Publications by authors named "Changlong Liu"

40 Publications

Metal ion implantation into transparent dielectric slab: an effective route to high-stability localized surface plasmon resonance sensors.

Nanotechnology 2021 Oct 12. Epub 2021 Oct 12.

College of Science, China University of Petroleum East China - Qingdao Campus, No. 66, West Changjiang Road, Huangdao District, Qingdao, Shandong, 266580, CHINA.

Ag/SiOand Au/SiOsamples were prepared by separately implanting 30 keV Ag and Au ions into 0.5-mm-thick SiOslabs at a fluence of 6 × 10ion/cm, and their optical and structural properties were studied in detail by using a fiber spectrometer and a transmission electron microscope, respectively. Our results showed that the two samples featured by their respective nanocomposite surface layers were asymmetrical in structure, and hence, their characteristic signals in the reflectance spectra excited by the lights incident from the rear surfaces were able to exhibit corresponding blueshifts when the overlays on the implanted surfaces were increased in refractive index with respect to air. Our results also showed that each of characteristic signals was strongly dependent on the localized surface plasmon resonance (LSPR) behavior of the involved Ag or Au nanoparticles (NPs), and it could not appear at a wavelength position smaller than or equal to that of the LSPR absorption peak since the involved Ag or Au NPs were quite small in size. These results meant that the two samples could be regarded as the LSPR sensors with a negative refractive index sensitivity (RIS), although their sensing abilities would lose when the overlays were very large in refractive index. Especially, the two samples were demonstrated to be relatively high in stability because the involved Ag and Au NPs were closely hugged and chemically protected by the matrices of SiO, and consequently, they could have a chance to become prospective sensing devices in some special fields as long as their RISs and linearities could be improved in the future. The above findings substantially confirmed that the metal ion implantation into transparent dielectric slab was an effective route to the high-stability LSPR sensors.
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http://dx.doi.org/10.1088/1361-6528/ac2f23DOI Listing
October 2021

Identification of one novel epitope targeting p54 protein of African swine fever virus using monoclonal antibody and development of a capable ELISA.

Res Vet Sci 2021 Oct 7;141:19-25. Epub 2021 Oct 7.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address:

African swine fever (ASF) is one of the most lethal viral diseases affecting both domestic pigs and wild boars. The acute infection of the ASF disease in domestic pigs leads to a 100% mortality rate with symptoms including high fever, vascular changes, cyanosis of the skin. Until now, there are no commercial vaccines and antiviral drugs available for ASF control. Therefore, the spread of ASF poses great economic losses to the pig industry and the ecosystems in the affected countries. A rapid and capable method was urgently needed to monitor ASFV-specific antibodies for controlling the spread of ASFV. In this study, we obtained one strain of monoclonal antibody (mAb) against the p54 protein of ASFV, and the target epitope of the mAb was determined to be YTHKDLENSL. The experimental results demonstrated that the monoclonal antibody could successfully recognize the exogenously expressed p54 protein and the chimeric virus constructed in our laboratory. The mAb could be used as a detection tool for the development of ASF vaccine strains. In addition, the ELISA established by using the obtained synthetic epitope peptide as the antigen had high sensitivity, good specificity and showed the great potential for ASF epidemic monitoring and control.
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http://dx.doi.org/10.1016/j.rvsc.2021.10.008DOI Listing
October 2021

The Novel PRRSV Strain HBap4-2018 with a Unique Recombinant Pattern Is Highly Pathogenic to Piglets.

Virol Sin 2021 Oct 12. Epub 2021 Oct 12.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China.

Currently, various porcine reproductive and respiratory syndrome virus (PRRSV) variants emerged worldwide with different genetic characteristics and pathogenicity, increasing the difficulty of PRRS control. In this study, a PRRSV strain named HBap4-2018 was isolated from swine herds suffering severe respiratory disease with high morbidity in Hebei Province of China in 2018. The genome of HBap4-2018 is 15,003 nucleotides in length, and compared with NADC30-like PRRSV, nsp2 of HBap4-2018 has an additional continuous deletion of five amino acids. Phylogenetic analysis based on complete genome and ORF5 showed that HBap4-2018 belonged to lineage 8 of PRRSV-2, which was characterized by highly variable genome. However, HBap4-2018 was classified into lineage 1 based on phylogenetic analysis of nsp2, sharing higher amino acid homology (85.3%-85.5%) with NADC30-like PRRSV. Further analysis suggested that HBap4-2018 was a novel natural recombinant PRRSV with three recombinant fragments in the genome, of which highly pathogenic PRRSV (HP-PRRSV) served as the major parental strains, while NADC30-like PRRSV served as the minor parental strains. Five recombination break points were identified in nsp2, nsp3, nsp5, nsp9 and ORF6, respectively, presenting a novel recombinant pattern in the genome. Piglets inoculated with HBap4-2018 presented typical clinical signs with a mortality rate of 60%. High levels of viremia and obvious macroscopic and histopathological lesions in the lungs were observed, revealing the high pathogenicity of HBap4-2018 in piglets.
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http://dx.doi.org/10.1007/s12250-021-00453-0DOI Listing
October 2021

Tunable and polarization-sensitive perfect absorber with a phase-gradient heterojunction metasurface in the mid-infrared.

