Yong Yang

Guangzhou University

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Tong‐Jun Lin

Dalhousie University

Jason N. Berman

University of Ottawa

Svetlana O. Carrigan

Dalhousie University

Adam J. MacNeil

Brock University

Yu Zhou

Yangtze University

Jeffery D. Molkentin

Cincinnati Children's Hospital Medical Center

Mojiao Zhao

Yongsheng Wang

Beijing Jiaotong University

Robert D. Junkins

University of North Carolina at Chapel Hill

Dan Lu

Jilin University

Cooperative Institutions

Jilin University

Sichuan University

Dalhousie University

West China Hospital of Sichuan University

Ministry of Agriculture and Rural Affairs

Chinese Academy of Medical Sciences & Peking Union Medical College

Jilin Medical University

Chinese Academy of Sciences

Capital Medical University

Izaak Walton Killam Health Centre

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MAPK Kinase 3 Specifically Regulates FcεRI-Mediated IL-4 Production by Mast Cells

The Journal of Immunology (2011)

Adam J. MacNeil Yong Yang Tong‐Jun Lin

Mast cells play a central role in allergic inflammation and are activated through cross-linking of FcεRI receptor-bound IgE, initiating a signaling cascade resulting in production of biologically potent mediators. Signaling pathways in the regulation of specific mediators remain incompletely defined. In this study, we examined the role of MAPK kinase 3 (MKK3) in IgE-dependent mast cell activation. In an in vivo model of passive cutaneous anaphylaxis, MKK3-deficient mice showed a deficit in late-phase IgE-dependent inflammation. To characterize the mechanism of this deficiency, we cultured bone marrow-derived mast cells (BMMCs) from wild-type and MKK3-deficient mice. We found that FcεRI-mediated mast cell activation induced rapid MKK3 phosphorylation by 5 min, diminishing slowly after 6 h. In MKK3-deficient BMMCs, phosphorylation of p38 was reduced at early and later time points. Among 40 cytokines tested using a protein array, IL-4 was the only cytokine specifically downregulated in MKK3-deficient BMMCs. Reduced IL-4 expression was seen in the local skin of MKK3-deficient mice following passive cutaneous allergic reaction. Furthermore, early growth response-1 (Egr1) bound to the promoter of IL-4 in FcεRI-activated mast cells, and Egr1 transcription factor activity was diminished in MKK3-deficient BMMCs. Finally, mast cell-deficient mice reconstituted with MKK3-deficient BMMCs displayed a significantly impaired late-phase allergic inflammatory response. Thus, mast cell MKK3 signaling contributes to IgE-dependent allergic inflammation and is a specific regulator of FcεRI-induced IL-4 production.

Allergic Inflammation

10.4049/jimmunol.1003126

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Citations (29)

Neuronal necrosis and spreading death in a Drosophila genetic model

Cell Death and Disease (2013)

Yong Yang Hou‐Wen Lin Y Li Jianbo Ni Lei Liu

Brain ischemia often results in neuronal necrosis, which may spread death to neighboring cells. However, the molecular events of neuronal necrosis and the mechanisms of this spreading death are poorly understood due to the limited genetic tools available for deciphering complicated responses in mammalian brains. Here, we engineered a Drosophila model of necrosis in a sub-population of neurons by expressing a leaky cation channel in the Drosophila eye. Expression of this channel caused necrosis in defined neurons as well as extensive spreading of cell death. Jun N-terminal kinase (JNK)-mediated, caspase-independent apoptosis was the primary mechanism of cell death in neurons, while caspase-dependent apoptosis was primarily involved in non-neuronal cell death. Furthermore, the JNK activation in surrounding neurons was triggered by reactive oxygen species (ROS) and Eiger (Drosophila tumor necrosis factor α (TNFα)) released from necrotic neurons. Because the Eiger/ROS/JNK signaling was also required for cell death induced by hypoxia and oxidative stress, our fly model of spreading death may be similar to brain ischemia in mammals. We performed large-scale genetic screens to search for novel genes functioning in necrosis and/or spreading death, from which we identified several classes of genes. Among them, Rho-associated kinase (ROCK) had been reported as a promising drug target for stroke treatment with undefined mechanisms. Our data indicate that ROCK and the related trafficking pathway genes regulate neuronal necrosis. We propose the suppression of the function of the trafficking system, ROS and cytokines, such as TNFα, as translational applications targeting necrosis and spreading death.

