Publications by authors named "Wei Pan"

1,032 Publications

  • Page 1 of 1

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells.

Biomed Res Int 2021 1;2021:9941253. Epub 2021 Jul 1.

Department of Orthopaedic Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223002, China.

Objective: To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells.

Methods: Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 M, 10 M, and 20 M). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13.

Results: PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells.

Conclusion: The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.
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http://dx.doi.org/10.1155/2021/9941253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270693PMC
July 2021

Clinical potentials of ginseng polysaccharide for treating gestational diabetes mellitus.

World J Clin Cases 2021 Jul;9(19):4959-4979

First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China.

Gestational diabetes mellitus (GDM) is the most common glucose metabolism complication or cause of potential impaired glucose tolerance that can occur either before or during pregnancy and lactation. The prevalence of GDM and its related complications in young women is increasing, and this condition may cause serious outcomes and health hazards to the foetus. However, traditional oral hypoglycaemic drugs have potential safety hazards; therefore, it is urgent to develop new, safe, effective, and easily administered agents and remedies. Ginseng polysaccharide (GPS), which is isolated from (P.) C. A. Meyer, exhibits notably promising biological activities and effects; specifically, it has been shown to lower blood glucose with mild, safe, and nontoxic characteristics, and it can also improve human bodily functions. Hence, we hypothesise that GPS might be used as an additional therapy and candidate agent for treating GDM. This review innovatively summarizes the available reports and evidence from basic studies to analyze the potential for and feasibility of using GPS as a new therapeutic agent for treating GDM. Additionally, for the first time, this review provides a rationale for the use of GPS. Our summarized results show that GPS may be developed as a novel antidiabetic drug and a remedy for use in preventing and treating GDM, with great application prospects.
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http://dx.doi.org/10.12998/wjcc.v9.i19.4959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283579PMC
July 2021

Deubiquitinating enzyme USP30 negatively regulates mitophagy and accelerates myocardial cell senescence through antagonism of Parkin.

Cell Death Discov 2021 Jul 21;7(1):187. Epub 2021 Jul 21.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, 563000, Zunyi, P. R. China.

Cell senescence is associated with age-related pathological changes. Increasing evidence has revealed that mitophagy can selectively remove dysfunctional mitochondria. Overexpression of ubiquitin-specific protease 30 (USP30) has been documented to influence mitophagy and deubiquitination of mitochondrial Parkin substrates. This study was conducted to evaluate the roles of USP30 and Parkin in myocardial cell senescence and mitophagy. Initially, myocardial cells were isolated from neonatal SD rats and subjected to D-gal treatment to induce cell senescence, after which the effects of D-gal on mitochondria damage, ROS production, cell senescence, and mitophagy were assessed. The myocardial cells were infected with lentiviruses bearing overexpression plasmids or shRNA targeting Parkin or USP30 to elucidate the effects of Parkin and USP30 on D-gal-induced mitophagy damage and cell senescence. Finally, aging was induced in rats by subcutaneous injection of D-gal to determine the role of Parkin and USP30 on cell senescence in vivo. D-gal was found to trigger mitochondria damage, ROS production, and cell senescence in myocardial cells. The overexpression of Parkin or silencing of USP30 reduced D-gal-induced mitochondrial damage and relieved D-gal-induced myocardial cell senescence. Moreover, the in vivo experiments validated that either elevation of Parkin or silencing USP30 could alleviate D-gal-induced myocardial cell senescence in rats. Silencing USP30 alleviates D-gal-induced mitochondrial damage and consequently suppresses myocardial cell senescence by activating Parkin. Our study highlights the potential of USP30 as a novel target against myocardial cell senescence.
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http://dx.doi.org/10.1038/s41420-021-00546-5DOI Listing
July 2021

Duplex-Specific Nuclease-Assisted CRISPR-Cas12a Strategy for MicroRNA Detection Using a Personal Glucose Meter.

