Publications by authors named "Qi Tong"

57 Publications

Failure Analysis and Prevention of Extraction Column for Methyl Methacrylate Production: Application of the 'Safety Design' Concept.

Materials (Basel) 2021 Jul 29;14(15). Epub 2021 Jul 29.

Department of Materials Science, Fudan University, Shanghai 200433, China.

To ensure safety and prevent failure of engineering equipment throughout its lifespan, the concept of 'Safety Design' is proposed, which covers all the cradle-to-grave phases of engineering equipment, considers at least ten essential factors of failure causes, and conducts root cause analysis at three different scales, in order to proactively control the safety risks before the occurrence of failure rather than passively conduct the remedial measures after failure. Herein, in order to demonstrate how to implement this effective and efficient concept in engineering practice, a case study of failure analysis and prevention is addressed on the extraction column in the production line for methyl methacrylate. Based on the analysis results, the causes were finally determined to be all derived from the stages before operation, including inappropriate design, limited quality inspection of fabrication and installation. Pertinent countermeasures were then proposed from the 'Safety Design' point of view, which would not only solve the failure problem for this sole equipment but also contribute to safety risk control of other engineering equipment before operation.
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http://dx.doi.org/10.3390/ma14154234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346975PMC
July 2021

Global analysis of protein lysine 2-hydroxyisobutyrylation (K) profiles in Chinese herb rhubarb (Dahuang).

BMC Genomics 2021 Jul 15;22(1):542. Epub 2021 Jul 15.

Shandong Provincial Key Laboratory of Dryland Farming Technology, College of Agronomy,, Qingdao Agricultural University, Shandong, 266109, Qingdao, China.

Background: Lysine 2-hydroxyisobutyrylation (K) is a newly discovered protein posttranslational modification (PTM) and is involved in the broad-spectrum regulation of cellular processes that are found in both prokaryotic and eukaryotic cells, including in plants. The Chinese herb rhubarb (Dahuang) is one of the most widely used traditional Chinese medicines in clinical applications. To better understand the physiological activities and mechanism of treating diseases with the herb, it is necessary to conduct intensive research on rhubarb. However, K modification has not been reported thus far in rhubarb.

Results: In this study, we performed the first global analysis of K-modified proteins in rhubarb by using sensitive affinity enrichment combined with high-accuracy HPLC-MS/MS tandem spectrometry. A total of 4333 overlapping K modification peptides matched on 1525 K-containing proteins were identified in three independent tests. Bioinformatics analysis showed that these K-containing proteins are involved in a wide range of cellular processes, particularly in protein biosynthesis and central carbon metabolism and are distributed mainly in chloroplasts, cytoplasm, nucleus and mitochondria. In addition, the amino acid sequence motif analysis showed that a negatively charged side chain residue (E), a positively charged residue (K), and an uncharged residue with the smallest side chain (G) were strongly preferred around the K site, and a total of 13 K modification motifs were identified. These identified motifs can be classified into three motif patterns, and some motif patterns are unique to rhubarb and have not been identified in other plants to date.

Conclusions: A total of 4333 K-modified peptides on 1525 proteins were identified. The K-modified proteins are mainly distributed in the chloroplast, cytoplasm, nucleus and mitochondria, and involved in a wide range of cellular processes. Moreover, three types of amino acid sequence motif patterns, including EK/KE, GK and k.kkk….K….kkkkk, were extracted from a total of 13 K-modified peptides. This study provides comprehensive K-proteome resource of rhubarb. The findings from the study contribute to a better understanding of the physiological roles of K modification, and the K proteome data will facilitate further investigations of the roles and mechanisms of K modification in rhubarb.
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http://dx.doi.org/10.1186/s12864-021-07847-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283887PMC
July 2021

IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.

Nat Microbiol 2021 07 13;6(7):932-945. Epub 2021 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during influenza virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the antiviral response.
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http://dx.doi.org/10.1038/s41564-021-00907-xDOI Listing
July 2021

Vitamin D status in women with dichorionic twin pregnancies and their neonates: a pilot study in China.

BMC Pregnancy Childbirth 2021 Apr 8;21(1):279. Epub 2021 Apr 8.

International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.

Background: Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth.

Methods: A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected.

Results: The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency.

Conclusions: Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight.

Trial Registration: Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.
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http://dx.doi.org/10.1186/s12884-021-03707-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034067PMC
April 2021

Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.

