Publications by authors named "Yuling Zhao"

97 Publications

Ultra-Fine Ruthenium Oxide Quantum Dots/Reduced Graphene Oxide Composite as Electrodes for High-Performance Supercapacitors.

Nanomaterials (Basel) 2022 Apr 4;12(7). Epub 2022 Apr 4.

College of Physics, Qingdao University, No. 308 Ningxia Road, Qingdao 266071, China.

This study synthesized ultra-fine nanometer-scaled ruthenium oxide (RuO) quantum dots (QDs) on reduced graphene oxide (rGO) surface by a facile and rapid microwave-assisted hydrothermal approach. Benefiting from the synergistic effect of RuO and rGO, RuO/rGO nanocomposite electrodes showed ultra-high capacitive performance. The impact of different RuO loadings in RuO/rGO nanocomposite on their electrochemical performance was investigated by various characterizations. The composite RG-2 with 38 wt.% RuO loadings exhibited a specific capacitance of 1120 F g at 1 A g. In addition, it has an excellent capacity retention rate of 84 % from 1A g to 10 A g, and excellent cycling stability of 89% retention after 10,000 cycles, indicating fast ion-involved redox reactions on the nanocomposite surfaces. These results illustrate that RuO/rGO composites prepared by this facile process can be an ideal candidate electrode for high-performance supercapacitors.
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http://dx.doi.org/10.3390/nano12071210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000793PMC
April 2022

Energy-Saving Synthesis of Functional CoS/rGO Interlayer With Enhanced Conversion Kinetics for High-Performance Lithium-Sulfur Batteries.

Front Chem 2021 10;9:830485. Epub 2022 Feb 10.

College of Physics, Qingdao University, Qingdao, China.

Lithium sulfur (Li-S) battery has exhibited great application potential in next-generation high-density secondary battery systems due to their excellent energy density and high specific capacity. However, the practical industrialization of Li-S battery is still affected by the low conductivity of sulfur and its discharge product (LiS/LiS), the shuttle effect of lithium polysulfide (LiS, 4 ≤ n ≤ 8) during charging/discharging process and so on. Here, cobalt disulfide/reduced graphene oxide (CoS/rGO) composites were easily and efficiently prepared through an energy-saving microwave-assisted hydrothermal method and employed as functional interlayer on commercial polypropylene separator to enhance the electrochemical performance of Li-S battery. As a physical barrier and second current collector, the porous conductive rGO can relieve the shuttle effect of polysulfides and ensure fast electron/ion transfer. Polar CoS nanoparticles uniformly distributed on rGO provide strong chemical adsorption to capture polysulfides. Benefitting from the synergy of physical and chemical constraints on polysulfides, the Li-S battery with CoS/rGO functional separator exhibits enhanced conversion kinetics and excellent electrochemical performance with a high cycling initial capacity of 1,122.3 mAh g at 0.2 C, good rate capabilities with 583.9 mAh g at 2 C, and long-term cycle stability (decay rate of 0.08% per cycle at 0.5 C). This work provides an efficient and energy/time-saving microwave hydrothermal method for the synthesis of functional materials in stable Li-S battery.
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http://dx.doi.org/10.3389/fchem.2021.830485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867214PMC
February 2022

Corrigendum to "GDNF-expressing macrophages restore motor functions at a severe late-stage and produce long-term neuroprotective effects at an early-stage of Parkinson's disease in transgenic Parkin Q311X(A) mice", [J Control Release, 315 (2019) 139-149].

J Control Release 2022 Mar 25;343:813-814. Epub 2022 Jan 25.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jconrel.2022.01.007DOI Listing
March 2022

A record ammonia adsorption by calcium chloride confined in covalent organic frameworks.

Chem Commun (Camb) 2022 Jan 25;58(8):1151-1154. Epub 2022 Jan 25.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, P. R. China.

Ammonia is a vital chemical raw material, but it is also a highly toxic environmenal pollutant. However, its highly efficient uptake and reversible release is a challenge. Herein, we have designed and synthesized a series of hybrid materials for efficient NH capture by confining calcium chloride (CaCl) in a porous covalent organic framework (COF). A high capture capacity of 26.5 mmol g is obtained at 25 °C and 1 bar, which is the highest value among existing porous materials, and NH can be easily desorbed at 80 °C under vacuum for 2 h. Particularly, the hybrid COF is highly efficient for the absorption of low NH content. Such excellent performance is ascribed to the highly dispersion of CaCl in the pores of the COF, and coordinating interaction of NH to Ca together with hydrogen bond interaction between NH and Cl.
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http://dx.doi.org/10.1039/d1cc06308aDOI Listing
January 2022

Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates.

Adv Biol (Weinh) 2022 02 22;6(2):e2101293. Epub 2021 Dec 22.