Anal Chem 2021 Jul 19. Epub 2021 Jul 19.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

A CRISPR-Cas system holds great promise as a next-generation biosensing technology for molecular diagnostics. Nevertheless, the current CRISPR-Cas12a-based detection strategies always need bulky instruments or auxiliary devices to obtain a quantitative signal output, which restrains its point-of-care testing application. Herein, we proposed a duplex-specific nuclease-assisted CRISPR-Cas12a strategy to detect microRNA (miRNA) with a personal glucose meter. The target miRNA was first converted into an amplified initiator DNA via duplex-specific nuclease. Afterward, the initiator DNA activated the collateral cleavage activity of CRISPR-Cas12a to cleave the single-strand DNA (ssDNA) linker on sucrase-ssDNA-modified magnetic beads, which led to the release of sucrase. The released sucrase was collected and then utilized to catalyze sucrose to glucose, which could be quantitatively detected by a personal glucose meter. The change in the glucose signal directly reflected the concentration of miRNA, which avoided expensive equipment for signal quantification. Two different miRNAs (miRNA21 and miRNA205) could be detected by simply changing the sequence of the template strand (H strand). The developed strategy showed high sensitivity with a limit of detection (LOD) of 2.4 and 1.1 pM for miRNA21 and miRNA205, respectively. In addition, good selectivity and anti-interference ability were achieved using this method, which enabled it promising for miRNA detection at the point-of-care.
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http://dx.doi.org/10.1021/acs.analchem.1c02478DOI Listing
July 2021

Deletion Aggravates Sepsis-Induced Cardiac Dysfunction by Regulating Macrophage Polarization.

Front Pharmacol 2021 2;12:632912. Epub 2021 Jul 2.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Cardiac dysfunction is a well-recognized complication of sepsis and is associated with the outcome and prognosis of septic patients. Evidence suggests that participates in the regulation of various cardiovascular diseases, including heart failure, hypertension and acute myocardial infarction. However, the effects of in sepsis-induced cardiac dysfunction remain unknown. In our study, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) model were used to mimic sepsis, and cardiac expression was assessed. In addition, knockout mice were used to detect the role of in sepsis-related cardiac dysfunction. We observed for the first time that expression is upregulated in mice after LPS treatment and macrophages were the main sources of In addition, our findings demonstrated that deletion aggravates LPS-induced cardiac dysfunction and injury, as evidenced by the increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). Moreover, deletion enhances LPS-induced macrophage accumulation and drives macrophages toward the M1 phenotype in LPS-treated mice. deletion also downregulated the activity of AMP-activated protein kinase (AMPK) but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). In addition, deletion aggravates CLP-induced cardiac dysfunction and injury. Treatment with the AMPK activator AICAR abolishes the deterioration effect of deletion on LPS-induced cardiac dysfunction. In conclusion, deletion aggravated LPS-induced cardiac dysfunction and injury by exacerbating the imbalance of M1 and M2 macrophages. Our data provide evidence that may represent an attractive target for sepsis-induced cardiac dysfunction.
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http://dx.doi.org/10.3389/fphar.2021.632912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284189PMC
July 2021

A graph convolutional neural network for gene expression data analysis with multiple gene networks.

Stat Med 2021 Jul 14. Epub 2021 Jul 14.

Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota, USA.

Spectral graph convolutional neural networks (GCN) are proposed to incorporate important information contained in graphs such as gene networks. In a standard spectral GCN, there is only one gene network to describe the relationships among genes. However, for genomic applications, due to condition- or tissue-specific gene function and regulation, multiple gene networks may be available; it is unclear how to apply GCNs to disease classification with multiple networks. Besides, which gene networks may provide more effective prior information for a given learning task is unknown a priori and is not straightforward to discover in many cases. A deep multiple graph convolutional neural network is therefore developed here to meet the challenge. The new approach not only computes a feature of a gene as the weighted average of those of itself and its neighbors through spectral GCNs, but also extracts features from gene-specific expression (or other feature) profiles via a feed-forward neural networks (FNN). We also provide two measures, the importance of a given gene and the relative importance score of each gene network, for the genes' and gene networks' contributions, respectively, to the learning task. To evaluate the new method, we conduct real data analyses using several breast cancer and diffuse large B-cell lymphoma datasets and incorporating multiple gene networks obtained from "GIANT 2.0" Compared with the standard FNN, GCN, and random forest, the new method not only yields high classification accuracy but also prioritizes the most important genes confirmed to be highly associated with cancer, strongly suggesting the usefulness of the new method in incorporating multiple gene networks.
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http://dx.doi.org/10.1002/sim.9140DOI Listing
July 2021

[Analysis of a child with holoprosencephaly due to variant of SIX3 gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jul;38(7):656-658

Guizhou Provincial Prenatal Diagnosis Center, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, China.

Objective: To explore the genetic basis of a child with holoprosencephaly.

