Publications by authors named "Jin Tian"

252 Publications

Frequency-Specific Alterations in Brain Function in Patients with Primary Dysmenorrhea.

Pain Med 2021 Jul 26. Epub 2021 Jul 26.

Acupuncture and Brain Science Research Center, A, cupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Objective: Recent neuroimaging studies have found that brain function is abnormal in primary dysmenorrhea (PDM). The present study aimed to explore frequency-specific brain alterations and their occurrence in the PDM.

Methods: Forty-seven patients with PDM and 36 matched healthy controls were enrolled in the study and underwent resting-state functional magnetic resonance imaging. The alterations in brain function in patients with PDM were assessed using different frequency filter bands (Slow5, Slow4, Slow3, and full low frequency) and functional connectivity density (FCD) approach. The clinical significance of the altered FCD was then explored. Additionally, mediation analysis was employed to detect the altered FCD-mediated clinical relationships in PDM.

Results: Frequency-specific FCD alterations have been observed in patients with PDM, especially in the central executive, default mode, sensorimotor networks, and the hippocampus. The altered full low-frequency FCD in the hippocampus was associated with the duration of disease and pain severity scores. The altered Slow 5 FCD in the second somatosensory area (S2) was associated with the severity of pain in PDM. Furthermore, the FCD in S2 mediated the duration associated with pain symptoms in PDM.

Conclusion: The present study identified frequency-specific FCD alterations in PDM and suggested that the S2 area is a potential treatment target for PDM.
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http://dx.doi.org/10.1093/pm/pnab225DOI Listing
July 2021

Prognostic factors for ovarian metastases in colorectal cancer patients.

World J Surg Oncol 2021 Jul 20;19(1):220. Epub 2021 Jul 20.

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang Province, 310009, People's Republic of China.

Purpose: The aim of this study was to analyze prognostic factors for ovarian metastases (OM) in colorectal cancer (CRC) using data from a Chinese center. In addition, the study aimed at developing a new clinical scoring system for prognosis of OM of CRC patients after surgery.

Patients And Methods: Data of CRC patients with OM were collected from a single Chinese institution (n = 67). Kaplan-Meier analysis was used to evaluate cumulative survival of patients. Factors associated with prognosis of overall survival (OS) were explored using Cox's proportional hazard regression models. A scoring system to determine effectiveness of prognosis was developed.

Results: Median OS values for patients with or without surgery were 22 and 7 months, respectively. Size of OM, number of OM, peritoneal metastasis (PM), Peritoneal cancer index (PCI), and completeness of cytoreduction (CC) were associated with OS of patients through univariate analysis. Multivariate analysis using a Cox regression model showed that only CC was an independent predictor for OS. Three variables (the size of OM >15cm, PCI ≥ 10, and carcinoembryonic antigen (CEA) >30 ng/mL) assigned one point each were used to develop a risk score. The resulting score was used for prognosis of OS.

Conclusion: Surgical treatment of metastatic sites is effective and safe for CRC patients with OM. CC-0 is recommended for improved prognosis. The scoring system developed in this study is effective for prediction of OS of patients after surgery.
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http://dx.doi.org/10.1186/s12957-021-02305-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293531PMC
July 2021

Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

J Hepatol 2021 Jun 3. Epub 2021 Jun 3.

Institute of Pharmaceutical Biotechnology and the First Affiliated Hospital Department of Radiation Oncology, Zhejiang University School of Medicine, Hangzhou, China; Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, China. Electronic address:

Background & Aims: The early prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to decrease its high mortality. This study aims to develop a new simplified prognostic score to accurately predict the outcome of these patients.

Methods: The prospective clinical data of 2409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated by an external group.

Results: A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to the 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of four other scores (COSSH-ACLFs, 0.793/0.784; CLIF-C ACLFs, 0.792/0.770; MELDs, 0.731/0.727; MELD-Nas, 0.730/0.726; all p<0.05). The prediction error rates of the new score for 28-day mortality were significantly lower than those of the COSSH-ACLFs (15.9%), CLIF-C ACLFs (16.3%), MELDs (35.3%) and MELD-Nas (35.6%). The probability density function evaluation and risk stratification of the new score also showed the highest predictive values for mortality. The external group further validated these results.

Conclusion: The new prognostic score based on six predictors without an assessment of organ failure can accurately predict and easily stratify the short-term mortality of patients with HBV-ACLF and might be used for early prognosis to decrease the high mortality.

Lay Summary: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome with a high short-term mortality rate. We developed a simplified prognostic score for these patients based on a prospective multicentre cohort that showed the best predictive performance compared with four other generic prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, MELDs and MELD-Nas).
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http://dx.doi.org/10.1016/j.jhep.2021.05.026DOI Listing
June 2021

On-Chip Multicolor Photoacoustic Imaging Flow Cytometry.