Opt Express 2021 Apr;29(9):12893-12902

Inspired by the growing family of Van der Waals materials, hBN supported phonon polaritons have attracted much attention due to their inherent hyperbolic dispersion properties in the mid-infrared. However, the lack of tunability imposes a severe restriction on the diversified, functional and integrated applications. Here, we propose a phase-gradient heterostructure metasurface to realize a dynamically tunable and polarization-sensitive perfect absorber in the mid-infrared through combining hBN and phase change VO. Narrow-band perfect absorption at 7.2 µm can be switched to broadband around 11.2 µm through controlling the temperature of VO. The governed physics of the bandwidth and absorption differences are demonstrated. Phonon polaritons in hBN phase-gradient configurations and plasmon polaritons in periodic VO blocks are respectively excited. We also investigate the absorption dependence on the polarization states of designed absorber. The method of engineering the absorption through controlling the temperature and polarization states opens up a new avenue for tunable applications such as data storage and integrated optical circuits.
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http://dx.doi.org/10.1364/OE.422519DOI Listing
April 2021

Influence of thermal growth of Au nanoparticles in the coupling efficiency of Au/SiOnanocomposite grating coupler.

Nanotechnology 2021 May 14;32(31). Epub 2021 May 14.

School of Science, Tianjin University, Tianjin 300072, People's Republic of China.

The Au/SiOnanocomposite grating coupler with a period of 600 nm was fabricated by implantation of 140 keV Au ions at a fluence of 6 × 10ions·cmin combination with subsequent electron-beam lithography and ion beam etching. The thermal evolution of Au nanoparticles and its influence on the vertical coupling efficiency of the prepared grating coupler has been investigated in detail. The results clearly show that the coupling efficiency of the nanocomposite grating coupler could be affected by the thermal evolution of Au nanoparticles, which increases in the annealing temperature range up to 800 °C, and then decreases at 900 °C and above. Theoretical calculation demonstrates that the change of the coupling efficiency should be closely related to the synergistic effect of the scattering effect and the variation in the volume fraction of Au nanoparticles due to the thermal growth.
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http://dx.doi.org/10.1088/1361-6528/abfc74DOI Listing
May 2021

Colossal Terahertz Photoresponse at Room Temperature: A Signature of Type-II Dirac Fermiology.

ACS Nano 2021 Mar 23;15(3):5138-5146. Epub 2021 Feb 23.

State Key Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, 500 Yu-Tian Road, Shanghai 200083, China.

The discovery of Dirac semimetal has stimulated bourgeoning interests for exploring exotic quantum-transport phenomena, holding great promise for manipulating the performance of photoelectric devices that are related to nontrivial band topology. Nevertheless, it still remains elusive on both the device implementation and immediate results, with some enhanced or technically applicable electronic properties signified by the Dirac fermiology. By means of Pt doping, a type-II Dirac semimetal IrPtTe with protected crystal structure and tunable Fermi level has been achieved in this work. It has been envisioned that the metal-semimetal-metal device exhibits an order of magnitude performance improvement at terahertz frequency when the Fermi level is aligned with the Dirac node (, ∼ 0.3) and a room-temperature photoresponsivity of 0.52 A·W at 0.12 THz and 0.45 A·W at 0.3 THz, which benefited from the excitation of type-II Dirac fermions. Furthermore, van der Waals integration with Dirac semimetals exhibits superb performance with noise equivalent power less than 24 pW·Hz, rivaling the state-of-the-art detectors. Our work provides a route to explore the nontrivial topology of Dirac semimetal for addressing targeted applications in imaging and biomedical sensing across a terahertz gap.
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http://dx.doi.org/10.1021/acsnano.0c10304DOI Listing
March 2021

Catalytic patch with redox Cr/CeO nanozyme of noninvasive intervention for brain trauma.

Theranostics 2021 1;11(6):2806-2821. Epub 2021 Jan 1.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Institute of Advanced Materials Physics, School of Sciences, Tianjin University, Tianjin, 300350, China.

Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed and . The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Herein, the prepared Cr-doped CeO (Cr/CeO) nanozyme increases the reduced Ce states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO. Furthermore, Cr/CeO nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The experiments show the Cr/CeO nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.
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http://dx.doi.org/10.7150/thno.51912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806487PMC
July 2021

HPV-inactive cell populations arise from HPV16-transformed human keratinocytes after p53 knockout.

Virology 2021 Feb 10;554:9-16. Epub 2020 Dec 10.