Methods: Genomic DNA of the child was extracted and subjected to whole exome sequencing. Suspected variant was verified by Sanger sequencing of her family members.

Results: Cranial MRI suggested lobulated holoprosencephaly with partial absence of corpus callosum. Genetic testing revealed that she has carried a heterozygous c.517C>G (p.His173Asp) variant of the SIX3 gene, for which both of her parents were of wild type. Based on the American College of Medical Genetics and Genomics guidelines, the c.517C>G variant of SIX3 gene was predicted to be pathogenic (PS2+PM1+PM2+PM5+PP3).

Conclusion: The SIX3 gene c.517C>G variant probably underlay the multiple malformations in this child. Above finding has enabled her definite diagnosis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200429-00315DOI Listing
July 2021

Pericardial-Peritoneal Window as an Alternative Treatment for Large and Recurrent Pericardial Effusion Post-Pericardiotomy.

Braz J Cardiovasc Surg 2021 Jul 7. Epub 2021 Jul 7.

Aerospace Breeding Research Centre of CASTC, Beijing, China.

Introduction: Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells.

Methods: The foam cell model was established in vitro by incubating HASMC with 20 μg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 μg/mL, 0.1 μg/mL, 0.5 μg/mL, 1 μg/mL, 5 μg/mL and 10 μg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 μg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours.

Results: After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 μg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 μg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 μg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti- IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells.

Conclusion: Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce antiinflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.
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http://dx.doi.org/10.21470/1678-9741-2020-0179DOI Listing
July 2021

Constrained maximum likelihood-based Mendelian randomization robust to both correlated and uncorrelated pleiotropic effects.

Am J Hum Genet 2021 Jul;108(7):1251-1269

Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

With the increasing availability of large-scale GWAS summary data on various complex traits and diseases, there have been tremendous interests in applications of Mendelian randomization (MR) to investigate causal relationships between pairs of traits using SNPs as instrumental variables (IVs) based on observational data. In spite of the potential significance of such applications, the validity of their causal conclusions critically depends on some strong modeling assumptions required by MR, which may be violated due to the widespread (horizontal) pleiotropy. Although many MR methods have been proposed recently to relax the assumptions by mainly dealing with uncorrelated pleiotropy, only a few can handle correlated pleiotropy, in which some SNPs/IVs may be associated with hidden confounders, such as some heritable factors shared by both traits. Here we propose a simple and effective approach based on constrained maximum likelihood and model averaging, called cML-MA, applicable to GWAS summary data. To deal with more challenging situations with many invalid IVs with only weak pleiotropic effects, we modify and improve it with data perturbation. Extensive simulations demonstrated that the proposed methods could control the type I error rate better while achieving higher power than other competitors. Applications to 48 risk factor-disease pairs based on large-scale GWAS summary data of 3 cardio-metabolic diseases (coronary artery disease, stroke, and type 2 diabetes), asthma, and 12 risk factors confirmed its superior performance.
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http://dx.doi.org/10.1016/j.ajhg.2021.05.014DOI Listing
July 2021

Self-Template Synthesis of Nitrogen-Doped Hollow Carbon Nanospheres with Rational Mesoporosity for Efficient Supercapacitors.

Materials (Basel) 2021 Jun 29;14(13). Epub 2021 Jun 29.

Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819, China.

Rational design and economic fabrication are essential to develop carbonic electrode materials with optimized porosity for high-performance supercapacitors. Herein, nitrogen-doped hollow carbon nanospheres (NHCSs) derived from resorcinol and formaldehyde resin are successfully prepared via a self-template strategy. The porosity and heteroatoms in the carbon shell can be adjusted by purposefully introducing various dosages of ammonium ferric citrate (AFC). Under the optimum AFC dosage (30 mg), the as-prepared NHCS-30 possesses hierarchical architecture, high specific surface area up to 1987 m·g, an ultrahigh mesopore proportion of 98%, and moderate contents of heteroatoms, and these features endow it with a high specific capacitance of 206.5 F·g at 0.2 A·g, with a good rate capability of 125 F·g at 20 A·g as well as outstanding electrochemical stability after 5000 cycles in a 6 M KOH electrolyte. Furthermore, the assembled NHCS-30 based symmetric supercapacitor delivers an energy density of 14.1 W·h·kg at a power density of 200 W·kg in a 6 M KOH electrolyte. This work provides not only an appealing model to study the effect of structural and component change on capacitance, but also general guidance to expand functionality electrode materials by the self-template method.
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http://dx.doi.org/10.3390/ma14133619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269615PMC
June 2021

Delivery nanoplatforms based on dynamic covalent chemistry.

