Publications by authors named "Qian Liu"

2,596 Publications

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A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Clin Immunol 2021 May 8:108751. Epub 2021 May 8.

Department of Pharmacology and Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.
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http://dx.doi.org/10.1016/j.clim.2021.108751DOI Listing
May 2021

Animal models for study on rotator cuff injury.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Apr;46(4):426-431

Department of Orthopaedics, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Rotator cuff injuries are the most common cause of shoulder pain and dysfunction. Ideal animal shoulder models should have similar shoulder anatomy and function as human, and are able to replicate the microenvironment change after tendon injury. At present, a variety of animal models including rat, mouse, rabbit, sheep, canine, bovine, and primate have been used to study the mechanism of rotator cuff injury, effects of different repair techniques, and factors affecting tendon to bone healing. Although large animal models are more anatomically similar to humans, small animal models are more convenient in revealing the biological mechanism of rotator cuff injury and healing. Choosing appropriate animal models based on research objectives and establishing new small animal models play a critical role in revealing the mechanism of rotator cuff diseases and developing novel treating strategies.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200064DOI Listing
April 2021

[Analysis and Enlightenment of Foreign Open Breast Image Datasets].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):271-277

Clinical Specimen Center,Chinese PLA General Hospital,Beijing 100853,China.

With the upsurge of medical artificial intelligence,the use of computer vision technology to study medical images,which can effectively help doctors to identify and screen diseases,has become a focus of researchers.This paper summarizes the basic situation,specific information,related research,and data sharing and utilizing ways of foreign breast image datasets.This review provides inspirations for the opening of Chinese medical and health data.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12006DOI Listing
April 2021

Nanoparticle-based approaches to target the lymphatic system for antitumor treatment.

Cell Mol Life Sci 2021 May 8. Epub 2021 May 8.

School of Biomedical Engineering, Hainan University, Haikou, 570228, Hainan, China.

Immunotherapies have been established as safe and efficient modalities for numerous tumor treatments. The lymphatic system, which is an important system, can modulate the immune system via a complex network, which includes lymph nodes, vessels, and lymphocytes. With the deepening understanding of tumor immunology, a plethora of immunotherapies, which include vaccines, photothermal therapy, and photodynamic therapy, have been established for antitumor treatments. However, the deleterious off-target effects and nonspecific targeting of therapeutic agents result in low efficacy of immunotherapy. Fortunately, nanoparticle-based approaches for targeting the lymphatic system afford a unique opportunity to manufacture drugs that can simultaneously tackle both aspects, thereby improving tumor treatments. Over the past decades, great strides have been made in the development of DC vaccines and nanomedicine as antitumor treatments in the field of lymphatic therapeutics and diagnosis. In this review, we summarize the current strategies through which nanoparticle technology has been designed to target the lymphatic system and describe applications of lymphatic imaging for the diagnosis and image-guided surgery of tumor metastasis. Moreover, improvements in the tumor specificity of nanovaccines and medicines, which have been realized through targeting or stimulating the lymphatic system, can provide amplified antitumor immune responses and reduce side effects, thereby promoting the paradigm of antitumor treatment into the clinic to benefit patients.
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http://dx.doi.org/10.1007/s00018-021-03842-6DOI Listing
May 2021

Effects of 27 CYP3A4 Protein Variants on saxagliptin metabolism in vitro.

Fundam Clin Pharmacol 2021 May 7. Epub 2021 May 7.

Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) can metabolize about 30% to 40% of therapeutic drugs. Individual differences caused by CYP3A4 genetic polymorphisms can lead to treatment failure, unpredictable side effects or severe drug toxicity. The aim of this study was to evaluate the catalytic activities of 27 CYP3A4 variants on saxagliptin metabolism in vitro, which were identified in human CYP alleles. We successfully constructed 27 kinds of wild-type and variant vectors of pFast-dual-OR-3A4 by overlap extension PCR, and prepared 27 kinds of CYP3A4 highly expressed cell microsomes by baculovirus insect cell expression system. The Ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to detect the concentrations of the metabolite of saxagliptin (5-hydroxysaxagliptin) and the internal standard. Compared with the wild type CYP3A4.1, the intrinsic clearance values of most varieties decreased to 1.91% to 77.08%. Most of these varieties showed a decrease in Vmax and an increase in Km values compared with wild type. We are the first to report the Vitro metabolic data of 27 CYP3A4 variants of the metabolism of saxagliptin which can deepen our understanding of individualized drug use by combining previous studies about the effects of CYP3A4 variants of drug metabolism. With further in vivo studies, we hope it can guide individualized drug use in the clinic when the variants with low metabolic activity to saxagliptin was sequenced in the human body.
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http://dx.doi.org/10.1111/fcp.12693DOI Listing
May 2021

Screening of tumor grade-related mRNAs and lncRNAs for Esophagus Squamous Cell Carcinoma.

J Clin Lab Anal 2021 May 7:e23797. Epub 2021 May 7.

Department of Radiotherapy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: The goal of our study was to screen tumor grade-related lncRNAs and mRNAs to reveal the underlying molecular mechanism of esophagus squamous cell carcinoma (ESCC).

Methods: The lncRNA and mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA). Tumor grade correlation analysis of lncRNAs and mRNAs was executed, followed by the functional enrichment analysis of all tumor grade-related mRNAs. The differentially expression mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were obtained. PPI network and DEmRNA-DElncRNA interaction analysis were constructed. The functional annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The expression levels of the candidate genes were validated using qRT-PCR.