Anal Chem 2021 06 28;93(23):8134-8142. Epub 2021 May 28.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

On-chip imaging flow cytometry has been widely used in cancer biology, immunology, microbiology, and drug discovery. Pure optical imaging combined with flow cytometry to derive chemical, structural, and morphological features of cells provides systematic insights into biological processes. However, due to the high concentration and strong optical attenuation of red blood cells, preprocessing is necessary for optical flow cytometry while dealing with whole blood. In this study, we develop an on-chip photoacoustic imaging flow cytometry (PAIFC), which combines multicolor high-speed photoacoustic microscopy and microfluidics for cell imaging. The device employs a micro-optical scanner to achieve a miniaturized outer size of 30 × 17 × 24 mm and ultrafast cross-sectional imaging at a frame rate of 1758 Hz and provides lateral and axial resolutions of 2.2 and 33 μm, respectively. Using a multicolor strategy, PAIFC is able to differentiate cells labeled by external contrast agents, detect melanoma cells with an endogenous contrast in whole blood, and image melanoma cells in blood samples from tumor-bearing mice. The results suggest that PAIFC has sufficient sensitivity and specificity for future cell-on-chip applications.
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http://dx.doi.org/10.1021/acs.analchem.0c05218DOI Listing
June 2021

Imaging GPCR-Mediated Signal Events Leading to Chemotaxis and Phagocytosis.

Authors:
Miao Pan Tian Jin

Methods Mol Biol 2021 ;2304:207-220

Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, NIH, Rockville, MD, USA.

Eukaryotic phagocytes locate microorganisms via chemotaxis and consume them through phagocytosis. The social amoeba Dictyostelium discoideum is a stereotypical phagocyte and a well-established model to study both processes. Recent studies show that a G-protein-coupled receptor (fAR1) mediate a signaling network to control reorganization of the actin cytoskeleton leading both the directional cell movement and the engulfment of bacteria. Many live cell imaging methods have been developed and applied to monitor these signaling events. In this chapter, we will introduce how to measure GPCR-mediated signaling events for cell migration and phagocytosis in Dictyostelium.
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http://dx.doi.org/10.1007/978-1-0716-1402-0_11DOI Listing
January 2021

Visualizing Key Signaling Components of Macropinocytosis and Phagocytosis Using Confocal Microscopy in the Model Organism Dictyostelium discoideum.

Methods Mol Biol 2021 ;2304:193-205

Chemotaxis Signaling Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

Macropinocytosis and phagocytosis are the processes by which eukaryotic cells use their plasma membrane to engulf liquid or a large particle and give rise to an internal compartment called the macropinosomes or phagosome, respectively. Dictyostelium discoideum provides a powerful system to understand the molecular mechanism of these two fundamental cellular processes that impact human health and disease. Recent developments in fluorescence microscopy allow direct visualization of intracellular signaling events with high temporal and spatial resolution. Here, we describe methods to visualize temporospatial activation or localization of key signaling components that are crucial for macropinocytosis and phagocytosis using confocal fluorescence microscopy.
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http://dx.doi.org/10.1007/978-1-0716-1402-0_10DOI Listing
January 2021

Feline Calicivirus Proteinase-Polymerase Protein Degrades mRNAs To Inhibit Host Gene Expression.

J Virol 2021 Jun 10;95(13):e0033621. Epub 2021 Jun 10.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China.

To replicate efficiently and evade the antiviral immune response of the host, some viruses degrade host mRNA to induce host gene shutoff via encoding shutoff factors. In this study, we found that feline calicivirus (FCV) infection promotes the degradation of endogenous and exogenous mRNAs and induces host gene shutoff, which results in global inhibition of host protein synthesis. Screening assays revealed that proteinase-polymerase (PP) is a most effective factor in reducing mRNA expression. Moreover, PP from differently virulent strains of FCV could induce mRNA degradation. Further, we found that the key sites of the PP protein required for its proteinase activity are also essential for its shutoff activity but also required for viral replication. The mechanism analysis showed that PP mainly targets Pol II-transcribed RNA in a ribosome-, 5' cap-, and 3' poly(A) tail-independent manner. Moreover, purified glutathione -transferase (GST)-PP fusion protein exhibits RNase activity in assays using green fluorescent protein (GFP) RNA transcribed as a substrate in the absence of other viral or cellular proteins. Finally, PP-induced shutoff requires host Xrn1 to complete further RNA degradation. This study provides a newly discovered strategy in which FCV PP protein induces host gene shutoff by promoting the degradation of host mRNAs. Virus infection-induced shutoff is the result of targeted or global manipulation of cellular gene expression and leads to efficient viral replication and immune evasion. FCV is a highly contagious pathogen that persistently infects cats. It is unknown how FCV blocks the host immune response and persistently exists in cats. In this study, we found that FCV infection promotes the degradation of host mRNAs and induces host gene shutoff via a common strategy. Further, PP protein for different FCV strains is a key factor that enhances mRNA degradation. An assay showed that the GST-PP fusion protein possesses RNase activity in the absence of other viral or cellular proteins. This study demonstrates that FCV induces host gene shutoff by promoting the degradation of host mRNAs, thereby introducing a potential mechanism by which FCV infection inhibits the immune response.
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http://dx.doi.org/10.1128/JVI.00336-21DOI Listing
June 2021

The Plasticity of Nanofibrous Matrix Regulates Fibroblast Activation in Fibrosis.

