Publications by authors named "Mengyao Zhao"

64 Publications

Potassium Channel Protein KCNK6 Promotes Breast Cancer Cell Proliferation, Invasion, and Migration.

Front Cell Dev Biol 2021 14;9:616784. Epub 2021 Jun 14.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Breast cancer is the most common malignant tumor in women, and its incidence is increasing each year. To effectively treat breast cancer, it is important to identify genes involved in its occurrence and development and to exploit them as potential drug therapy targets. Here, we found that potassium channel subfamily K member 6 (KCNK6) is significantly overexpressed in breast cancer, however, its function in tumors has not been reported. We further verified that KCNK6 expression is upregulated in breast cancer biopsies. Moreover, overexpressed KCNK6 was found to enhance the proliferation, invasion, and migration ability of breast cancer cells. These effects may occur by weakening cell adhesion and reducing cell hardness, thus affecting the malignant phenotype of breast cancer cells. Our study confirmed, for the first time, that increased KCNK6 expression in breast cancer cells may promote their proliferation, invasion, and migration. Moreover, considering that ion channels serve as therapeutic targets for many small molecular drugs in clinical treatment, targeting KCNK6 may represent a novel strategy for breast cancer therapies. Hence, the results of this study provide a theoretical basis for KCNK6 to become a potential molecular target for breast cancer treatment in the future.
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http://dx.doi.org/10.3389/fcell.2021.616784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237943PMC
June 2021

Activatable fluorescence sensors for bio-detection in the second near-infrared window.

Chem Sci 2020 Nov 12;12(10):3448-3459. Epub 2020 Nov 12.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, iChem, Fudan University Shanghai 200433 P. R. China

Fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has exhibited advantages of high optical resolution at deeper penetration ( 5-20 mm) in bio-tissues owing to the reduced photon scattering, absorption and tissue autofluorescence. However, the non-responsive and "always on" sensors lack the ability of selective imaging of lesion areas, leading to the low signal-to-background ratio (SBR) and poor sensitivity during bio-detection. In contrast, activatable sensors show signal variation in fluorescence intensity, spectral wavelength and fluorescence lifetime after responding to the micro-environment stimuli, leading to the high detection sensitivity and reliability in bio-sensing. This minireview summarizes the design and detection ability of recently reported NIR-II activatable sensors. Furthermore, the challenges, opportunities and prospects of NIR-II activatable bio-sensing are also discussed.
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http://dx.doi.org/10.1039/d0sc04789aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179418PMC
November 2020

Nitrogen-carbon materials base on pyrolytic graphene hydrogel for oxygen reduction.

J Colloid Interface Sci 2021 Jun 8;602:274-281. Epub 2021 Jun 8.

Lab of Advanced Nano-structures & Transfer Processes, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China; Chemistry and Chemical Engineering Guangdong Laboratory, Shantou 515031 China. Electronic address:

Hypothesis: Oxygen reduction reaction (ORR) has played a significant role in the utilization of energy nowadays. Nitrogen-doped carbon materials are seen as promising catalysts for ORR, so it is of great significance in studying the functions of different nitrogen moieties.

Experiments: The graphene hydrogel-based nitrogen-arbon materials (GH N-C) were fabricated by first obtaining a gel through hydrothermal treatment using graphene oxide (GO) as precursor, and then calcined in an ammonia atmosphere at different temperatures to form N-doped graphitized materials with divers nitrogen configuration.

Findings: GH N-C materials with tunable nitrogen configuration were synthesized by a two-step method base on graphene hydrogel. Benefiting from the 3D hydrogel structure, rich defects and optimized chemical properties, GH N-C-900 prepared by NH pyrolysis at 900 °C exhibits an excellent electrocatalytic performance toward ORR, with the onset potential of 0.947 ± 0.013 V versus RHE, half-wave potential of 0.830 ± 0.010 V versus RHE, electron transfer number of 3.61-3.99, along as methanol tolerance and superior long-term stability. Comprehensive studies have shown that there is a positive correlation between the total amount of pyrrolic-N and quaternary-N and the catalytic performance of ORR.
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http://dx.doi.org/10.1016/j.jcis.2021.06.036DOI Listing
June 2021

X-ray-activated persistent luminescence nanomaterials for NIR-II imaging.

Nat Nanotechnol 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers and iChem, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, China.

Persistent luminescence is not affected by background autofluorescence, and thus holds the promise of high-contrast bioimaging. However, at present, persistent luminescent materials for in vivo imaging are mainly bulk crystals characterized by a non-uniform size and morphology, inaccessible core-shell structures and short emission wavelengths. Here we report a series of X-ray-activated, lanthanide-doped nanoparticles with an extended emission lifetime in the second near-infrared window (NIR-II, 1,000-1,700 nm). Core-shell engineering enables a tunable NIR-II persistent luminescence, which outperforms NIR-II fluorescence in signal-to-noise ratios and the accuracy of in vivo multiplexed encoding and multilevel encryption, as well as in resolving mouse abdominal vessels, tumours and ureters in deep tissue (~2-4 mm), with up to fourfold higher signal-to-noise ratios and a threefold greater sharpness. These rationally designed nanoparticles also allow the high-contrast multiplexed imaging of viscera and multimodal NIR-II persistent luminescence-magnetic resonance-positron emission tomography imaging of murine tumours.
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http://dx.doi.org/10.1038/s41565-021-00922-3DOI Listing
June 2021

Bimetallic ZIF-Derived Co/N-Codoped Porous Carbon Supported Ruthenium Catalysts for Highly Efficient Hydrogen Evolution Reaction.