Results: A total of 1864 tumor grade-related mRNAs (846 positively related and 1018 negatively related) and 552 tumor grade-related lncRNAs (331 positively related and 221 negatively related) were obtained. The top 10 significantly grade-related mRNAs and lncRNAs included CA12, FABP4, DECR1, BAIAP2, IL1RAPL2, PPARD, LAD1, TSPAN10, LDOC1, ZNF853, RP11-25G10.2, RP11-557H15.3, RP11-521D12.5, CHKB-AS1, RP11-219B4.3, CH17-335B8.4, RP11-99 J16-A.2, CTB-111H14.1, ADNP-AS1, and JHDM1D-AS1. SFN, IL1RAPL2, and RP11-25G10.2 were overlapped from grade 1, grade 2, and grade 3. PPI network showed that top 10 proteins with higher degrees, including GNAI1, RAP2B, GNAZ, SHH, ADCY1, PRKAR2B, SH3GL1, GNA15, and ARRB1. A DElncRNAs-nearby DEmRNAs network was constructed to obtain hub lncRNAs including ADAMTS9-AS2, RP11-210 M15.2, RP11-13 K12.1, ZBED3-AS1, and RP11-25G10.2. Except for RP11-25G10.2, ADAMTS9-AS1, ZBED3-AS1, SFN, ATP1A2, and GNA15 were consistent with our TCGA analysis.

Conclusions: Alterations of DEmRNAs and DElncRNAs may provide key insights into the molecular mechanisms of ESCC.
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http://dx.doi.org/10.1002/jcla.23797DOI Listing
May 2021

One delayed diagnosis of paragonimiasis case and literature review.

Respirol Case Rep 2021 May 28;9(5):e00750. Epub 2021 Apr 28.

Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China.

Human paragonimiasis has been appearing all over the world due to increased human migration, international travel, and worldwide food trading. However, delayed and missed diagnosis rates are also increasing due to atypical clinical manifestations and the lack of disease understanding by clinical workers. We describe the case of a 43-year-old man, who was hospitalized with cough and chest pain for two months. Chest computed tomography (CT) revealed bilateral emphysema, left pleural effusion, and bilateral atelectasis. The hypereosinophilia gave us a clue; ultimately, the diagnosis of paragonimiasis was made through a diet history and a positive result of serum sp. immunoglobulin (Ig) G antibody. Moreover, 27 misdiagnosed paragonimiasis cases in the past decade have been reported. We draw conclusions by summarizing their characteristics for suspicious eosinophilic paragonimiasis patients; we should inquire diet history carefully, test serum IgG antibodies, and try to detect eggs. Once diagnosed, praziquantel is preferred for treatment.
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http://dx.doi.org/10.1002/rcr2.750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080295PMC
May 2021

Case report: Secondary sclerosing cholangitis induced by lapatinib and vinorelbine in a metastasis breast cancer patient.

Thorac Cancer 2021 May 6. Epub 2021 May 6.

Department of Pharmacy, Peking University First Hospital, Beijing, China.

Secondary sclerosing cholangitis (SSC) is a rare cholestatic liver disease that may have a severe clinical course. A 61-year-old woman with a history of metastasis breast cancer was admitted to our hospital for the second cycle of chemotherapy with lapatinib and vinorelbine. The patient had no reports of elevated liver function tests (LFTs) in the previous multiple chemotherapies or history of liver disease. However, the admission laboratory results showed severe cholestatic liver injury with the possibility of SSC by magnetic resonance cholangiopancreatography. Although chemotherapy was discontinued and patient was treated with hepatoprotective drugs, the LFTs did not improve and liver biopsy indicated mild injury of intrahepatic bile duct epithelium and hepatocyte. We added ursodeoxycholic acid and prednisolone to protect the liver, and laboratory data showed a response. To prevent the progression, lapatinib and vinorelbine were reintroduced and transient increases in alanine aminotransferase and γ-glutamyl transpeptidase were observed. With no evidence of viral or autoimmune liver disease, SSC induced by lapatinib and vinorelbine was diagnosed. This is the first case report of tyrosine kinase inhibitors and vinorelbine induced SSC and clinicians should be aware of the possibility of it. More case reports about this adverse drug reaction are needed to delineate optimal management.
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http://dx.doi.org/10.1111/1759-7714.13986DOI Listing
May 2021

Effect of dental malocclusion on cerebellar neuron activation via the dorsomedial part of the principal sensory trigeminal nucleus.

Eur J Oral Sci 2021 May 4:e12788. Epub 2021 May 4.

School of Stomatology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Occlusion has been proposed to play a role for body posture and balance, both of which are mediated mainly by the cerebellum. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) has direct projection to the cerebellum. The experimental unilateral anterior crossbite (UAC) has an impact on the motor nuclei in the brain stem via trigeminal mesencephalic nucleus (Vme). The current aim was to explore whether UAC has an impact on Vpdm-cerebellum circuit. The inferior alveolar nerve was injected into cholera toxin B subunit (CTb), the cerebellum was injected into fluoro-gold (FG), and the Vpdm was injected into biotinylated dextran amine (BDA) to identify the activation of Vpdm-cerebellum circuit by UAC. Data indicated that there were more neuronal nuclei (NeuN)/CTb/FG triple-labelled neurons and NeuN/CTb/vesicular glutamate transporter 1(VGLUT1) triple-labelled neurons in the Vpdm, and more NeuN/BDA/ VGLUT1 triple-labelled neurons in the cerebellum of rats with UAC than in control rats. The VGLUT1 expression in the Vpdm and cerebellum in the UAC group was higher than that in control rats. These findings indicate an excitatory impact of UAC on the Vpdm-cerebellum pathway and support the role of occlusion for body posture and balance.
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http://dx.doi.org/10.1111/eos.12788DOI Listing
May 2021

Deep learning-based downscaling of tropospheric nitrogen dioxide using ground-level and satellite observations.