Adv Healthc Mater 2021 04 29;10(8):e2001856. Epub 2021 Jan 29.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Natural extracellular matrix (ECM) mostly has a fibrous structure that supports and mechanically interacts with local residing cells to guide their behaviors. The effect of ECM elasticity on cell behaviors has been extensively investigated, while less attention has been paid to the effect of matrix fiber-network plasticity at microscale, although plastic remodeling of fibrous matrix is a common phenomenon in fibrosis. Here, a significant decrease is found in plasticity of native fibrotic tissues, which is associated with an increase in matrix crosslinking. To explore the role of plasticity in fibrosis development, a set of 3D collagen nanofibrous matrix with constant modulus but tunable plasticity is constructed by adjusting the crosslinking degree. Using plasticity-controlled 3D culture models, it is demonstrated that the decrease of matrix plasticity promotes fibroblast activation and spreading. Further, a coarse-grained molecular dynamic model is developed to simulate the cell-matrix interaction at microscale. Combining with molecular experiments, it is revealed that the enhanced fibroblast activation is mediated through cytoskeletal tension and nuclear translocation of Yes-associated protein. Taken together, the results clarify the effects of crosslinking-induced plasticity changes of nanofibrous matrix on the development of fibrotic diseases and highlight plasticity as an important mechanical cue in understanding cell-matrix interactions.
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http://dx.doi.org/10.1002/adhm.202001856DOI Listing
April 2021

A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction.

Open Med (Wars) 2020 10;15(1):644-653. Epub 2020 Jul 10.

Department of Health Statistics, Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, Shanxi Province 030001, People's Republic of China.

Purpose: A model for predicting the prognosis of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) is currently not available. This study aimed to develop an age-biomarker-clinical history prognostic index (ABC-PI) and validate it for the assessment of individual prognosis.

Patients And Methods: A total of 5,974 HFrEF patients were enrolled and 1,529 were included in this study after excluding missing values and loss to follow-up. Variables that significantly contributed to prediction of all-cause mortality were assessed by Cox regression and latent trait analysis (LTA) was used to validate discrimination of variables.

Results: After Cox regression, the following seven most significant variables were selected: age, N-terminal pro-B-type natriuretic peptide, renal dysfunction, left ventricular mass index, percutaneous coronary intervention, atrial fibrillation, and New York Heart Association (C-index: 0.801 ± 0.013). After verification by LTA, discrimination of these seven variables was proven. A nomogram was used to form the ABC-PI, and then the total score was set to 100 points. A lower score indicated a higher risk. After verification, the 3-year mortality rate was 34.7% in the high-risk group and only 2.6% in the low-risk group.

Conclusion: Our novel ABC-PI shows a good performance and does not require re-input in the original model. The ABC-PI can be used to effectively and practically predict the prognosis of HFrEF patients.
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http://dx.doi.org/10.1515/med-2020-0209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712124PMC
July 2020

Efficient Quantum Simulation of an Anti--Pseudo-Hermitian Two-Level System.

Entropy (Basel) 2020 Jul 24;22(8). Epub 2020 Jul 24.

State Key Laboratory of Low-Dimensional Quantum Physics and Department of Physics, Tsinghua University, Beijing 100084, China.

Besides Hermitian systems, quantum simulation has become a strong tool to investigate non-Hermitian systems, such as PT-symmetric, anti-PT-symmetric, and pseudo-Hermitian systems. In this work, we theoretically investigate quantum simulation of an anti--pseudo-Hermitian two-level system in different dimensional Hilbert spaces. In an arbitrary phase, we find that six dimensions are the minimum to construct the anti--pseudo-Hermitian two-level subsystem, and it has a higher success probability than using eight dimensions. We find that the dimensions can be reduced further to four or two when the system is in the anti-PT-symmetric or Hermitian phase, respectively. Both qubit-qudit hybrid and pure-qubit systems are able to realize the simulation, enabling experimental implementations in the near future.
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http://dx.doi.org/10.3390/e22080812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517382PMC
July 2020

Large-scale one-pot synthesis of water-soluble and biocompatible upconversion nanoparticles for dual-modal imaging.

