Publications by authors named "Jing Mu"

81 Publications

IGFBP7 overexpression promotes acquired resistance to AZD9291 in non-small cell lung cancer.

Biochem Biophys Res Commun 2021 Jul 21;571:38-45. Epub 2021 Jul 21.

Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China. Electronic address:

AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR-mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.055DOI Listing
July 2021

Effects of sulfur application on cadmium accumulation in brown rice under wheat-rice rotation.

Environ Pollut 2021 Jun 16;287:117601. Epub 2021 Jun 16.

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 101408, China; Sino-Danish Centre for Education and Research (SDC), Beijing, 101408, China. Electronic address:

We investigated how sulfur (S) application prior to wheat cultivation under wheat-rice rotation influences the uptake of cadmium (Cd) in rice grown in low- and high-Cd soils. A pot experiment was conducted with four S levels (0, 30, 60, 120 mg S kg) and two Cd rates (low and high, 0.35 and 10.35 mg Cd kg) supplied to wheat. Part of the wheat straw was returned to the soil before planting rice, which was cultivated for 132 days. To explore the key mechanisms by which S application controlled Cd accumulation in brown rice, (1) soil pore water at the key growth stages was sampled, and dissolved Cd and S species concentrations were determined; (2) rice plant tissues (including iron plaque on the root surface) were sampled at maturity for Cd and S analysis. With increasing S level, Cd accumulation in brown rice peaked at 60 mg S kg, irrespective of soil Cd levels. For high-Cd soils, concentrations of Cd in brown rice increased by 57%, 228%, and 100% at 30, 60, and 120 mg S kg, respectively, compared with no S treatment. The increase in brown rice Cd by low S levels (0-60 mg kg) could be attributed to (1) the S-induced increase in soil pore water sulfate increasing the Cd influx into rice roots and (2) the S-induced increase in leaf S promoting Cd translocation into brown rice. However, brown rice Cd decreased at 120 mg S kg due to (1) low Cd solubility at 120 mg S kg and (2) root and leaf S uptake, which inhibited Cd uptake. Sulfur application to wheat crop increased the risk of Cd accumulation in brown rice. Thus, applying S-containing fertilizers to Cd-contaminated paddy soils is not recommended.
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http://dx.doi.org/10.1016/j.envpol.2021.117601DOI Listing
June 2021

Self-assembling modified neuropeptide S enhances nose-to-brain penetration and exerts a prolonged anxiolytic-like effect.

Biomater Sci 2021 Jul 26;9(13):4765-4777. Epub 2021 May 26.

Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Anxiety disorders are the most common mental diseases and can greatly disrupt everyday life. Although there has been substantial research on anxiety disorders, novel therapeutics are needed. Neuropeptide S (NPS) is a potential therapeutic candidate owing to its strong anxiolytic activity; however, some disadvantages, such as its poor metabolic stability and inability to cross the blood-brain barrier (BBB), limit its use in the clinic. Herein, inspired by nose-to-brain drug delivery strategies, an endogenous 20-amino-acid-long mNPS peptide was modified by incorporating palmitic acid into its functional Lys side chain (M-3), which was expected to facilitate nose-to-brain penetration and exert a prolonged anxiolytic-like effect compared to mNPS. We found that M-3 assembled into nanofibers that retained the bioactivity of NPS and exhibited obvious improvements in metabolic stability. Notably, as expected, self-assembled M-3 was able to penetrate into the brain and exert anxiolytic effects. The elevated plus-maze (EPM) results further revealed that M-3 could produce prolonged anxiolytic-like effects in mice. In vivo imaging studies revealed that self-assembled M-3 could be efficiently transported from the nasal cavity to the brain. Furthermore, when intranasally administered, this molecule exhibited a significantly prolonged anxiolytic-like effect, which further illustrated that this molecule has a potent nose-to-brain penetration in vivo. Overall, this self-assembled nanofiber showed potent nose-to-brain penetration ability and prolonged bioactivity.
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http://dx.doi.org/10.1039/d1bm00380aDOI Listing
July 2021

Deletion of inhibits neointima formation by enhancing KAT2A/GCN5-mediated acetylation of TUBA/α-tubulin .

Autophagy 2021 May 14:1-18. Epub 2021 May 14.

Center of Molecular and Translational Medicine, Georgia State University, Atlanta, Georgia.