Nanomaterials (Basel) 2021 May 6;11(5). Epub 2021 May 6.

Lab of Advanced Nano-Structure and Transfer Process, Department of Chemical Engineering, Tianjin University, Tianjin 300354, China.

Exploring the economical, powerful, and durable electrocatalysts for hydrogen evolution reaction (HER) is highly required for practical application. Herein, nanoclusters-decorated ruthenium, cobalt nanoparticles, and nitrogen codoped porous carbon ([email protected]) are prepared with bimetallic zeolite imidazole frameworks (ZnCo-ZIF) as the precursor. Thus, the prepared [email protected] catalyst with a low Ru loading of 3.13 wt% exhibits impressive HER catalytic behavior in 1 M KOH, with an overpotential of only 30 mV at the current density of 10 mA cm, Tafel slope as low as 32.1 mV dec, and superior stability for long-time running with a commercial 20 wt% Pt/C. The excellent electrocatalytic properties are primarily by virtue of the highly specific surface area and porosity of carbon support, uniformly dispersed Ru active species, and rapid reaction kinetics of the interaction between Ru and O.
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http://dx.doi.org/10.3390/nano11051228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148513PMC
May 2021

N6-methyladenosine-dependent signalling in cancer progression and insights into cancer therapies.

J Exp Clin Cancer Res 2021 Apr 29;40(1):146. Epub 2021 Apr 29.

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

The N6-methyladenosine (m6A) modification is a dynamic and reversible epigenetic modification, which is co-transcriptionally deposited by a methyltransferase complex, removed by a demethylase, and recognized by reader proteins. Mechanistically, m6A modification regulates the expression levels of mRNA and nocoding RNA by modulating the fate of modified RNA molecules, such as RNA splicing, nuclear transport, translation, and stability. Several studies have shown that m6A modification is dysregulated in the progression of multiple diseases, especially human tumors. We emphasized that the dysregulation of m6A modification affects different signal transduction pathways and involves in the biological processes underlying tumor cell proliferation, apoptosis, invasion and migration, and metabolic reprogramming, and discuss the effects on different cancer treatment.
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http://dx.doi.org/10.1186/s13046-021-01952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082653PMC
April 2021

Prodrug-Based Versatile Nanomedicine with Simultaneous Physical and Physiological Tumor Penetration for Enhanced Cancer Chemo-Immunotherapy.

Nano Lett 2021 05 23;21(9):3721-3730. Epub 2021 Apr 23.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.

Chemo-immunotherapy combination effect remains to be a great challenge due to the poor tumor penetration of therapeutic agents that resulted from condensed extracellular matrix (ECM), T cell-related immune escape, and thus the potential recurrence. Herein, a helix self-assembly camptothecin (CPT) prodrug with simultaneous physical and physiological tumor penetration was constructed to realize effective chemo-immunotherapy. Specifically, CPT was modified with arginine to self-assemble into nanofibers to physically improve tumor penetration. Two plasmids, shPD-L1 and Spam1 for expressing small hairpin RNA PD-L1 and hyaluronidase, respectively, were loaded to down-regulate tumor surface PD-L1 expression for converting anergic state of T cells into the tumor-reactive T cells and produce hyaluronidase to physiologically degrade ECM for further enhanced tumor penetration. Moreover, the degraded ECM could also increase immune cells' infiltration into tumor sites, which may exert a synergistic antitumor immunity combined with immune checkpoint inhibition. Such a nanomedicine could cause significant inhibition of primary, distant tumors, and effective prevention of tumor recurrence.
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http://dx.doi.org/10.1021/acs.nanolett.0c04772DOI Listing
May 2021

Current innovations in nutraceuticals and functional foods for intervention of non-alcoholic fatty liver disease.

Pharmacol Res 2021 Apr 24;166:105517. Epub 2021 Feb 24.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai 200237, China; School of Life Science, Shandong University of Technology, Zibo, Shandong 255000, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai 200237, China. Electronic address:

As innovations in global agricultural production and food trading systems lead to major dietary shifts, high morbidity rates from non-alcoholic fatty liver disease (NAFLD), accompanied by elevated risk of lipid metabolism-related complications, has emerged as a growing problem worldwide. Treatment and prevention of NAFLD and chronic liver disease depends on the availability of safe, effective, and diverse therapeutic agents, the development of which is urgently needed. Supported by a growing body of evidence, considerable attention is now focused on interventional approaches that combines nutraceuticals and functional foods. In this review, we summarize the pathological progression of NAFLD and discuss the beneficial effects of nutraceuticals and the active ingredients in functional foods. We also describe the underlying mechanisms of these compounds in the intervention of NAFLD, including their effects on regulation of lipid homeostasis, activation of signaling pathways, and their role in gut microbial community dynamics and the gut-liver axis. In order to identify novel targets for treatment of lipid metabolism-related diseases, this work broadly explores the molecular mechanism linking nutraceuticals and functional foods, host physiology, and gut microbiota. Additionally, the limitations in existing knowledge and promising research areas for development of active interventions and treatments against NAFLD are discussed.
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http://dx.doi.org/10.1016/j.phrs.2021.105517DOI Listing
April 2021

Butylphthalide Inhibits Autophagy and Promotes Multiterritory Perforator Flap Survival.

