the proposed lens antenna prototype. The high radiation performance with low side lobe level of the fabricated lens prototype is validated from 8.2GHz to 12.5GHz, demonstrating 23.8 dBi realized gain at 10 GHz with 3-dB beamwidth of 9° and 2-dB fractional gain bandwidth of 41.6%. Besides, the total radiation efficiency is above ∼40% across all tested frequencies, which suggests the proposed H-S lens itself has a broadband response. The simplicity and low-cost fabrication using additive manufacturing of its lens design indicates great potential in broadband high directive antenna applications.
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http://dx.doi.org/10.1364/OE.426824DOI Listing
June 2021

Risk factors for anastomotic complications after one-stage anastomosis for oesophageal atresia.

J Cardiothorac Surg 2021 Jun 19;16(1):176. Epub 2021 Jun 19.

Department of Cardiothoracic Surgery, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Background: Oesophageal atresia is a congenital malformation of the oesophagus and a serious malformation of the digestive system, postoperative complications include acute respiratory failure, pneumonia, anastomotic fistula, anastomotic stenosis, tracheal stenosis, gastroesophageal reflux and eosinophilic oesophagitis, anastomotic fistula is one of the important causes of postoperative death. The objective of this study is to identify the risk factors for anastomotic complications after one-stage anastomosis for oesophageal atresia.

Methods: A retrospective analysis was performed on the clinical data of 107 children with congenital oesophageal atresia who underwent one-stage anastomosis in our hospital from January 2013 to December 2018. Single-factor and multivariate logistic regression analyses were performed to determine the risk factors for anastomotic fistula and anastomotic stenosis.

Results: A total of 107 children with oesophageal atresia underwent one-stage anastomosis, and the incidence of anastomotic fistula was 26.2%. The probability of anastomotic stenosis in the long term was 52.3%, and the incidence of refractory stenosis (dilation ≥5 times) was 13.1%. Analysis of the clinical count data in the anastomotic fistula group and non-anastomotic fistula group showed that preoperative albumin (F = 4.199, P = 0.043), low birth weight (F = 7.668, P = 0.007) and long gap defects (F = 6.107, P = 0.015) were risk factors for postoperative anastomotic fistula. Further multivariate logistic regression analysis showed that low birth weight (Wald2 = 4.499, P = 0.034, OR = 2.775) and long gap defects (Wald2 = 6.769, P = 0.009, OR = 4.939) were independent risk factors for postoperative anastomotic fistula. Premature delivery (F = 5.338, P = 0.023), anastomotic fistula (F = 11.381, P = 0.001), endoscopic surgery (F = 6.343, P = 0.013), preoperative neutrophil count (F = 8.602, P = 0.004), preoperative low albumin (F = 8.410, P = 0.005), and a preoperative prognostic nutritional index < 54 (F = 5.54, P = 0.02) were risk factors for refractory anastomotic stenosis in children. Further multivariate logistic regression analysis showed that postoperative anastomotic fistula (Wald2 = 11.417, P = 0.001, OR = 8.798), endoscopic surgery (Wald2 = 9.633, P = 0.002, OR = 4.808), and a prognostic nutritional index < 54 (Wald2 = 4.540, P = 0.002, OR = 2.3798) were independent risk factors for refractory anastomotic stenosis.

Conclusion: Low birth weight and long gap defects are important predictors of postoperative anastomotic fistula, and the possibility of refractory anastomotic stenosis should be considered. The long-term risk of anastomotic stenosis was increased in children undergoing endoscopic surgery and in those with a preoperative prognostic nutritional index < 54.
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http://dx.doi.org/10.1186/s13019-021-01557-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214267PMC
June 2021

Quality of life analysis of children with patent ductus arteriosus after closure treatment: A single-centre study.

J Paediatr Child Health 2021 Jun 18. Epub 2021 Jun 18.

Department of Cardiac Surgery, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Aim: To explore the changes in quality of life (QoL) in children who underwent patent ductus arteriosus (PDA) closure and the difference in the QoL between the post-operative patients and healthy children.

Methods: The Pediatric Quality of Life Inventory 4.0 scale was used to assess the QoL of 48 children before and after receiving PDA closure and 50 healthy children who underwent physical examination in our hospital. Relevant clinical data were collected and analysed.

Results: In this study, a total of 45 patients completed the follow-up, and all the children in the control group completed the follow-up. The results showed that the patients' QoL had been improved after PDA closure, and the scores of emotional functioning and social functioning had been significantly improved compared with those in the pre-operative status. In comparing the QoL between the patient group and the control group, the results before treatment were worse than those of the control group. After treatment, the gap between the score of QoL of the patients and the healthy control group was reduced to some extent. However, in terms of social functioning, the patients' feedback was not as positive as healthy children.

