Publications by authors named "Yiqi Huang"

9 Publications

  • Page 1 of 1

Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through 'reverse phenotyping'.

Nat Commun 2021 07 26;12(1):4515. Epub 2021 Jul 26.

Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.

The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we use single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for 'reverse phenotyping'. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.
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http://dx.doi.org/10.1038/s41467-021-24730-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313584PMC
July 2021

Berberine administrated with different routes attenuates inhaled LPS-induced acute respiratory distress syndrome through TLR4/NF-κB and JAK2/STAT3 inhibition.

Eur J Pharmacol 2021 Oct 17;908:174349. Epub 2021 Jul 17.

Pharmaceutical Research Center, Xiamen Medicine Research Institute, Xiamen, 361008, Fujian province, PR China.

Accumulating evidence showed that berberine possessed the anti-inflammatory action in various diseases caused by inflammation. However, it was still unclear whether both inhalation and injection with berberine produced pulmonary protective role in acute respiratory distress syndrome (ARDS). This study was aimed to evaluate the effects of both administration routes including inhalation and injection with berberine in ARDS induced by lipopolysaccharide (LPS) inhalation. Histopathological examination and weight of lung were evaluated. Phosphorylation of NF-κB, JAK2 and STAT3 were measured to assess the activity of inflammation related signaling pathways. Proinflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum were also detected. The results showed that LPS caused the lung injury, while both administration routes with berberine attenuated the injury and improved the pulmonary morphology. In addition, the primary TLR4/NF-κB and secondary JAK2/STAT3 signaling pathways which were activated by LPS in lung were totally inhibited by berberine administration. Moreover, proinflammatory cytokines in both BALF and serum were decreased by berberine. Considering that molecular docking simulation indicated that berberine could bind with TLR4, the present suggested that the inhibition of the inflammation related TLR4/NF-κB and JAK2/STAT3 signaling pathways might be involved in the pulmonary protective effect of berberine in LPS-induced ARDS.
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http://dx.doi.org/10.1016/j.ejphar.2021.174349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285933PMC
October 2021

Hyperspectral Imaging for Identification of an Invasive Plant Kunth.

Front Plant Sci 2021 30;12:626516. Epub 2021 Apr 30.

Lingnan Guangdong Laboratory of Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Area, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Mile-a-minute weed ( Kunth) is considered as one of top 100 most dangerous invasive species in the world. A fast and accurate detection technology will be needed to identify . It will help to mitigate the extensive ecologic and economic damage on our ecosystems caused by this alien plant. Hyperspectral technology fulfills the above requirement. However, when working with hyperspectral images, preprocessing, dimension reduction, and classifier are fundamental to achieving reliable recognition accuracy and efficiency. The spectral data of were collected using hyperspectral imaging in the spectral range of 450-998 nm. A different combination of preprocessing methods, principal component analysis (for dimension reduction), and three classifiers were used to analyze the collected hyperspectral images. The results showed that a combination of Savitzky-Golay (SG) smoothing, principal component analysis (PCA), and random forest (RF) achieved an accuracy (A) of 88.71%, an average accuracy (AA) of 88.68%, and a Kappa of 0.7740 with an execution time of 9.647 ms. In contrast, the combination of SG, PCA and a support vector machine (SVM) resulted in a weaker performance in terms of A (84.68%), AA(84.66%), and Kappa (0.6934), but with less execution time (1.318 ms). According to the requirements for specific identification accuracy and time cost, SG-PCA-RF and SG-PCA-SVM might represent two promising methods for recognizing in the wild.
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http://dx.doi.org/10.3389/fpls.2021.626516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119880PMC
April 2021

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV.

Nature 2021 06 12;594(7862):246-252. Epub 2021 Apr 12.

Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany.

The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. Here we report a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactomes of both viruses, as well as their influence on the transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon infection with SARS-CoV-2 and SARS-CoV at different levels and enabled identification of distinct and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy was specifically dysregulated by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org ) highlights many hotspots that could be targeted by existing drugs and may be used to guide rational design of virus- and host-directed therapies, which we exemplify by identifying inhibitors of kinases and matrix metalloproteases with potent antiviral effects against SARS-CoV-2.
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http://dx.doi.org/10.1038/s41586-021-03493-4DOI Listing
June 2021

Systematic analysis to identify transcriptome-wide dysregulation of Alzheimer's disease in genes and isoforms.