ULK1 (unc-51 like autophagy activating kinase) has a central role in initiating macroautophagy/autophagy, a process that contributes to atherosclerosis and neointima hyperplasia, or excessive tissue growth that leads to vessel dysfunction. However, the role of ULK1 in neointima formation remains unclear. We aimed to determine how deletion affected neointima formation and to investigate the underlying mechanisms. We measured autophagy activity, vascular smooth muscle cell (VSMC) migration and neointima hyperplasia in cultured VSMCs and ligation-injured mouse carotid arteries from male wild-type (WT, C57BL/6 J) and VSMC-specific knockout ( KO) mice. Carotid artery ligation in WT mice increased ULK1 protein expression, and concurrently increased autophagic flux and neointima formation. Treating human aortic smooth muscle cells (HASMCs) with PDGF (platelet derived growth factor) increased ULK1 expression, activated autophagy, and promoted cell migration. Further, smooth muscle cell-specific deletion of suppressed autophagy, inhibited VSMC migration, and impeded neointima hyperplasia. Mechanistically, deletion inhibited autophagic degradation of histone acetyltransferase protein KAT2A/GCN5 (K[lysine] acetyltransferase 2A), resulting in accumulation of KAT2A that directly acetylated TUBA/α-tubulin and subsequently increased protein levels of acetylated TUBA. The acetylation of TUBA increased microtubule stability and inhibited VSMC directional migration and neointima formation. Finally, local transfection of siRNA decreased TUBA acetylation and prevented the attenuation of vascular injury-induced neointima formation in KO mice. These findings suggest that deletion inhibits neointima formation by reducing autophagic degradation of KAT2A and increasing TUBA acetylation in VSMCs. ACTA2/α-SMA: actin, alpha 2, smooth muscle, aorta; ACTB: actin beta; ATAT1: alpha tubulin acetyltransferase 1; ATG: autophagy related; BECN1: beclin 1; BP: blood pressure; CAL: carotid artery ligation; CQ: chloroquine diphosphate; EC: endothelial cells; EEL: external elastic layer; FBS: fetal bovine serum; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; HASMCs: human aortic smooth muscle cells; HAT1: histone acetyltransferase 1; HDAC: histone deacetylase; IEL: inner elastic layer; IP: immunoprecipitation; KAT2A/GCN5: K(lysine) acetyltransferase 2A; KAT8/hMOF: lysine acetyltransferase 8; MAP1LC3: microtubule associated protein 1 light chain 3; MYH11: myosin heavy chain 11; PBS: phosphate-buffered saline; PDGF: platelet derived growth factor; PECAM1/CD31: platelet and endothelial cell adhesion molecule 1; RAC3: Rac family small GTPase 3; SIRT2: sirtuin 2; SPP1/OPN: secreted phosphoprotein 1; SQSTM1/p62: sequestosome 1; TAGLN/SM22: transgelin; TUBA: tubulin alpha; ULK1: unc-51 like autophagy activating kinase; VSMC: vascular smooth muscle cell; VVG: Verhoeff Van Gieson; WT: wild type.
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http://dx.doi.org/10.1080/15548627.2021.1911018DOI Listing
May 2021

Rationally Programming Nanomaterials with DNA for Biomedical Applications.

Adv Sci (Weinh) 2021 04 24;8(8):2003775. Epub 2021 Feb 24.

Yong Loo Lin School of Medicine and Faculty of Engineering National University of Singapore Singapore 117597 Singapore.

DNA is not only a carrier of genetic information, but also a versatile structural tool for the engineering and self-assembling of nanostructures. In this regard, the DNA template has dramatically enhanced the scalability, programmability, and functionality of the self-assembled DNA nanostructures. These capabilities provide opportunities for a wide range of biomedical applications in biosensing, bioimaging, drug delivery, and disease therapy. In this review, the importance and advantages of DNA for programming and fabricating of DNA nanostructures are first highlighted. The recent progress in design and construction of DNA nanostructures are then summarized, including DNA conjugated nanoparticle systems, DNA-based clusters and extended organizations, and DNA origami-templated assemblies. An overview on biomedical applications of the self-assembled DNA nanostructures is provided. Finally, the conclusion and perspectives on the self-assembled DNA nanostructures are presented.
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http://dx.doi.org/10.1002/advs.202003775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061415PMC
April 2021

The complete chloroplast genome of thunb.(Rosaceae), an ornamental and medicinal plant.

Mitochondrial DNA B Resour 2021 Jan 13;6(1):112-114. Epub 2021 Jan 13.

National Resource Center for Chinese Meteria Medica, China Academy of Chinese Medical Sciences, Beijing, China.

is an ornamental and medicinal plant that is widely cultivated. The complete chloroplast genome of was sequenced using Illumina Hiseq X Ten platform. The chloroplast genome was 158,080 bp in length, containing two short inverted repeat (IRa and IRb) regions of 26,385 bp, which was separated by a large single copy (LSC) region of 86,270 bp and a small single copy (SSC) region of 19,040 bp. The GC content of the whole chloroplast genome was 36.8%. The chloroplast DNA of comprised 112 distinct genes, including 78 protein-coding genes, 4 ribosomal RNA genes and 30 transfer RNA genes. Phylogenetic analysis indicated that all species of formed a monophyletic group, was closely related to .
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http://dx.doi.org/10.1080/23802359.2020.1848477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819125PMC
January 2021

A Novel Prognostic Model of Endometrial Carcinoma Based on Clinical Variables and Oncogenomic Gene Signature.

Front Mol Biosci 2020 7;7:587822. Epub 2021 Jan 7.

School of Mathematics and Statistics, Hunan Normal University, Changsha, China.