Colloids Surf B Biointerfaces 2021 Feb 21;198:111480. Epub 2020 Nov 21.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, PR China.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attentions in the area of molecular imaging, targeted therapy and diagnosis. The UCNPs synthesized by conventional methods are usually hydrophobic and require additional surface modification to give them water solubility and biocompatibility. Herein, we designed a simple and convenient strategy for the direct synthesis of water-soluble and biocompatible lanthanum-doped UCNPs through a one-pot reaction without further purification and screening. The doping amount of lanthanide can be adjusted by simply changing the proportion of precursor in the reaction solution. The resulting water-soluble UCNPs possess excellent colloidal stability in physiological media. Under 980 nm excitation, NaGdF:Yb/Er and NaGdF:Yb/Tm nanoparticles exhibited a dominant green emission band (S→I) of Er and a dominant blue emission band (G→H) of Tm, respectively. Toxic response was not observed with concentration up to 50 mg/L. The hemolysis to rabbit red blood cells was less than 2% in the concentration up to 20 mg/L. The NaGdF:Yb/Er nanoparticles exhibited a high r relaxivity of 4.7 mMs, demonstrating that the water-soluble and biocompatible UCNPs can be efficient T contrast agents. The in vivo results show that UCNPs exhibit excellent T-weighted imaging and fluorescence imaging abilities simultaneously, and can be used as a versatile promising theranostic nanoplatform.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111480DOI Listing
February 2021

Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HT receptors and cAMP-dependent mechanisms.

Neuropharmacology 2021 02 18;184:108408. Epub 2020 Nov 18.

Department of Integrative Biology and Pharmacology, McGovern Medical School at UT Health, Houston, TX, 77030, USA. Electronic address:

Ongoing activity in nociceptors, a driver of spontaneous pain, can be generated in dorsal root ganglion neurons in the absence of sensory generator potentials if one or more of three neurophysiological alterations occur - prolonged depolarization of resting membrane potential (RMP), hyperpolarization of action potential (AP) threshold, and/or increased amplitude of depolarizing spontaneous fluctuations of membrane potential (DSFs) to bridge the gap between RMP and AP threshold. Previous work showed that acute, sustained exposure to serotonin (5-HT) hyperpolarized AP threshold and potentiated DSFs, leading to ongoing activity if a separate source of maintained depolarization was present. Cellular signaling pathways that increase DSF amplitude and promote ongoing activity acutely in nociceptors are not known for any neuromodulator. Here, isolated DRG neurons from male rats were used to define the pathway by which low concentrations of 5-HT enhance DSFs, hyperpolarize AP threshold, and promote ongoing activity. A selective 5-HT receptor antagonist blocked these 5-HT-induced hyperexcitable effects, while a selective 5-HT agonist mimicked the effects of 5-HT. Inhibition of cAMP effectors, protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), attenuated 5-HT's hyperexcitable effects, but a blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels had no significant effect. 5-HT-dependent PKA activation was specific to DRG neurons that bind isolectin B4 (a nonpeptidergic nociceptor marker). 5-HT's effects on AP threshold, DSFs, and ongoing activity were mimicked by a cAMP analog. Sustained exposure to 5-HT promotes ongoing activity in nonpeptidergic nociceptors through the G-coupled 5-HT receptor and downstream cAMP signaling involving both PKA and EPAC.
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http://dx.doi.org/10.1016/j.neuropharm.2020.108408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856035PMC
February 2021

Effects of infrapatellar fat pad preservation versus resection on clinical outcomes after total knee arthroplasty in patients with knee osteoarthritis (IPAKA): study protocol for a multicentre, randomised, controlled clinical trial.

BMJ Open 2020 10 23;10(10):e043088. Epub 2020 Oct 23.

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China

Introduction: The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal qualities, rather than abnormal qualities, should be preserved during TKA. The aim of this study is to compare, over a 1-year period, the postoperative clinical outcomes of IPFP preservation versus resection after TKA in patients with normal or abnormal IPFP signal intensity alteration on MRI.

Methods And Analysis: Three hundred and sixty people with end-stage knee osteoarthritis and on the waiting list for TKA will be recruited and identified as normal IPFP quality (signal intensity alteration score ≤1) or abnormal IPFP quality (signal intensity alteration score ≥2). Patients in each hospital will then be randomly allocated to IPFP resection group or preservation group. The primary outcomes are the summed score of self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS subscales assessing function in daily activities and function in sport and recreation. Secondary endpoints will be included: KOOS subscales (pain, symptoms and quality of life), Knee Society Score, 100 mm Visual Analogue Scale (VAS) Pain, timed up-and-go test, patellar tendon shortening, 100 mm VAS self-reported efficacy of reduced pain and increased quality of life, and Insall-Salvati index assessed on plain X-ray. Adverse events will be recorded. Intention-to-treat analyses will be used.

Ethics And Dissemination: The study is approved by the local Medical Ethics Committee (Zhujiang Hospital Ethics Committee, reference number 2017-GJGBK-001) and will be conducted according to the principle of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard, and in compliance with the Medical Research Involving Human Subjects Act . Data will be published in peer-reviewed journals and presented at conferences, both nationally and internationally.