Authors:
Manzhu Yu Qian Liu

Sci Total Environ 2021 Jun 6;773:145145. Epub 2021 Feb 6.

NSF Spatiotemporal Innovation Center, Department of Geography and GeoInformation Science, George Mason University, USA.

Air quality is one of the major issues within an urban area that affect people's living environment and health conditions. Existing observations are not adequate to provide a spatiotemporally comprehensive air quality information for vulnerable populations to plan ahead. Launched in 2017, TROPOspheric Monitoring Instrument (TROPOMI) provides a high spatial resolution (~5 km) tropospheric air quality measurement that captures the spatial variability of air pollution, but still limited by its daily overpass in the temporal dimension and relatively short historical records. Integrating with the hourly available AirNOW observations by ground-level discrete stations, we proposed and compared two deep learning methods that learn the relationship between the ground-level nitrogen dioxide (NO) observation from AirNOW and the tropospheric NO column density from TROPOMI to downscale the daily NO to an hourly resolution. The input predictors include the locations of AirNOW stations, AirNOW NO observations, boundary layer height, other meteorological status, elevation, major roads, and power plants. The learned relationship can be used to produce NO emission estimates at the sub-urban scale on an hourly basis. The two methods include 1) an integrated method between inverse weighted distance and a feed forward neural network (IDW + DNN), and 2) a deep matrix network (DMN) that maps the discrete AirNOW observations directly to the distribution of TROPOMI observations. We further compared the accuracies of both models using different configurations of input predictors and validated their average Root Mean Squared Error (RMSE), average Mean Absolute Error (MAE) and the spatial distribution of errors. Results show that DMN generates more reliable NO estimates and captures a better spatial distribution of NO concentrations than the IDW + DNN model.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145145DOI Listing
June 2021

N-doped carbon nanotubes supported CoSe nanoparticles: A highly efficient and stable catalyst for HO electrosynthesis in acidic media.

Nano Res 2021 Apr 26:1-6. Epub 2021 Apr 26.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, 610054 China.

Electrocatalytic oxygen reduction reaction (ORR) provides an attractive alternative to anthraquinone process for HO synthesis. Rational design of earth-abundant electrocatalysts for HO synthesis via a two-electron ORR process in acids is attractive but still very challenging. In this work, we report that nitrogen-doped carbon nanotubes as a multi-functional support for CoSe nanoparticles not only keep CoSe nanoparticles well dispersed but alter the crystal structure, which in turn improves the overall catalytic behaviors and thereby renders high O-to-HO conversion efficiency. In 0.1 M HClO, such CoSe@NCNTs hybrid delivers a high HO selectivity of 93.2% and a large HO yield rate of 172 ppm·h with excellent durability up to 24 h. Moreover, CoSe@NCNTs performs effectively for organic dye degradation via electro-Fenton process.

Electronic Supplementary Material: Supplementary material (SEM images, EDX mapping images, XPS spectrum, XRD patterns, RRDE voltammogram, Tafel plots, cyclic voltammograms, UV-Vis spectra, and Tables S1) is available in the online version of this article at 10.1007/s12274-021-3474-0.
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http://dx.doi.org/10.1007/s12274-021-3474-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074700PMC
April 2021

T217-Phosphorylation Exacerbates Tau Pathologies and Tau-Induced Cognitive Impairment.

J Alzheimers Dis 2021 Apr 28. Epub 2021 Apr 28.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Recent studies show that an increased T217-phosphorylation of tau in plasma could diagnose AD at an early stage with high accuracy and high specificity, while the potential toxic role of tau T217-phosphorylation is not known.

Objective: To study the potential toxic role of tau T217-phosphorylation.

Methods: We performed stereotactic brain injection, behavioral testing, immunohistochemistry and immunofluorescence, western blotting, Golgi staining, in vitro recombinant tau polymerization, and other measurements.

Results: We first constructed tau T217-wild-type (T217), T217-phospho-mimic (T217E), and T217-non-phospho-mimic (T217A) plasmids or their virus vectors on the basis of wild-type tau. We found that expressing tau-T217E induced a significantly increased tau phosphorylation at multiple AD-associated sites with inhibited proteolysis and increased cleavage/fibrillization of tau, while expressing tau-T217A abolished the above changes of tau both in vitro and in vivo. By mutating T217E on tau-P301L, a dominant mutation identified in patients with frontotemporal dementia, we did not observe significant exacerbation of tau-P301L phosphorylation and cognitive impairment although the increased tau cleavage and propagation were shown.

Conclusion: T217-phosphorylation exacerbates wild-type tau hyperphosphorylation with aggravated tau cleavage/fibrillization and cognitive impairments, while overexpressing T217E on the basis P301L does not exacerbate tau phosphorylation or the P301L-induced cognitive deficits, although it aggravates tau cleavage and propagation.
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http://dx.doi.org/10.3233/JAD-210297DOI Listing
April 2021

In Situ Derived Bi Nanoparticles Confined in Carbon Rods as an Efficient Electrocatalyst for Ambient N Reduction to NH.