J Virol 2021 Mar 17. Epub 2021 Mar 17.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.Avian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.
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http://dx.doi.org/10.1128/JVI.01578-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139711PMC
March 2021

Large-area display textiles integrated with functional systems.

Nature 2021 03 10;591(7849):240-245. Epub 2021 Mar 10.

State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.

Displays are basic building blocks of modern electronics. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices. Display textiles serve to bridge human-machine interactions, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating, sensing and supplying electricity have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 10 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.
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http://dx.doi.org/10.1038/s41586-021-03295-8DOI Listing
March 2021

Mink is a highly susceptible host species to circulating human and avian influenza viruses.

Emerg Microbes Infect 2021 Dec;10(1):472-480

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive "mixing vessels" for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented.
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http://dx.doi.org/10.1080/22221751.2021.1899058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993395PMC
December 2021

Ultrasensitive electrochemical determination of phosphate in water by using hydrophilic TiO modified glassy carbon electrodes.

Anal Methods 2021 02 3;13(8):996-1002. Epub 2021 Feb 3.

College of Sciences, Shanghai Institute of Technology, Shanghai 201418, China.

In this paper, ultrasensitive electrochemical determination of phosphate in water is achieved by using hydrophilic TiO modified glassy carbon electrodes for the first time. The differential pulse voltammetry (DPV) method is proposed to measure phosphate in water as pulse techniques offer higher sensitivity compared with the conventional cyclic voltammetry (CV) method. Hydrophilic TiO films were obtained upon ultraviolet (UV) illumination after TiO precursor emulsions were coated on the surfaces of glassy carbon electrodes, and used for phosphate determination. Contact angle measurements (around 23.4°) proved the good hydrophilicity of the TiO modified surface upon UV illumination. A detection limit of 0.1 μg L is obtained, and a linear relationship (R = 0.99) between the phosphate concentration (ranging from 0.1 μg L to 1 μg L) and the peak current was observed.
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http://dx.doi.org/10.1039/d0ay01854fDOI Listing
February 2021

Perinatal outcomes and offspring growth profiles in twin pregnancies complicated by gestational diabetes mellitus: A longitudinal cohort study.

Diabetes Res Clin Pract 2021 Jan 13;171:108623. Epub 2020 Dec 13.

College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK.

Aims: To evaluate the influence of gestational diabetes mellitus (GDM) on the perinatal outcomes of twin pregnancies and its impact on fetal growth profiles of twin offspring from 6 weeks to 12 months of corrected age.

Methods: A longitudinal cohort study was conducted among pregnant women with twins and their twin offspring. All information on perinatal outcomes and child growth trajectories from 6 weeks to 12 months of corrected age were obtained and analyzed using a general linear model and logistic regression models.

Results: GDM was not correlated with adverse perinatal outcomes of twin pregnancies; however, in monochorionic diamniotic (MCDA), but not dichorionic diamniotic (DCDA) twin pregnancies, GDM was correlated with gestational hypertension disorder and a fetus being small for gestational age (OR, 2.68; 95% CI 1.16-6.04 and OR, 0.35; 95% CI 0.16-0.76, respectively). In both MCDA and DCDA groups, GDM was positively associated with a higher risk of childhood overweight at 6 months of corrected age (2.32 [1.05, 5.09] and 2.00 [1.13, 3.53]).

Conclusions: GDM had a greater impact on MCDA twin pregnancies in terms of maternal gestational hypertension disease and small for gestational age of newborns. Additionally, twin offspring exposed to GDM had a higher risk of being overweight at 6 months of corrected age irrespective of chorionicity.

Clinical Trial Registration: ChiCTR-OOC-16008203.
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http://dx.doi.org/10.1016/j.diabres.2020.108623DOI Listing
January 2021

Gold nanoprism/Tollens' reagent complex as plasmonic sensor in headspace single-drop microextraction for colorimetric detection of formaldehyde in food samples using smartphone readout.