Chem Commun (Camb) 2021 Jul;57(58):7067-7082

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

As a paramount factor to restrict the potential action of drugs and biologics, nanoplatforms based on dynamic covalent chemistry have been demonstrated as promising candidates to fulfill the full requirements during the whole delivery process by the virtue of their remarkable features such as adaptiveness, stimuli-responsiveness, specificity, reversibility and feasibility. This contribution summarizes the latest progress in dynamic covalent bond-based nanoplatforms with improved delivery efficiency and therapeutic performance. In addition, major challenges and perspectives in this field are also discussed. We expect that this feature article will provide a valuable and systematic reference for the further development of dynamic covalent bond-based nanoplatforms.
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http://dx.doi.org/10.1039/d1cc02246fDOI Listing
July 2021

Intelligent stimuli-responsive nano immunomodulators for cancer immunotherapy.

Chem Sci 2021 Feb 10;12(9):3130-3145. Epub 2021 Feb 10.

College of Chemistry, Chemical Engineering and Materials Science Key Laboratory of Molecular and Nano Probes, Ministry of Education Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Cancer immunotherapy is a revolutionary treatment method in oncology, which uses a human's own immune system against cancer. Many immunomodulators that trigger an immune response have been developed and applied in cancer immunotherapy. However, there is the risk of causing an excessive immune response upon directly injecting common immunomodulators into the human body to trigger an immune response. Therefore, the development of intelligent stimuli-responsive immunomodulators to elicit controlled immune responses in cancer immunotherapy is of great significance. Nanotechnology offers the possibility of designing smart nanomedicine to amplify the antitumor response in a safe and effective manner. Progress relating to intelligent stimuli-responsive nano immunomodulators for cancer immunotherapy is highlighted as a new creative direction in the field. Considering the clinical demand for cancer immunotherapy, we put forward some suggestions for constructing new intelligent stimuli-responsive nano immunomodulators, which will advance the development of cancer immunotherapy.
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http://dx.doi.org/10.1039/d0sc06557aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179382PMC
February 2021

Entry of bovine parainfluenza virus type 3 into MDBK cells occurs via clathrin-mediated endocytosis and macropinocytosis in a acid-dependent manner.

Vet Microbiol 2021 Aug 15;259:109148. Epub 2021 Jun 15.

Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, 250014, China; Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, Jinan, 250014, China. Electronic address:

Bovine parainfluenza virus 3 (BPIV3) is an important respiratory pathogen of both young and adult cattle. No specific therapies are available for BPIV3. Understanding the viral internalization pathway of BPIV3 will provide new strategies for the development of antiviral treatments. Here, the entry mechanism of BPIV3 into MDBK cells was analyzed using chemical inhibitors and RNA silencing. Our data demonstrated that treatment with an inhibitor targeting the clathrin-mediated pathway or clathrin heavy chain (CHC) knockdown suppressed the entry of BPIV3 into MDBK cells. In contrast, sequestration of cellular cholesterol by nystatin or silencing of caveolin-1 had no effect on viral entry. Moreover, inhibition of critical modulators of macropinocytosis significantly reduced BPIV3 uptake. In addition, fluid-phase uptake was significantly increased in cells infected with BPIV3, which is indicative of virus-induced facilitation of macropinocytosis. These results suggest that BPIV3 enters MDBK cells via macropinocytosis and clathrin- but not caveolar-dependent endocytosis. Furthermore, inhibition of endosomal acidification and activation of cathepsin blocked BPIV3 entry, demonstrating that BPIV3 entered MDBK cells in a acid-dependent manner and required cathepsin L. Finally, we demonstrated that macropinocytosis but not clathrin-mediated endocytosis is dependent on actin dynamics during BPIV3 infection.
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http://dx.doi.org/10.1016/j.vetmic.2021.109148DOI Listing
August 2021

Caregiver Characteristics Associated With Cognitive Complaints in Women With Breast Cancer.

Oncol Nurs Forum 2021 07;48(4):453-464

Duke University.

Objectives: To explore whether caregiver characteristics were associated with cognitive complaints reported by women with breast cancer undergoing chemotherapy.

Sample & Setting: 61 dyads of women with breast cancer and their caregivers were recruited at Duke Women's Cancer Care Raleigh in North Carolina.