Center for NanotechFnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Discovery of novel drug delivery systems to the brain remains a key task for successful treatment of neurodegenerative disorders. Herein, the biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs), and monocyte-derived EVs are investigated in adult rhesus macaques using longitudinal PET/MRI imaging. Cu-labeled drug carriers are introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images are acquired at 1, 24, and 48 h post injection of Cu-labeled drug carriers, and standardized uptake values (SUV and SUV ) in the main organs are estimated. The brain retention for both types of carriers increases based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produces higher brain retention compared to IT injection of EVs. In contrast, EVs show superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrates no cytotoxic effects of either carrier. Overall, living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery.
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http://dx.doi.org/10.1002/adbi.202101293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825682PMC
February 2022

Extracellular Vesicles as Drug Delivery System for Treatment of Neurodegenerative Disorders: Optimization of the Cell Source.

Adv Nanobiomed Res 2021 Dec 29;1(12). Epub 2021 Jun 29.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Extracellular vesicles (EVs) represent a next generation drug delivery system that combines nanoparticle size with extraordinary ability to cross biological barriers, reduced immunogenicity, and low offsite toxicity profiles. A successful application of this natural way of delivering biological compounds requires deep understanding EVs intrinsic properties inherited from their parent cells. Herein, we evaluated EVs released by cells of different origin, with respect to drug delivery to the brain for treatment of neurodegenerative disorders. The morphology, size, and zeta potential of EVs secreted by primary macrophages (mEVs), neurons (nEVs), and astrocytes (aEVs) were examined by nanoparticle NTA, DLS, cryoTEM, and AFM. Spherical nanoparticles with average size 110-130 nm and zeta potential around -20 mV were identified for all EVs types. mEVs showed the highest levels of tetraspanins and integrins compared to nEVs and aEVs, suggesting superior adhesion and targeting to the inflamed tissues by mEVs. Strikingly, aEVs were preferentially taken up by neuronal cells , followed by mEVs and nEVs. Nevertheless, the brain accumulation levels of mEVs in a transgenic mouse model of Parkinson's disease were significantly higher than those of nEVs or aEVs. Therefore, mEVs were suggested as the most promising nanocarrier system for drug delivery to the brain.
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http://dx.doi.org/10.1002/anbr.202100064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680291PMC
December 2021

Diagnostic significance of microRNA-1255b-5p in prostate cancer patients and its effect on cancer cell function.

Bioengineered 2021 12;12(2):11451-11460

Department of Disinfection Supply Center, Traditional Chinese Medical Hospital of Huangdao District Qingdao, Qingdao Shandong, China.

Discerning between indolent and aggressive types is a big challenge of prostate cancer clinically to guide the adequate therapeutic regimen. We aimed to examine the relationship between miR-1255b-p expression and prostate cancer and elucidate the function of miR-1255b-5p in prostate cancer. miR-1255b-5p were measured using Quantitative Real-Time PCR from the blood 103 benign prostate hyperplasia (BPH) and 153 prostate cancer patients (117 indolent cases and 36 upgrading cases). Using receiver operating characteristic (ROC) curve analysis, the discriminating ability of miR-1255b-5p was accessed between BPH and prostate cancer participants, or indolent and aggressive type. Using CCK-8 and Transwell assays, the function of miR-1255b-5p on prostate cancer cells was investigated. The levels of miR-1255b-5p were significantly raised in prostate cancer patients when compared with BPH participants. MiR-1255b-5p level can distinguish prostate cancer patients from BPH or indolent type from aggressive type. Downregulation of miR-1255b-5p can suppress the proliferative, invasive, and migratory capacity, but this effect can be eradicated by inhibition. The measurement of miR-1255b-5p in blood may provide a new noninvasive approach for the diagnosis of prostate cancer. miR-1255b-5p may become a potential therapeutic target for prostate cancer.
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http://dx.doi.org/10.1080/21655979.2021.2009413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810192PMC
December 2021

MicroRNA-4732 is downregulated in non-small cell lung cancer and inhibits tumor cell proliferation, migration, and invasion.

Respir Med Res 2021 Nov 21;80:100865. Epub 2021 Oct 21.

Department of Laboratory, Traditional Chinese medical hospital of Huangdao District Qingdao, 158 Hainan Island Road, Qingdao 266550, Shandong, China. Electronic address:

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death with increasing morbidity and mortality. MicroRNA-4732-5p (miR-4732-5p) has been reported to be dysregulated in various cancers and identified as a tumor suppressor. This study aims to explore the expression and role of miR-4732-5p in NSCLC.

Methods: Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) assay was employed to detect the expression of miR-4732-5p in NSCLC. With the help of Kaplan-Meier survival and Cox regression, the prognostic significance of miR-4732-5p was investigated. Meanwhile, the effects of miR-4732-5p on cell proliferation, migration, and invasion were also studied.