Trial Registration Number: This trial was registered at Clinicaltrial.gov website on 19 October 2018 with identify number NCT03763448.
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http://dx.doi.org/10.1136/bmjopen-2020-043088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590360PMC
October 2020

Feline calicivirus strain 2280 p30 antagonizes type I interferon-mediated antiviral innate immunity through directly degrading IFNAR1 mRNA.

PLoS Pathog 2020 10 19;16(10):e1008944. Epub 2020 Oct 19.

Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, P. R. China.

Feline calicivirus (FCV) belongs to the Caliciviridae, which comprises small RNA viruses of both medical and veterinary importance. Once infection has occurred, FCV can persist in the cat population, but the molecular mechanism of how it escapes the innate immune response is still unknown. In this study, we found FCV strain 2280 to be relatively resistant to treatment with IFN-β. FCV 2280 infection inhibited IFN-induced activation of the ISRE (Interferon-stimulated response element) promoter and transcription of ISGs (Interferon-stimulated genes). The mechanistic analysis showed that the expression of IFNAR1, but not IFNAR2, was markedly reduced in FCV 2280-infected cells by inducing the degradation of IFNAR1 mRNA, which inhibited the phosphorylation of downstream adaptors. Further, overexpression of the FCV 2280 nonstructural protein p30, but not p30 of the attenuated strain F9, downregulated the expression of IFNAR1 mRNA. His-p30 fusion proteins were produced in Escherichia coli and purified, and an in vitro digestion assay was performed. The results showed that 2280 His-p30 could directly degrade IFNAR1 RNA but not IFNAR2 RNA. Moreover, the 5'UTR of IFNAR1 mRNA renders it directly susceptible to cleavage by 2280 p30. Next, we constructed two chimeric viruses: rFCV 2280-F9 p30 and rFCV F9-2280 p30. Compared to infection with the parental virus, rFCV 2280-F9 p30 infection displayed attenuated activities in reducing the level of IFNAR1 and inhibiting the phosphorylation of STAT1 and STAT2, whereas rFCV F9-2280 p30 displayed enhanced activities. Animal experiments showed that the virulence of rFCV 2280-F9 p30 infection was attenuated but that the virulence of rFCV F9-2280 p30 was increased compared to that of the parental viruses. Collectively, these data show that FCV 2280 p30 could directly and selectively degrade IFNAR1 mRNA, thus blocking the type I interferon-induced activation of the JAK-STAT signalling pathway, which may contribute to the pathogenesis of FCV infection.
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http://dx.doi.org/10.1371/journal.ppat.1008944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571719PMC
October 2020

Resting-State Functional Connectivity Patterns Predict Acupuncture Treatment Response in Primary Dysmenorrhea.

Front Neurosci 2020 8;14:559191. Epub 2020 Sep 8.

Brain Research Center, Department of Acupuncture & Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Primary dysmenorrhea (PDM) is a common complaint in women throughout the menstrual years. Acupuncture has been shown to be effective in dysmenorrhea; however, there are large interindividual differences in patients' responses to acupuncture treatment. Fifty-four patients with PDM were recruited and randomized into real or sham acupuncture treatment groups (over the course of three menstrual cycles). Pain-related functional connectivity (FC) matrices were constructed at baseline and post-treatment period. The different neural mechanisms altered by real and sham acupuncture were detected with multivariate analysis of variance. Multivariate pattern analysis (MVPA) based on a machine learning approach was used to explore whether the different FC patterns predicted the acupuncture treatment response in the PDM patients. The results showed that real but not sham acupuncture significantly relieved pain severity in PDM patients. Real and sham acupuncture displayed differences in FC alterations between the descending pain modulatory system (DPMS) and sensorimotor network (SMN), the salience network (SN) and SMN, and the SN and default mode network (DMN). Furthermore, MVPA found that these FC patterns at baseline could predict the acupuncture treatment response in PDM patients. The present study verified differentially altered brain mechanisms underlying real and sham acupuncture in PDM patients and supported the use of neuroimaging biomarkers for individual-based precise acupuncture treatment in patients with PDM.
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http://dx.doi.org/10.3389/fnins.2020.559191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506136PMC
September 2020

A CRISPR-based method for testing the essentiality of a gene.

Sci Rep 2020 09 8;10(1):14779. Epub 2020 Sep 8.

Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.

The CRISPR/Cas9 system is a powerful method of editing genes by randomly introducing errors into the target sites. Here, we describe a CRISPR-based test for gene essentiality (CRISPR-E test) that allows the identification of essential genes. Specifically, we use sgRNA-mediated CRISPR/Cas9 to target the open reading frame of a gene in the genome and analyze the in-frame (3n) and frameshift (3n + 1 and 3n + 2) mutations in the targeted region of the gene in surviving cells. If the gene is non-essential, the cells would carry both in-frame (3n) and frameshift (3n + 1 and 3n + 2) mutations. In contrast, the cells would carry only in-frame (3n) mutations if the targeted gene is essential, and this selective elimination of frameshift (3n + 1 and 3n + 2) mutations of the gene indicate its essentiality. As a proof of concept, we have used this CRISPR-E test in the model organism Dictyostelium discoideum to demonstrate that Dync1li1 is an essential gene while KIF1A and fAR1 are not. We further propose a simple method for quantifying the essentiality of a gene using the CRISPR-E test.
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http://dx.doi.org/10.1038/s41598-020-71690-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478968PMC
September 2020

Resilient trade-offs between safety and profitability: perspectives of sharp-end drivers in the Beijing taxi service system.