Due to the difficulty in predicting the prognosis of endometrial carcinoma (EC) patients by clinical variables alone, this study aims to build a new EC prognosis model integrating clinical and molecular information, so as to improve the accuracy of predicting the prognosis of EC. The clinical and gene expression data of 496 EC patients in the TCGA database were used to establish and validate this model. General Cox regression was applied to analyze clinical variables and RNAs. Elastic net-penalized Cox proportional hazard regression was employed to select the best EC prognosis-related RNAs, and ridge regression was used to construct the EC prognostic model. The predictive ability of the prognostic model was evaluated by the Kaplan-Meier curve and the area under the receiver operating characteristic curve (AUC-ROC). A clinical-RNA prognostic model integrating two clinical variables and 28 RNAs was established. The 5-year AUC of the clinical-RNA prognostic model was 0.932, which is higher than that of the clinical-alone (0.897) or RNA-alone prognostic model (0.836). This clinical-RNA prognostic model can better classify the prognosis risk of EC patients. In the training group (396 patients), the overall survival of EC patients was lower in the high-risk group than in the low-risk group [HR = 32.263, (95% CI, 7.707-135.058), = 8e-14]. The same comparison result was also observed for the validation group. A novel EC prognosis model integrating clinical variables and RNAs was established, which can better predict the prognosis and help to improve the clinical management of EC patients.
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http://dx.doi.org/10.3389/fmolb.2020.587822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817972PMC
January 2021

A hybrid semiconducting organosilica-based O nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy.

Nat Commun 2021 01 22;12(1):523. Epub 2021 Jan 22.

Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, 117597, Singapore, Singapore.

The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O nanoeconomizer pHPFON-NO/O to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O interacts with the acidic tumor microenvironment to release NO for endogenous O conservation; second, it releases O in response to mild photothermal effect to enable exogenous O infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.
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http://dx.doi.org/10.1038/s41467-020-20860-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822893PMC
January 2021

Performance of the MeltPro MTB Assays in the Diagnosis of Drug-Resistant Tuberculosis Using Formalin-Fixed, Paraffin-Embedded Tissues.

Am J Clin Pathol 2021 Jun;156(1):34-41

Department of Pathology, Key Laboratory of Head and Neck Molecular Diagnosis Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

Objectives: The MeltPro MTB assays for detection of resistance to antituberculosis (TB) drugs perform well in genotypic drug susceptibility testing (DST) of clinical samples, but their effectiveness with formalin-fixed, paraffin-embedded (FFPE) tissues is unknown.

Methods: FFPE tissues were obtained from 334 patients with TB. Susceptibility to rifampicin (RIF), isoniazid (INH), and fluoroquinolones was examined using the MeltPro MTB assays, with Xpert MTB/RIF (Xpert) and/or phenotypic DST (pDST) results as references. Samples with discordant results were analyzed by multiplex polymerase chain reaction-targeted amplicon sequencing (MTA-seq).

Results: With pDST as the reference, the MeltPro MTB assays sensitivity for RIF, INH, levofloxacin (LVX), and moxifloxacin (MXF) was 95.00%, 96.00%, 100%, and 100%, respectively, and the specificity was 95.15%, 95.92%, 94.69%, and 89.92%, respectively. Concordance was 99.08% between the MeltPro MTB and Xpert (κ = 0.956) for RIF and 95.12% (κ = 0.834), 95.93% (κ = 0.880), 95.12% (κ = 0.744), and 90.24% (κ = 0.367) between the MeltPro MTB and pDST for RIF, INH, LVX, and MXF, respectively. MTA-seq confirmed the discordancy between the MeltPro MTB and pDST for 26 (89.66%) of 29 samples.

Conclusions: The MeltPro MTB assays rapidly and efficiently predict Mycobacterium tuberculosis resistance to the main first- and second-line anti-TB drugs in FFPE tissues.
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http://dx.doi.org/10.1093/ajcp/aqaa203DOI Listing
June 2021

Diverse clinical processes of 16 COVID-19 cases who concentrated infection in the same workplace in Beijing, China: An observational study.

Medicine (Baltimore) 2020 Dec;99(52):e23800

Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, Beijing, China.

Abstract: Since December 2019, an outbreak of COVID-19 sweeping the world. Understanding the clinical and SARS-CoV-2 dynamic changes of mild and ordinary patients of COVID-19, so as to provide basis for the prevention and control of COVID-19.On February 1st, 2020, 16 SARS-CoV-2 RNA positive patients diagnosed in the same site in Beijing. The patients symptoms, signs, medication, and SARS-CoV-2 results were recorded.Of the 16 patients, 12 were female. Although they were infected at the same time in the same workplace, their clinical processes were very different and can be roughly divided into three different types: persistent sputum positive, persistent stool positive and persistent both positive. In 7 patients with mild clinical manifestations, the median days of SARS-CoV-2 RNA negative conversion in sputum samples were significantly later than those with obvious lung injury (27 days [range: 18 to 36]; 17 days, [range 6 to 25], P = .021). The negative conversion of SARS-CoV-2 RNA in stool was significant later than in sputum.There were various clinical manifestations after SARS-CoV-2 infection, even if they were infected by the same source of infection in the same place. The presence of SARS-CoV-2 virus RNA in stool samples was longer than that in respiratory tract.
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http://dx.doi.org/10.1097/MD.0000000000023800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769349PMC
December 2020

Reactive Oxygen Species Activatable Heterodimeric Prodrug as Tumor-Selective Nanotheranostics.

ACS Nano 2020 Nov 18. Epub 2020 Nov 18.

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda, Maryland 20892, United States.