Methods & Variables: An exploratory, cross-sectional design was used. Data were obtained on patients and caregivers. Patient cognitive complaints were represented by cognitive impairment (CI) and cognitive ability (CA).

Results: Two significant associations were found.

Implications For Nursing: Healthcare providers should consider caregivers when assessing and managing patients' cognitive symptoms. This study suggests the value of including caregivers when establishing interventions for patients who have cognitive complaints.
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http://dx.doi.org/10.1188/21.ONF.453-464DOI Listing
July 2021

Stimuli-activated molecular photothermal agents for cancer therapy.

Chem Commun (Camb) 2021 Jul;57(54):6584-6595

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

Taking advantage of activatable and imaging-guided properties, stimuli-activated molecular photothermal agents (MPTAs) have drawn great attention in photothermal therapy (PTT) over the past decades. In this review, the recent progress in the study of stimuli-activated MPTAs is summarized from different stimuli, including pH, bioactive small molecules, and enzymes. The features and challenges of stimuli-activated MPTAs are also discussed. This review aims to motivate readers to design and synthesise more efficient MPTAs.
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http://dx.doi.org/10.1039/d1cc02116hDOI Listing
July 2021

Green tea protects against hippocampal neuronal apoptosis in diabetic encephalopathy by inhibiting JNK/MLCK signaling.

Mol Med Rep 2021 Aug 16;24(2). Epub 2021 Jun 16.

Department of Medical Laboratory, Affiliated Hospital of Guizhou Medical University, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.

Although diabetic encephalopathy (DE) is a major late complication of diabetes, the pathophysiology of postural instability in DE remains poorly understood. Prior studies have suggested that neuronal apoptosis is closely associated with cognitive function, but the mechanism remains to be elucidated. Green tea, which is a non‑fermented tea, contains a number of tea polyphenols, alkaloids, amino acids, polysaccharides and other components. Some studies have found that drinking green tea can reduce the incidence of neurodegenerative diseases and improve cognitive dysfunction. We previously found that myosin light chain kinase (MLCK) regulates apoptosis in high glucose‑induced hippocampal neurons. In neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, activation of the JNK signaling pathway promotes neuronal apoptosis. However, the relationship between JNK and MLCK remains to be elucidated. Green tea serum was obtained using seropharmacological methods and applied to hippocampal neurons. In addition, a type 1 diabetes rat model was established and green tea extract was administered, and the Morris water maze test, Cell Counting Kit‑8 assays, flow cytometry, western blotting and terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labelling assays were used to examine the effects of green tea on hippocampal neuronal apoptosis in diabetic rats. The results demonstrated that green tea can protect against hippocampal neuronal apoptosis by inhibiting the JNK/MLCK pathway and ultimately improves cognitive function in diabetic rats. The present study provided novel insights into the neuroprotective effects of green tea.
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http://dx.doi.org/10.3892/mmr.2021.12214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223107PMC
August 2021

Dual-targeted photothermal agents for enhanced cancer therapy.

Chem Sci 2020 Jul 17;11(31):8055-8072. Epub 2020 Jul 17.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Centre of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Photothermal therapy, in which light is converted into heat and triggers local hyperthermia to ablate tumors, presents an inherently specific and noninvasive treatment for tumor tissues. In this area, the development of efficient photothermal agents (PTAs) has always been a central topic. Although many efforts have been made on the investigation of novel molecular architectures and photothermal materials over the past decades, PTAs can cause severe damage to normal tissues because of the poor tumor aggregate ability and high irradiation density. Recently, dual-targeted photothermal agents (DTPTAs) provide an attractive strategy to overcome these problems and enhance cancer therapy. DTPTAs are functionalized with two classes of targeting units, including tumor environment targeting sites, tumor targeting sites and organelle targeting sites. In this perspective, typical targeted ligands and representative examples of photothermal therapeutic agents with dual-targeted properties are systematically summarized and recent advances using DTPTAs in tumor therapy are highlighted.
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http://dx.doi.org/10.1039/d0sc03173aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163445PMC
July 2020

A tumor acidity activatable and Ca-assisted immuno-nanoagent enhances breast cancer therapy and suppresses cancer recurrence.