Front Pharmacol 2020 29;11:612932. Epub 2021 Jan 29.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Multiterritory perforator flap is an important plastic surgery technique, yet its efficacy can be limited by partial necrosis at the choke Ⅱ zone. Butylphthalide (NBP) has been used for many diseases but has not been studied in the multiterritory perforator flap. With the effect of NBP, we observed increasing in capillary density, inhibition of autophagy and oxidative stress, and a reduction in apoptosis of cells, all consistent with increased flap survival. However, the protective effect of NBP on multiterritory perforator flap was lost following administration of the autophagy agonist rapamycin (Rap). Through the above results, we assumed that NBP promotes flap survival by inhibiting autophagy. Thus, this study has found a new pharmacological effect of NBP on the multiterritory perforator by inhibiting autophagy to prevent distal postoperative necrosis and exert effects on angiogenesis, oxidative stress, and apoptosis within the flap.
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http://dx.doi.org/10.3389/fphar.2020.612932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878674PMC
January 2021

Neutrophil-like Cell-Membrane-Coated Nanozyme Therapy for Ischemic Brain Damage and Long-Term Neurological Functional Recovery.

ACS Nano 2021 02 11;15(2):2263-2280. Epub 2021 Jan 11.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and iChem, Fudan University, Shanghai 200433, People's Republic of China.

Oxidative stress and a series of excessive inflammatory responses are major obstacles for neurological functional recovery after ischemic stroke. Effective noninvasive anti-inflammatory therapies are urgently needed. However, unsatisfactory therapeutic efficacy of current drugs and inadequate drug delivery to the damaged brain are major problems. Nanozymes with robust anti-inflammatory and antioxidative stress properties possess therapeutic possibility for ischemic stroke. However, insufficiency of nanozyme accumulation in the ischemic brain by noninvasive administration hindered their application. Herein, we report a neutrophil-like cell-membrane-coated mesoporous Prussian blue nanozyme ([email protected]) to realize noninvasive active-targeting therapy for ischemic stroke by improving the delivery of a nanozyme to the damaged brain based on the innate connection between inflamed brain microvascular endothelial cells and neutrophils after stroke. The long-term therapeutic efficacy of [email protected] for ischemic stroke was illustrated in detail after being delivered into the damaged brain and uptake by microglia. Moreover, the detailed mechanism of ischemic stroke therapy [email protected] uptake by microglia was further studied, including microglia polarization toward M2, reduced recruitment of neutrophils, decreased apoptosis of neurons, and proliferation of neural stem cells, neuronal precursors, and neurons. This strategy may provide an applicative perspective for nanozyme therapy in brain diseases.
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http://dx.doi.org/10.1021/acsnano.0c07973DOI Listing
February 2021

NIR-II pH Sensor with a FRET Adjustable Transition Point for In Situ Dynamic Tumor Microenvironment Visualization.

Angew Chem Int Ed Engl 2021 03 26;60(10):5091-5095. Epub 2021 Jan 26.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers and iChem, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200433, China.

Monitoring the pH in tumor lesions provides abundant physiological information. However, currently developed pH sensors only achieve sensitive detection in the settled response region around the pH transition point (pH ). To realize tumor pH monitoring with high sensitivity within a wider response region, reported here are serial pH adjustable sensors (pTAS) that simply regulate the component ratio of second near-infrared (NIR-II) emission aza-BODIPY (NAB) donor and pH sensitive rhodamine-based pre-acceptor (NRh) in Förster resonance energy transfer system. Combining the pH response regions of pTAS, a twofold widened pH detection range (6.11-7.22) is obtained compared to the pH settled sensor (6.38-6.94). With an adjustable pH , in vivo tumor pH increase and decrease processes could be dynamically visualized through dual-channel ratiometric bioimaging within the NIR-II window, with a coefficient of variation under 1 % compared to the standard pH meter.
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http://dx.doi.org/10.1002/anie.202012021DOI Listing
March 2021

Bright and Stable NIR-II J-Aggregated AIE Dibodipy-Based Fluorescent Probe for Dynamic In Vivo Bioimaging.

Angew Chem Int Ed Engl 2021 02 23;60(8):3967-3973. Epub 2020 Dec 23.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers and iChem, Shanghai Key Laboratory of Molecular Catalysis and Innovative Material, Fudan University, Shanghai, 200433, China.