Int J Occup Saf Ergon 2020 Oct 9:1-13. Epub 2020 Oct 9.

Beihang University, People's Republic of China.

Trade-offs are common behaviors of resilient systems, when the systems adapt to changing situations to meet multiple goals. In the context of the Beijing taxi service system (BTSS), this work investigates the sharp-end taxi drivers' trade-offs between work safety and business profitability, demonstrates their resilience in balancing these two goals and identifies factors that contribute to the trade-offs. An empirical framework incorporating questionnaire surveys, semi-structured interviews, field observation, data screening and categorization was adopted. Data were collected from a random sample of 70 taxi drivers. In the drivers' decisions we found a slight bias in favor of profitability rather than safety (regardless of their finances), and a high level of resilience that the drivers had developed in making strategies for the trade-offs. Trip distance, possibility of traffic congestion, redundant consumption, weather conditions, road features and real-time broadcast information were identified as determinants of the drivers' decision-making. The findings inform BTSS organizational layers and regulators about the sharp-end drivers' needs for productive safety, and provide an evidence base for making more definitive recommendations about support provision and resource re-allocation in an effective and proactive manner.
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http://dx.doi.org/10.1080/10803548.2020.1821511DOI Listing
October 2020

Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis.

J Nanobiotechnology 2020 Jul 8;18(1):94. Epub 2020 Jul 8.

Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Background: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine ([email protected]), which is of high solubility for osteoarthritis intra-articular injection treatment.

Methods: The [email protected] were assembled and the characteristics were measured. The [email protected] was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of [email protected]

Results: [email protected] was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in [email protected] group. Paw withdrawal threshold in [email protected] group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in [email protected] group.

Conclusion: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable [email protected] with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
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http://dx.doi.org/10.1186/s12951-020-00651-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346635PMC
July 2020

Disrupted hypothalamic CRH neuron responsiveness contributes to diet-induced obesity.

EMBO Rep 2020 07 27;21(7):e49210. Epub 2020 May 27.

Brown Foundation Institute of Molecular Medicine of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both of which showed HFD-mimicking, blunted PVH CRH neuron responsiveness. Strikingly, both models developed rapid HFD-induced obesity, associated with HFD-mimicking, reduced diurnal rhythmicity in feeding and energy expenditure. Thus, blunted responsiveness of PVH CRH neurons, but not their absolute activity levels, underlies HFD-induced obesity and may also contribute to stress-induced obesity.
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http://dx.doi.org/10.15252/embr.201949210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332802PMC
July 2020

miR-101 inhibits feline herpesvirus 1 replication by targeting cellular suppressor of cytokine signaling 5 (SOCS5).

Vet Microbiol 2020 Jun 29;245:108707. Epub 2020 Apr 29.

Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China. Electronic address:

Feline viral rhinotracheitis is a prevalent disease among cats caused by feline herpesvirus 1 (FHV-1). microRNAs (miRNAs), which serve as important regulatory factors in the host, participate in the regulation of the host innate immune response to virus infection. However, the roles of miRNAs in the FHV-1 life cycle remain unclear. In this study, we found that a new miRNA, miR-101, could suppress FHV-1 replication. FHV-1 infection upregulated the expression level of miR-101 in a cGAS-dependent manner. Furthermore, miR-101 could significantly enhance type I interferon antiviral signaling by targeting suppressor of cytokine signaling 5 (SOCS5), a negative regulator of the JAK-STAT pathway. Likewise, knockdown of cellular SOCS5 also suppressed FHV-1 replication due to the enhancement of IFN-I-induced signaling cascades. Taken together, our data demonstrated a new strategy for miR-101-mediated defense against FHV-1 infection by enhancing IFN-I antiviral signaling and increased the knowledge of miRNAs regulating innate immune signaling pathways.
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http://dx.doi.org/10.1016/j.vetmic.2020.108707DOI Listing
June 2020

The challenges of urgent radical sigmoid colorectal cancer resection in a COVID-19 patient: A case report.

Int J Surg Case Rep 2020 11;71:147-150. Epub 2020 May 11.

Department of Medicine, Winchester Medical Center, 1840 Amherst Street, Winchester, VA 22601, USA. Electronic address:

Introduction: The COVID-19 pandemic presents a unique global health challenge further complicating surgical management of COVID-19 positive patients due to a lack of published literature.