Inorg Chem 2021 Apr 30. Epub 2021 Apr 30.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China.

Electrocatalytic N reduction is deemed as a prospective strategy toward low-carbon and environmentally friendly NH production under mild conditions, but its further application is still plagued by low NH yield and poor faradaic efficiency (FE). Thus, electrocatalysts endowing with high activity and satisfying selectivity are highly needed. Herein, Bi nanoparticles in situ confined in carbon rods (Bi NPs@CRs) are reported, which are fabricated via thermal annealing of a Bi-MOF precursor as a high-efficiency electrocatalyst for artificial NH synthesis with favorable selectivity. Such an electrocatalyst conducted in 0.1 M HCl achieves a high FE of 11.50% and a large NH yield of 20.80 μg h mg at -0.55 and -0.60 V versus reversible hydrogen electrode, respectively, which also possesses high electrochemical durability.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01130DOI Listing
April 2021

Active Nanointerfaces Based on Enzyme Carbonic Anhydrase and Metal-Organic Framework for Carbon Dioxide Reduction.

Nanomaterials (Basel) 2021 Apr 15;11(4). Epub 2021 Apr 15.

Department of Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV 26506, USA.

Carbonic anhydrases are enzymes capable of transforming carbon dioxide into bicarbonate to maintain functionality of biological systems. Synthetic isolation and implementation of carbonic anhydrases into membrane have recently raised hopes for emerging and efficient strategies that could reduce greenhouse emission and the footprint of anthropogenic activities. However, implementation of such enzymes is currently challenged by the resulting membrane's wetting capability, overall membrane performance for gas sensing, adsorption and transformation, and by the low solubility of carbon dioxide in water, the required medium for enzyme functionality. We developed the next generation of enzyme-based interfaces capable to efficiently adsorb and reduce carbon dioxide at room temperature. For this, we integrated carbonic anhydrase with a hydrophilic, user-synthesized metal-organic framework; we showed how the framework's porosity and controlled morphology contribute to viable enzyme binding to create functional surfaces for the adsorption and reduction of carbon dioxide. Our analysis based on electron and atomic microscopy, infrared spectroscopy, and colorimetric assays demonstrated the functionality of such interfaces, while Brunauer-Emmett-Teller analysis and gas chromatography analysis allowed additional evaluation of the efficiency of carbon dioxide adsorption and reduction. Our study is expected to impact the design and development of active interfaces based on enzymes to be used as green approaches for carbon dioxide transformation and mitigation of global anthropogenic activities.
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http://dx.doi.org/10.3390/nano11041008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071118PMC
April 2021

Identification and Validation of an Immune-Associated RNA-Binding Proteins Signature to Predict Clinical Outcomes and Therapeutic Responses in Glioma Patients.

Cancers (Basel) 2021 Apr 6;13(7). Epub 2021 Apr 6.

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, No.131 Dong'an Road, Xuhui District, Shanghai 200032, China.

The prognosis of patients with glioma is largely related to both the tumor-infiltrating immune cells and the expression of RNA-binding proteins (RBPs) that are able to regulate various pro-inflammatory and oncogenic mediators. However, immune-associated RBPs in glioma remain unexplored. In this study, we captured patient data from The Cancer Genome Atlas (TCGA) and divided them into two immune subtype groups according to the difference in infiltration of immune cells. After differential expression and co-expression analysis, we identified 216 RBPs defined as immune-associated RBPs. After narrowing down processes, eight RBPs were selected out to construct a risk signature that proven to be a novel and independent prognostic factor. The patients were divided into high- and low-risk groups on the basis of risk score. Higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints such as PD1 and CTLA4. In addition, analyses of pathway enrichment, somatic mutation, copy number variations and immuno-/chemotherapeutic response prediction were performed in high- and low-risk groups and compared with each other. For the first time, we demonstrated a novel signature composed of eight immune-associated RBPs that was valuable in predicting the survival of glioma patients and directing immunotherapy and chemotherapy.
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http://dx.doi.org/10.3390/cancers13071730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038676PMC
April 2021

Quantification of thonningianin a in rat plasma by liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.

Pharm Biol 2021 Dec;59(1):525-531

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, PR China.

Context: Thonningianin A is an ellagitannin substance and displays multiple pharmacological activities.

Objective: This study investigated the pharmacokinetic characteristics of thonningianin A after oral administration in rats using a fully validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.

Materials And Methods: A sensitive and selective LC-MS/MS assay was developed for quantifying thonningianin A. Eighteen Wistar rats were randomly divided into three groups ( = 6), which were given at a single dose of 10, 20, or 40 mg/kg thonningianin A by gavage. Blood samples (200 µL) were collected from the orbit vein at designated time points and analyzed using the LC-MS/MS method to measure the levels of thonningianin A.

Results: Thonningianin A and internal standard (IS) were eluted at 1.5 and ∼3.0 min, respectively. The selected reaction mode transitions monitored were 873.2 > 300.3 and 819.3 > 610.6 for thonningianin A and the IS, respectively. The calibration range was 10-1200 ng/mL. The intra- and the inter-day accuracy and precision met the acceptance criteria. No carryover and matrix effect were observed. The plasma concentrations of thonningianin A increased rapidly after oral administration of three dosages and reached the mean peak concentrations () within 0.61-0.83 h. Meanwhile, AUC/AUC of the three dosage groups was more than 89.0% (10 mg/kg), 95.7% (20 mg/kg), and 97.0% (40 mg/kg).