Organic dyes emitting in the second near-infrared (NIR-II, 900-1700 nm) window, with high molar extinction coefficients (MEC) and quantum yields (QY) in aqueous, are essential for in vivo bioimaging and biosensing. In this work, we developed a dibodipy-based aggregation-induced emission (AIE) fluorescent probe, THPP, to meet this aim. THPP exhibits a high MEC and has intensified absorption and emission in J-aggregated state, which significantly enhance the fluorescence intensity (≈55 folds) and extend the maximal absorption/emission wavelengths to 970/1010 nm in NIR-II region. Based on the bright THPP, imaging with a high frame rate (34 frames per second) at a deep "valid penetration depth" up to 6 mm can be achieved. This enabled simultaneous and dynamic imaging of vasculatures and deep tissues. Besides, we succeeded in monitoring the respiratory rate of acute-lung-injury mice and tracing the collateral circulation process with a high frame rate.
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http://dx.doi.org/10.1002/anie.202012427DOI Listing
February 2021

NIR-II bioluminescence for in vivo high contrast imaging and in situ ATP-mediated metastases tracing.

Nat Commun 2020 08 21;11(1):4192. Epub 2020 Aug 21.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers and iChem, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, 200433, Shanghai, P.R. China.

Bioluminescence imaging has been widely used in life sciences and biomedical applications. However, conventional bioluminescence imaging usually operates in the visible region, which hampers the high-performance in vivo optical imaging due to the strong tissue absorption and scattering. To address this challenge, here we present bioluminescence probes (BPs) with emission in the second near infrared (NIR-II) region at 1029 nm by employing bioluminescence resonance energy transfer (BRET) and two-step fluorescence resonance energy transfer (FRET) with a specially designed cyanine dye FD-1029. The biocompatible NIR-II-BPs are successfully applied to vessels and lymphatics imaging in mice, which gives ~5 times higher signal-to-noise ratios and ~1.5 times higher spatial resolution than those obtained by NIR-II fluorescence imaging and conventional bioluminescence imaging. Their capability of multiplexed imaging is also well displayed. Taking advantage of the ATP-responding character, the NIR-II-BPs are able to recognize tumor metastasis with a high tumor-to-normal tissue ratio at 83.4.
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http://dx.doi.org/10.1038/s41467-020-18051-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442788PMC
August 2020

Allicin inhibits osteoblast apoptosis and steroid-induced necrosis of femoral head progression by activating the PI3K/AKT pathway.

Food Funct 2020 Sep;11(9):7830-7841

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a major complication of long-term or excessive clinical use of glucocorticoids. Allicin is a classical ingredient extracted from garlic and has many functions such as anti-apoptosis and antibacterial effects. The purpose of this study was to investigate the effect and the mechanism of allicin on apoptosis of osteoblasts induced by dexamethasone (Dex) and SANFH in rats. In vitro, we performed CCK-8, western blotting, TUNEL and other experiments, and the results of these experiments showed that allicin could inhibit the Dex-induced abnormal expression of C-caspase3, C-caspase9, Bax, cytochrome C and Bcl-2 by activating the PI3K/AKT pathway. In vivo, the results of micro-CT, hematoxylin-eosin staining and immunohistochemical analysis suggested that allicin could effectively inhibit the progress of SANFH in rats. In summary, our experiments indicate that allicin is a potential drug for the treatment of SANFH.
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http://dx.doi.org/10.1039/d0fo00837kDOI Listing
September 2020

Multifunctional Smart Yolk-Shell Nanostructure with Mesoporous MnO Shell for Enhanced Cancer Therapy.

ACS Appl Mater Interfaces 2020 Sep 20;12(35):38906-38917. Epub 2020 Aug 20.

Department of Chemistry, Fudan University, Shanghai 200438, P. R. China.

Manganese dioxide (MnO) nanostructures have aroused great interest among analytical and biological medicine researchers as a unique type of tumor microenvironment (TME)-responsive nanomaterial. However, reliable approaches for synthesizing yolk-shell nanostructures (YSNs) with mesoporous MnO shell still remain exciting challenges. Herein, a YSN (size, ∼75 nm) containing a mesoporous MnO shell and Er-doped upconversion/downconversion nanoparticle (UCNP) core with a large cavity is demonstrated for the first time. This nanostructure not only integrates diverse functional components including MnO, UCNPs, and YSNs into one system but also endows a size-controllable hollow cavity and thickness-tunable MnO layers, which can load various guest molecules like photosensitizers, methylene blue (MB), and the anticancer drugs doxorubicin (DOX). NIR-II fluorescence and photoacoustic (PA) imaging from UCNP and MB, respectively, can monitor the enrichment of the nanomaterials in the tumors for guiding chemo-photodynamic therapy (PDT) . In the TME, degradation of the mMnO shell by HO and GSH not only generates Mn for tumor-specific T-MR imaging but also releases O and drugs for tumor-specific treatment. The result confirmed that imaging-guided enhanced chemo-PDT combination therapy that benefited from the unique structural features of YSNs could substantially improve the therapeutic effectiveness toward malignant tumors compared to monotherapy.
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http://dx.doi.org/10.1021/acsami.0c08389DOI Listing
September 2020

Bioactive Indolyl Diketopiperazines from the Marine Derived Endophytic DY180635.