Nanotheranostics based on tumor-selective small molecular prodrugs could be more advantageous in clinical translation for cancer treatment, given its defined chemical structure, high drug loading efficiency, controlled drug release, and reduced side effects. To this end, we have designed and synthesized a reactive oxygen species (ROS)-activatable heterodimeric prodrug, namely, HRC, and nanoformulated it for tumor-selective imaging and synergistic chemo- and photodynamic therapy. The prodrug consists of the chemodrug camptothecin (CPT), the photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), and a thioketal linker. Compared to CPT- or HPPH-loaded polymeric nanoparticles (NPs), HRC-loaded NPs possess higher drug loading capacity, better colloidal stability, and less premature drug leakage. Interestingly, HRC NPs were almost nonfluorescent due to the strong π-π stacking and could be effectively activated by endogenous ROS once entering cells. Thanks to the higher ROS levels in cancer cells than normal cells, HRC NPs could selectively light up the cancer cells and exhibit much more potent cytotoxicity to cancer cells. Moreover, HRC NPs demonstrated highly effective tumor accumulation and synergistic tumor inhibition with reduced side effects on mice.
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http://dx.doi.org/10.1021/acsnano.0c05722DOI Listing
November 2020

Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles.

Adv Mater 2020 Nov 21;32(47):e2004853. Epub 2020 Oct 21.

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.
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http://dx.doi.org/10.1002/adma.202004853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686299PMC
November 2020

Comparison of Steady-State Visual Evoked Potential (SSVEP) with LCD vs. LED Stimulation.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:2946-2949

The steady-state visual evoked potential (SSVEP) is a robust brain activity that has been used in brain-computer interface (BCI) applications. However, previous studies of SSVEP-based BCIs give contradictory results on which stimulation medium provides the best performance. This paper describes a comparison of electroencephalography (EEG) decoding accuracy between using an LCD screen, clear LEDs, and frosted LEDs to deliver flashing light stimulation. The LCD screen and frosted LEDs achieved similar mean accuracies, and both of them were significantly better than clear LEDs. Background contrast with the LEDs did not significantly influence SSVEP decoding accuracy. A strong correlation was found between SSVEP accuracy and frequency domain magnitudes of EEG measurements.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175838DOI Listing
July 2020

Cascade Reactions Catalyzed by Planar Metal-Organic Framework Hybrid Architecture for Combined Cancer Therapy.

Small 2020 10 28;16(42):e2004016. Epub 2020 Sep 28.

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

Chemical transformation in cellular environment is critical for regulating biological processes and metabolic pathways. Harnessing biocatalytic cascades to produce chemicals of interest has become a research focus to benefit industrial and pharmaceutic areas. Nanoreactors, which can act as artificial cell-like devices to organize cascade reactions, have been recently proposed for potential therapeutic applications for life-threatening illnesses. Among various types of nanomaterials, there is a growing interest in 2D metal-organic frameworks (MOFs). By virtue of the ultralarge specific surface area, high porosity, and structural diversity, 2D MOF nanosheets hold great promise for a broad spectrum of biomedical use. Herein, a unique planar MOF-based hybrid architecture (GMOF-LA) is introduced by incorporating ultrasmall gold nanoparticles (Au NPs) as nanozyme and l-Arginine (l-Arg) as nitric oxide (NO) donor. The prepared Au NPs enable oxidation of glucose into hydrogen peroxide, which drives biocatalytic cascades to covert l-Arg into NO. Interestingly, the well-designed nanosheets not only possess excellent catalytical activity for NO generation, resulting in gas therapeutic effect, but also serve as a desired photosensitizer for photodynamic therapy. This study establishes a good example of exploring bioinspired nanoreactors for cooperative anticancer effect, which may pave the path for future "bench-to-bedside" design of nanomedicine.
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http://dx.doi.org/10.1002/smll.202004016DOI Listing
October 2020

BRD4 inhibition by JQ1 prevents high-fat diet-induced diabetic cardiomyopathy by activating PINK1/Parkin-mediated mitophagy in vivo.

J Mol Cell Cardiol 2020 12 15;149:1-14. Epub 2020 Sep 15.

Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States of America; Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA 30303, United States of America. Electronic address:

BRD4 is a member of the BET family of epigenetic regulators. Inhibition of BRD4 by the selective bromodomain inhibitor JQ1, alleviates thoracic aortic constriction-induced cardiac hypertrophy and heart failure. However, whether BRD4 inhibition by JQ1 has therapeutic effect on diabetic cardiomyopathy, a major cause of heart failure in patients with Type 2 diabetes, remains unknown. Here, we discover a novel link between BRD4 and PINK1/Parkin-mediated mitophagy during diabetic cardiomyopathy. Upregulation of BRD4 in diabetic mouse hearts inhibits PINK1/Parkin-mediated mitophagy, resulting in accumulation of damaged mitochondria and subsequent impairment of cardiac structure and function. BRD4 inhibition by JQ1 improves mitochondrial function, and repairs the cardiac structure and function of the diabetic heart. These effects depended on rewiring of the BRD4-driven transcription and repression of PINK1. Deletion of Pink1 suppresses mitophagy, exacerbates cardiomyopathy, and abrogates the therapeutic effect of JQ1 on diabetic cardiomyopathy. Our results illustrate a valid therapeutic strategy for treating diabetic cardiomyopathy by inhibition of BRD4.
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http://dx.doi.org/10.1016/j.yjmcc.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736123PMC
December 2020

Engineering of Nanoscale Coordination Polymers with Biomolecules for Advanced Applications.

Coord Chem Rev 2019 Nov 4;399. Epub 2019 Sep 4.

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA.