Talanta 2020 Dec 11;220:121388. Epub 2020 Jul 11.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore; National University of Singapore Environmental Research Institute, T-Lab Building #02-01, 5A Engineering Drive 1, Singapore, 117411, Singapore; Tropical Marine Science Institute, National University of Singapore, S2S Building, 18 Kent Ridge Road, Singapore, 119227, Singapore. Electronic address:

In this work, an assay with high sensitivity and selectivity for the detection of formaldehyde (FA) is presented. The assay applied a gold nanoprism/Tollens' reagent (Au-np/TR) complex as the sensor used in headspace single-drop microextraction (HS-SDME). A surface plasmon resonance signal enhancement as well as color change was caused by the formation of [email protected] after a redox reaction between FA and TR during the HS-SDME process. With the utilization of smartphone nanocolorimetry (SNC), the FA could be detected and quantified. For HS-SDME-SNC, a linearity calibration curve ranging from 0.1 to 100 μM was obtained, and the limit of detection was determined to be 30 nM. Successful attempts to determine FA were demonstrated by analysis of the analyte in (adulterated) raw food samples (octopus and chicken flesh). Matrix effects from real samples were avoided by using HS-SDME, and only a 3-μL droplet of solvent was needed in the assay.
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http://dx.doi.org/10.1016/j.talanta.2020.121388DOI Listing
December 2020

Magnetic Three-Phase Single-Drop Microextraction for Rapid Amplification of the Signals of DNA and MicroRNA Analysis.

Anal Chem 2020 09 1;92(18):12290-12296. Epub 2020 Sep 1.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.

The detection of nucleic acids usually suffers from a lengthy amplification process. To obtain an enhanced signal within several seconds, a magnetic three-phase single-drop microextraction (MTP-SDME) approach was developed for the quantification of nucleic acids. First, a target-triggered recycling amplification strategy was used to constitute magnetic branched DNA/FeO networks, which displayed peroxidase-like catalytic activity toward the 3,3',5,5'-tetramethylbenzidine colorimetric reaction. The networks were separated and enriched by rapid (6 s) MTP-SDME (with only 6 μL of solvent required), thereby producing highly sensitive signals for the quantification of nucleic acids. The signals were significantly amplified by the triple strategy (network formation, MTP-SDME, and catalytic reaction). The application of magnetic extraction minimized the background signal, avoided sample matrix effects, and enhanced the analyte signals. This assay achieved linear calibration curves of between 0.5 aM and 1 pM for microRNA-122 (miRNA-122) and between 1 aM and 1 pM for HBV-T (a DNA fragment from hepatitis B virus). Limits of detection of 0.15 aM for miRNA-122 and 0.34 aM for HBV-T were attained, with relative standard deviations of <5.0% ( = 3). Furthermore, the procedure was applied to determine miRNA-122 and HBV-T in genuine serum samples from hepatocellular carcinoma patients.
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http://dx.doi.org/10.1021/acs.analchem.0c01936DOI Listing
September 2020

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection.

Proc Natl Acad Sci U S A 2020 07 29;117(29):17204-17210. Epub 2020 Jun 29.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 100193 Beijing, China;

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.
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http://dx.doi.org/10.1073/pnas.1921186117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382246PMC
July 2020

Truncation of PA-X Contributes to Virulence and Transmission of H3N8 and H3N2 Canine Influenza Viruses in Dogs.

J Virol 2020 07 16;94(15). Epub 2020 Jul 16.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

Equine-origin H3N8 and avian-origin H3N2 canine influenza viruses (CIVs) prevalent in dogs are thought to pose a public health threat arising from intimate contact between dogs and humans. However, our understanding of CIV virulence is still limited. Influenza A virus PA-X is a fusion protein encoded in part by a +1 frameshifted open reading frame (X-ORF) in segment 3. The X-ORF can be translated in full-length (61-amino-acid) or truncated (41-amino-acid) form. Genetic analysis indicated that the X-ORFs of equine H3N8 and avian H3N2 influenza viruses encoded 61 amino acids but were truncated after introduction into dogs. To determine the effect of PA-X truncation on the biological characteristics of CIVs, we constructed four recombinant viruses on H3N8 and H3N2 CIV backgrounds bearing truncated or full-length PA-Xs. We observed that truncation of PA-X increased growth of both H3N8 and H3N2 CIVs in MDCK cells and suppressed expression from cotransfected plasmids in MDCK cells. Furthermore, truncation of PA-X enhanced viral pathogenicity in dogs, as shown by aggravated clinical symptoms and histopathological changes, increased viral replication in the respiratory system, and prolonged virus shedding. Additionally, CIVs with truncated PA-Xs were transmitted more efficiently in dogs. Global gene expression profiling of the lungs of infected dogs revealed that differentially expressed genes were mainly associated with inflammatory responses, which might contribute to the pathogenicity of PA-X-truncated CIVs. Our findings revealed that truncation of PA-X might be important for the adaptation of influenza viruses to dogs. Epidemics of equine-origin H3N8 and avian-origin H3N2 influenza viruses in canine populations are examples of successful cross-species transmission of influenza A viruses. Genetic analysis showed that the PA-X genes of equine H3N8 or avian H3N2 influenza viruses were full-length, with X-ORFs encoding 61 amino acids; however, those of equine-origin H3N8 or avian-origin H3N2 CIVs were truncated, suggesting that PA-X truncation occurred after transmission to dogs. In this study, we extended the PA-X genes of H3N8 and H3N2 CIVs and compared the biological characteristics of CIVs bearing different lengths of PA-X. We demonstrated that for both H3N8 and H3N2 viruses, truncation of PA-X increased virus yields in MDCK cells and enhanced viral replication, pathogenicity, and transmission in dogs. These results might reflect enhanced suppression of host gene expression and upregulation of genes related to inflammatory responses. Collectively, our data partially explain the conservation of truncated PA-X in CIVs.
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http://dx.doi.org/10.1128/JVI.00949-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375373PMC
July 2020