Mar Drugs 2020 Jun 28;18(7). Epub 2020 Jun 28.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China.

Four new indolyl diketopiperazines, aspamides A-E (- and two new diketopiperazines, aspamides F-G (), along with 11 known diketopiperazines and intermediates were isolated from the solid culture of , which is an endophyte with the sea crab ( ). Further chiral high-performance liquid chromatography resolution gave enantiomers (+)- and (-)-, respectively. The structures and absolute configurations of compounds - were determined by the comprehensive analyses of nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) calculation. All isolated compounds were selected for the virtual screening on the coronavirus 3-chymoretpsin-like protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the docking scores of compounds -, , , and were top among all screened molecules, may be helpful in fighting with Corona Virus Disease-19 (COVID-19) after further studies.
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http://dx.doi.org/10.3390/md18070338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401283PMC
June 2020

Organic NIR-II molecule with long blood half-life for in vivo dynamic vascular imaging.

Nat Commun 2020 06 18;11(1):3102. Epub 2020 Jun 18.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and iChem, Fudan University, Shanghai, 200433, PR China.

Real-time monitoring of vessel dysfunction is of great significance in preclinical research. Optical bioimaging in the second near-infrared (NIR-II) window provides advantages including high resolution and fast feedback. However, the reported molecular dyes are hampered by limited blood circulation time (~ 5-60 min) and short absorption and emission wavelength, which impede the accurate long-term monitoring. Here, we report a NIR-II molecule (LZ-1105) with absorption and emission beyond 1000 nm. Thanks to the long blood circulation time (half-life of 3.2 h), the fluorophore is used for continuous real-time monitoring of dynamic vascular processes, including ischemic reperfusion in hindlimbs, thrombolysis in carotid artery and opening and recovery of the blood brain barrier (BBB). LZ-1105 provides an approach for researchers to assess vessel dysfunction due to the long excitation and emission wavelength and long-term blood circulation properties.
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http://dx.doi.org/10.1038/s41467-020-16924-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303218PMC
June 2020

A Tumor-Microenvironment-Responsive Lanthanide-Cyanine FRET Sensor for NIR-II Luminescence-Lifetime In Situ Imaging of Hepatocellular Carcinoma.

Adv Mater 2020 Jul 3;32(28):e2001172. Epub 2020 Jun 3.

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers and iChem, Fudan University, Shanghai, 200433, P. R. China.

Deep tissue imaging in the second near-infrared (NIR-II) window holds great promise for widespread fundamental research. However, inhomogeneous signal attenuation due to tissue absorption and scattering hampers its application for accurate in vivo biosensing. Here, lifetime-based in situ hepatocellular carcinoma (HCC) detection in NIR-II region is presented using a tumor-microenvironment (peroxynitrite, ONOO )-responsive lanthanide-cyanine Förster resonance energy transfer (FRET) nanosensor. A specially designed ONOO -responsive NIR-II dye, MY-1057, is synthesized as the FRET acceptor. Robust lifetime sensing is demonstrated to be independent of tissue penetration depth. Tumor lesions are accurately distinguished from normal tissue due to the recovery lifetime. Magnetic resonance imaging and liver dissection results illustrate the reliability of lifetime-based detection in single and multiple HCC models. Moreover, the ONOO amount can be calculated according to the standard curve.
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http://dx.doi.org/10.1002/adma.202001172DOI Listing
July 2020

Real-time monitoring and accurate diagnosis of drug-induced hepatotoxicity in vivo by ratio-fluorescence and photoacoustic imaging of peroxynitrite.

Nanoscale 2020 May;12(18):10216-10225

Department of Chemistry, Fudan University, Shanghai 200438, P. R. China.

Because of the low tissue penetration depth and poor photostability of organic cyanine dye, in addition to environmental interference, it is a great challenge to monitor the degree of drug-induced hepatotoxicity by the in vivo detection of peroxynitrite (ONOO-). Herein, we fabricated heptamethine cyanine dye (P-cy7)-coordinated upconversion nanoparticles (UCNPs), namely UCY7, as a fluorescent nanoprobe for evaluating drug-induced hepatotoxicity. Due to the luminescence resonance energy transfer (LRET) between UCNPs and the cyanine dye (P-cy7), the irradiation changed from visible light at 660 nm to near infrared (NIR) light at 980 nm; therefore, the issues of poor photostability and severe photobleaching of cyanine dye can be effectively solved. After injecting via the tail vein, the nanoprobes are rapidly concentrated in the liver. Since the level of ONOO- is up-regulated during the drug-induced liver injury, the LRET between UCNPs and P-cy7 is disrupted to release the upconversion luminescence at 656 nm, while the upconversion luminescence at 800 nm remains constant, thus achieving the ratio-fluorescent imaging (RFLI) of ONOO- in the liver to calibrate the influence of the environment. In addition, the reduction in the absorption of nanoprobes in the presence of ONOO- allows for sensitive photoacoustic imaging (PAI). Based on the RFLI and PAI of the liver, the real-time monitoring and accurate diagnosis of different degrees of hepatotoxicity using the model of Acetaminophen (APAP) induction was achieved successfully, providing a new approach for the clinical evaluation of drug-induced hepatotoxicity.
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http://dx.doi.org/10.1039/d0nr00963fDOI Listing
May 2020

Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration.