Case: Within we discuss a 48-year-old Chinese man, presenting with acute gastrointestinal obstruction due to sigmoid colonic mass. The patient was screened and tested positive for COVID 19 due to his employment in Wuhan, China at the COVID-19 pandemic epicenter. The patient was subsequently taken for open sigmoid colonic resection, however the case presented multiple challenges due to the patient's COVID-19 positive status.

Discussion: The challenges of surgical management of COVID-19 positive patients exist are four-fold. First the unknown efficacy of pre-surgical risk stratification in COVID-19 positive patients, second the risk of aerosolized COVID-19 transmission during intubation for surgery, third the risk of fecal COVID-19 transmission to surgical staff during large bowel resection, and fourth the post-operative challenges of caring for COVID-19 positive patients.

Conclusion: Further research is needed into these topics, as well as the medical management of COVID-19 surgical patients.
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http://dx.doi.org/10.1016/j.ijscr.2020.04.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212967PMC
May 2020

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.

EBioMedicine 2020 May 18;55:102763. Epub 2020 Apr 18.

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear.

Methods: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays.

Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8 T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.

Interpretation: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases.

Funding: The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.
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http://dx.doi.org/10.1016/j.ebiom.2020.102763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165294PMC
May 2020

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives.

Trends Mol Med 2020 05 21;26(5):483-495. Epub 2020 Mar 21.

MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. Electronic address:

The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic.
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http://dx.doi.org/10.1016/j.molmed.2020.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118693PMC
May 2020

[Survey on pesticide use in Crataegi Fructus and analysis of pesticide residues based on LC-ESI-MS/MS].

Zhongguo Zhong Yao Za Zhi 2019 Dec;44(23):5088-5093

Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100193,China.

In order to study the pesticide residues of the medicinal Crataegi Fructus,this study aims to establish an analysis method for pesticide residues( mainly containing insecticides and fungicides) suitable for the actual situation of medicinal Crataegi Fructus based on the survey of the pesticides of the Crataegi Fructus base,combined with the blind screening results of the LC-ESI-MS/MS pesticide screening platform established by the research team in the early stage. Then,the pesticide residues in medicinal Crataegi Fructus from Shandong,Hebei,Henan,Shanxi,and Liaoning( main cultivation areas) were analyzed. The samples were pretreated by the modified Qu ECh ERS method,i.e.,extracted with acetonitrile-water( 9 ∶1),purified by PSA,C_(18),GCB,silica gel. The detection of pesticides was performed by LC-MS/MS. The ion source was ESI with positive scanning mode,and the linearity of 11 kinds of pesticides in the range of 5-300 μg·kg~(-1) was acceptable( R~2>0. 996 9). All the recoveries of pesticides were within 70. 02%~(-1)12. 0% in the low,medium and high levels,with RSD≤17%. The results showed that the detection rate of carbendazim,chlorpyrifos and difenoconazole is 79%,82%,56%,respectively. Besides,the prohibition pesticide carbofuran were detected in some of the batches,indicating the security risk. This study provides methodological references and basic data for risk assessment of Crataegi Fructus and government regulation.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190926.201DOI Listing
December 2019

Pancreatic mass found to be Castleman disease, a rare case report.

Asian J Surg 2020 Jul 11;43(7):767-768. Epub 2020 Mar 11.

Winchester Medical center, Department of Medicine, 1840 Amherst Street, Winchester, VA, 22601, USA. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2020.02.007DOI Listing
July 2020

Surpassing the detection limit and accuracy of the electrochemical DNA sensor through the application of CRISPR Cas systems.

Biosens Bioelectron 2020 May 18;155:112100. Epub 2020 Feb 18.

Department of Chemical and Biomolecular Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA; Electronics Design Center, Case Western Reserve University, Cleveland, OH, 44106, USA.

Robust developments of personalized medicine for next-generation healthcare highlight the need for sensitive and accurate point-of-care platforms for quantification of disease biomarkers. Broad presentations of clustered regularly interspaced short palindromic repeats (CRISPR) as an accurate gene editing tool also indicate that the high-specificity and programmability of CRISPR system can be utilized for the development of biosensing systems. Herein, we present a CRISPR Cas system enhanced electrochemical DNA (E-DNA) sensor with unprecedented sensitivity and accuracy. The principle of the E-DNA sensor is the target induced conformational change of the surface signaling probe (containing an electrochemical tag), leading to the variation of the electron transfer rate of the electrochemical tag. With the introduction of CRISPR cleavage activity into the E-DNA sensor, a more apparent signal change between with and without the presence of the target can be achieved. We compared the performance of Cas9 and Cas12a enhanced E-DNA sensor and optimized the chemical environment of CRISPR, achieving a femto-molar detection limit without enzymatic amplification. Moreover, we correlated the CRISPR cleavage signal with the original E-DNA signal as a strategy to indicate potential mismatches in the target sequence. Comparing with classic DNA electrochemistry based mutation detection strategy, CRISPR enhanced E-DNA sensor can determine the presence of a single mutation at an unknown concentration condition. Overall, we believe that the CRISPR enhanced E-DNA sensing strategy will be of especially high utility for point-of-care systems owing to the programmability, modularity, high-sensitivity and high-accuracy.
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http://dx.doi.org/10.1016/j.bios.2020.112100DOI Listing
May 2020

Correction to: Hymenobacter oligotrophus sp. nov., isolated from a contaminated agar plate.