A D200N hemagglutinin substitution contributes to antigenic changes and increased replication of avian H9N2 influenza virus.

Vet Microbiol 2020 Jun 30;245:108669. Epub 2020 Apr 30.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. Electronic address:

Influenza virus hemagglutinin (HA) plays an important role in viral antigenicity, replication and host range. However, few amino acid positions in HA were reported to play multiple functions in both viral antigenicity and replication. In the present study, through analyzing the amino acid sequences of H9N2 avian influenza viruses (AIVs) isolated from China, we identified a multi-functional substitution of D200N in HA1 protein. Firstly, the substitution of D200N changed the antigenicity of H9N2 AIVs. Secondly, the D200N increased the HA cleavage efficiency and reduced acid and thermal stability of HA protein, which triggered viral-endosomal membrane fusion whereby promoted the release of viral genome into the host cytoplasm. Finally, residue 200-N increased the replication of H9N2 viruses in both chicken embryo fibroblast (CEF) cells and chicken embryonated eggs. In summary, the D200N substitution is a newly identified antigenicity and replication determinant of H9N2 AIVs, which should be paid more attention during surveillance.
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http://dx.doi.org/10.1016/j.vetmic.2020.108669DOI Listing
June 2020

Pre-pregnancy body mass index and time to pregnancy among couples pregnant within a year: A China cohort study.

PLoS One 2020 23;15(4):e0231751. Epub 2020 Apr 23.

NHC Key Lab. of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai, China.

Background: Extreme pre-pregnancy body mass index (BMI) values have been associated with reduced fecundability and prolonged time to pregnancy in previous studies. However, the effect in fertile couples is unclear.

Objectives: This study aimed to evaluate the association between pre-pregnancy BMI and fecundability, measured as time to pregnancy (TTP), among couples that achieved pregnancy within 1 year.

Methods: This was a retrospective cohort study of 50,927 couples wishing to conceive, enrolled in the National Free Preconception Health Examination Project (NFPHEP) in Chongqing, China, during 2012-2016. Participants' weight and height were measured by NFPHEP-trained preconception guidance physicians. TTP measured in months was used to determine subfecundity (TTP >6 months). The strength of association between BMI and TTP/subfecundity was measured with fecundability odds ratios (FOR)/odds ratios (OR) and their corresponding 95% confidence intervals (CI), calculated with Cox and logistic regression analysis. We used restricted cubic spline regression (RCS) to test the observed FOR trends.

Results: Compared to women with normal BMI, women with pre-pregnancy overweight/obesity had longer TTP (FOR = 0.96, 95% CI: 0.94-0.99) and increased risk of subfecundity (OR = 1.08, 95% CI: 1.00-1.17). There was no association between TTP and male BMI. RCS trends varied when data were stratified by male pre-pregnancy BMI, with the greatest change detected in pre-pregnancy underweight men.

Conclusions: Pre-pregnancy overweight/obesity was associated with longer TTP and subfecundity among women who became pregnant within 1 year; this effect was likely mediated by their partners' pre-pregnancy BMI. These findings indicate that BMI could affect fecundability, independently of affecting the risk of sterility. Advice on weight management and maintaining healthy weight should be included in couples' preconception guidance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231751PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179844PMC
July 2020

An R195K Mutation in the PA-X Protein Increases the Virulence and Transmission of Influenza A Virus in Mammalian Hosts.