Chem Sci 2020 Feb 3;11(10):2819-2827. Epub 2020 Feb 3.

Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Chemistry for Energy Materials (2011-iChEM), Fudan University Shanghai 200433 P. R. China

A series of biological barriers in a nanoparticle-formulated drug delivery process inevitably result in the current low delivery efficiency, limited tumor penetration and insufficient cellular internalization of drugs. These multiple biological barriers are intimately related to the physicochemical properties of nanoparticles, especially the contradictory demand on size and surface charge for long blood circulation (larger and negative) and deep tumor penetration (smaller) as well as efficient cellular internalization (positive). Herein, we report tumor microenvironment triggered size and charge dual-transformable nanoassemblies. The nanoassembly is realized by immobilizing positive up/downconverting luminescent nanoparticles (U/DCNPs) onto large mesoporous silica nanoparticles (MSNs) acid-labile bonds to form [email protected] structured [email protected]/DCNPs nanoassemblies, and subsequent capping of charge reversible polymers. At physiological pH, the integrated nanoassemblies with a larger size (∼180 nm) and negative charge can effectively achieve a prolonged blood circulation and high tumor accumulation. While under an acidic tumor microenvironment, the charge reversal of outer polymers and cleavage of linkers between MSNs and U/DCNPs can induce disintegration of the nanoassemblies into isolated MSNs and smaller U/DCNPs, both with a positively charged surface, which thereby potentiate the tumor penetration and cell uptake of dissociated nanoparticles. Combined with the independent near-infrared (NIR)-to-visible and NIR-to-NIR luminescence of U/DCNPs and high surface area of MSNs, the nanoassemblies can implement NIR bioimaging guided chemo- and photodynamic combined therapy with remarkable antitumor efficiency because of the high accumulation and deep tumor penetration induced by the dual transformability of the nanoassemblies.
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http://dx.doi.org/10.1039/c9sc06260bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157500PMC
February 2020

The feasibility and survival mechanism of a large free flap supported by a novel hybrid perfusion mode.

Oral Oncol 2020 02 18;101:104506. Epub 2019 Dec 18.

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Orthopedics of Zhejiang Province, The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China. Electronic address:

Objectives: In this study, we presented a novel hybrid perfusion mode in an attempt to provide a new strategy to improve the survival of an extended large flap and discuss its possible mechanisms.

Materials And Methods: A 14 × 10 cm flap was designed on the rabbit abdomen. Ninety-six rabbits were randomly divided into three groups based on the flap perfusion mode: control group I (CON 1, physiological perfusion mode with bilateral deep inferior epigastric vascular pedicles intact), control group II (CON 2, physiological perfusion mode with single deep inferior epigastric vascular pedicle intact), hybrid nourished group (physiological perfusion as in CON 2 combined with arterialized venous nonphysiological perfusion mode, referred to as a hybrid perfusion mode). Flap survival, status of vascular perfusion, microvasculature, histopathology, expression of CD34, eNOs, VEGF and metabolic status of the flaps by LC-MS were assessed in each group.

Results: The results of "hybrid nourished" flaps were similar to the traditional flaps in terms of flap survival, level of vascular perfusion and microvasculature except the status of metabolites.

Conclusions: The feasibility of this novel hybrid perfusion mode will greatly extend the indications of flap transfer and efficiently improve the survival reliability of large flaps. In a sense, this mode will be an ideological emancipation for the field of flap surgery.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104506DOI Listing
February 2020

-Aggregates of Cyanine Dye for NIR-II Dynamic Vascular Imaging beyond 1500 nm.

J Am Chem Soc 2019 12 27;141(49):19221-19225. Epub 2019 Nov 27.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and iChem , Fudan University , Shanghai 200433 , P. R. China.

Light in the second near-infrared window, especially beyond 1500 nm, shows enhanced tissue transparency for high-resolution optical bioimaging due to decreased tissue scattering, absorption, and autofluorescence. Despite some inorganic luminescent nanoparticles have been developed to improve the bioimaging around 1500 nm, it is still a great challenge to synthesize organic molecules with the absorption and emission toward this region. Here, we present -aggregates with 1360 nm absorption and 1370 nm emission formed by self-assembly of amphiphilic cyanine dye FD-1080 and 1,2-dimyristoyl--glycero-3-phosphocholine. Molecular dynamics simulations were further employed to illustrate the self-assembly process. Superior spatial resolution and high signal-to-background ratio of -aggregates were demonstrated for noninvasive brain and hindlimb vasculature bioimaging beyond 1500 nm. The efficacy evaluation of the clinically used hypotensor is successfully achieved by high-resolution dynamic vascular imaging with -aggregates.
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http://dx.doi.org/10.1021/jacs.9b10043DOI Listing
December 2019

Proteomic profiling of primary astrocytes and co-cultured astrocytes/microglia exposed to acrylamide.

Neurotoxicology 2019 12 8;75:78-88. Epub 2019 Sep 8.

Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.neuro.2019.09.005DOI Listing
December 2019

Chitooligosaccharides display anti-tumor effects against human cervical cancer cells via the apoptotic and autophagic pathways.

Carbohydr Polym 2019 Nov 9;224:115171. Epub 2019 Aug 9.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai 200237, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai 200237, China. Electronic address:

Gynecological cancers are the most commonly diagnosed forms of cancer among the female population. Chitooligosaccharides (COS)-hydrolysis products from chitosan-display high bioavailability, high water solubility, and low molecular weight properties. Here, we investigated the influence of COS on 11 gynecological tumor cell types, and subsequently elucidated molecular mechanisms through which the observed inhibition occurred. Initially, we used a controllable enzyme-membrane coupling reactor system to obtain COS with a high degree of polymerization; the yield of high-degree-polymerized COS (DP 5-12) obtained with this reactor system accounted for ∼75% yields (w/w). Using these COS materials, cell line assays showed that COS elicited the most significant anti-tumor activity against C33A cells, with anti-tumor mechanisms related to oxidative stress, as well as activation of intrinsic mitochondrial apoptosis and autophagic signaling. Thus, we provide experimental evidence to demonstrate how the enzyme-membrane coupling reactor system can generate COS that exert bioactivity against gynecological cancers.
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http://dx.doi.org/10.1016/j.carbpol.2019.115171DOI Listing
November 2019

Inhibitory effect of chitooligosaccharides on retinol metabolism and bioavailability in mice.

J Food Biochem 2019 05 12;43(5):e12831. Epub 2019 Mar 12.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, China.

This study investigated the intervention effects of chitooligosaccharides (COS) on retinol metabolism and included comparisons of the retinol level, retinol binding protein 4 (RBP4) content, key genes, and protein expression between mice on a COS-enriched diet and a normal diet. The results showed that COS markedly decreased the retinol and RBP4 concentrations in the serum and liver. Furthermore, COS suppressed the mRNA and protein expression of RBP4, cellular retinol binding protein 1 (CRBP1), lecithin: retinol acyltransferase (LRAT) and cytochrome P45026A1 (CYP26A1). In addition, COS inhibited the mRNA expression of stimulated by retinoic acid 6 (STRA6). However, the protein expression of STRA6 was not significantly decreased. Thus, COS reduced the retinol concentration in the serum and disrupted the metabolism of retinol. The intervention mechanism of COS on retinol metabolism may be attributed to the modulation of RBP4, CRBP1, LRAT, STRA6, and CYP26A1 expression at the mRNA and protein levels. PRACTICAL APPLICATIONS: Chitooligosaccharides (COS), known to be the degradation products of chitosan, have been found to induce pinkeye in industrial workers who participate in the manufacturing of COS. Meanwhile, 5% population with COS dietary supplement also have similar phenomenon. The aim of this study is to explore the possible mechanism underlay of this potential risk. The results of this study showed that high exposure to COS during manufacture influences retinol metabolism and leads to a decrease in retinol content, ultimately causing pinkeye. These findings provide new evidence for understanding COS-induced retinol metabolism alteration and drawing attention toward the prevention of potential risk in high-exposure populations.
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http://dx.doi.org/10.1111/jfbc.12831DOI Listing
May 2019

Development of a novel model dough based on mechanically activated cassava starch and gluten protein: Application in bread.

Food Chem 2019 Dec 16;300:125196. Epub 2019 Jul 16.

School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.

This study focused on the development of a novel model dough for leavened food production, which was obtained by blending gluten protein with damaged cassava starch (DCS) induced by mechanical activation (MA). The characteristics of model dough and the interaction between DCS and gluten were investigated, and the quality of bread made from the model dough was also evaluated. The results showed that both the addition of gluten and the increased damage of DCS could improve the strength of model dough. The damage of cassava starch prevented the formation of gluten network. The enhanced DCS-gluten interaction had an impact on the performance of dough, attributing to the interaction of hydrogen bonds between both of them. Moderate interaction was required to obtain the bread with desired quality, and MA for moderating structural damage to starch was an effective approach in promoting the interaction between starch and gluten protein.
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http://dx.doi.org/10.1016/j.foodchem.2019.125196DOI Listing
December 2019

Damaged starch derived carbon foam-supported heteropolyacid for catalytic conversion of cellulose: Improved catalytic performance and efficient reusability.

Bioresour Technol 2019 Sep 22;288:121532. Epub 2019 May 22.

School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China.

To develop an efficient heterogeneous catalyst with good stability and reusability for catalytic conversion of cellulose to platform compounds, carbon foam (CF) was used to immobilize phosphotungstic acid (HPW) to prepare CF-supported HPW (HPW/CF) catalyst. Three-dimensional CF was prepared by carbonization of bread (precursor of CF) with mechanical activation (MA)-damaged starch, gluten protein, and yeast as materials. CF30 (30 wt% of gluten protein) exhibited good mechanical strength, relatively high specific surface area, and desired hierarchical porous structure. HPW was successfully anchored onto CF30 by grafting to prepare HPW/CF30 catalyst, which could effectively catalyze the hydrolysis of cellulose to produce glucose, especially for the hydrolysis of MA-pretreated cellulose with small granules and amorphous structure. The affinity between free hydroxyl groups of MA-pretreated cellulose and oxygen-containing groups of CF30 enhanced the catalytic efficiency of HPW/CF30. In addition, HPW/CF30 catalyst exhibited good reusability and was easily separated from reaction system for recycling.
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http://dx.doi.org/10.1016/j.biortech.2019.121532DOI Listing
September 2019

In Vivo Assembly and Disassembly of Probes to Improve Near-Infrared Optical Bioimaging.