Results: The expression of miR-4732-5p decreased in NSCLC tissues and cells. The downregulation of miR-4732-5p was closely associated with lymph node metastasis, TNM stage, and poor prognosis. Multivariate Cox regression analysis results showed that miR-4732-5p was an independent prognosis factor for NSCLC. In addition, the overexpression of miR-4732-5p inhibited the proliferation, migration, and invasion of NSCLC cells through modulating TSPAN13.

Conclusions: These data showed that miR-4732-5p might be involved in the development of NSCLC, which can act as an independent prognostic biomarker and therapeutic target.
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http://dx.doi.org/10.1016/j.resmer.2021.100865DOI Listing
November 2021

Corrigendum to "Exosomes as drug delivery vehicles for Parkinson's disease therapy" [Journal of Controlled Release 207, (2015) 18-30].

J Control Release 2021 Nov 2;339:232-234. Epub 2021 Oct 2.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jconrel.2021.09.027DOI Listing
November 2021

Surveillance of Antimalarial Drug-Resistance Genes in Imported Isolates From Nigeria in Henan, China, 2012-2019.

Front Cell Infect Microbiol 2021 23;11:644576. Epub 2021 Apr 23.

Department of Parasite Disease Control and Prevention, Henan Provincial Center for Disease Control and Prevention, Henan Key Laboratory of Infectious Disease Microbiology, Zhengzhou, China.

Malaria remains a major public health issue in Nigeria, and Nigeria is one of the main sources of imported malaria in China. Antimalarial drug resistance is a significant obstacle to the control and prevention of malaria globally. The molecular markers associated with antimalarial drug resistance can provide early warnings about the emergence of resistance. The prevalence of antimalarial drug resistant genes and mutants, including , , , , and , was evaluated among the imported isolates from Nigeria in Henan, China, from 2012 to 2019. Among the 167 imported isolates, the wild-type frequency of , , , , and was 98.7, 63.9, 34.8, 3.1, and 3.1%, respectively. The mutation of was rare, with just two nonsynonymous (S693F and Q613H) and two synonymous mutations (C469C and G496G) identified from four isolates. The prevalence of mutation at codon 74-76 decreased year-by-year, while the prevalence of 86Y also decreased significantly with time. The prevalence of and mutants was high. Combined mutations of and had a high prevalence of the quadruple mutant IRN-G (39.0%), followed by the octal mutant IRN-VAGGS (17.0%). These molecular findings update the known data on antimalarial drug-resistance genes and provide supplemental information for Nigeria.
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http://dx.doi.org/10.3389/fcimb.2021.644576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102827PMC
July 2021

Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer.

J Pers Med 2021 Apr 24;11(5). Epub 2021 Apr 24.

Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, D-81675 Munich, Germany.

The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors represents a potent strategy for cancer therapy. Due to the complex molecular network that regulates cell cycle progression, cancer cells often acquire resistance mechanisms against these inhibitors. Previously, our group identified molecular factors conferring resistance to CDK4/6 inhibition in bladder cancer (BLCA) that also included components within the DNA repair pathway. In this study, we validated whether a combinatory treatment approach of the CDK4/6 inhibitor Palbociclib with Poly-(ADP-Ribose) Polymerase (PARP) inhibitors improves therapy response in BLCA. First, a comparison of PARP inhibitors Talazoparib and Olaparib showed superior efficacy of Talazoparib in vitro and displayed high antitumor activity in xenografts in the chicken chorioallantoic membrane (CAM) model. Moreover, the combination of Talazoparib and the CDK4/6 inhibitor Palbociclib synergistically reduced tumor growth in Retinoblastoma protein (RB)-positive BLCA in vitro and in a CAM model, an effect that relies on Palbociclib-induced cell cycle arrest in G0/G1-phase complemented by a G2 arrest induced by Talazoparib. Interestingly, Talazoparib-induced apoptosis was reduced by Palbociclib. The combination of Palbociclib and Talazoparib effectively enhances BLCA therapy, and RB is a molecular biomarker of response to this treatment regimen.
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http://dx.doi.org/10.3390/jpm11050340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145096PMC
April 2021

An Ultrastable Crystalline Acylhydrazone-Linked Covalent Organic Framework for Efficient Removal of Organic Micropollutants from Water.

Chemistry 2021 Jun 19;27(36):9391-9397. Epub 2021 May 19.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, 453007, P. R. China.