J Virol 2020 05 18;94(11). Epub 2020 May 18.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

In the 21st century, the emergence of H7N9 and H1N1/2009 influenza viruses, originating from animals and causing severe human infections, has prompted investigations into the genetic alterations required for cross-species transmission. We previously found that replacement of the human-origin PA gene segment in avian influenza virus (AIV) could overcome barriers to cross-species transmission. Recently, it was reported that the PA gene segment encodes both the PA protein and a second protein, PA-X. Here, we investigated the role of PA-X. We found that an H9N2 avian influenza reassortant virus bearing a human-origin H1N1/2009 PA gene was attenuated in mice after the loss of PA-X. Reverse genetics analyses of PA-X substitutions conserved in human influenza viruses indicated that R195K, K206R, and P210L substitutions conferred significantly increased replication and pathogenicity on H9N2 virus in mice and ferrets. PA-X R195K was present in all human H7N9 and H1N1/2009 viruses and predominated in human H5N6 viruses. Compared with PA-X 195R, H7N9 influenza viruses bearing PA-X 195K showed increased replication and transmission in ferrets. We further showed that PA-X 195K enhanced lung inflammatory responses, potentially due to decreased host shutoff function. A competitive transmission study in ferrets indicated that 195K provides a replicative advantage over 195R in H1N1/2009 viruses. In contrast, PA-X 195K did not influence the virulence of H9N2 AIV in chickens, suggesting that the effects of the substitution were mammal specific. Therefore, future surveillance efforts should scrutinize this region of PA-X because of its potential impact on cross-species transmission of influenza viruses. Four influenza pandemics in humans (the Spanish flu of 1918 [H1N1], the Asian flu of 1957 [H2N2], the Hong Kong flu of 1968 [H3N2], and the swine origin flu of 2009 [H1N1]) are all proposed to have been caused by avian or swine influenza viruses that acquired virulence factors through adaptive mutation or reassortment with circulating human viruses. Currently, influenza viruses circulating in animals are repeatedly transmitted to humans, posing a significant threat to public health. However, the molecular properties accounting for interspecies transmission of influenza viruses remain unclear. In the present study, we demonstrated that PA-X plays an important role in cross-species transmission of influenza viruses. At least three human-specific amino acid substitutions in PA-X dramatically enhanced the adaptation of animal influenza viruses in mammals. In particular, PA-X 195K might have contributed to cross-species transmission of H7N9, H5N6, and H1N1/2009 viruses from animal reservoirs to humans.
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http://dx.doi.org/10.1128/JVI.01817-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269435PMC
May 2020

Highly Sensitive Detection of Multiple MicroRNAs by High-Performance Liquid Chromatography Coupled with Long and Short Probe-Based Recycling Amplification.

Anal Chem 2020 04 20;92(7):5033-5040. Epub 2020 Mar 20.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.

This report demonstrated the utility of high-performance liquid chromatography (HPLC)-fluorescence detection for selective separation and sensitive quantification of multiple microRNAs (miRNAs). A duplex specific nuclease (DSN)-assisted target recycling amplification strategy was developed to enhance the signals of miRNAs, which alleviates the low sensitivity of conventional HPLC to nucleic acids. To separate the signals of different miRNAs, DNA probes with different lengths and base sequences were immobilized on magnetic beads. The application of an effective magnetic separation minimized the background signal and extended the dynamic range. This assay achieved a limit of detection of 0.39 fM for miRNA-122, 0.30 fM for miRNA-155, and 0.26 fM for miRNA-21, respectively. The proposed assay was successfully applied to detect simultaneously miRNA-122, miRNA-155, and miRNA-21 in serum samples from healthy persons and cervical cancer patients, and the results were then compared with those of quantitative real-time-polymerase chain reaction amplification.
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http://dx.doi.org/10.1021/acs.analchem.9b05301DOI Listing
April 2020

Direct immersion single-drop microextraction of semi-volatile organic compounds in environmental samples: A review.