Conclusion: For children with PDA, closure treatment can significantly improve their clinical symptoms and QoL. However, there is still a gap compared with healthy children, so health education and further intervention after treatment are still necessary.
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http://dx.doi.org/10.1111/jpc.15617DOI Listing
June 2021

Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect.

Sci Adv 2021 May 19;7(21). Epub 2021 May 19.

Laboratory of Natural and Targeted Small Molecule Drugs, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.

Microtubules, composed of αβ-tubulin heterodimers, have remained popular anticancer targets for decades. Six known binding sites on tubulin dimers have been identified thus far, with five sites on β-tubulin and only one site on α-tubulin, hinting that compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our x-ray crystallography study reveals that, in addition to binding to the vinblastine site, cevipabulin also binds to a new site on α-tubulin. We find that cevipabulin at this site pushes the αT5 loop outward, making the nonexchangeable GTP exchangeable, which reduces the stability of tubulin, leading to its destabilization and degradation. Our results confirm the existence of a new agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of antimicrotubule drugs targeting this novel site.
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http://dx.doi.org/10.1126/sciadv.abg4168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133757PMC
May 2021

The Abundance of the Gene Became Higher and the -Containing Diazotrophic Bacterial Communities Changed During Primary Succession in the Hailuogou Glacier Chronosequence, China.

Front Microbiol 2021 31;12:672656. Epub 2021 May 31.

Department of Microbiology, College of Resource Sciences and Technology, Sichuan Agricultural University, Chengdu, China.

Primary successional ecosystems and the related soil development are often N limited. To date, N-fixing communities during primary succession in alpine ecosystems have remained underexplored. In this study, we applied quantitative PCR (qPCR) quantitation and targeted amplicon sequencing of in the Hailuogou Glacier foreland to investigate the succession of N-fixing communities in five sites along a 62-year chronosequence. The abundance of the gene increased along the primary succession in the chronosequence and correlated positively with pH, acetylene reduction activity, and water, organic C, total and available N, and available P contents. The increases in alpha diversity along the chronosequence may have been partly due to less competition for resources. In contrast to the clear separation based on soil properties, the changes in the diazotrophic community composition lacked a clear trend and were associated mostly with changes in soil available K and organic C contents. The changes among differentially abundant genera were possibly due to the changes in plant coverage and species composition. The whole primary succession of the diazotrophic communities was consistent with stochastic community assembly, which is indicative of low competitive pressure.
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http://dx.doi.org/10.3389/fmicb.2021.672656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200853PMC
May 2021

A generative-discriminative framework that integrates imaging, genetic, and diagnosis into coupled low dimensional space.

Neuroimage 2021 Jun 10;238:118200. Epub 2021 Jun 10.

Department of Electrical and Computer Engineering, Johns Hopkins University, USA.

We propose a novel optimization framework that integrates imaging and genetics data for simultaneous biomarker identification and disease classification. The generative component of our model uses a dictionary learning framework to project the imaging and genetic data into a shared low dimensional space. We have coupled both the data modalities by tying the linear projection coefficients to the same latent space. The discriminative component of our model uses logistic regression on the projection vectors for disease diagnosis. This prediction task implicitly guides our framework to find interpretable biomarkers that are substantially different between a healthy and disease population. We exploit the interconnectedness of different brain regions by incorporating a graph regularization penalty into the joint objective function. We also use a group sparsity penalty to find a representative set of genetic basis vectors that span a low dimensional space where subjects are easily separable between patients and controls. We have evaluated our model on a population study of schizophrenia that includes two task fMRI paradigms and single nucleotide polymorphism (SNP) data. Using ten-fold cross validation, we compare our generative-discriminative framework with canonical correlation analysis (CCA) of imaging and genetics data, parallel independent component analysis (pICA) of imaging and genetics data, random forest (RF) classification, and a linear support vector machine (SVM). We also quantify the reproducibility of the imaging and genetics biomarkers via subsampling. Our framework achieves higher class prediction accuracy and identifies robust biomarkers. Moreover, the implicated brain regions and genetic variants underlie the well documented deficits in schizophrenia.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118200DOI Listing
June 2021

Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea).

Free Radic Biol Med 2021 Jun 8;172:213-225. Epub 2021 Jun 8.

Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China. Electronic address:

Lipid overload-induced hepatic steatosis is a major public health problem worldwide. However, the potential molecular mechanism is not completely understood. Herein, we found that high-fat diet (HFD) or oleic acid (OA) treatment induced oxidative stress which prevented the entry of hepatocyte nuclear factor 4 alpha (HNF4α) into the nucleus by activating protein kinase C delta (PKCδ) in vivo and in vitro in large yellow croaker (Larimichthys crocea). This reduced the level of microsomal triglyceride transfer protein (MTP) transcription, resulting in the impaired secretion of very-low-density lipoprotein (VLDL) and the abnormal accumulation of triglyceride (TG) in hepatocytes. Meanwhile, the detrimental effects induced by lipid overload could be partly alleviated by pretreating hepatocytes with Go6983 (PKCδ inhibitor) or N-acetylcysteine (NAC, reactive oxygen species (ROS) scavenger). In conclusion, for the first time, we revealed that lipid overload impaired hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in fish. This study may provide critical insights into potential intervention strategies against lipid overload-induced hepatic steatosis of fish and human beings.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.06.001DOI Listing
June 2021

Realizing High Comprehensive Energy Storage and Ultrahigh Hardness in Lead-Free Ceramics.

ACS Appl Mater Interfaces 2021 Jun 9;13(24):28472-28483. Epub 2021 Jun 9.

College of Materials Science and Engineering, Sichuan University, 610064 Chengdu, China.

Due to the presence of pores and low density, a high recoverable energy density () value is usually obtained at the cost of energy storage efficiency (η) in lead-free potassium sodium niobate [(K, Na)NbO, KNN] based ceramics, which also affects the hardness of ceramics, finally limiting the further development of practical applications. A high (∼3.60 J/cm ) and a high η (∼74.2%) are obtained in 0.975KNaNbO-0.025LaBiO (0.975KNN-0.025LB) ceramics simultaneously under a high dielectric breakdown strength (DBS) of 340 kV/cm, together with a fast discharge rate ( ∼ 46 ns) and high power density ( ∼ 49.4 MW/cm). Further analysis of the intrinsic electronic structure is carried out via the first-principles calculation based on the density functional theory (DFT). An ultrahigh hardness () of 6.63 GPa can be accordingly obtained. This work combines excellent energy storage properties and ultrahigh hardness, which provides significant guidelines for applications in pulsed-power systems.
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http://dx.doi.org/10.1021/acsami.1c05153DOI Listing
June 2021

Degradation of Rhodamine B by activation of peroxymonosulfate using CoO-rice husk ash composites.

Sci Total Environ 2021 Aug 21;784:147258. Epub 2021 Apr 21.

State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering, Ningxia University, Yinchuan 750021, PR China.

Rice husk is an agricultural residue in rice producing process with a worldwide annual output of more than 190 million tons. To investigate the possibility of disposal method, rice husk ash (RHA) derived from the rice husk residue was treated as a support material thus synthesizing a Co-based heterogeneous catalyst for peroxymonosulfate activation. The interconnected architecture of the CoO nanoflakes grown vertically on the surface of RHA provided high surface area and structure stability. The as-synthesized heterogeneous catalyst exhibited enhanced ability for peroxymonosulfate activation towards Rhodamine B degradation. Degradation efficiency of Rhodamine B achieved 96.3% within 60 min by using CoO-0.5 RHA catalyst, while only 44.1% Rhodamine B was degraded for bare CoO. The effects of pH, catalyst dosage, peroxymonosulfate dosage, Rhodamine B concentration, inorganic ions and temperature were evaluated. Radical scavenging experiments revealed that O and O other than SO and •OH were the main active species. Furthermore, the addition of rice husk ash proved to be capable of reducing the dissolution of Co and extended the lifetime of the catalyst. This study elucidated a new opportunity for both utilizing agricultural residue and reducing contaminants in wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147258DOI Listing
August 2021

The effect of mind-body exercise on the cervical spine mobility of people with neck discomfort: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e26112

Department of Psychiatry, Guangxi Zhuang Autonomous Region Brain Hospital, Liuzhou, Guangxi, China.

Background: With the development of the economy and society, the pace of in-person work has gradually accelerated, resulting in longer and more intense work hours. Long-term and high-intensity work can lead to considerable discomfort in people's cervical spines.

Objectives: This study aims to explore the effect of mind-body exercise intervention on the cervical spine mobility of people with neck discomfort through meta-analysis.

Methods: This study's researchers will search a total of 5 research databases for data retrieval: China National Knowledge Infrastructure (from 1979), Web of Science (from 1950), PubMed (from 1965), Cochrane (from 1991), and EBSCO (from 1949) (Date of retrieval: March 10, 2021). Two authors will independently search literature records, scan titles, abstracts, and full texts, collect data, and assess materials for risk of bias. Stata14.0 software will be used for the data analysis.

Results: The current study is a systematic review and meta-analysis program with no results. Data analysis will be completed after the program has been completed.

Discussion: There is potential evidence that exercise can have a positive effect on the cervical spine mobility of people with cervical spine discomfort. In addition, direct evidence of the benefits of mind-body exercise intervention may be more important.