As an important member of crystalline porous polymers, acylhydrazone-linked covalent organic frameworks (COFs) have gained much attention in recent years. However, the low structural stability imparts a limit on their practical applications. To tackle this problem, we report a simple strategy to increase the chemical stability of acylhydrazone-linked COFs by incorporating azobenzene groups in the conjugated framework. Through reinforcing the π-π stacking interactions between the adjacent layers with increased π-surface, it is surprising to find that the resulting materials exhibit extreme stability in harsh environments, such as in strong acid, strong base, aqueous educing agent and boiling water, even exposed to air for one year. As a proof-of-concept, such frameworks have been used to remove various organic micropollutants such as antibiotics, plastic components, endocrine disruptors, and carcinogens from water with high capacity, fast speed and excellent reusability over a wide pH range at environmentally relevant concentrations. The results provide a new avenue to significantly enhance the stability of COFs for practical applications.
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http://dx.doi.org/10.1002/chem.202100671DOI Listing
June 2021

Targeting Beclin1 as an Adjunctive Therapy against HIV Using Mannosylated Polyethylenimine Nanoparticles.

Pharmaceutics 2021 Feb 6;13(2). Epub 2021 Feb 6.

Department of Immunology and Nanomedicine, Florida International University, Herbert Wertheim College of Medicine, Miami, FL 33199, USA.

Using nanoparticle-based RNA interference (RNAi), we have previously shown that silencing the host autophagic protein, Beclin1, in HIV-infected human microglia and astrocytes restricts HIV replication and its viral-associated inflammatory responses. Here, we confirmed the efficacy of Beclin1 small interfering RNA (siBeclin1) as an adjunctive antiviral and anti-inflammatory therapy in myeloid human microglia and primary human astrocytes infected with HIV, both with and without exposure to combined antiretroviral (cART) drugs. To specifically target human microglia and human astrocytes, we used a nanoparticle (NP) comprised of linear cationic polyethylenimine (PEI) conjugated with mannose (Man) and encapsulated with siBeclin1. The target specificity of the PEI-Man NP was confirmed in vitro using human neuronal and glial cells transfected with the NP encapsulated with fluorescein isothiocyanate (FITC). PEI-Man-siBeclin1 NPs were intranasally delivered to healthy C57BL/6 mice in order to report the biodistribution of siBeclin1 in different areas of the brain, measured using stem-loop RT-PCR. Postmortem brains recovered at 1-48 h post-treatment with the PEI-Man-siRNA NP showed no significant changes in the secretion of the chemokines regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) and showed significant decreases in the secretion of the cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) when compared to phosphate-buffered saline (PBS)-treated brains. Nissl staining showed minimal differences between the neuronal structures when compared to PBS-treated brains, which correlated with no adverse behavioral affects. To confirm the brain and peripheral organ distribution of PEI-siBeclin1 in living mice, we used the In vivo Imaging System (IVIS) and demonstrated a significant brain accumulation of siBeclin1 through intranasal administration.
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http://dx.doi.org/10.3390/pharmaceutics13020223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915950PMC
February 2021

Light-Responsive, Reversible Emulsification and Demulsification of Oil-in-Water Pickering Emulsions for Catalysis.

Angew Chem Int Ed Engl 2021 Feb 27;60(8):3928-3933. Epub 2020 Dec 27.

Collaborative Innovation Center of Henan Province for, Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, 453007, P. R. China.

Pickering emulsions are an excellent platform for interfacial catalysis. However, developing simple and efficient strategies to achieve product separation and catalyst and emulsifier recovery is still a challenge. Herein, we report the reversible transition between emulsification and demulsification of a light-responsive Pickering emulsion, triggered by alternating between UV and visible light irradiation. The Pickering emulsion is fabricated from Pd-supported silica nanoparticles, azobenzene ionic liquid surfactant, n-octane, and water. This phase behavior is attributed to the adsorption of azobenzene ionic liquid surfactant on the surface of the nanoparticles and the light-responsive activity of ionic liquid surfactant. The Pickering emulsion can be used as a microreactor that enables catalytic reaction, product separation as well as emulsifier and catalyst recycling. Catalytic hydrogenation of unsaturated hydrocarbons at room temperature and atmospheric pressure has been performed in this system to demonstrate product separation and emulsifier and catalyst re-use.
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http://dx.doi.org/10.1002/anie.202010750DOI Listing
February 2021

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes.