Nanoscale coordination polymers (NCPs) have shown extraordinary advantages in various research areas due to their structural diversity and multifunctionality. Recently, integration of biomolecules with NCPs received extensive attention and the formed hybrid materials exhibit superior properties over the individual NCPs or biomolecules. In this review, the state-of-the-art of approaches to engineer NCPs with different types of guest biomolecules, such as amino acids, nucleic acids, enzymes and lipids are systematically introduced. Additionally, advanced applications of these biomolecule-NCP composites in the areas of sensing, catalysis, molecular imaging and therapy are thoroughly summarized. Finally, current challenges and prospects are also discussed.
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http://dx.doi.org/10.1016/j.ccr.2019.213039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453726PMC
November 2019

Preparation of biochar as a coating material for biochar-coated urea.

Sci Total Environ 2020 Aug 29;731:139063. Epub 2020 Apr 29.

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China; Sino-Danish Center for Education and Research, Beijing 100190, China.

Biochar was used as a coating material for slow release urea. However, influence of biochar performance on preparing biochar-coated urea (BCU) and nitrogen release characteristics is rarely reported. In this study, total of 24 biochars were prepared and characterized from six biomass residues (rice straw, chicken manure, vinasse, Phyllostachys pubescens, Arundo donax and sugarcane bagasse) at four pyrolysis temperatures (400-700 °C). Grey correlation analysis (GCA) was used to select biochar as a coating material for BCU based on biochar performance indicators. The feasibility (BCU formability) for preparing BCU and characteristics of nitrogen release in BCU based on hydrostatic dissolution test and soil column leaching experiment were evaluated. Biochar prepared at low pyrolysis temperature was not suitable as a coating material for BCU due to low specific surface area. Biochars derived from pyrolysis of Phyllostachys pubescens (B), vinasse (B) and rice straw (B) at 600 °C were selected as coating materials for BCU based on grey correlation analysis (GCA). The adhesion of biochar to urea surface was related to biomass type that preparing biochar. B was recommended for use as coating material for BCU because the feasibility of the biochars followed the order B > B > B, and the practicality of the biochars followed the order B > B > B. The findings suggest that biochar with a high specific surface area, hydrophilic oxygen-containing functional groups and low pH is a suitable material for BCU.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139063DOI Listing
August 2020

Solvent-Assisted Self-Assembly of a Metal-Organic Framework Based Biocatalyst for Cascade Reaction Driven Photodynamic Therapy.

J Am Chem Soc 2020 04 30;142(14):6822-6832. Epub 2020 Mar 30.

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.

Biocatalytic reactions in living cells involve complex transformations in the spatially confined microenvironments. Inspired by biological transformation processes, we demonstrate effective biocatalytic cascade driven photodynamic therapy in tumor-bearing mice by the integration of an artificial enzyme (ultrasmall Au nanoparticles) with upconversion nanoparticles ([email protected]:[email protected])zirconium/iron porphyrin metal-organic framework core-shell nanoparticles (UMOF NPs) which act as biocatalysts and nanoreactors. The construction of core-shell UMOF NPs are realized by using a unique "solvent-assisted self-assembly" method. The integration of ultrasmall AuNPs on the UMOFs matrix leads to glucose depletion, providing Au-mediated cancer therapy via glucose oxidase like catalytic activity. Meanwhile, the UMOF matrix acts as a near-infrared (NIR) light photon-activated singlet oxygen generator through a continuous supply of oxygen via hydrogen peroxide decomposition upon irradiation. Such kinds of biocatalysts offer exciting opportunities for biomedical, catalytical ,and energy applications.
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http://dx.doi.org/10.1021/jacs.0c02497DOI Listing
April 2020

Graph-Based Non-Convex Low-Rank Regularization for Image Compression Artifact Reduction.

IEEE Trans Image Process 2020 Mar 3. Epub 2020 Mar 3.

Block transform coded images usually suffer from annoying artifacts at low bit-rates, because of the independent quantization of DCT coefficients. Image prior models play an important role in compressed image reconstruction. Natural image patches in a small neighborhood of the high-dimensional image space usually exhibit an underlying sub-manifold structure. To model the distribution of signal, we extract sub-manifold structure as prior knowledge. We utilize graph Laplacian regularization to characterize the sub-manifold structure at patch level. And similar patches are exploited as samples to estimate distribution of a particular patch. Instead of using Euclidean distance as similarity metric, we propose to use graph-domain distance to measure the patch similarity. Then we perform low-rank regularization on the similar-patch group, and incorporate a non-convex lp penalty to surrogate matrix rank. Finally, an alternatively minimizing strategy is employed to solve the non-convex problem. Experimental results show that our proposed method is capable of achieving more accurate reconstruction than the state-of-the-art methods in both objective and perceptual qualities.
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http://dx.doi.org/10.1109/TIP.2020.2975931DOI Listing
March 2020

Prognostic value of miR-21 in gliomas: comprehensive study based on meta-analysis and TCGA dataset validation.

Sci Rep 2020 03 6;10(1):4220. Epub 2020 Mar 6.

Department of Epidemiology and Health Statistics, Xiangya Public Health School, Central South University, Changsha, 410078, Hunan, P.R. China.