Department of Pathology, Microbiology, & Immunology, School of Medicine, University of South Carolina, USA. Electronic address:

HPV-inactive head and neck and cervical cancers contain HPV DNA but do not express HPV E6/E7. HPV-positive primary head and neck tumors usually express E6/E7, however they may produce HPV-inactive metastases. These observations led to our hypothesis that HPV-inactive cancers begin as HPV-active lesions, losing dependence on E6/E7 expression during progression. Because HPV-inactive cervical cancers often have mutated p53, we investigated whether p53 loss may play a role in the genesis of HPV-inactive cancers. p53 knockout (p53-KO) by CRISPR-Cas9 resulted in a 5-fold reduction of E7 mRNA in differentiation-resistant HPV16 immortalized human keratinocytes (HKc/DR). E7 expression was restored by 5-Aza-2 deoxycytidine in p53 KO lines, suggesting a role of DNA methylation in this process. In-situ hybridization showed that p53 KO lines consist of mixed populations of E6/E7-positive and negative cells. Hence, loss of p53 predisposes HPV16 transformed cells to losing dependence on the continuous expression of HPV oncogenes for proliferation.
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http://dx.doi.org/10.1016/j.virol.2020.12.005DOI Listing
February 2021

Development of a Monoclonal Antibody Against Porcine CD163 SRCR5 Domain Which Partially Blocks Infection of PRRSV.

Front Vet Sci 2020 5;7:597843. Epub 2020 Nov 5.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Porcine reproductive and respiratory syndrome virus (PRRSV), which seriously endangers the world pig industry, invades host cells through receptor-mediated endocytosis involving clathrin. CD163 is an essential receptor for PRRSV during its infection of cells. The scavenger receptor cysteine-rich 5 (SRCR5) domain of the CD163 molecule is necessary for PRRSV infection, and interacts with glycoproteins GP2a and GP4 of PRRSV, allowing the virus to infect the host cells. In this study, a monoclonal antibody (mAb) against the SRCR5-6 region of porcine CD163 was developed, and the target epitope of the mAb was determined as TWGTVCDSDF, which is directly adjacent to the ligand-binding pocket (LBP) domain (487-495aa) of CD163. Further study indicated that the mAb could partially block PRRSV infection of its target cells, pulmonary alveolar macrophages. The mAb developed in the study may provide a foundation of antiviral therapy for PRRSV.
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http://dx.doi.org/10.3389/fvets.2020.597843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674782PMC
November 2020

Single-atom nanozymes for biological applications.

Biomater Sci 2020 Dec 3;8(23):6428-6441. Epub 2020 Nov 3.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin 300350, China.

Nanozymes have been widely used as highly active and stable arterial enzymes due to their controllable electronic transfer and unique catalytic reaction route. However, the development of nanozymes is hindered by their ambiguous structure, insufficient activity and inadequate substrate selectivity. In comparison, single-atom nanozymes (SAzymes) hold superior catalytic activity 10-100 times higher than conventional nanozymes by maximizing the utilization of metal atom dispersion, and exhibit versatile catalytic selectivity through precisely adjusting the atom spatial configuration. In this review, we highlight several well-defined SAzymes, and discuss their accurate atom configuration, catalytic mechanisms, enzyme-like activity, and applications in cancer treatment, brain disease, and wound healing. It is of great significance to understand the advantages and properties of SAzymes for further medical development.
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http://dx.doi.org/10.1039/d0bm01447hDOI Listing
December 2020

Evaluation of immune efficacy of recombinant PRRSV vectored vaccine rPRRSV-E2 in piglets with maternal derived antibodies.

Vet Microbiol 2020 Sep 27;248:108833. Epub 2020 Aug 27.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address:

Currently live attenuated porcine reproductive and respiratory syndrome (PRRS) and classical swine fever (CSF) vaccines are widely used in Chinese swine herds. However, the mutual effects of vaccination procedures and severe stress caused by successive vaccinations harm piglets and make it difficult to stimulate robust and effective immune responses. In our previous study, a recombinant PRRS virus (PRRSV) vectored vaccine candidate rPRRSV-E2, which expresses CSF virus (CSFV) E2 protein, has been demonstrated being able to protect piglets against lethal challenge of highly-pathogenic (HP)-PRRSV and CSFV. In this study, we determine whether preexisting maternally derived antibodies (MDA) interfere with the immune efficacy of rPRRSV-E2. 8 experimental groups of piglets, with or without PRRSV MDAs or CSFV MDAs were immunized with a single dose of 10 TCID rPRRSV-E2 or DMEM and challenged with HP-PRRSV or CSFV. Clinical characteristics, PRRSV- or CSFV-specific antibodies, viremia and pathological changes were monitored, examined and analyzed. The results showed that rPRRSV-E2-vaccinated piglets, either with or without MDAs directed against PRRSV or CSFV were completely protected from the lethal challenge of HP-PRRSV or CSFV. These results demonstrate that the MDAs do not interfere with the immune efficacy of rPRRSV-E2, which indicates that rPRRSV-E2 could have great significance in the effective prevention and control of HP-PRRSV and CSFV.
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http://dx.doi.org/10.1016/j.vetmic.2020.108833DOI Listing
September 2020

Porcine Reproductive and Respiratory Syndrome Virus Antagonizes PCSK9's Antiviral Effect via Nsp11 Endoribonuclease Activity.