Discussion And Conclusions: The present method is the first report in terms of the simple precipitation procedure, high sensitivity, and high-throughput efficiency. This validated assay was successfully applied to determine the pharmacokinetic behaviours of thonningianin A in rats. This study should be helpful for providing references for understanding the action mechanism and further application of .
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http://dx.doi.org/10.1080/13880209.2021.1913188DOI Listing
December 2021

A pilot study of thiamin and folic acid in hemodialysis patients with cognitive impairment.

Ren Fail 2021 Dec;43(1):766-773

Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: This study aimed to explore the effectiveness of thiamin and folic acid supplementation on the improvement of the cognitive function in patients with maintenance hemodialysis.

Method: In the present study, we randomly assigned patients undergoing hemodialysis who had the Montreal Cognitive Assessment (MoCA) score lower than 26 to treatment group ( = 25, thiamin 90 mg/day combined with folic acid 30 mg/day) or control group ( = 25, nonintervention). All subjects were followed up for 96 weeks. The primary outcome was the improvement of the MoCA score. The secondary outcomes included homocysteine level, survival and safety.

Results: Patients in treatment group had an increase of the MoCA score from 21.95 ± 3.81 at baseline to 25.68 ± 1.96 at week 96 ( < 0.001, primary outcome), as compared with the MoCA score from 20.69 ± 3.40 to 19.62 ± 3.58 in control group. Thiamin combined with folic acid treatment also resulted in lower level of serum homocysteine in treatment group compare with control group at week 96 ( < 0.05, secondary outcome). 3 patients and 9 patients died during follow-up period in treatment and control group respectively ( = 0.048). The proportion of adverse events in treatment group was significantly lower than that in control group.

Conclusion: Hemodialysis patients with cognitive impairment treated with thiamin and folic acid had a significant improvement in MoCA score.
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http://dx.doi.org/10.1080/0886022X.2021.1914656DOI Listing
December 2021

[Application of Vectra 3D facial imaging technology in orthodontic teaching program].

Shanghai Kou Qiang Yi Xue 2021 Feb;30(1):109-112

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, School of Stomatology, Air Force Military Medical University. Xi'an 710032, Shaanxi Province, China.

Purpose: To evaluate the effectiveness of Vectra 3D facial imaging technology in enhancing orthodontic teaching and training efficiency.

Methods: Thirty-two dental students, enrolled in 2014 as five-year and eight-year curriculum in School of Somatology, Air Force Military Medical University were selected as the subjects of this research. As an important teaching facility for training the students to practice orthodontic clinical examinations, 2D and 3D facial imaging systems were selected in this study for the students to collect and analyze the data relating to the facial complexion and appearance. The students were at first instructed to use the traditional 2D facial imaging system for 20 minutes, and then Vectra 3D facial imaging system for another 20 minutes. The students were required to deliberate on the specifically designed questionnaires to input their own assessment on these two modalities. The outcomes were quantitatively analyzed using SPSS 24.0 software package.

Results: As to the items 2, 5, 6 and 7 in the questionnaire, which indicated the following queries respectively: whether the use of imaging systems could inspire students' learning interest, whether the results drawn from these two imaging facial systems were accurate and reliable, whether the subjective bias were trivial , and whether these two imaging systems were feasible for orthodontic treatment appraisals. The results showed that there were significant differences in these four items between the two groups(P<0.05). As to the Items 1, 3 and 4 , namely, whether the acquisition of the teaching materials was an easy access, whether these two facial analytical regimes were beneficial for the students to obtain the new knowledge, and whether this specific teaching facility was easy for the students to manage, there was no significant difference between the two groups (P>0.05).

Conclusions: Served as a new teaching syllabus facilitation, Vectra three-dimensional facial imaging system demonstrates a more satisfactory impetus for the students to learn than the traditional two-dimensional imaging system. Pragmatically, the analytical data resulted from the former remains more accountable than that of the latter.
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February 2021

Argonaute integrated single-tube PCR system enables supersensitive detection of rare mutations.

Nucleic Acids Res 2021 Apr 27. Epub 2021 Apr 27.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Technological advances in rare DNA mutations detection have revolutionized the diagnosis and monitoring of tumors, but they are still limited by the lack of supersensitive and high-coverage procedures for identifying low-abundance mutations. Here, we describe a single-tube, multiplex PCR-based system, A-Star, that involves a hyperthermophilic Argonaute from Pyrococcus furiosus (PfAgo) for highly efficient detection of rare mutations beneficial from its compatibility with DNA polymerase. This novel technique uses a specific guide design strategy to allow PfAgo selective cleavage with single-nucleotide resolution at 94°C, thus mostly eliminating wild-type DNA in the denaturation step and efficiently amplifying rare mutant DNA during the PCR process. The integrated single-tube system achieved great efficiency for enriching rare mutations compared with a divided system separating the cleavage and amplification. Thus, A-Star enables easy detection and quantification of 0.01% rare mutations with ≥5500-fold increase in efficiency. The feasibility of A-Star was also demonstrated for detecting oncogenic mutations in solid tumor tissues and blood samples. Remarkably, A-Star achieved simultaneous detection of multiple oncogenes through a simple single-tube reaction by orthogonal guide-directed specific cleavage. This study demonstrates a supersensitive and rapid nucleic acid detection system with promising potential for both research and therapeutic applications.
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http://dx.doi.org/10.1093/nar/gkab274DOI Listing
April 2021

Wnt5a up-regulates Periostin through CaMKII pathway to influence periodontal tissue destruction in early periodontitis.