Chem Sci 2020 Jun 29;11(28):7429-7437. Epub 2020 Jun 29.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University Jinan 250014 P. R. China

Breast cancer recurrence is the greatest contributor to patient death. As the immune system has a long-term immune memory effect, immunotherapy has great potential for preventing cancer recurrence. However, cancer immunotherapy is often limited due to T cell activation being blocked by insufficient tumor immunogenicity and the complex immunosuppressive tumor microenvironment. Here we show a tumor acidity activatable and Ca-assisted immuno-nanoagent to synergistically promote T cell activation and enhance cancer immunotherapy. When the immuno-nanoagent reaches the acidic tumor microenvironment, the CaCO matrix disintegrates to release immune stimulants (CpG ODNs and IDOi) and Ca. CpG ODNs are responsible for triggering dendritic cell maturation to increase the immunogenicity for activation of T cells. And IDOi can inhibit the oxidative catabolism of tryptophan to kynurenine for preventing T-cell anergy and apoptosis. Due to the complexity of the immunosuppressive microenvironment, it is difficult to restore T cell activation by inhibiting only one pathway. Fortunately, the released Ca can promote the activation and proliferation of T cells with the support of the immune stimulants. experiments demonstrate that our Ca-assisted immuno-nanoagent can significantly suppress tumor progression and protect mice from tumor rechallenge due to the long-term memory effect. This immunotherapeutic strategy may provide more possibilities for clinical applications such as treating cancer and preventing relapse.
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http://dx.doi.org/10.1039/d0sc00293cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159290PMC
June 2020

Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity.

Front Immunol 2021 27;12:661241. Epub 2021 May 27.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, China.

As a relatively successful pathogen, several parasites can establish long-term infection in host. This "harmonious symbiosis" status relies on the "precise" manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.
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http://dx.doi.org/10.3389/fimmu.2021.661241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191844PMC
May 2021

Changes in trabecular bone score and bone mineral density in Chinese HIV-Infected individuals after one year of antiretroviral therapy.

J Orthop Translat 2021 Jul 20;29:72-77. Epub 2021 May 20.

Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.

Objective: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART.

Methods: We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS.

Results: Our study included 233 ​PWH (mean age ​= ​36.6 ​± ​11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population.

Conclusions: We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents.

The Translational Potential Of This Article: The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.
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http://dx.doi.org/10.1016/j.jot.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164002PMC
July 2021

Root Extract of (Sims) Kosterm. Modulates the Th17/Treg Balance to Attenuate DSS-Induced Colitis in Mice by IL-6/STAT3 Signaling Pathway.

Front Pharmacol 2021 13;12:615506. Epub 2021 May 13.

Center of Safety Evaluation, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), Hangzhou, China.

Ulcerative colitis (UC) is a chronic, idiopathic and relapsing inflammatory disease of the gastrointestinal tract that has a prolonged disease duration. (Sims) Kosterm. is a traditional Chinese herb which has been used to treat gastrointestinal diseases for thousand years. However, there are few reports about the application of in the treatment of UC at present. Herein, we investigated the therapeutic effect of the root extract of (LREE) against UC and explored its underlying mechanisms based on IL-6 signaling pathway and the balance of T helper (Th) 17 and regulatory T (Treg) cells. Results showed that LREE could not only decrease the production and secretion of IL-6, but also could inhibit the signal transduction of IL-6/STAT3 signaling pathway. Moreover, LREE could significantly inhibit the differentiation of CD4 T cells to Th17 cells and decrease the proportion of Th17 cells in mesenteric lymph nodes (MLNs) of model mice . Besides, LREE could also alleviate the disease symptoms, reduce intestinal permeability and improve histopathological changes of colitis model mice. Together, LREE can significantly inhibit the production and secretion of IL-6, regulate IL-6/STAT3 signal transduction, and modulate the balance of Th17 and Treg cells and effectively attenuate UC.
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http://dx.doi.org/10.3389/fphar.2021.615506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170699PMC
May 2021

Relational processes in heart failure care transitions: A data-driven case report.

Heart Lung 2021 Jun 3;50(5):622-626. Epub 2021 Jun 3.

Duke University School of Nursing, Durham, NC, USA; Heart Center Nursing Research Program, Duke University Health System and School of Nursing, Durham, NC, USA.

Background: Effective patient care transitions require consideration of social and clinical context, yet how these factors and relational processes in care coordination relate remains poorly described. This case report aims to describe provider networks and the clinical care and social context involved during longitudinal care transitions across settings.