Viruses 2020 06 17;12(6). Epub 2020 Jun 17.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry worldwide. Our previous study had indicated that proprotein convertase subtilisin/kexin type 9 (PCSK9) was a responsive gene in porcine alveolar macrophages (PAMs) upon PRRSV infection. However, whether PCSK9 impacts the PRRSV replication and how the PRRSV modulates host PCSK9 remains elusive. Here, we demonstrated that PCSK9 protein suppressed the replication of both type-1 and type-2 PRRSV species. More specifically, the C-terminal domain of PCSK9 was responsible for the antiviral activity. Besides, we showed that PCSK9 inhibited PRRSV replication by targeting the virus receptor CD163 for degradation through the lysosome. In turn, PRRSV could down-regulate the expression of PCSK9 in both PAMs and MARC-145 cells. By screening the nonstructural proteins (nsps) of PRRSV, we showed that nsp11 could antagonize PCSK9's antiviral activity. Furthermore, mutagenic analyses of PRRSV nsp11 revealed that the endoribonuclease activity of nsp11 was critical for antagonizing the antiviral effect of PCSK9. Collectively, our data provide further insights into the interaction between PRRSV and the cell host and offer a new potential target for the antiviral therapy of PRRSV.
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http://dx.doi.org/10.3390/v12060655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354446PMC
June 2020

Genetic Diversity of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) From 1996 to 2017 in China.

Front Microbiol 2020 24;11:618. Epub 2020 Apr 24.

Research Team on Porcine Viral Reproductive Disorder Syndrome, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating diseases of the global swine industry. The causative agent (PRRSV) was first isolated in China in 1996 and has evolved quickly during the last two decades. To fully understand virus diversity, epidemic situation in the field, and make future predictions, a total of 365 PRRSV strains were used for evolution and genome analysis in which 353 strains were isolated from mainland China. The results showed that high diversity was found among PRRSV isolates. Total PRRSV isolates could be divided into eight subgroups. Among these subgroups strains, Original HP-PRRSV, NADC30-like, and Intermediate PRRSV were the major epidemic PRRSV strains circling in the field and would play a major role in PRRS epidemic in the future. Deletions, insertions, and recombinations have occurred frequently in the PRRSV genome. Deletions were the main driving force of viral evolution before 2006 and may also contribute further to the virus' evolution in a relatively closed or low strain diversity circumstance. The recombinant strains could be divided into three groups: the Inner group, Extensional group, and Propagating group. The evolutionary directions of the isolates in the Extensional and Propagating groups have changed, and the routes of recombination in the Propagating group were analyzed and sorted into three types. The increases in recombinant strains and high rates of recombination in recent years indicate that recombination has played a very important role in the virus' evolution. Isolates, which incorporate the advantages of their parental strains, will influence PRRSV evolution and make adverse effects on PRRS control in the future.
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http://dx.doi.org/10.3389/fmicb.2020.00618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193098PMC
April 2020

Sensitive Terahertz Detection and Imaging Driven by the Photothermoelectric Effect in Ultrashort-Channel Black Phosphorus Devices.

Adv Sci (Weinh) 2020 Mar 19;7(5):1902699. Epub 2020 Jan 19.

State Key Laboratory of Infrared Physics Shanghai Institute of Technical Physics Chinese Academy of Sciences 500 Yu-Tian Road Shanghai 200083 China.

Terahertz (THz) photon detection is of particular appealing for myriad applications, but it still lags behind efficient manipulation with electronics and photonics due to the lack of a suitable principle satisfying both high sensitivity and fast response at room temperature. Here, a new strategy is proposed to overcome these limitations by exploring the photothermoelectric (PTE) effect in an ultrashort (down to 30 nm) channel with black phosphorus as a photoactive material. The preferential flow of hot carriers is enabled by the asymmetric Cr/Au and Ti/Au metallization with the titled-angle evaporation technique. Most intriguingly, orders of magnitude field-enhancement beyond the skin-depth limit and photon absorption across a broadband frequency can be achieved. The PTE detector has excellent sensitivity of 297 V W, noise equivalent power less than 58 pW/Hz, and response time below 0.8 ms, which is superior to other thermal-based detectors at room temperature. A rigorous comparison with existing THz detectors, together with verification by further optical-pumping and imaging experiments, substantiates the importance of the localized field effect in the skin-depth limit. The results allow solid understanding on the role of PTE effect played in the THz photoresponse, opening up new opportunities for developing highly sensitive THz detectors for addressing targeted applications.
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http://dx.doi.org/10.1002/advs.201902699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055554PMC
March 2020

Carbon dot targeting to nitrogen signaling molecules for inhibiting neuronal death.