Sci Rep 2020 07 16;10(1):11818. Epub 2020 Jul 16.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Cell-based drug delivery systems have generated an increasing interest in recent years. We previously demonstrated that systemically administered macrophages deliver therapeutics to CNS, including glial cell line-derived neurotrophic factor (GDNF), and produce potent effects in Parkinson's disease (PD) mouse models. Herein, we report fundamental changes in biodistribution and brain bioavailability of macrophage-based formulations upon different routes of administration: intravenous, intraperitoneal, or intrathecal injections. The brain accumulation of adoptively transferred macrophages was evaluated by various imaging methods in transgenic Parkin Q311(X)A mice and compared with those in healthy wild type littermates. Neuroinflammation manifested in PD mice warranted targeting macrophages to the brain for each route of administration. The maximum amount of cell-carriers in the brain, up to 8.1% ID/g, was recorded followed a single intrathecal injection. GDNF-transfected macrophages administered through intrathecal route provided significant increases of GDNF levels in different brain sub-regions, including midbrain, cerebellum, frontal cortex, and pons. No significant offsite toxicity of the cell-based formulations in mouse brain and peripheral organs was observed. Overall, intrathecal injection appeared to be the optimal administration route for genetically modified macrophages, which accomplished targeted gene delivery, and significant expression of reporter and therapeutic genes in the brain.
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http://dx.doi.org/10.1038/s41598-020-68874-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366622PMC
July 2020

Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes.

Cells 2020 05 20;9(5). Epub 2020 May 20.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

CLN2 Batten disease (BD) is one of a broad class of lysosomal storage disorders that is characterized by the deficiency of lysosomal enzyme, TPP1, resulting in a build-up of toxic intracellular storage material in all organs and subsequent damage. A major challenge for BD therapeutics is delivery of enzymatically active TPP1 to the brain to attenuate progressive loss of neurological functions. To accomplish this daunting task, we propose the harnessing of naturally occurring nanoparticles, extracellular vesicles (EVs). Herein, we incorporated TPP1 into EVs released by immune cells, macrophages, and examined biodistribution and therapeutic efficacy of EV-TPP1 in BD mouse model, using various routes of administration. Administration through intrathecal and intranasal routes resulted in high TPP1 accumulation in the brain, decreased neurodegeneration and neuroinflammation, and reduced aggregation of lysosomal storage material in BD mouse model, CLN2 knock-out mice. Parenteral intravenous and intraperitoneal administrations led to TPP1 delivery to peripheral organs: liver, kidney, spleen, and lungs. A combination of intrathecal and intraperitoneal EV-TPP1 injections significantly prolonged lifespan in BD mice. Overall, the optimization of treatment strategies is crucial for successful applications of EVs-based therapeutics for BD.
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http://dx.doi.org/10.3390/cells9051273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290714PMC
May 2020

The "1-3-7" Approach to Malaria Surveillance and Response - Henan Province, China, 2012-2018.

China CDC Wkly 2020 Apr;2(17):289-292

Henan Center for Disease Prevention and Control, Zhengzhou, China.

The "1-3-7" approach to malaria surveillance and response was a key measure for malaria elimination in China and was first introduced into the World Health Organization (WHO) as an international guideline for malaria surveillance and response in 2018.



The "1-3-7" approach was well implemented in Henan Province from 2012-2018. Over this study period, a total of 1,294 malaria cases were detected and reported, and all cases were diagnosed and reported within 1 day with 99.23% (1,284/1,294) of cases were investigated within 3 days. In addition, 93.7% (1,212/1,294) of foci were investigated and vector control was implemented within 7 days at all residual non-active foci to prevent further spread.



The "1-3-7" controlling pattern would be an effective and approachable method for implementation especially in malaria-eliminating countries and regions, but the interval from symptom onset to diagnosis cannot be ignored. Thus, the roles and responsibilities that all actors involved in the health sector must be specified too.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422168PMC
April 2020

Macrophage-Derived Extracellular Vesicles as Drug Delivery Systems for Triple Negative Breast Cancer (TNBC) Therapy.

J Neuroimmune Pharmacol 2020 09 13;15(3):487-500. Epub 2019 Nov 13.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Efficient targeted delivery of anticancer agents to TNBC cells remains one of the greatest challenges to developing therapies. The lack of tumor-specific markers, aggressive nature of the tumor, and unique propensity to recur and metastasize make TNBC tumors more difficult to treat than other subtypes. We propose to exploit natural ability of macrophages to target cancer cells by means of extracellular vesicles (EVs) as drug delivery vehicles for chemotherapeutic agents, paclitaxel (PTX) and doxorubicin (Dox). We demonstrated earlier that macrophage-derived EVs loaded with PTX (EV-PTX) and Dox (EV-Dox) target cancer cells and exhibited high anticancer efficacy in a mouse model of pulmonary metastases. Herein, we report a manufacture and characterization of novel EV-based drug formulations using different loading procedures that were optimized by varying pH, temperature, and sonication conditions. Selected EV-based formulations showed a high drug loading, efficient accumulation in TNBC cells in vitro, and pronounced anti-proliferation effect. Drug-loaded EVs target TNBC in vivo, including the orthotopic mouse T11 tumors in immune competent BALB/C mice, and human MDA-MB-231 tumors in athymic nu/nu mice, and abolished tumor growth. Overall, EV-based formulations can provide a novel solution to a currently unmet clinical need and reduce the morbidity and mortality of TNBC patients. Graphical Abstract Macrophage-derived extracellular vesicles (EVs) for targeted drug delivery to TNBC tumors. Chemotherapeutics with different water solubility (Dox or PTX, i.e. hydrophilic or hydrophobic drugs, respectively) were loaded into macrophage-derived EVs through parental cells (Dox), or into naïve EVs (Dox or PTX), and their antitumor efficacy was demonstrated in mouse orthotopic TNBC model.
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http://dx.doi.org/10.1007/s11481-019-09884-9DOI Listing
September 2020