Case: We examined the utilization and provider networks of an oldest old woman with heart failure (HF) before and after her first hospitalization for HF. She used primary care for care management and had insurance, strong caregiver support, and comprehensive discharge planning; however, after the hospitalization, Mrs. A's ambulatory provider networks were more diverse yet sparser and less strongly connected.

Conclusions: Turbulence in care transition can result from sources other than transitioning between settings. The data-driven case report approach using electronic health records uncovered relational processes important for care coordination and may inform patient-centered approaches to improve care for patients with HF.
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http://dx.doi.org/10.1016/j.hrtlng.2021.04.012DOI Listing
June 2021

Toward Flexible Zinc-Air Batteries with Self-Supported Air Electrodes.

Small 2021 Jun 4:e2006773. Epub 2021 Jun 4.

Key Laboratory for Colloid and Interface Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, P. R. China.

The compelling demand for higher energy performance, flexibility, and miniaturization is the main driving force of the energy storage and conversion industry's quest for flexible devices based on new integration and fabrication process. Herein, the recent advances on the development of flexible zinc-air batteries based on self-supported air electrodes are summarized, focusing on the multiscale and systematic design principles for the design of flexible air electrodes. With the electrocatalytic activity regulation and structural engineering strategies, the rational design of self-supported air electrodes is discussed in integrated devices to underpin the good flexibility for wearable requirement. The perspectives on promising developments of flexible zinc-air batteries and the accumulated knowledge from other flexible devices are also addressed for promoting the advances on flexible zinc-air batteries.
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http://dx.doi.org/10.1002/smll.202006773DOI Listing
June 2021

Analysis of endometrial thickness patterns and pregnancy outcomes considering 12,991 fresh IVF cycles.

BMC Med Inform Decis Mak 2021 06 3;21(1):176. Epub 2021 Jun 3.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China.

Background: Different endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.

Methods: This retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: < 8 mm; Group 2: ≥ 8 and ≤ 11 mm; Group 3: > 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate.

Results: We found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.

Conclusions: Different endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.
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http://dx.doi.org/10.1186/s12911-021-01538-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173785PMC
June 2021

Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens.

J Med Chem 2021 Jun 3;64(12):8644-8665. Epub 2021 Jun 3.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-]indole derivatives represented by GP-1 demonstrated excellent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria but were limited by hERG inhibition and poor pharmacokinetics profile. To improve their drug-like properties, we designed a series of novel pyrimido[4,5-]indole derivatives based on the tricyclic scaffold of GP-1 and the C-7 moiety of acorafloxacin. These efforts have culminated in the discovery of a promising compound with reduced hERG liability and an improved PK profile. Compound exhibited superior broad-spectrum antibacterial activity compared to GP-1, including a variety of clinical multidrug G pathogens, especially , and the efficacy was also demonstrated in a neutropenic mouse thigh model of infection with multidrug-resistant .
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http://dx.doi.org/10.1021/acs.jmedchem.1c00621DOI Listing
June 2021

Bovine Parainfluenza Virus Type 3 (BPIV3) Enters HeLa Cells via Clathrin-Mediated Endocytosis in a Cholesterol- and Dynamin-Dependent Manner.

Viruses 2021 May 31;13(6). Epub 2021 May 31.

Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan 250014, China.

Bovine parainfluenza virus 3 (BPIV3) is a crucial causative agent of respiratory disease in young and adult cattle. No specific therapies are available for BPIV3 infection. Understanding the internalization pathway of the virus will provide a new strategy for the development of antiviral therapy. Here, the mechanism of BPIV3 entry into HeLa cells was analyzed using RNA silencing and pharmacological inhibitors. Treatment of HeLa cells with hypertonic medium prevented BPIV3 internalization. These results indicated that BPIV3 entered HeLa cells via receptor-mediated endocytosis. Moreover, removing cell membrane cholesterol through MβCD treatment hampered viral penetration but not viral replication. In addition, BPIV3 infection was inhibited by pretreatment with dynasore or chlorpromazine (CPZ) or knockdown of dynamin II or clathrin heavy chain. However, virus entry was unaffected by nystatin, EIPA, wortmannin, or cytochalasin D treatment or caveolin-1 knockdown. These data demonstrated that the entry of BPIV3 into HeLa cells was dependent on clathrin-mediated endocytosis but not on caveolae-mediated endocytosis or the macropinocytosis pathway. Many viruses are transported to endosomes, which provide an acidic environment and release their genome upon separation from primary endocytic vesicles. However, we found that BPIV3 infection required endosomal cathepsins, but not a low pH. In summary, we show, for the first time, that BPIV3 enters HeLa cells through the clathrin-mediated endocytosis pathway, presenting novel insights into the invasion mechanism of Paramyxoviridae.
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http://dx.doi.org/10.3390/v13061035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228847PMC
May 2021

The relationship between stress, resilience, and quality of life in Chinese high school students.