J Hazard Mater 2020 07 24;393:122403. Epub 2020 Feb 24.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore. Electronic address:

Single-drop microextraction (SDME) techniques are efficient approaches to pretreatment of aqueous samples. The main advantage of SDME lies in the miniaturization of the solvent extraction process, minimizing the hazards associated with the use of toxic organic solvents. Thus, SDME techniques are cost-effective, and represent less harm to the environment, subscribing to green analytical chemistry principles. In practice, two main approaches can be used to perform SDME - direct immersion (DI)-SDME and headspace (HS)-SDME. Even though the DI-SDME has been shown to be quite effective for extraction and enrichment of various organic compounds, applications of DI-SDME are normally more suitable for moderately polar and non-polar semi-volatile organic compounds (SVOCs) using organic solvents which are immiscible with water. In this review, we present a historical overview and current advances in DI-SDME, including the common analytical tools which are usually coupled with DI-SDME. The review also focuses on applications concerning SVOCs in environmental samples. Currents trends in DI-SDME and possible future direction of the procedure are discussed.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122403DOI Listing
July 2020

Synthesis of chromone-containing polycyclic compounds via palladium-catalyzed [2 + 2 + 1] annulation.

Org Biomol Chem 2020 02 27;18(6):1112-1116. Epub 2020 Jan 27.

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563006, P. R. China. and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, P. R. China.

A palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, α-bromo carbonyl compounds, and tetracyclododecene (TCD) is described. This approach provides a facile, efficient and atom-economical route to a variety of chromone-containing polycyclic compounds bearing fused/bridged-ring systems in good yields (up to 81%) with excellent diastereoselectivities (99 : 1 dr in all cases).
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http://dx.doi.org/10.1039/c9ob02690hDOI Listing
February 2020

Mouse-adapted H9N2 avian influenza virus causes systemic infection in mice.

Virol J 2019 11 12;16(1):135. Epub 2019 Nov 12.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

Background: H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages - A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage -and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses.

Finding: ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses.

Conclusions: Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.
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http://dx.doi.org/10.1186/s12985-019-1227-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852949PMC
November 2019

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling.

PLoS Pathog 2019 10 4;15(10):e1008062. Epub 2019 Oct 4.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-κB and IRF3 signaling. Furthermore, we showed that PGRN directly interacted with NF-κB essential modulator (NEMO) via its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that macrophage played a major source of PGRN during influenza virus infection, and PGRN neutralizing antibodies could protect against influenza virus-induced lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway exploited by influenza virus with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of PGRN in innate immunity.
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http://dx.doi.org/10.1371/journal.ppat.1008062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795447PMC
October 2019

Redox-Activated Porphyrin-Based Liposome Remote-Loaded with Indoleamine 2,3-Dioxygenase (IDO) Inhibitor for Synergistic Photoimmunotherapy through Induction of Immunogenic Cell Death and Blockage of IDO Pathway.

Nano Lett 2019 10 24;19(10):6964-6976. Epub 2019 Sep 24.

State Key Laboratory of Natural and Biomimetic Drugs , Peking University , Beijing 100191 , China.

Immunotherapy through stimulating the host immune system has emerged as a powerful therapeutic strategy for various malignant and metastatic tumors in the clinic. However, harnessing the immune system for cancer treatment often fails to obtain a durable response rate due to the poor immunogenicity and the strong immunosuppressive milieu in the tumor site. Herein, a redox-activated liposome was developed from the self-assembly of the porphyrin-phospholipid conjugate and coencapsulation of indoleamine 2,3-dioxygenase (IDO) inhibitor into the interior lumen via remote-loading for simultaneous induction of immunogenic cell death (ICD) and reversing of suppressive tumor microenvironment. The nanoparticle exhibited prolonged blood circulation and enhanced tumor accumulation in the 4T1 tumor-bearing mice after intravenous injection. The nanovesicle could render exponential activation of fluorescence signal and photodynamic therapy (PDT) activity (>100-fold) in response to the high level of intracellular glutathione after endocytosed by tumor cells, thereby achieving effective inhibition of tumor growth and reduced phototoxicity to normal tissues owing to the activatable design of the nanoparticle. More importantly, redox-activated PDT induced intratumoral infiltration of cytotoxic T lymphocytes by induction of ICD of tumor cells. After combining with the IDO inhibitor, the systemic antitumor immune response was further augmented. Hence, we believe that the present nanovesicle strategy has the potential for the synergistic immunotherapy of the metastatic cancers.
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http://dx.doi.org/10.1021/acs.nanolett.9b02306DOI Listing
October 2019

Changes in the Prevalence of Induced Abortion in the Floating Population in Major Cities of China 2007-2014.

Int J Environ Res Public Health 2019 09 9;16(18). Epub 2019 Sep 9.