J Mater Chem B 2020 03;8(11):2321-2330

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin 300350, China. and Tianjin International Joint Research Center for Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.

Free radical-induced oxidative damage and nitrosative stress have been identified as key factors in neuroinflammation responses after traumatic brain injury (TBI), with which reactive oxygen and nitrogen species (RONS), especially nitrogen signaling molecules, are strongly associated. Here, we prepared ultrasmall carbon dot (CD) by using a simple and facile method. In vitro assessment experiments show that the antioxidative CD exhibits an ultrahigh target-scavenging effect for nitrogen signaling molecules, especially the highly reactive ˙NO and ONOO-. However, CD can only partially eliminate conventional oxygen radials such as O2˙- and ˙OH, indicating CD has a preference for RNS modulation. Moreover, in vitro cell experiments and in vivo mice experiments reveal that CD can reduce the reactive oxygen species (ROS) level and lipid peroxidation, enhance superoxide dismutase (SOD) activity and GSSG level, and further improve the survival rate of neuron cells and TBI mice. These results declare that antioxidative CD could serve as an effective therapeutic for TBI.
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http://dx.doi.org/10.1039/c9tb02447fDOI Listing
March 2020

Carbogenic Nanozyme with Ultrahigh Reactive Nitrogen Species Selectivity for Traumatic Brain Injury.

Nano Lett 2019 07 20;19(7):4527-4534. Epub 2019 Jun 20.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences , Tianjin University , Tianjin 300350 , China.

Reactive oxygen and nitrogen species (RONS), especially reactive nitrogen species (RNS) are intermediate products during incidence of nervous system diseases, showing continuous damage for traumatic brain injury (TBI). Here, we developed a carbogenic nanozyme, which shows an antioxidant activity 12 times higher than ascorbic acid (AA) and behaves as multienzyme mimetics. Importantly, the nanozyme exhibits an ultrahigh scavenging efficiency (∼16 times higher than AA) toward highly active RNS, such as NO and ONOO as well as traditional reactive oxygen species (ROS) including O, HO, and OH. In vitro experiments show that neuron cells injured by HO or lipopolysaccharide can be significantly recovered after carbogenic nanozyme treatment via scavenging all kinds of RONS. Moreover, the carbogenic nanozyme can serve as various enzyme mimetics and eliminate the harmful peroxide and glutathione disulfide from injured mice, demonstrating its potential as a therapeutic for acute TBI.
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http://dx.doi.org/10.1021/acs.nanolett.9b01333DOI Listing
July 2019

Spindle Assembly Checkpoint Inhibition Can Resensitize p53-Null Stem Cells to Cancer Chemotherapy.

Cancer Res 2019 05 12;79(9):2392-2403. Epub 2019 Mar 12.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina

TP53 mutations are common in most human cancers, but few therapeutic options for TP53-mutant tumors exist. To identify potential therapeutic options for cancer patients with TP53 mutations, we profiled 127 FDA-approved chemotherapy drugs against human embryonic stem cells (hESC) in which we engineered TP53 deletion by genome editing. We identified 27 cancer therapeutic drugs for which TP53 mutations conferred resistance; most of these drugs target DNA synthesis or topoisomerase and cause DNA damage. We then performed a genome-wide CRISPR/Cas9 knockout screen in the TP53-null hESC in the presence and absence of sublethal concentrations of cisplatin and identified 137 genes whose loss selectively resensitized the p53-null cells to this chemotherapeutic agent. Gene ontology classification of the resensitizing loci revealed significant overrepresentation of spindle checkpoint pathway genes. Moreover, we confirmed that targeting ZNF207/BuGZ sensitizes p53-null hESC to cisplatin. These data indicate that targeted inhibition of spindle assembly checkpoints (SAC) and chromosomal organizing centers may provide a way to treat p53-deficient cancer cells with standard chemotherapy drugs. Development of small-molecule inhibitors of SAC proteins may be a useful strategy for rescuing DNA-damaging chemotherapeutics in TP53-mutant cancers. SIGNIFICANCE: These findings show that inhibition of spindle assembly checkpoints and chromosomal organizing centers may provide a new way to treat p53-deficient cancer cells with standard chemotherapy drugs.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-3024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497569PMC
May 2019

Redox Trimetallic Nanozyme with Neutral Environment Preference for Brain Injury.

ACS Nano 2019 02 15;13(2):1870-1884. Epub 2019 Feb 15.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Institute of Advanced Materials Physics, School of Sciences , Tianjin University , Tianjin 300350 , China.

Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as O, HO, OH, and NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the OH, O, and NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.
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http://dx.doi.org/10.1021/acsnano.8b08045DOI Listing
February 2019

PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids.