Recent studies have highlighted the value of microRNA-21 (miR-21) as a prognostic biomarker in gliomas. However, the role of miR-21 in predicting prognosis remains controversial. We performed a comprehensive study based upon a meta-analysis and The Cancer Genome Atlas (TCGA) glioma dataset validation to clarify the prognostic significance of miR-21 in glioma patients. In this study, we searched Embase, PubMed, Web of science, CNKI, SinoMed, and Wanfang databases for records up to May 2018. Relevant data were extracted to assess the correlation between miR-21 expression and survival in glioma patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to describe association strength. We further used multivariate Cox regression analysis to assess miR-21 expression in the TCGA glioma dataset to validate the relationship between miR-21 expression and survival. Nine studies were included in the meta-analysis. Among them, eight studies provided data on overall survival (OS) with a pooled HR of 1.91 (95% CI: 1.34, 2.73), indicating that higher expression of miR-21 was significantly associated with worse OS in glioma patients; for the other study, which provided data on progression-free survival (PFS), no statistically significant HR was reported for PFS in the glioma patients (HR = 1.23, 95% CI: 0.41, 3.72). A multivariate Cox regression analysis of the miR-21 expression in the TCGA glioma dataset revealed that overexpression of miR-21 was a potential independent prognostic biomarker of poorer OS (HR = 1.27, 95% CI: 1.01, 1.59) and poorer PFS (HR = 1.46, 95% CI: 1.17, 1.82). Our findings suggest that higher expression of miR-21 is correlated with poorer glioma prognosis.
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http://dx.doi.org/10.1038/s41598-020-61155-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060265PMC
March 2020

Small-sized gadolinium oxide based nanoparticles for high-efficiency theranostics of orthotopic glioblastoma.

Biomaterials 2020 03 13;235:119783. Epub 2020 Jan 13.

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institute of Health, Bethesda, MD, 20892, USA. Electronic address:

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (i.e., high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthesized in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]}) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (r = 60.8 mM s, r/r = 1.1). The maximum signal enhancement (ΔSNR) for T-weighted MRI of tumors reached up to 423 ± 42% at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (<80%). ES-GON-rBSA-LF-RGD2 exhibited high biocompatibility and can transport across the in vitro BBB model and the in vivo BBB of mice due to its small particle size (d = 13.4 nm) and LF receptor mediated transcytosis. Orthotopic GBM studies reinforce that ES-GON-rBSA3-LF-RGD2 can accumulate in the orthotopic GBM and enhance the radiation therapy of GBM as an effective radiosensitizing agent.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024018PMC
March 2020

A Phototheranostic Strategy to Continuously Deliver Singlet Oxygen in the Dark and Hypoxic Tumor Microenvironment.

Angew Chem Int Ed Engl 2020 06 4;59(23):8833-8838. Epub 2020 Feb 4.

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

Continuous irradiation during photodynamic therapy (PDT) inevitably induces tumor hypoxia, thereby weakening the PDT effect. In PDT-induced hypoxia, providing singlet oxygen from stored chemical energy may enhance the cell-killing effect and boost the therapeutic effect. Herein, we present a phototheranostic ([email protected] NPs) prepared by using a 2-pyridone-based diblock polymer (PEG-Py) to encapsulate a semiconducting, heavy-atom-free pyrrolopyrrolidone-tetraphenylethylene (DPPTPE) with high singlet-oxygen-generation ability both in dichloromethane and water. The PEG-Py can trap the O generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then release O in the dark, hypoxic tumor microenvironment. Furthermore, fluorescence-imaging-guided phototherapy demonstrates that this phototheranostic could completely inhibit tumor growth with the help of laser irradiation.
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http://dx.doi.org/10.1002/anie.201914384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250713PMC
June 2020

Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation.

Autophagy 2020 10 27;16(10):1753-1770. Epub 2019 Dec 27.

Center of Molecular and Translational Medicine, Georgia State University , Atlanta, GA, USA.

Macroautophagy/autophagy, a fundamental process for degradation of macromolecules and organelles, occurs constitutively at a basal level and is upregulated in response to stress. Whether autophagy regulates protein acetylation and microtubule stability in vascular smooth muscle cells (VSMCs) migration, however, remains unknown. Here, we demonstrate that the histone acetyltransferase KAT2A/GCN5 (lysine acetyltransferase 2) binds directly to the autophagosome protein MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) via a conserved LC3-interacting region (LIR) domain. This interaction is required for KAT2A sequestration in autophagosomes and degradation by lysosomal acid hydrolases. Suppression of autophagy results in KAT2A accumulation. KAT2A functions as an acetyltransferase to increase TUBA/α-tubulin acetylation, promote microtubule polymerization and stability, ultimately inhibiting directional cell migration. Our findings indicate that deacetylation of TUBA and perturbation of microtubule stability via selective autophagic degradation of KAT2A are essential for autophagy-promoting VSMC migration. ACTB: actin beta; ATAT1: alpha tubulin acetyltransferase 1; ATG: autophagy-related; BECN1: beclin 1; CQ: chloroquine; FBS: fetal bovine serum; GST: glutathione S-transferase; H4K16ac: histone H4 lysine 16 acetylation; HASMCs: human aortic smooth muscle cells; HBSS: Hank's buffered salt solution; HDAC6: histone deacetylase 6; hMOF: human males absent on the first; IP: immunoprecipitation; KAT2A/GCN5: lysine acetyltransferase 2A; Lacta: lactacystin; LIR: LC3-interaction region; MAP1LC3: microtubule associated protein 1 light chain 3; MEFs: mouse embryonic fibroblasts; MTOC: microtubule-organizing center; PE: phosphatidylethanolamine; PtdIns3K: class III phosphatidylinositol 3-kinase; RUNX2: runt-related transcription factor 2; SIRT1: sirtuin 1; SIRT2: sirtuin 2; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; VSMCs: vascular smooth muscle cells; WT: wild-type.
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http://dx.doi.org/10.1080/15548627.2019.1707488DOI Listing
October 2020

Preparation of a silicon-iron amendment from acid-extracted copper tailings for remediating multi-metal-contaminated soils.