Shanxi Reproductive Health Technology Service Center, Taiyuan 030012, China.

Objective: Our aim was to assess the changes in induced abortion in different migrant groups in China between 2007 and 2014 and the contraceptive methods used prior to induced abortion.

Methods: The studies of two population-based cross sections were conducted in urban China, involving 9146 sexually active migrant women. Within the selected sociodemographic subgroups, the changes in the percentage of women who had induced abortions, the proportion of pregnancies ending in induced abortions, the causes of induced abortions, and the methods of contraception were identified. A chi-squared test was used to calculate the differences in induced abortion in the subgroups.

Results: Between 2007 and 2014, in the study groups from the major cities of China, the percentage of sexually active migrant women who had induced abortions increased 10.1%, from 21.8% to 24.0%. The proportion of pregnancies ending in induced abortions increased 23.7%, from 21.5% to 26.6%. Both of the aforementioned statistics increased significantly within most of the selected sociodemographic subgroups, especially in the 18-19 and 45-49 age groups. Over 50% of pregnancies were aborted in the cohabiting group, although this figure declined by 12.3% over the course of the seven-year study period. Contraceptive failure was the primary cause of induced abortion, although its contribution to induced abortion declined from 51.3% to 42.4%. The proportion of women not using contraception prior to induced abortion increased from 30.9% to 41.2%.

Conclusion: The prevalence of induced abortion is high and continues to increase among sexually active migrant women in China. An increasing trend is forecasted over the next few decades. Special attention should be paid to the younger cohort of migrant women, especially 18-19-year-olds, and unmarried cohabitants, who are increasingly seeking induced abortions.
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http://dx.doi.org/10.3390/ijerph16183305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765927PMC
September 2019

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-β induction in human cells.

J Gen Virol 2019 09 15;100(9):1273-1281. Epub 2019 Jul 15.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-β induction than that of its predecessor PB2-292I. IFN-β attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-β. In the mouse model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.
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http://dx.doi.org/10.1099/jgv.0.001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414430PMC
September 2019

Antimony-doped tin oxide nanoparticles as peroxidase mimics for paper-based colorimetric detection of glucose using smartphone read-out.

Mikrochim Acta 2019 06 10;186(7):403. Epub 2019 Jun 10.

Key Laboratory of Mesoscopic Chemistry of MOE and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, Jiangsu, China.

Antimony-doped tin oxide nanoparticles (ATO NPs) were loaded on a filter paper where they act as a peroxidase mimic without electrochemical or photochemical assistance. The peroxidase mimicking activity is distinctly improved compared to most known nanomaterials and to natural horseradish peroxidase. The catalytic properties depend on the amount of antimony doped into the ATO NPs. A glucose assay was worked out that is based on (a) the oxidation of glucose by glucose oxidase under formation of HO, (b) the oxidation of 3,3,5,5-tetramethybenzidine (TMB) catalyzed by ATO NPs to form blue-green colored oxidized TMB on the surface of the paper. The coloration was analyzed with a smartphone. The method has a 21 μM limit of detection and a linear range that extends from 0.5 to 80 mM. Graphical abstract Antimony-doped tin oxide nanoparticles (ATO NPs) combined with 3,3,5,5-tetramethybenzidine (TMB) and triethylamine were coated on the filter paper. After addition of sample solution, the blue-green colored oxidized TMB was generated and recorded by a digital camera.
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http://dx.doi.org/10.1007/s00604-019-3506-6DOI Listing
June 2019

Infection of chicken H9N2 influenza viruses in different species of domestic ducks.

Vet Microbiol 2019 Jun 12;233:1-4. Epub 2019 Apr 12.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China. Electronic address:

Domestic ducks are considered as the interface between wild aquatic birds and terrestrial poultry and play an important role in the transmission and evolution of avian influenza viruses (AIVs). However, the infectivity of H9N2 AIVs in different domestic duck species has not been systematically evaluated. Here we investigated the infectivity of various genotypes of chicken H9N2 AIVs in Pekin duck (Anas Platyrhynchos), Mallard duck (Anas Platyrhynchos) and Muscovy duck (Cairina Moschata) through intranasal inoculation. We found that Pekin ducks and Mallard ducks were generally resistant to chicken H9N2 virus infection, while Muscovy ducks were relatively susceptible to H9N2 AIVs. All the tested viruses were isolated from oropharynx, trachea and lung tissues of Muscovy ducks. Additionally, genotype 57 (G57) H9N2 AIVs, which was predominant in chickens since 2010, showed increased virus replication in this duck species, indicating an improved interspecies transmission ability of recent H9N2 viruses from chickens to ducks. Our results demonstrated the role of Muscovy ducks in the ecology of H9N2 AIVs. More attentions should be paid to this host during viral surveillances. Additionally, inactivated H9N2 vaccine may be unnecessarily used in Pekin and Mallard ducks.
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http://dx.doi.org/10.1016/j.vetmic.2019.04.018DOI Listing
June 2019

A pH-Activatable nanoparticle for dual-stage precisely mitochondria-targeted photodynamic anticancer therapy.