Proc Natl Acad Sci U S A 2018 05 14;115(22):E5066-E5075. Epub 2018 May 14.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208;

PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes. Finally, we show that forced expression of PRDM1 in human colon cancer organoids prevents the formation and growth of colon tumor organoids in vitro. These results suggest that p53 may exert tumor-suppressive effects in part through a PRDM1-dependent silencing of stem cell genes, depleting the size of the normal intestinal stem cell compartment in response to DNA damage.
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http://dx.doi.org/10.1073/pnas.1802902115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984534PMC
May 2018

Graphene-based broadband terahertz detector integrated with a square-spiral antenna.

Opt Lett 2018 Apr;43(8):1647-1650

Raising interest in terahertz radiation (loosely defined as the 0.1∼10  THz frequency range) for the application-oriented issues in everyday life requires progressive development of fast, sensitive, and portable photodetectors. In this Letter, a broadband graphene-based terahertz detector with good integrability and sensitivity at room temperature is proposed. It is based on the chemical vapor deposited-grown graphene integrated with a square-spiral metal antenna which, on one hand, improves the efficiency for electromagnetic coupling and, on the other hand, facilitates the hot-electron photo-thermoelectric process for photodetection. Sensitivity over 28 V/W at room temperature and noise-equivalent power of less than 0.35  nW/Hz are demonstrated in reference to the incident power. The presented results appealingly open an alternative way to realize chip-level graphene-based terahertz optoelectronics with good scalability and expected performance for targeted terahertz applications.
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http://dx.doi.org/10.1364/OL.43.001647DOI Listing
April 2018

Top-gated black phosphorus phototransistor for sensitive broadband detection.

Nanoscale 2018 Mar;10(13):5852-5858

State Key Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, 500 Yutian Road, Shanghai 200083, China. and Synergetic Innovation Center of Quantum Information & Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

The present work reports on a graphene-like material that is promising for photodetection applications due to its high optical absorption and layer-dependent properties. To date, only narrowband photodetectors have been realized; therefore, extending the working wavelength is becoming more imperative for applications such as high-contrast imaging and remote sensing. In this work, we developed a novel detection technique that provides enhanced performance across the infrared and terahertz bands by using an antenna-assisted top-gated black phosphorus phototransistor. By using the proposed sophisticated design, the adverse effect due to the back-gate that is generally employed for a long-wavelength photon coupling can be eliminated. Moreover, the antenna-assisted near-field and dark current can be further tailored electromagnetically and electrostatically by employing a gate finger, thus resulting in improved detection efficiency. Various detection mechanisms such as thermoelectric, bolometric, and electron-hole generation are differentiated on the basis of the device geometry and incident wavelength. The proposed photodetector demonstrated superior performance-excellent sensitivity of more than 10 V W-1, a noise equivalent power value of less than 0.1 nW Hz-0.5, and a fast response time across disparate wavebands. Thus, the photodetector can satisfy diverse application requirements.
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http://dx.doi.org/10.1039/C7NR09545GDOI Listing
March 2018

Hollow PtPdRh Nanocubes with Enhanced Catalytic Activities for In Vivo Clearance of Radiation-Induced ROS via Surface-Mediated Bond Breaking.

Small 2018 03 9;14(13):e1703736. Epub 2018 Feb 9.

Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin, 300350, China.

Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H O via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.
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http://dx.doi.org/10.1002/smll.201703736DOI Listing
March 2018

Growth of rutile TiO nanorods in Ti and Cu ion sequentially implanted SiO and the involved mechanisms.

Nanotechnology 2018 01;29(2):025601

School of Science, Tianjin University, Tianjin 300350, People's Republic of China.

TiO in nanoscale exhibits unique physicochemical and optoelectronic properties and has attracted much more interest of the researchers. In this work, TiO nanostructures are synthesized in amorphous SiO slices by implanting Ti ions, or sequentially implanting Ti and Cu ions combined with annealing at high temperature. The morphology, structure, spatial distribution and optical properties of the formed nanostructures have been investigated in detail. Our results clearly show that the thermal growth of TiO nanostructures in SiO substrate is significantly enhanced by presence of post Cu ion implantation, which depends strongly on the applied Cu ion fluence, as well as the annealing atmosphere. Due to the formation of CuO in the substrate, rutile TiO nanorods of large size have been well fabricated in the Ti and Cu sequentially implanted SiO after annealing in N atmosphere, in which CuO plays a role as a catalyst. Moreover, the sample with well-fabricated TiO nanorods exhibits a narrowed band gap, an enhanced optical absorption in visible region, and catalase-/peroxidase-like catalytic characteristics. Our findings provide an effective route to fabricate functional TiO nanorods in SiO via ion implantation.
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http://dx.doi.org/10.1088/1361-6528/aa9bc9DOI Listing
January 2018

Ultrasmall Pt Clusters Reducing Radiation-Induced Injuries via Scavenging Free Radicals.