GDNF-expressing macrophages restore motor functions at a severe late-stage, and produce long-term neuroprotective effects at an early-stage of Parkinson's disease in transgenic Parkin Q311X(A) mice.

J Control Release 2019 12 31;315:139-149. Epub 2019 Oct 31.

Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address:

There is an unmet medical need in the area of Parkinson's disease (PD) to develop novel therapeutic approaches that can stop and reverse the underlying mechanisms responsible for the neuronal death. We previously demonstrated that systemically administered autologous macrophages transfected ex vivo to produce glial cell line-derived neurotrophic factor (GDNF) readily migrate to the mouse brain with acute toxin-induced neuroinflammation and ameliorate neurodegeneration in PD mouse models. We hypothesized that the high level of cytokines due to inflammatory process attracted GDNF-expressing macrophages and ensured targeted drug delivery to the PD brain. Herein, we validated a therapeutic potential of GDNF-transfected macrophages in a transgenic Parkin Q311X(A) mice with slow progression and mild brain inflammation. Systemic administration of GDNF-macrophages at a severe late stage of the disease leaded to a near complete restoration of motor functions in Parkin Q311X(A) mice and improved brain tissue integrity with healthy neuronal morphology. Furthermore, intravenous injections of GDNF-macrophages at an early stage of disease resulted in potent sustained therapeutic effects in PD mice for more than a year after the treatment. Importantly, multiple lines of evidence for therapeutic efficacy were observed including: diminished neuroinflammation and α-synuclein aggregation, increased survival of dopaminergic neurons, and improved locomotor functions. In summary, GDNF-transfected macrophages represent a promising therapeutic strategy for PD at both late- and early-stages of the disease.
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http://dx.doi.org/10.1016/j.jconrel.2019.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927551PMC
December 2019

LLG2/3 Are Co-receptors in BUPS/ANX-RALF Signaling to Regulate Arabidopsis Pollen Tube Integrity.

Curr Biol 2019 10 26;29(19):3256-3265.e5. Epub 2019 Sep 26.

State Key Laboratory for Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences at College of Life Sciences, Peking University, Beijing 100871, China; The National Plant Gene Research Center (Beijing), Beijing 100101, China. Electronic address:

In angiosperms, two sperm cells are transported and delivered by the pollen tube to the ovule to achieve double fertilization. Extensive communication takes place between the pollen tube and the female tissues until the sperm cell cargo is ultimately released. During this process, a pollen tube surface-located receptor complex composed of ANXUR1/2 (ANX1/2) and Buddha's Paper Seal 1/2 (BUPS1/2) was reported to control the maintenance of pollen tube integrity by perceiving the autocrine peptide ligands rapid alkalinization factor 4 and 19 (RALF4/19). It was further hypothesized that pollen-tube rupture to release sperm is caused by the paracrine RALF34 peptide from the ovule interfering with this signaling pathway. In this study, we identified two Arabidopsis pollen-tube-expressed glycosylphosphatidylinositol-anchored proteins (GPI-APs), LORELEI-like-GPI-anchored protein 2 (LLG2) and LLG3, as co-receptors in the BUPS-ANX receptor complex. llg2 llg3 double mutants exhibit severe fertility defects. Mutant pollen tubes rupture early during the pollination process. Furthermore, LLG2 and LLG3 interact with ectodomains of both BUPSs and ANXURs, and this interaction is remarkably enhanced by the presence of RALF4/19 peptides. We further demonstrate that the N terminus (including a YISY motif) of the RALF4 peptide ligand interacts strongly with BUPS-ANX receptors but weakly with LLGs and is essential for its biological function, and its C-terminal region is sufficient for LLG binding. In conclusion, we propose that LLG2/3 serve as co-receptors during BUPS/ANX-RALF signaling and thereby further establish the importance of GPI-APs as key regulators in plant reproduction processes.
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http://dx.doi.org/10.1016/j.cub.2019.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179479PMC
October 2019

A novel crystalline azine-linked three-dimensional covalent organic framework for CO capture and conversion.

Chem Commun (Camb) 2019 Oct;55(83):12459-12462

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China.