J Mol Histol 2021 Apr 26. Epub 2021 Apr 26.

Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

Periostin is essential for periodontal tissue integrity and homeostasis and also associated with periodontitis and periodontitis healing. This study aims to investigate the temporal and spatial expression of Periostin and Wnt5a/CaMKII in periodontitis and how the Wnt5a regulates Periostin through CaMKII signaling pathway in PDLCs in inflammatory environment. The experimental periodontitis mice were adopted to clarify the temporal and spatial expression of Wnt5a, CaMKII and Periostin during early periodontitis. And the Wnt5a, CaMKII and Periostin expression pattern and regulation mechanism in PDLCs were clarified in Porphyromonas gingivalis Lipopolysaccharide (P.g. LPS) induced inflammatory condition. Along with the periodontitis development, Wnt5a, CaMKII and Periostin significantly increased in periodontal ligament and partially increased in gingiva during 0 to 6 day (P < 0.05). They were involved in early periodontitis homeostasis especially in periodontal ligament tissue. Meanwhile, Wnt5a, CaMKII and Periostin were significantly decreased at 12 h (P < 0.05) and increased at 48 h (P < 0.05) in PDLCs after induced by P.g. LPS. Besides, Wnt5a significantly enhanced total CaMKII protein (P < 0.05), pCaMKII (P < 0.001) and Periostin (P < 0.001), and this could be blocked by CaMKII inhibitor KN93 (P < 0.05). In conclusions, in early periodontitis, Wnt5a/CaMKII and Periostin should be involved in maintaining periodontal homeostasis and Wnt5a could up-regulate Periostin via CaMKII pathway in inflammation, which would provide new clues for us to understand the pathogenesis of periodontitis and develop better therapeutic strategies.
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http://dx.doi.org/10.1007/s10735-021-09975-zDOI Listing
April 2021

Inherited and acquired corona of coronavirus in the host: Inspiration from the biomolecular corona of nanoparticles.

Nano Today 2021 Aug 17;39:101161. Epub 2021 Apr 17.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The family of coronavirus are named for their crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known "viral corona" is considered an "inherited corona". After contact with mucosa or the entrance into the host, bare coronaviruses can become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. The layers acquired from the surrounding environment are named the "acquired corona". We highlight here the possible role of the acquired corona in the pathogenesis of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions.
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http://dx.doi.org/10.1016/j.nantod.2021.101161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052473PMC
August 2021

Toad venom: A comprehensive review of chemical constituents, anticancer activities, and mechanisms.

Arch Pharm (Weinheim) 2021 Apr 22:e2100060. Epub 2021 Apr 22.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

Toad venom, a traditional natural medicine, has been used for hundreds of years in China for treating different diseases. Many studies have been performed to elucidate the cardiotonic and analgesic activities of toad venom. Until the last decade, an increasing number of studies have documented that toad venom is a source of lead compound(s) for the development of potential cancer treatment drugs. Research has shown that toad venom contains 96 types of bufadienolide monomers and 23 types of indole alkaloids, such as bufalin, cinobufagin, arenobufagin, and resibufogenin, which exhibit a wide range of anticancer activities in vitro and, in particular, in vivo for a range of cancers. The main antitumor mechanisms are likely to be apoptosis or/and autophagy induction, cell cycle arrest, cell metastasis suppression, reversal of drug resistance, or growth inhibition of cancer cells. This review summarizes the chemical constituents of toad venom, analyzing their anticancer activities and molecular mechanisms for cancer treatments. We also outline the importance of further studies regarding the material basis and anticancer mechanisms of toad venom.
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http://dx.doi.org/10.1002/ardp.202100060DOI Listing
April 2021

Oxiracetam Mediates Neuroprotection Through the Regulation of Microglia Under Hypoxia-Ischemia Neonatal Brain Injury in Mice.

Mol Neurobiol 2021 Apr 22. Epub 2021 Apr 22.

Department of Histology and Embryology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, 44# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

In neonatal hypoxic-ischemic brain damage (HIBD), in addition to damage caused by hypoxia and ischemia, over-activation of inflammation leads to further deterioration of the condition, thus greatly shortening the optimal treatment time window. Ischemic penumbra, the edematous area encompassing the infarct core, is characterized by typical activation of microglia and overt inflammation, and prone to incorporate into the infarct core gradually after ischemia onset. If treated in time, the cells located in the penumbra can survive, thereby impeding the expansion of the infarction. We demonstrated for the first time that in the acute phase of HIBD in neonatal mice, treatment of Oxiracetam (ORC) significantly curtailed the size of ischemic penumbra together with drastic reduction of infarction. By staining various cellular markers, we found that the penumbra was defined and concentrated with activated microglia. We also analyzed transmission electron microscopy and Luminex assay results to elucidate the mechanisms involved. We further confirmed that ORC switched polarization of microglia from the inflammatory towards the alternatively activated phenotype, thus promoting microglia from being neurotoxic into neuroprotective. Meanwhile, ORC decreased proliferation of microglia; however, their functions of phagocytosis and autophagy were otherwise enhanced. Last, we clarified that ORC promoted autophagy through the AMPK/mTOR pathway, which further induced the transition of the inflammatory to the alternatively activated phenotype in microglia. The pro-inflammatory factors secretion was inhibited as well, thereby reducing the progression of the infarction. Taken together, it is concluded that Oxiracetam reduced the expansion of ischemic infarction in part via regulating the interplay between microglia activation and autophagy, which would delay the progression of HIBD and effectively prolong the time window for the clinical treatment of HIBD.
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http://dx.doi.org/10.1007/s12035-021-02376-zDOI Listing
April 2021

Effectiveness of ultrasound-assisted immersion thawing on the thawing rate and physicochemical properties of chicken breast muscle.