Environ Pollut 2020 Feb 4;257:113565. Epub 2019 Nov 4.

Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark; Sino-Danish Center for Education and Research, Beijing 100190, China.

Industrial by-products provide materials for remediation measures. In this study, a silicon-iron amendment was prepared from residue originating from acid-extracted copper (Cu) tailings based on thermal activation at temperatures ranging from 550 °C to 1150 °C for 30 min with the use of additives (CaO, NaCO, NaOH). The remediation performance of the amendment was evaluated through soil incubation and greenhouse pot experiments with vetiver (Vetiveria zizanioides). The results showed that the highest levels of soluble Si (6.11% of the total Si) and Fe (2.3% of the total Fe) in the amendment were achieved with thermal activation at 1150 °C for 30 min using an optimal ratio between residue and additives (residue: CaO: NaCO: NaOH = 1: 0.4: 0.4: 0.2). Heavy metal release indicated that the amendment could be safely used for soil remediation. The incubation experiments showed that the DTPA-extractable Cd, Cr and Pb in contaminated soils decreased with increasing amendment rate, which was not observed for As. The amendment-induced decrease in the Cd, Cr and Pb availability in contaminated soils could be explained by pH-change induced immobilization, Fe-induced chemisorption, Si-induced co-precipitation, and Ca-induced ion exchange. Correlation analysis suggested that there were significant negative correlations between DTPA-extractable Cd, Cr and Pb and the pH, Fe, Si, and Ca in soil pore water and soil. The most suitable amendment rate was determined to be 1% by balancing the efficacy and wise utilization of the amendment. The pot experiment demonstrated that the amendment promoted the vetiver growth and stimulated the accumulation of Cd and Cr in the roots. The amendment was proved to be promising for the phytostabilization of Cd, Cr and Pb in contaminated soils. Further investigations are required to determine whether the amendment is a tool for the long-term remediation of multi-metal-contaminated soils at the field scale.
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http://dx.doi.org/10.1016/j.envpol.2019.113565DOI Listing
February 2020

Abnormally localized DLK1 interacts with NCOR1 in non-small cell lung cancer cell nuclear.

Biosci Rep 2019 12;39(12)

State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Delta-like homolog 1 (DLK1) regulates noncanonical Notch signaling pathway as ligand. DLK1 was abnormally expressed in a variety of tumors, affecting tumorigenesis and developments. The biological function of DLK1 toward cell proliferation and signaling activation was controversial across different cell types. Two currently known isoforms of DLK1, which are membrane-tethered isoform and soluble isoform, are believed to be the key of DLK1 dual behaviors. While these isoforms are not enough to explain the phenomena, our observations offer the possibility of a third isoform of DLK1. In the present study, we verified the nuclear localization of DLK1 in lung cancer cells. The nuclear localized DLK1 was observed in 107 of 351 non-small cell lung cancer (NSCLC) samples and was associated with tissue differentiation and tumor size. Through co-immunoprecipitation (co-IP) combined mass spectrometry (MS), we identified nuclear receptor corepressor 1 (NCOR1) as DLK1's novel interaction protein and confirmed their interaction in nuclear. We analyzed the expression of NCOR1 in two independent cohorts and demonstrated that NCOR1 is a tumor suppressor and has prognosis potential in lung squamous carcinomas. At last, we analyzed the colocalization of DLK1 and NCOR1 in 147 NSCLC samples by immunohistochemistry (IHC). The result indicated NCOR1 might participate with nuclear localized DLK1 in regulating cell differentiation.
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http://dx.doi.org/10.1042/BSR20192362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911156PMC
December 2019

MiRNA-211 triggers an autophagy-dependent apoptosis in cervical cancer cells: regulation of Bcl-2.

Naunyn Schmiedebergs Arch Pharmacol 2020 03 21;393(3):359-370. Epub 2019 Oct 21.

Department of Gynecology, Cancer Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081, People's Republic of China.

Cervical cancer is a significant cause of morbidity and mortality in gynecological malignancies. Although autophagy plays a critical role in affecting cell apoptosis and proliferation, the role of hsa-miR-211-5p (miR-211) in modulating autophagy of cervical cancer cells remains unclear. In the current study, the level of miR-211 was downregulated in cervical cancer specimens, compared to the paired para-carcinoma tissues. While Bcl-2 was upregulated, LC3-II/I was decreased in the tumors, indicating inhibited apoptosis and autophagy. The forced expression of miR-211 inhibited proliferation, and promoted apoptosis in SiHa cervical cancer cells, evidenced by increased expression of apoptotic proteins, caspase-3, and PARP. While the miR-211 inhibitor exerted reverse effects on C-33A cervical cancer cells. Further, miR-211 induced autophagy in cervical cancer cells, as manifested by the presence of LC3 puncta, increased LC3-II/I and Beclin1 levels, and decreased p62 level. The miR-211-induced apoptosis was alleviated by an autophagy inhibitor 3-methyladenine (3-MA). In addition, Bcl-2 was identified as a target of miR-211. Besides, the apoptosis and autophagy triggered by miR-211 were attenuated by Bcl-2 in SiHa cells. In summary, our work indicates that miR-211 induced autophagy and autophagy-dependent apoptosis by regulating Bcl-2 in cervical cancer cells, which provided further understanding of autophagy in cervical carcinogenesis.
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http://dx.doi.org/10.1007/s00210-019-01720-4DOI Listing
March 2020

Influence of CaO-activated silicon-based slag amendment on the growth and heavy metal uptake of vetiver grass (Vetiveria zizanioides) grown in multi-metal-contaminated soils.