The targeted synthesis of three-dimensional covalent organic frameworks (3D COFs) is a great challenge, especially those synthesized by using a new kind of organic linkage. Herein, for the first time, a novel 3D azine-linked COF (3D-HNU5) has been synthesized and characterized. It is shown that the obtained 3D COF has a 2-fold interpenetrated diamond topology, and shows good chemical/thermal stability and a narrow pore size distribution, which exhibits excellent performance in the selective uptake of CO2 over N2. Moreover, the 3D-HNU5 is found to be an efficient catalyst for the cycloaddition of propargylic alcohols with CO2 into carbonates with excellent catalytic activity under mild conditions.
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http://dx.doi.org/10.1039/c9cc05710bDOI Listing
October 2019

Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China.

Antimicrob Agents Chemother 2019 10 23;63(10). Epub 2019 Sep 23.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People's Republic of China

Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as , , , , and This study evaluated the drug resistance of the 180 imported isolates from Angola via nested PCR using Sanger sequencing. The prevalences of CVMNK, NYSND, ANCSDI, and SAAKA were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in , , , and were generally shown as multiple mutations. The mutant prevalence of reduced gradually, but and still showed high mutant prevalence, while was relatively low. The mutation of the gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.
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http://dx.doi.org/10.1128/AAC.00552-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761537PMC
October 2019

Engineered xCas9 and SpCas9-NG variants broaden PAM recognition sites to generate mutations in Arabidopsis plants.

Plant Biotechnol J 2019 10 29;17(10):1865-1867. Epub 2019 May 29.

State Key Laboratory for Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences at College of Life Sciences, Peking University, Beijing, China.

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http://dx.doi.org/10.1111/pbi.13148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737014PMC
October 2019

MiR-153 regulates cardiomyocyte apoptosis by targeting Nrf2/HO-1 signaling.

Chromosome Res 2019 09 29;27(3):167-178. Epub 2019 Apr 29.

Department of Nursing, Yidu Central Hospital of Wei Fang, No. 4138, South Linglongshan Road, Weifang, 262500, Shandong, China.

MicroRNAs (miRNAs) play various roles in the regulation of human disease, including cardiovascular diseases. MiR-153 has been previously shown to be involved in regulating neuron survival during cerebral ischemia/reperfusion (I/R) injury. However, whether miR-153 is involved in I/R-induced cardiomyocyte apoptosis remains to be elucidated. In this study, we aimed to explore the role of miR-153 in the regulation of I/R-induced cardiomyocyte apoptosis and to investigate the miR-153-mediated molecular signaling pathway responsible for its effect on cardiomyocytes using an oxygen-glucose deprivation and reoxygenation (OGD/R) cellular model. We found that OGD/R treatment induced significant upregulation of miR-153 in cardiomyocytes causing reactive oxygen species (ROS) production and cell apoptosis signaling activation and subsequently leading to cardiomyocyte apoptosis. Suppression of miR-153 protected cardiomyocytes against OGD/R treatment. We further identified that nuclear factor-like 2 (Nrf2) is a functional target of miR-153. Nrf2/ heme oxygenase-1 (HO-1) signaling plays a critical role in miR-153 regulated OGD/R-induced cardiomyocyte apoptosis. Our study indicates that the inhibition of miR-153 or restoration of Nrf2 may serve as a potential therapeutic strategy for ischemia/reperfusion injury prevention.
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http://dx.doi.org/10.1007/s10577-019-09608-yDOI Listing
September 2019

TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease.

Adv Healthc Mater 2019 06 18;8(11):e1801271. Epub 2019 Apr 18.

Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV-producing macrophages with TPP1-encoding plasmid DNA (pDNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1-encoding pDNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV-TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV-TPP1 (≈70%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late-infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV-TPP1.
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http://dx.doi.org/10.1002/adhm.201801271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584948PMC
June 2019

Photo-Triggered Reversible Phase Transfer of Azobenzene-Based Ionic Liquid Surfactants between Oil and Water.

Int J Mol Sci 2019 Apr 4;20(7). Epub 2019 Apr 4.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.

The reversible phase transfer of compounds between two immiscible liquid phases has many applications in a wide range of fields, and ionic liquids have been widely used as potential functional solvents and catalysts. However, photo-triggered reversible phase transfer of ionic liquids between the organic phase and water phase has not been reported so far. In the present work, the reversible phase transfer of six kinds of azobenzene-based ionic liquid surfactants between the organic phase and water phase is investigated by alternative irradiation of UV and visible light. Factors affecting the transfer efficiency, such as chemical structure and concentration of the ionic liquid surfactants, equilibrium photo-isomerization degree, and the aggregation state of ionic liquid surfactants are investigated in detail. It is shown that transfer efficiency greater than 89% was achieved under optimal conditions, equilibrium photo-isomerization degree of the ionic liquid surfactants is the main factor to determine their transfer efficiencies, and the aggregation of -isomers is not beneficial for the transfer.
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http://dx.doi.org/10.3390/ijms20071685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479859PMC
April 2019

Cu(I)/Ionic Liquids Promote the Conversion of Carbon Dioxide into Oxazolidinones at Room Temperature.