J Food Sci 2021 Apr 21. Epub 2021 Apr 21.

College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang, China.

This study evaluated the effect of air thawing (AT), water thawing (WT), and ultrasound-assisted immersion thawing (UT) at different power levels (200, 300, 400, and 500 W) on the thawing rate, physicochemical properties, and protein structure of chicken breast muscle (pectoralis), and the weight of each sample was approximately 106 ± 3 g. UT shortened the total thawing time and decreased the cutting force with increasing ultrasound power. Additionally, UT at 300 W (UT-300) remarkably reduced the thawing and cooking losses of the samples compared to AT, WT, and other UT powers (p < 0.05). Low-field nuclear magnetic resonance spectroscopy showed that the T and T of the UT-300 samples were shorter than those of the AT and WT samples (p < 0.05), which revealed that UT-300 reduced the mobility and losses of both immobilized and free water. Moreover, UT-300 remarkably reduced the damage to the myofibrillar protein (MP) structure. Overall, with appropriate ultrasonic power, the thawing rate increased and changes in the MP structure were reduced. PRACTICAL APPLICATION: This study found that compared to that of AT samples, the thawing time of the UT-300 samples markedly decreased by 57%. In addition, UT-300 could reduce the damage to the myofibrillar protein structure, which was very beneficial for further processing of frozen foods.
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http://dx.doi.org/10.1111/1750-3841.15699DOI Listing
April 2021

Identification, Quantification, and Imaging of the Biodistribution of Soot Particles by Mass Spectral Fingerprinting.

Anal Chem 2021 05 21;93(17):6665-6672. Epub 2021 Apr 21.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Soot is ubiquitous and has large detrimental effects on climate, air quality, and human health. However, identification of soot in carbonaceous media is very challenging due to its nanoscale carbon nature and complex sources. Due to the shortage in the methodology, until now, the fate and health effect of soot particles after inhalation are still poorly understood. Here, we report a new method for label-free identification, quantification, and imaging of soot particles in complex media based on laser desorption/ionization mass spectrometry fingerprinting. We found that soot particles from different origins and with different morphologies showed highly consistent mass spectral fingerprints deriving from peak ratios of small carbon cluster anions (C-C), which enabled both accurate quantification of soot in fine particulate matter (PM) samples and label-free imaging of soot particles in biological media. By using this technique, we tracked and imaged the suborgan distribution of soot particles in mice after exposure to PM. The results showed that the lung is the main target organ for short-term inhalation exposure to soot particles. This study helps to better understand the inhalation toxicology of soot and also provides a practical novel methodological platform for identification, tracing, and toxicological studies of elemental carbon-based nanomaterials.
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http://dx.doi.org/10.1021/acs.analchem.0c05180DOI Listing
May 2021

Electrophysiological and histomorphological changes of cochlea in miniature pigs after abrasion of round window niches.

Acta Otolaryngol 2021 Apr 21:1-10. Epub 2021 Apr 21.

Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology of PLA, Chinese PLA General Hospital, Beijing, P.R. China.

In operations of cochlea implantation (CI), many surgeons choose to drill a window on the bone wall of cochlea basic rotation, when more and more patients receive CI with residual hearing, what damage this step would result in is unclear. To study the effect to inner ear hair cells which is caused by drilling during CI. 6 miniature pigs are equally divided into two groups, Round window niche of each pig in the experimental group was milled, while the pigs in control group wasn't. After implanting depth of 6.5, 11.5 and 20 mm, round window electrocochleography was recorded to analyze the change of cochlea microphonic (CM) potentials respectively, histomorphological changes was observed. Thresholds of CM in experimental group were higher than that of control group at different depth, amplitudes were smaller. In further group, cilia of inner hair cells (IHC) at bottom rotation were significantly damaged. After operation, ABR hearing threshold of experimental group was higher, differences at low frequency region were more obvious. Damage caused by mulling round window niche may seriously affect the function of the hair cells. Damage of the IHC is greater than OHC. CI through round window may protect residual hearing.
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http://dx.doi.org/10.1080/00016489.2021.1899281DOI Listing
April 2021

A rapid LC-MS/MS method for simultaneous determination of berberine and irbesartan in rat plasma: Application to the drug-drug pharmacokinetic interaction study after oral administration in rats.

Biomed Chromatogr 2021 Apr 20:e5144. Epub 2021 Apr 20.

Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.