Inplasy Registration Number: INPLASY202140126.
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http://dx.doi.org/10.1097/MD.0000000000026112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183790PMC
June 2021

Effect of WeChat follow-up education on breastfeeding efficiency of infants after congenital cardiac surgery and parents' satisfaction: A short-term follow-up study.

J Paediatr Child Health 2021 Jun 4. Epub 2021 Jun 4.

Department of Cardiac Surgery, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Aim: This study aimed to investigate the impact of WeChat follow-up education on infants' breastfeeding efficiency after congenital cardiac surgery and parents' satisfaction.

Methods: A prospective study was conducted in a provincial hospital in China. Sixty participants were divided into two groups: 30 participants in the study group received WeChat follow-up health education, and 30 participants in the control group received postoperative routine nursing education for infants after congenital cardiac surgery. The infants' breastfeeding efficiency, parents' satisfaction and relevant clinical data were recorded and analysed.

Results: After the WeChat follow-up intervention, the breastfeeding efficacy score, the parents' satisfaction score and the exclusive breastfeeding rate in the study group were significantly higher than those in the control group (P < 0.05). There was no significant difference in the incidence of feeding intolerance, abdominal distension, dyspeptic diarrhoea, weight gain or recurrent vomiting between the two groups during the 3-month follow-up period.

Conclusion: WeChat education can improve infants' breastfeeding efficiency after congenital cardiac surgery and can improve parents' satisfaction and exclusive breastfeeding rate during the short-term follow-up period.
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http://dx.doi.org/10.1111/jpc.15605DOI Listing
June 2021

RetFluidNet: Retinal Fluid Segmentation for SD-OCT Images Using Convolutional Neural Network.

J Digit Imaging 2021 Jun 2. Epub 2021 Jun 2.

School of Computer Science and Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei, Nanjing, 210094, China.

Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness and is characterized by fluid-related accumulations such as intra-retinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED). Spectral-domain optical coherence tomography (SD-OCT) is the primary modality used to diagnose AMD, yet it does not have algorithms that directly detect and quantify the fluid. This work presents an improved convolutional neural network (CNN)-based architecture called RetFluidNet to segment three types of fluid abnormalities from SD-OCT images. The model assimilates different skip-connect operations and atrous spatial pyramid pooling (ASPP) to integrate multi-scale contextual information; thus, achieving the best performance. This work also investigates between consequential and comparatively inconsequential hyperparameters and skip-connect techniques for fluid segmentation from the SD-OCT image to indicate the starting choice for future related researches. RetFluidNet was trained and tested on SD-OCT images from 124 patients and achieved an accuracy of 80.05%, 92.74%, and 95.53% for IRF, PED, and SRF, respectively. RetFluidNet showed significant improvement over competitive works to be clinically applicable in reasonable accuracy and time efficiency. RetFluidNet is a fully automated method that can support early detection and follow-up of AMD.
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http://dx.doi.org/10.1007/s10278-021-00459-wDOI Listing
June 2021

miR-506-loaded gelatin nanospheres target PENK and inactivate the ERK/Fos signaling pathway to suppress triple-negative breast cancer aggressiveness.

Mol Carcinog 2021 Aug 1;60(8):538-555. Epub 2021 Jun 1.

Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.
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http://dx.doi.org/10.1002/mc.23310DOI Listing
August 2021

Performance of remote health education via WeChat to improve the pre-operative nutritional status of infants with non-restrictive ventricular septal defects: A prospective randomised controlled study.

J Paediatr Child Health 2021 May 31. Epub 2021 May 31.

Department of Cardiac Surgery, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Aim: This study aimed to explore the effect of performing remote health education via WeChat to improve the pre-operative nutritional status of non-restrictive ventricular septal defects (VSD).

Methods: A prospective randomised controlled study was conducted in a provincial maternity and child hospital in China. Participants were randomised regarding education to the intervention group (WeChat) and the control group (leaflets). The nutritional status and complications of the patients were compared after intervening for 1 month.

Results: Nutrient status comparison at 1 month after intervention showed that the body weight, head circumference, haemoglobin, albumin and pre-albumin of the WeChat group were significantly higher than those of the leaflet group (P < 0.05). The STRONGkids score of the WeChat group was significantly lower than that of the leaflet group (P < 0.05). The incidence of feeding intolerance and respiratory tract infection in the WeChat group was significantly lower than that found in the leaflet group (P < 0.05). There was no significant difference in the incidence of liver insufficiency and jaundice between the two groups (P > 0.05).

Conclusion: Providing pre-operative feeding and care guidance for parents of infants with non-restrictive VSD, via remote health education through WeChat, can effectively improve nutritional status and reduce the risk of malnutrition and feeding complications.
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http://dx.doi.org/10.1111/jpc.15590DOI Listing
May 2021