Ann Palliat Med 2021 May 12;10(5):5483-5493. Epub 2021 May 12.

School of Educational Science, International Joint Laboratory of Behavior and Cognitive Science, Zhengzhou Normal University, Zhengzhou, China.

Background: Stress is an important factor affecting the dynamic process of resilience. This study aimed to explore the role of stress levels in the relationship between resilience and health consequences by investigating high school students undergoing the National College Entrance Examination (CEE), which often involves intense stressful conditions for students in China, at different stages.

Methods: The CD-RISC [Conner-Davidson Resiliency Scale] and SF-36 [the short form 36 health survey questionnaire, one measurement of the quality of life (QoL)] were used to investigate 435 high school students, including 208 students in grade two (low stress group) and 227 students in grade three (high stress group).

Results: This study found that the SF-36 scores under high-stress conditions were significantly lower than those under low-stress conditions, however there were no significant differences in the mental resilience scores. Additionally, under low-stress conditions, mental resilience was found to be significantly correlated with various factors of SF-36, but no significant correlation was observed under high-stress conditions. It was also discovered that stress levels can mediate the relationship between psychological resilience and QoL (the quality of life).

Conclusions: Stress level is an important factor affecting the expression of resilience. This study also discussed the integration of the concept of resilience.
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http://dx.doi.org/10.21037/apm-21-929DOI Listing
May 2021

Review of the Mechanisms of Ventilator Induced Lung Injury and the Principles of Intraoperative Lung Protective Ventilation.

AANA J 2021 Jun;89(3):227-233

is employed by Duke University School of Nursing, Durham, North Carolina.

Intraoperative ventilator induced lung injury is associated with development of postoperative pulmonary complications. Despite advances in modes and methods of mechanical ventilation, postoperative pulmonary complications remain as one of the leading causes of adverse outcomes following surgery and anesthesia. In an attempt to reduce the incidence of postoperative pulmonary complications, the use of an intraoperative ventilatory technique to minimize lung injury has been introduced. Lung protective ventilation typically entails the use of a physiologic tidal volume, positive end expiratory pressure, extended inspiratory time, and an alveolar recruitment maneuver. The goal of intraoperative lung protective ventilation is to prevent or at least minimize development of ventilator induced lung injury by maintaining a homogeneous lung and alveolar stability during and after a surgical procedure. To appreciate the value of the application of an intraoperative lung protective ventilation strategy, the pathophysiology and developmental processes of ventilator induced lung injury must first be understood. The primary purpose of this paper is to provide a basic understanding of the relationship between conventional intraoperative mechanical ventilation, pulmonary derangement and lung injury as well as a rationale for the use of individualized lung protective ventilation to optimize surgical patient pulmonary outcomes.
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June 2021

Selenium-engineered covalent organic frameworks for high-efficiency and long-acting cancer therapy.

Chem Commun (Camb) 2021 Jun;57(50):6145-6148

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

A porphyrin-containing covalent organic framework (COF) was synthesized as a substrate for decorating selenium nanoparticles (Se NPs) via in situ reduction. Se NP-mediated therapy (SeT) was carried out in conjunction with photodynamic therapy (PDT) to provide an increased anticancer effect and remedy the constrained efficacy of PDT.
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http://dx.doi.org/10.1039/d1cc01830bDOI Listing
June 2021

Ultrathin functionalized covalent organic framework nanosheets for tumor-targeted photodynamic therapy.

Chem Commun (Camb) 2021 Jun;57(49):6082-6085

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

We developed a modification-facilitated exfoliation strategy for the one-step preparation of ultrathin 2D functionalized covalent organic framework nanosheets (COF NSs). Hyaluronic acid-functionalized ultrathin porphyrin COF NSs (about 5-8 nm) with enhanced reactive oxygen species (ROS) generation effect were readily prepared for tumor-targeted photodynamic therapy.
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http://dx.doi.org/10.1039/d1cc02124aDOI Listing
June 2021
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