A sensitive, reproducible, and specific liquid chromatography tandem mass spectrometry method was developed and validated to simultaneously determine the concentration of berberine (BBR) and irbesartan in Sprague-Dawley rat plasma, and applied to study the pharmacokinetic drug-drug interaction (DDI) between BBR and irbesartan in rats. In this method, diphenhydramine was used as the internal standard, and the liquid-liquid extraction method using ethyl acetate as the extraction agent was used for sample preparation. After extraction, the prepared samples were run on an Agilent Welchrom C column with the mobile phase consisting of methanol-acetonitrile-water solution with 0.5% formic acid (45:50:5, v/v/v) at a flow rate of 0.8 mL·min . The analytes BBR, irbesartan, and diphenhydramine (IS) were detected using multiple reactions monitoring mode, with the ion transitions being m/z 336.1 → m/z 320.0, m/z 429.1 → m/z 206.9, and m/z 256.2 → m/z 167.0, respectively. In the rats' plasma, BBR had good linearity in the range of 0.5-100 ng·mL with the lower limit of quantitation of 0.5 ng·mL , and the accuracy, intra-day, and inter-day precision were less than 12.33%. Irbesartan had good linearity in the range of 20-1200 ng·mL with the lower limit of quantification of 20 ng·mL , and the accuracy, intra-day, and inter-day precision were less than 13.55%. The validated method was verified to meet the determination requirements of biological samples. It was the first time to study the pharmacokinetics of DDI between BBR and irbesartan successfully, which would be necessary and beneficial to explore the clinical safety and efficacy of the combination of BBR and irbesartan in the treatment of diabetic nephropathy.
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http://dx.doi.org/10.1002/bmc.5144DOI Listing
April 2021

Improving the Precision of Base Editing by Bubble Hairpin Single Guide RNA.

mBio 2021 04 20;12(2). Epub 2021 Apr 20.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, People's Republic of China

Base editing is a powerful genome editing approach that enables single-nucleotide changes without double-stranded DNA breaks (DSBs). However, off-target effects as well as other undesired editings at on-target sites remain obstacles for its application. Here, we report that bubble hairpin single guide RNAs (BH-sgRNAs), which contain a hairpin structure with a bubble region on the 5' end of the guide sequence, can be efficiently applied to both cytosine base editor (CBE) and adenine base editor (ABE) and significantly decrease off-target editing without sacrificing on-target editing efficiency. Meanwhile, such a design also improves the purity of C-to-T conversions induced by base editor 3 (BE3) at on-target sites. Our results present a distinctive and effective strategy to improve the specificity of base editing. Base editors are DSB-free genome editing tools and have been widely used in diverse living systems. However, it is reported that these tools can cause substantial off-target editings. To meet this challenge, we developed a new approach to improve the specificity of base editors by using hairpin sgRNAs with a bubble. Furthermore, our sgRNA design also dramatically reduced indels and unwanted base substitutions at on-target sites. We believe that the BH-sgRNA design is a significant improvement over existing sgRNAs of base editors, and our design promises to be adaptable to various base editors. We expect that it will make contributions to improving the safety of gene therapy.
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http://dx.doi.org/10.1128/mBio.00342-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092237PMC
April 2021

Light-Responsive Luminescent Materials for Information Encryption Against Burst Force Attack.

Small 2021 Apr 18:e2100377. Epub 2021 Apr 18.

Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, China.

Optical encryption with easy operation, multichannel and high security has been one of the most significant technologies for information security. Stimuli-responsive luminescent materials have emerged as an ideal candidate for optical encryption, owing to its smart responsive property and high security. Herein, a type of light-responsive multicolor luminescent materials for high-security information encryption, which are fabricated by combining sensitizer, consumption unit, and emitter is developed. Different types of sensitizers to achieve different stimulus light responses, and multicolor light-responsive luminescent can be obtained by varying the composition of perovskite nanocrystals emitter can be selected. Both stimulus light and emission color can be used as distinguishable encoding dimensions, which enable multiplexed encoding with high capacity and complexity. Importantly, the controllable consumption can be manipulated by varying the concentration of consumption unit, so the programmed information encoded in different channels can be selectively read and erased simultaneously by varying stimulus light. The method makes the encryption information highly resistive to brute force trial-and-error attacks, which achieves high security level of information protection.
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http://dx.doi.org/10.1002/smll.202100377DOI Listing
April 2021

The novel pathogen-responsive glycosyltransferase UGT73C7 mediates the redirection of phenylpropanoid metabolism and promotes SNC1-dependent Arabidopsis immunity.

Plant J 2021 Apr 18. Epub 2021 Apr 18.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao, 266237, China.

Recent studies have shown that global metabolic reprogramming is a common event in plant innate immunity; however, the relevant molecular mechanisms remain largely unknown. Here, we identified a pathogen-induced glycosyltransferase, UGT73C7, that plays a critical role in Arabidopsis disease resistance through mediating redirection of the phenylpropanoid pathway. Loss of UGT73C7 function resulted in significantly decreased resistance to Pseudomonas syringae pv. tomato DC3000, whereas constitutive overexpression of UGT73C7 led to an enhanced defense response. UGT73C7-activated immunity was demonstrated to be dependent on the upregulated expression of SNC1, a Toll/interleukin 1 receptor-type NLR gene. Furthermore, in vitro and in vivo assays indicated that UGT73C7 could glycosylate p-coumaric acid and ferulic acid, the upstream metabolites in the phenylpropanoid pathway. Mutations that lead to the loss of UGT73C7 enzyme activities resulted in the failure to induce SNC1 expression. Moreover, glycosylation activity of UGT73C7 resulted in the redirection of phenylpropanoid metabolic flux to biosynthesis of hydroxycinnamic acids and coumarins. The disruption of the phenylpropanoid pathway suppressed UGT73C7-promoted SNC1 expression and the immune response. This study not only identified UGT73C7 as an important regulator that adjusts phenylpropanoid metabolism upon pathogen challenge, but also provided a link between phenylpropanoid metabolism and an NLR gene.
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http://dx.doi.org/10.1111/tpj.15280DOI Listing
April 2021