Environ Sci Pollut Res Int 2019 Nov 9;26(31):32243-32254. Epub 2019 Sep 9.

Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg, Denmark.

Few plant species used for revegetation grow well in multi-metal-contaminated soils. Vetiver grass (Vetiveria zizanioides) is known to be tolerant of heavy metals. Vetiver has been reported to be effective for revegetation and heavy metal phytoextraction by applying targeted amendments due to its large biomass. In this study, a greenhouse vetiver pot experiment and soil incubation were performed to investigate the growth and Cd, Cr, Cu, Pb, and Zn uptake of vetiver grown in multi-metal-contaminated soils treated with a CaO-activated Si-based slag amendment (0, 0.5, 1.0, and 2.0% w/w). The results showed that the effects of slag amendment on plant growth and heavy metal uptake and distribution were dependent on the amendment dosages and metal species. Although vetiver could grow in contaminated soils, its growth was obviously inhibited. The slag amendment enhanced the vetiver growth and the highest biomass (2.62-fold over the control) was determined at a 1.0% amendment rate. The slag amendment improved plant growth by alleviating the toxicity of heavy metals in plants. This result was mainly attributed to the increases in soil pH and citric acid-extractable Si caused by alkaline amendment. The results suggest that vetiver can be applied to remediate multi-metal-contaminated soils in conjunction with the application of CaO-activated Si-based slag amendment.
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http://dx.doi.org/10.1007/s11356-019-06429-8DOI Listing
November 2019

In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects.

Small 2019 02 15;15(6):e1803866. Epub 2019 Jan 15.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Carson International Cancer Center, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.

The detection of Cu in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe (denoted as LET-2) is developed for Cu detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET-2 shifts from 625 to 715 nm after the interaction with Cu , thus producing strong PA signal output at 715 nm (PA ) as an indicator. The PA value is increased as a function of the concentration of Cu (0 × 10 -20 × 10 m), with a calculated limit of detection of 10.8 × 10 m. More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as-prepared LET-2 PA probe is highly sensitive and selective for Cu detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.
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http://dx.doi.org/10.1002/smll.201803866DOI Listing
February 2019

Spatiotemporal-Controlled Reporter for Cell-Surface Proteolytic Enzyme Activity Visualization.

Chembiochem 2019 02 28;20(4):561-567. Epub 2018 Nov 28.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Live-cell imaging of cell-surface-associated proteolytic enzymes is crucial to understand their biological roles and functions in both physiological and pathological processes. However, the complexity of the cell membrane environment increases difficulties in specifically investigating targeted proteolytic activities within the microenvironment. Towards this end, a unique, photoremovable, furin-responsive peptide probe that can undergo spatiotemporal control through UV-light illumination has been designed and synthesized to aid in visualizing the activity of a cell-surface-associated protease enzyme, furin, in live cells. Prior to light irradiation, the photolabile moiety, 4,5-dimethoxy-2-nitrobenzyl, in the peptide sequence of the reporter will block furin-like enzymatic hydrolysis, and thus, no fluorescence will be observed. Upon simple light illumination, photolysis will occur, thereby revealing the uncaged peptide probe, which can undergo enzyme hydrolysis and lead to an increase in fluorescence signal; this allows the real-time imaging of endogenous cell-surface-associated furin-like enzyme function in living cells through precise spatial and temporal resolution.
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http://dx.doi.org/10.1002/cbic.201800445DOI Listing
February 2019

Development of endogenous enzyme-responsive nanomaterials for theranostics.

Chem Soc Rev 2018 Jul;47(15):5554-5573

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China.

The development of stimuli-responsive nanomaterials provides great potential for accurate diagnosis, effective treatment and precision theranostics. Among the sources of endogenous stimuli (e.g. enzymes, pH, redox, hypoxia, etc.) and exogenous stimuli (e.g. temperature, light, magnetic field, ultrasound, light, etc.), enzymes with intrinsic merits such as high relevance for numerous diseases, specific substrate selectivity and high catalytic efficiency have been widely employed for the design of responsive materials. The catalytic mechanisms mainly include the reduction/oxidation of substrates and the formation/cleavage of chemical bonds. So far, many enzymes such as proteases, phosphatases, kinases and oxidoreductases have been used in stimuli-responsive nanomaterials for theranostics. This tutorial review summarizes the recent progress in endogenous enzyme-responsive nanomaterials based on different building blocks such as polymers, liposomes, small organic molecules, or inorganic/organic hybrid materials; their design principles are also elaborated. In the end, the challenges and prospects of enzyme-responsive biomaterials-based theranostics are also discussed.
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http://dx.doi.org/10.1039/c7cs00663bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066418PMC
July 2018
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