J Biomed Nanotechnol 2017 Nov;13(11):1512-1521

High energy ionizing radiation was widely used in medical diagnosis and cancer radiation therapy. The high dose of X ray or ray can cause the damage of cancerous tissue as well as healthy tissue during therapy. Therefore, it is urgent to develop chemical agents to protect the healthy tissue from high energy ray invasion. Here, the ultrasmall Pt clusters were employed as the anti-radiation agents for protecting healthy cells and improving survival rate of irradiated mice. It was found that Pt clusters can reduce the DNA damages in irradiated cells. experiments show that the Pt clusters treatment can improve the survival rate of irradiated mice up to 30%. As a contrast, only-irradiated mice without Pt clusters treatment completely died after 15 days. The detailed biological experiments showed that Pt clusters can recover the bone marrow DNA level and superoxide dismutase activities via scavenging free radicals. Importantly, the ultrasmall Pt clusters can be excreted rapidly by kidney and do not cause long-term toxicity.
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http://dx.doi.org/10.1166/jbn.2017.2468DOI Listing
November 2017

Black Phosphorus Quantum Dot Induced Oxidative Stress and Toxicity in Living Cells and Mice.

ACS Appl Mater Interfaces 2017 Jun 6;9(24):20399-20409. Epub 2017 Jun 6.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Institute of Advanced Materials Physics, School of Sciences, Tianjin University , Tianjin 300350, China.

Black phosphorus (BP), as an emerging successor to layered two-dimensional materials, has attracted extensive interest in cancer therapy. Toxicological studies on BP are of great importance for potential biomedical applications, yet not systemically explored. Herein, toxicity and oxidative stress of BP quantum dots (BPQDs) at cellular, tissue, and whole-body levels are evaluated by performing the systemic in vivo and in vitro experiments. In vitro investigations show that BPQDs at high concentration (200 μg/mL) exhibit significant apoptotic effects on HeLa cells. In vivo investigations indicate that oxidative stress, including lipid peroxidation, reduction of catalase activity, DNA breaks, and bone marrow nucleated cells (BMNC) damage, can be induced by BPQDs transiently but recovered gradually to healthy levels. No apparent pathological damages are observed in all organs, especially in the spleen and kidneys, during the 30-day period. This work clearly shows that BPQDs can cause acute toxicities by oxidative stress responses, but the inflammatory reactions can be recovered gradually with time for up to 30 days. Thus, BPQDs do not give rise to long-term appreciable toxicological responses.
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http://dx.doi.org/10.1021/acsami.7b02900DOI Listing
June 2017

Hematopoietic stem/progenitor cell differentiation towards myeloid lineage is modulated by LIGHT/LIGHT receptor signaling.

J Cell Physiol 2018 Feb 24;233(2):1095-1103. Epub 2017 May 24.

Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai, China.

The cytokine LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) is a member of the tumor necrosis factor (TNF) superfamily. It is expressed primarily on activated T lymphocytes, and detectable on monocytes, granulocytes, and immune dendritic cells. It mainly plays a role in immune regulation including T cell activation and dendritic cell maturation. We recently reported its role as an inducer in embryonic stem cell differentiation, but its role in regulation of adult stem cell has not been defined. In the present study, we examined the expression of LIGHT receptor in Lin c-kit Sca-1 hematopoietic stem/progenitor cells (HSC/HPCs). We found that HSC express HVEM, a LIGHT receptor, on its surface. We further identified the role of LIGHT in promoting myeloid differentiation of HSCs driven by granulocyte-monocyte colony stimulating factor (GM-CSF). Further studies showed that LIGHT enhances both GM-CSF and GM-CSF receptor (GM-CSFR) expression in HSCs. LIGHT stimulation increases PU.1 expression in HSC/HPCs. In vivo administration of LIGHT increases the colony-forming unit-granulocyte/monocyte (CFU-GM) colony formation and plasma GM-CSF level. Altogether, the data suggest LIGHT promote myeloid differentiation of HSC/HPCs.
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http://dx.doi.org/10.1002/jcp.25967DOI Listing
February 2018

Ultrasmall WS Quantum Dots with Visible Fluorescence for Protection of Cells and Animal Models from Radiation-Induced Damages.

ACS Biomater Sci Eng 2017 Mar 9;3(3):460-470. Epub 2017 Feb 9.

Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Institute of Advanced Materials Physics, School of Sciences, Tianjin 300350, China.

Two-dimensional WS materials have attracted wide attention in condensed physics and materials science due to its unique geometric and electronic structures. Particularly, WS shows extraordinary catalytic activities when its size decreases to ultrasmall, which provides potential opportunities for medical applications. In this work, WS quantum dots with strong catalytic properties were used for in vitro and in vivo protection from ionizing radiation induced cell damages. WS quantum dots possess unique optical properties of blue photoluminescence emission and excitation-wavelength dependent emission profiles. In vitro studies showed that cell viability can be considerably improved and cellular reactive oxygen species (ROS) can be removed by WS quantum dots. In vivo studies showed WS quantum dots can effectively protect the hematopoietic system and DNA from damages caused by high-energy radiation through removing whole-body excessive ROS. Furthermore, WS quantum dots showed nearly 80% renal clearance within 24 h post injection and did not cause any obvious toxicities in up to 30 days after treatment.
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http://dx.doi.org/10.1021/acsbiomaterials.6b00714DOI Listing
March 2017

Identification and characterization of HPV-independent cervical cancers.