Antonie Van Leeuwenhoek 2020 06;113(6):861

China Center for Type Culture Collection (CCTCC), College of Life Sciences, Wuhan University, Wuhan, 430072, China.

In the original publication, the deposit number of strain sh-6 was incorrectly published as "CCTCC AB 2016064" throughout the article.
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http://dx.doi.org/10.1007/s10482-020-01389-3DOI Listing
June 2020

Feline Infectious Peritonitis Virus Nsp5 Inhibits Type I Interferon Production by Cleaving NEMO at Multiple Sites.

Viruses 2019 12 30;12(1). Epub 2019 Dec 30.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

Feline infectious peritonitis (FIP), caused by virulent feline coronavirus, is the leading infectious cause of death in cats. The type I interferon (type I IFN)-mediated immune responses provide host protection from infectious diseases. Several coronaviruses have been reported to evolve diverse strategies to evade host IFN response. However, whether feline infectious peritonitis virus (FIPV) antagonizes the type I IFN signaling remains unclear. In this study, we demonstrated that FIPV strain DF2 infection not only failed to induce interferon-β (IFN-β) and interferon-stimulated gene (ISG) production, but also inhibited Sendai virus (SEV) or polyinosinic-polycytidylic acid (poly(I:C))-induced IFN-β production. Subsequently, we found that one of the non-structural proteins encoded by the FIPV genome, nsp5, interrupted type I IFN signaling in a protease-dependent manner by cleaving the nuclear factor κB (NF-κB) essential modulator (NEMO) at three sites-glutamine132 (Q132), Q205, and Q231. Further investigation revealed that the cleavage products of NEMO lost the ability to activate the IFN-β promoter. Mechanistically, the nsp5-mediated NEMO cleavage disrupted the recruitment of the TRAF family member-associated NF-κB activator (TANK) to NEMO, which reduced the phosphorylation of interferon regulatory factor 3 (IRF3), leading to the inhibition of type I IFN production. Our research provides new insights into the mechanism for FIPV to counteract host innate immune response.
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http://dx.doi.org/10.3390/v12010043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019732PMC
December 2019

Construction of a US7/US8/UL23/US3-deleted recombinant pseudorabies virus and evaluation of its pathogenicity in dogs.

Vet Microbiol 2020 Jan 3;240:108543. Epub 2019 Dec 3.

Division of Zoonosis of Natural Foci, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China. Electronic address:

Since 2011, to control the spread of pseudorabies (PR), US7/US8/UL23-deleted recombinant PRV (rPRV) vaccines based on current variants have been developed. The vaccines can provide effective immune protection to pigs, but fur-bearing animals, such as dogs, foxes, and minks, are increasingly infected by PRV due to consuming contaminated raw meat or offal from immunized pigs. It is suspected that the attenuated PRV vaccine strain is not safe for these fur-bearing animals. To confirm this, we construct a US7/US8/UL23-deleted and a US7/US8/UL23/US3-deleted rPRV based on PRV GL isolated from fox using the CRISPR/Cas9 method. Growth kinetics in vitro and pathogenicity in dogs were compared between the wild type and both rPRVs. The results showed that the growth kinetics of wild-type PRV and US7/US8/UL23-deleted rPRV were faster than those of US7/US8/UL23/US3-deleted recombinant PRV from 24 h to 48 h post infection. Moreover, PRV GL- and rPRV-infected cells formed cell-cell fusion, but the rPRV-infected cells did not. Dogs challenged with wild-type PRV or US7/US8/UL23-deleted rPRV showed obvious nervous symptoms, and all the dogs died, but the group challenged with the US7/US8/UL23/US3-deleted rPRV did not show any nervous symptoms, and all the dogs survived for the duration of the experiment. Tissue viral load analyses also showed that the virulence of the US7/US8/UL23/US3-deleted rPRV was significantly reduced in dogs. This study provides evidence that the US7/US8/UL23-deleted rPRV variant still exhibits high virulence for dogs and also highlights the role of the US3 gene in the pathogenicity of PRV in dogs and provides a strategy for developing a safer vaccine.
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http://dx.doi.org/10.1016/j.vetmic.2019.108543DOI Listing
January 2020

Recent advances in the discovery and development of glyoxalase I inhibitors.

Bioorg Med Chem 2020 02 2;28(4):115243. Epub 2019 Dec 2.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, People's Republic of China. Electronic address:

Glyoxalase I (GLO1) is a homodimeric Zn-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.
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http://dx.doi.org/10.1016/j.bmc.2019.115243DOI Listing
February 2020
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