Genetic screen

10.1038/cddis.2013.232

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Citations (42)

A genome-wide cross-trait analysis identifying shared genetic basis and causal relationships between Hunner-type interstitial cystitis and autoimmune diseases in East Asian populations

Frontiers in Immunology (2024)

Xinyi Lyu Liao Peng Xueyuan Xu Fan Yang Yong Yang

Purpose Epidemiological studies have demonstrated the clinical link between Hunner interstitial cystitis (HIC) and autoimmune diseases (ADs), suggesting potential shared genetic bases for their comorbidity. We aimed to investigate the shared genetic architecture and causal relationships between HIC and ADs. Methods We conducted a genome-wide cross-trait study with ~170000 individuals of East Asian ancestry to investigate the shared architecture between HIC and ADs. Bidirectional Mendelian randomization (MR) was used to assess potential causal relationships and a multi-trait analysis of GWAS (MTAG) was conducted to identify their associated pleiotropic loci. Fine-mapping analysis narrowed candidate gene susceptibility loci and colocalization analysis was performed to identify shared variants at specific locus. Lastly, transcriptome-wide association (TWAS) and functional analysis were utilized to explore potential shared gene-tissue associations. Results Through bidirectional MR analysis, we observed a positive causal effect of AIH(OR IVW =1.09, P IVW =1.00×10 -3 ) and RA (OR IVW =1.47, P IVW <1.00×10 -4 ) on HIC and a negative causal effect of UC on HIC (OR IVW =0.89, P IVW < 1.00×10 -4 ). Furthermore, we unveiled a robust positive causal effect of HIC on T1D(OR ConMix =1.05, P ConMix =1.77×10 -3 ). Cross-trait meta-analysis identified a total of 64 independent SNPs associated with HIC and ADs. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to the autoimmune system. Conclusions Our findings might offer insights into the shared underlying etiology of HIC and ADs.

Genome-wide Association Study

Genetic architecture

Mendelian Randomization

Genetic Association

10.3389/fimmu.2024.1417899

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Fatigue and Fatigue Resistance in S1 Excited State Diarylethenes in Electric fields

Authorea (Authorea) (2020)

Xing Nie Yong Yang Tianlv Xu Steven R. Kirk Samantha Jenkins

The effect of a directional electric-field on the bonding of the undoped and sulphur doped diarylethene (DTE) switch molecule is investigated using next generation QTAIM (NG-QTAIM). We introduce chemical bonding concepts in the form of the least and most preferred directions of charge density accumulation relative to the associated bond-path, namely the precessions K and Kʹ that are demonstrated to be much more responsive to the electric-field than the Laplacian ∇2ρ(rb). A concept of bond fatigue is presented in terms of the tendency for a bond-path to rupture that provides directional versions of familiar bonding QTAIM concepts. Examples are included where the applied directional electric-field reduces the tendency towards bond-path rupture and also the converse. A brief discussion is undertaken of applications of the precessions K and Kʹ including switches, ring opening reactions and molecular rotary motors in the presence of fields that cause a redistribution of ρ(r).

Redistribution

Atoms in molecules

10.22541/au.158981302.22961095

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Antibody-biotin-streptavidin-horseradish peroxidase (HRP) sensor for rapid and ultra-sensitive detection of fumonisins

Food Chemistry (2020)

Hualin Yang Qi Zhang Xiaolei Liu Yuying Yang Yong Yang

Streptavidin

Horseradish peroxidase

Linear range

10.1016/j.foodchem.2020.126356

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Citations (36)

Natural Xanthine Oxidase Inhibitor 5-O-Caffeoylshikimic Acid Ameliorates Kidney Injury Caused by Hyperuricemia in Mice

Molecules (2021)

Dong Zhang Mojiao Zhao Yumei Li Dafang Zhang Yong Yang

Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50 of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of -8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

Hypoxanthine

Xanthine oxidase inhibitor

10.3390/molecules26237307

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Citations (21)

Dicentrine and Dicentrinone Isolated from Stephania tetrandrae Radix Suppress HepG2 Proliferation through Inhibiting PDI Activity

Records of Natural Products (2021)