Molecules 2019 Mar 29;24(7). Epub 2019 Mar 29.

College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, Shandong, China.

Recently, the efficient chemical fixation of carbon dioxide (CO₂) into high value chemicals without using noble metal catalysts has become extremely appealing from the viewpoint of sustainable chemistry. In this work, a one-pot three component reaction of propargylic alcohols, anines and CO₂ that can proceed in an atom economy and environmentally benign manner by combination of CuI and tetrabutylphosphonium imidazol ([P][Im]) as a catalyst was described. Catalysis studies indicate that this catalytic system is an effective catalyst for the conversion of CO₂ into oxazolidinones at room temperature and ambient pressure without any solvent. The results provide a useful way to design novel noble metal-free catalyst systems for the transformation of CO₂ into other valuable compounds.
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http://dx.doi.org/10.3390/molecules24071241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480545PMC
March 2019

Imidazolium-Salt-Functionalized Covalent Organic Frameworks for Highly Efficient Catalysis of CO Conversion.

ChemSusChem 2019 Jun 2;12(11):2421-2427. Epub 2019 May 2.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan, P. R. China.

The conversion of CO into valuable chemicals is an ideal pathway for CO utilization in industry, although the development of highly efficient catalysts remains a challenge. Herein, the design and synthesis of two covalent organic frameworks (COFs) functionalized with imidazolium salts were reported as catalysts for CO conversion. The resultant COFs possessed highly crystalline structures, showed high stability and surface area, and contained dense catalytic active sites on the pore walls. They exhibited outstanding catalytic performances for the reaction of CO with epoxides without any solvent or cocatalyst under mild conditions and afforded a record turnover number of 495 000. In addition, the COFs could serve as effective catalysts in the reductive reaction of CO with amines. The results presented here thus demonstrate the exceptional potential of the functionalized COFs for various challenging CO transformations.
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http://dx.doi.org/10.1002/cssc.201900570DOI Listing
June 2019

Controlled Synthesis of Hollow α-FeO Microspheres Assembled With Ionic Liquid for Enhanced Visible-Light Photocatalytic Activity.

Front Chem 2019 27;7:58. Epub 2019 Feb 27.

College of Physics and State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao, China.

Porous self-assembled α-FeO hollow microspheres were fabricated via an ionic liquid-assisted solvothermal reaction and sequential calcinations. The concentration of the ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate [CMim]BF) was found to play a crucial role in the control of these α-FeO hollow structures. Trace amounts ionic liquid was used as the soft template to synthesize α-FeO hollow spheres with a large specific surface (up to 220 m/g). Based on time-dependent experiments, the proposed formation mechanisms were presented. Under UV light irradiation, the as-synthesized α-FeO hollow spheres exhibited excellent photocatalysis in Rhodamine B (RhB) photodegradation and the rate constant was 2-3 times higher than α-FeO particles. The magnetic properties of α-FeO hollow structures were found to be closely associated with the shape anisotropy.
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http://dx.doi.org/10.3389/fchem.2019.00058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402386PMC
February 2019

Characterization of Plasmodium ovale spp. imported from Africa to Henan Province, China.

Sci Rep 2019 02 18;9(1):2191. Epub 2019 Feb 18.

Department of Parasite Disease Control and Prevention, Henan Province Center for Disease Control and Prevention, Zhengzhou, 450016, P. R. China.

As indigenous malaria has decreased over recent decades, the increasing number of imported malaria cases has provided a new challenge for China. The proportion of imported cases due to Plasmodium ovale has increased during this time, and the difference between P. ovale curtisi and P. ovale wallikeri is of importance. To better understand P. ovale epidemiology and the differences between the two subspecies, information on imported malaria in Henan Province was collected during 2010-2017. We carried out a descriptive study to analyze the prevalence, proportion, distribution, and origin of P. o. curtisi and P. o. wallikeri. It showed that imported P. ovale spp. accounts for a large proportion of total malaria cases in Henan Province, even more than that of P. vivax. This suggests that the proportion of P. ovale cases is underestimated in Africa. Among these cases, the latency period of P. o. curtisi was significantly longer than that of P. o. wallikeri. More attention should be paid to imported ovale malaria to avoid the reintroduction of these two subspecies into China.
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http://dx.doi.org/10.1038/s41598-019-38629-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379410PMC
February 2019
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