Oncotarget 2017 Feb;8(8):13375-13386

University of South Carolina College of Pharmacy, Columbia, SC, USA.

Background: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies.

Results: While virtually all cervical cancers contained HPV DNA, and most expressed E6/E7 (HPV-active), a subset (8%) of HPV DNA-positive cervical cancers did not express HPV transcripts (HPV-inactive). HPV-inactive tumors occurred in older women (median 54 vs. 45 years, p = 0.02) and were associated with poorer survival (median 715 vs 3046 days, p = 0.0003). Gene expression profiles of HPV-active and -inactive tumors were distinct. HPV-active tumors expressed E2F target genes and increased AKT/MTOR signaling. HPV-inactive tumors had increased WNT/β-catenin and Sonic Hedgehog signaling. Substantial genome-wide differences in DNA methylation were observed. HPV-inactive tumors had a global decrease in DNA methylation; however, many promoter-associated CpGs were hypermethylated. Many inflammatory response genes showed promoter methylation and decreased expression. The somatic mutation landscapes were significantly different. HPV-active tumors carried few somatic mutations in driver genes, whereas HPV-inactive tumors were enriched for non-synonymous somatic mutations (p-value < 0.0000001) specifically targeting TP53, ARID, WNT, and PI3K pathways.

Materials And Methods: The Cancer Genome Atlas (TCGA) cervical cancer data were analyzed.

Conclusions: Many of the gene expression changes and somatic mutations found in HPV-inactive tumors alter pathways for which targeted therapeutics are available. Treatment strategies focused on WNT, PI3K, or TP53 mutations may be effective against HPV-inactive tumors and could improve survival for these cervical cancer patients.
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http://dx.doi.org/10.18632/oncotarget.14533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355105PMC
February 2017

Dynamic metamaterial based on the graphene split ring high-Q Fano-resonnator for sensing applications.

Nanoscale 2016 Aug;8(33):15196-204

National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, 500 Yu Tian Road, Shanghai, Shanghai 200083, China. and Synergetic Innovation Center of Quantum Information & Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China and University of Chinese Academy of Science, 19 Yuquan Road, Beijing 100049, China.

Structured plasmonic metamaterials offer a new way to design functionalized optical and electrical components, since they can be size-scaled for operation across the whole electromagnetic spectrum. Here, we theoretically investigated electrical active split ring resonators based on graphene metamaterials on a SiO2/Si substrate that shows tunable frequency and amplitude modulation. For the symmetrical structure, the modulation depth of the frequency and amplitude can reach 58.58% and 99.35%, and 59.53% and 97.7% respectively in the two crossed-polarization orientations. Once asymmetry is introduced in the structure, the higher order mode which is inaccessible in the symmetrical structure can be excited, and a strong interaction among the modes in the split ring resonator forms a transparency window in the absorption band of the dipole resonance. Such metamaterials could facilitate the design of active modulation, and slow light effect for terahertz waves. Potential outcomes such as higher sensing abilities and higher-Q resonances at terahertz frequencies are demonstrated through numerical simulations with realistic parameters.
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http://dx.doi.org/10.1039/c6nr02321eDOI Listing
August 2016

Highly Catalytic Nanodots with Renal Clearance for Radiation Protection.

ACS Nano 2016 04 28;10(4):4511-9. Epub 2016 Mar 28.

Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.

Ionizing radiation (gamma and X-ray) is widely used in industry and medicine, but it can also pose a significant hazardous effect on health and induce cancer, physical deformity, and even death, due to DNA damage and invasion of free radicals. There is therefore an urgent unmet demand in designing highly efficient radioprotectants with synergetic integration of effective renal clearance and low toxicity. In this study, we designed ultrasmall (sub-5 nm) highly catalytically active and cysteine-protected MoS2 dots as radioprotectants and investigated their application in protection against ionizing radiation. In vivo preclinical studies showed that the surviving fraction of MoS2-treated mice can appreciably increase to up to 79% when they were exposed to high-energy ionizing radiation. Furthermore, MoS2 dots can contribute in cleaning up the accumulated free radicals within the body, repairing DNA damage, and recovering all vital chemical and biochemical indicators, suggesting their unique role as free radical scavengers. MoS2 dots showed rapid and efficient urinary excretion with more than 80% injected dose eliminated from the body after 24 h due to their ultrasmall hydrodynamic size and did not cause any noticeable toxic responses up to 30 days.
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http://dx.doi.org/10.1021/acsnano.6b00321DOI Listing
April 2016
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