Mojiao Zhao Chao Zhang Dong Zhang Siyu Zhu Tianjiao Liu

Inhibition of protein disulfide isomerase (PDI) has been attempted as a promising anti-cancer strategy. However, there is still no currently available PDI inhibitors approved for clinical use. Here, we isolated seven high yield alkaloids from Stephaniae tetrandrae Radix (STR), a medical herb frequently prescribed in anti-tumor condition, and identified two potent natural PDI inhibitors, dicentrine and dicentrinone. Among the seven alkaloids isolated, dicentrinone (1), dicentrine (2), tetrandrine (4), and fangchinoline (5) could significantly reduce cell viability in a dosage dependent manner detected by MTT assay in human hepatoma cells. To examine whether the candidate compounds are potent PDI inhibitors, we performed insulin turbidity assay and found dicentrine and dicentrinone, but not tetrandrine and fangchinoline, could effectively inhibit PDI activity, with IC50 of 56.70 μM and 43.95 μM respectively. Meanwhile, dicentrine and dicentrinone failed to further reduce the cell number index when co-treated with siRNA of PDI, suggesting the compounds behave as PDI inhibitors. Furthermore, dicentrinone and dicentrine have been successfully docked to the active pocket of PDI (PDB #3UEM) by molecular docking, suggesting the existence of physical interaction between compounds and PDI. Our results suggested that dicentrine and dicentrinone may be developed into safe PDI inhibitors.

Tetrandrine

MTT assay

Viability assay

Docking (animal)

IC50

10.25135/rnp.231.21.01.1929

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Citations (2)

IFN Regulatory Factor 3 Contributes to the Host Response during Pseudomonas aeruginosa Lung Infection in Mice

The Journal of Immunology (2010)

Svetlana O. Carrigan Robert D. Junkins Yong Yang Adam J. MacNeil Christopher T. Richardson

Pseudomonas aeruginosa is a major opportunistic pathogen. However, host defense mechanisms involved in P. aeruginosa lung infection remain incompletely defined. The transcription factor IFN regulatory factor 3 (IRF3) is primarily associated with host defense against viral infections, and a role of IRF3 in P. aeruginosa infection has not been reported previously. In this study, we showed that IRF3 deficiency led to impaired clearance of P. aeruginosa from the lungs of infected mice. P. aeruginosa infection induced IRF3 translocation to the nucleus, activation of IFN-stimulated response elements (ISRE), and production of IFN-beta, suggesting that P. aeruginosa activates the IRF3-ISRE-IFN pathway. In vitro, macrophages from IRF3-deficient mice showed complete inhibition of CCL5 (RANTES) and CXCL10 (IP-10) production, partial inhibition of TNF, but no effect on CXCL2 (MIP-2) or CXCL1 (keratinocyte-derived chemokine) in response to P. aeruginosa stimulation. In vivo, IRF3-deficient mice showed complete inhibition of CCL5 production and partial or no effects on production of other cytokines and chemokines in the bronchoalveolar lavage fluids and lung tissues. Profiling of immune cells in the airways revealed that neutrophil and macrophage recruitment into the airspace was reduced, whereas B cell, T cell, NK cell, and NKT cell infiltration was unaffected in IRF3-deficient mice following P. aeruginosa lung infection. These data suggest that IRF3 regulates a distinct profile of cytokines and chemokines and selectively modulates neutrophil and macrophage recruitment during P. aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection.

IRF3

10.4049/jimmunol.0903429

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Citations (54)

Analysis of the Influencing Factors of Quality Factor of Series Resonance System with Large Capacity

Yong Yang Rui Han Yongtao Jin Ruixiang Tao Te Li

In Zhoushan transmission project, 500kV XLPE submarine cable lines are used for the first time in the world. In order to strictly assess the quality of cable laying and attachment installation of 500kV XLPE submarine cable lines, a large capacity series resonance system with high quality factor which is suitable for AC withstand voltage test is developed. In order to improve the energy utilization efficiency of AC withstand voltage test system, based on the physical significance of quality factor, combined with practical application scene, the main factors affecting the quality factor of large-capacity series resonance system are analyzed. The optimization method of quality factor of large capacity series resonance system is proposed qualitatively from two aspects of reducing reactor loss and external loss. The test results show that the quality factor of large capacity series resonance voltage test is up to 169.2, fully meet the 17km submarine cable line ac withstand voltage test requirements.

Q factor

High Voltage

Line (geometry)

10.1109/iccsd.2019.8843160

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Citations (1)

Preparation of Crayfish Flavoring by Fermentation

Advanced materials research (2011)

Jian Bo Jia Yong Yang

The crayfish flavoring was prepared from pretreated crayfish residues after enzymatic hydrolysis, fermentation with Lactobacillus helveticus, complex formulation with auxiliary odoriferous spices from spice plants and food additives, homogenization and sterilization. The results of orthogonal experiments showed that the content of the flavor agent alkyl pyrazine in the fermentation broth was 0.54ng/mL. The product with tastiness of crayfish, nutrition and biological activity functions was obtained when the contents of taurine, soluble peptide and the nitrogen of the free amino acid in the crayfish flavoring were 0.025g/100g, 1.41g/100g and 0.66g/100g, respectively.

10.4028/www.scientific.net/amr.317-319.2383

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Citations (1)