Adv Healthc Mater 2019 07 15;8(13):e1801650. Epub 2019 May 15.

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers and iChem, Fudan University, Shanghai, 200433, P. R. China.

The near-infrared range (NIR, 700-1700 nm) has been used as a superior optical window for non-invasive bioimaging. Increasing signal-to-noise ratio (SNR) is the most fundamental method to improve NIR bioimaging. However, the low delivery efficiency of fluorescent contrast agents leads to weak signal at lesions. Moreover, non-specific accumulation and "always on" signals will cause "false positive" signals and high background noise, all of which result in low SNR and potential long-term biotoxicity. Thus, to reach precise detection of lesions, strong bioimaging signals and low background interference are the two important pre-requisites. This review provides an overview of in vivo assembly and disassembly strategies to improve tumor-specific accumulation, "turn-on" the silent signals, and reduce the background noise in NIR bioimaging windows. In vivo assembly and disassembly occurring spontaneously, responding to disease micro-environment or external stimuli, including pH, enzymes, reactive oxygen species, redox, light, and specific recognition is summarized, which may provide ideas and approaches to further enhance bioimaging and reduce long-term biotoxicity concerns.
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http://dx.doi.org/10.1002/adhm.201801650DOI Listing
July 2019

Enhanced Low Molecular Weight Poly-γ-Glutamic Acid Production in Recombinant Bacillus subtilis 1A751 with Zinc Ion.

Appl Biochem Biotechnol 2019 Oct 30;189(2):411-423. Epub 2019 Apr 30.

School of Biotechnology, State Key Laboratory of Bioreactor Engineering, R&D Center of Separation and Extraction Technology in Fermentation Industry, East China University of Science and Technology, Shanghai, 200237, China.

Poly-γ-glutamic acid (γ-PGA) is a novel biodegradable polyamide material. Microbial fermentation is the only way to produce γ-PGA, but the molecular weight of γ-PGA varied depending on different strains and culture conditions used. The molecular weight of γ-PGA is a main factor affecting the utilization of γ-PGA. It is urgent to find an efficient way to prepare γ-PGA with specific molecular weight, especially low molecular weight. Bacillus subtilis ECUST is a glutamate-dependent strain that produces γ-PGA. In this study, a recombinant B. subtilis harboring the γ-PGA synthase gene cluster pgsBCAE of our preciously identified γ-PGA-producing B. subtilis ECUST was constructed. Assay of γ-PGA contents and properties showed that recombinant B. subtilis 1A751-pBNS2-pgsBCAE obtained the ability to synthesize γ-PGA with low molecular weight (about 10 kDa). The excessive addition of glutamate inhibited the γ-PGA synthesis, while the addition of Zn could promote the synthesis of γ-PGA by increasing the transcription of pgsB but had no effect on the molecular weight of synthesized γ-PGA. Under optimized conditions, γ-PGA produced by recombinant B. subtilis 1A751-pBNS2-pgsBCAE increased from initial 0.54 g/L to 3.9 g/L, and the glutamate conversion rate reached 78%. Recombinant B. subtilis 1A751-pBNS2-pgsBCAE has the potential for efficient preparation of low molecular weight γ-PGA.
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http://dx.doi.org/10.1007/s12010-019-03004-2DOI Listing
October 2019

Absorption Characteristics of Chitobiose and Chitopentaose in the Human Intestinal Cell Line Caco-2 and Everted Gut Sacs.

J Agric Food Chem 2019 Apr 9;67(16):4513-4523. Epub 2019 Apr 9.

Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT) , Shanghai 200237 , China.

The everted gut sacs and Caco-2 cell models were used to investigate the intestinal absorptive characteristics and subcellular localization of chitobiose and chitopentaose in this study. In everted gut sacs, the absorptive pattern showed no concentration-dependent manner when the concentration was lower than 10 mM. In the presence of phlorizin (100 μM) and phloretin (100 μM), the chitobiose absorption rates decreased by (4.97 ± 0.89)% and (19.2 ± 2.77)%, and they were (10.4 ± 2.43)% and (27.5 ± 1.68)% for chitopentaose. In Caco-2 cells, the concentration showed influences similar to those with the everted gut sacs results. After adding phlorizin and phloretin in the apical side, the P of chitobiose and chitopentaose significantly decreased. Considering the translocation, they were enriched in endoplasmic reticulum and mitochondrion. This study indicated that concentration and active transporter were capable of mediating the absorption of chitobiose and chitopentaose, and the subcellular localization of them could help to study the mechanisms of their effects.
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http://dx.doi.org/10.1021/acs.jafc.9b01355DOI Listing
April 2019