Biomaterials 2019 08 18;213:119219. Epub 2019 May 18.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Beijing Key Laboratory of Molecular Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address:

Mitochondria-targeted photodynamic therapy (PDT) has emerged as one of the most efficient antitumor strategies. However, the therapeutic outcome of mitochondria-targeted PDT nanocarriers has been hampered by its poor capability of endosome escape and always-ON mode which induces normal tissue damage. To tackle these limitations, herein a novel pH-activatable nanoparticle is developed with dual-stage targeting capacity of early endosome and mitochondria for exponential activation of fluorescent signals and photodynamic efficacy. This nanoparticle is composed of pH-responsive mPEG-b-PDPA-Cy7.5 fluorescent copolymer and mitochondria-targeted photosensitizer (TPPa). The TPPa-encapsulated nanoparticles (M-TPPa) exhibit 111- and 151-fold enhancement in fluorescent signal and singlet oxygen generation (SOG) on encounting acidic pH environment, respectively. The M-TPPa can be quickly endocytosed by cancer cells and immediately dissociate at acidic early endosome to activate fluorescent signals and photoactivity. Subsequently, the activated TPPa quickly translocates from early endosome to mitochondria. Under laser irradiation, singlet oxygen could be generated in mitochondria, inducing intrinsic apoptosis in human HO8910 ovarian cancer cells. M-TPPa also exhibits high tumor imaging contrast and remarkable inhibition on tumor progression without obvious toxicity in HO8910-tumor bearing mice. Therefore, the rationally designed nanoparticles, with precise dual-targeting of distinct organelles and theranostic signal amplification, provides a promising strategy for efficient cancer treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2019.05.030DOI Listing
August 2019

Quick-Responsive Polymer-Based Thermosensitive Liposomes for Controlled Doxorubicin Release and Chemotherapy.

ACS Biomater Sci Eng 2019 May 16;5(5):2316-2329. Epub 2019 Apr 16.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Thermosensitive liposomes (TSLs) have been widely investigated for controlled drug release at specific pathophysiological sites. Although excellent thermo-sensitivity under hyperthermia (HT) was already realized for TSLs, their stability under physiological temperature still remains challenging. To overcome this limitation, optimized polymer-based thermosensitive liposomes (P-TSLs) with good thermo-sensitivity as well as satisfactory stability were developed in this study for tumor-specific controlled delivery of doxorubicin (DOX). In particular, polymers including p(NIPAM--HPMA) and p(HPMA--APMA) were successfully synthesized based on a reversible addition-fragmentation chain transfer (RAFT) technique. Next, thermosensitive polymer p(NIPAM--HPMA) was first proposed to be inserted into the lipid bilayer of TTSL by a postinsertion method. The resulting P-TTSL had a phase transition temperature () of around 42 °C and displayed excellent thermo-sensitivity under HT: nearly 70% of DOX was released within 1 min when only 1% p(NIPAM--HPMA) was incorporated. Moreover, its stability was maintained at 37 °C. Compared with TTSL, significantly higher cellular uptake of DOX under HT was noticed in P-TTSL, indicating a burst release of DOX at 42 °C. In addition, both tumor spheroid experiments and tumor slices demonstrated an enhanced DOX deep penetration when treated by P-TTSL under HT. To achieve imaging and local HT under NIR, p (HPMA--APMA) was labeled by Cy7.5 and coinserted into TTSL, and the best drug efficacy was observed in CY-P-TTSL with HT along with prolonged blood circulation time. We have further investigated the biocompatibility of the developed CY-P-TTSL, and reduced cardiotoxicity was observed even under HT in comparison with free DOX, demonstrating it is a reliable thermosensitive drug carrier for improving drug stability and therapeutic efficacy.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00343DOI Listing
May 2019
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