Hum Genet 2021 Apr 2;140(4):609-623. Epub 2020 Nov 2.

Department of Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang West Road, Guangzhou, 500001, People's Republic of China.

Alzheimer's disease (AD) is one of the most common neurodegeneration diseases caused by multiple factors. The mechanistic insight of AD remains limited. To disclose molecular mechanisms of AD, many studies have been proposed from transcriptome analyses. However, no analysis across multiple levels of transcription has been conducted to discover co-expression networks of AD. We performed gene-level and isoform-level analyses of RNA sequencing (RNA-seq) data from 544 brain tissues of AD patients, mild cognitive impaired (MCI) patients, and healthy controls. Gene and isoform levels of co-expression modules were constructed by RNA-seq data. The associations of modules with AD were evaluated by integrating cognitive scores of patients, Genome-wide association studies (GWAS), alternative splicing analysis, and dementia-related genes expressed in brain tissues. Totally, 29 co-expression modules were found with expressions significantly correlated with the cognitive scores. Among them, two isoform modules were enriched with AD-associated SNPs and genes whose mRNA splicing displayed significant alteration in relation to AD disease. These two modules were further found enriched with dementia-related genes expressed in four brain regions of 125 AD patients. Analyzing expressions of these two modules revealed expressions of 39 isoforms (corresponding to 35 genes) significantly correlated with cognitive scores of AD patients, in which 38 isoforms were significantly up-regulated in AD patients comparing to controls, and 33 isoforms (corresponding to 29 genes) were not reported as AD-related previously. Employing the co-expression modules and the drug-induced gene expression data from Connectivity Map (CMAP), 12 drugs were predicted as significant in restoring the gene expression of AD patients towards health, which include nine drugs reported for relieving AD. In comparison, four of the top 12 significant drugs were known for relieving AD if the drug prediction was performed by the genes expressed significantly different in AD and healthy controls. Analysis of multiple levels of the transcriptomic organization is useful in suggesting AD-related co-expression networks and discovering drugs.
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http://dx.doi.org/10.1007/s00439-020-02230-7DOI Listing
April 2021

Downregulating NF-κB signaling pathway with triterpenoids for attenuating inflammation: in vitro and in vivo studies.

Food Funct 2019 Aug 30;10(8):5080-5090. Epub 2019 Jul 30.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, Guangdong, China.

Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1β. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.
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http://dx.doi.org/10.1039/c9fo00561gDOI Listing
August 2019

Ruthenium(II) Acetate Catalyzed Synthesis of Silylated Oxazoles via C-H Silylation and Dehalogenation.

Org Lett 2019 02 1;21(4):1134-1138. Epub 2019 Feb 1.

School of Biotechnology and Health Sciences , Wuyi University , 22 Dongchengcun , Jiangmen 529020 , P.R. China.

An efficient ruthenium(II)-catalyzed intermolecular selective ortho C-H silylation of 2-aryloxazoles has been described for the first time, which provides a convenient and practical pathway for the synthesis of versatile organosilane compounds with good functional group tolerance and regioselectivity. This catalytic system could be also applied to the dehalogenation of Cl or Br group.
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http://dx.doi.org/10.1021/acs.orglett.9b00085DOI Listing
February 2019

Vaccarin alleviates hypertension and nephropathy in renovascular hypertensive rats.

Exp Ther Med 2018 Jan 6;15(1):924-932. Epub 2017 Nov 6.

Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

The kidney is an important organ in the regulation of blood pressure, and it is also one of the primary target organs of hypertension. Kidney damage in response to hypertension eventually leads to renal insufficiency. The authors previously demonstrated that vaccarin exhibits a protective role in endothelial injury. However, the effects of vaccarin on the two-kidney, one clip (2K1C) renovascular hypertension model and subsequent kidney injury have yet to be fully elucidated. The present study was designed to investigate the roles and mechanisms of vaccarin in attenuating hypertension and whether vaccarin had beneficial effects on kidney injury. The 2K1C rats had greater fibrosis, apoptosis, reactive oxygen species production, inflammation, angiotensin II (Ang II) and angiotensin type 1 (AT1) receptors in the right kidney compared with normotensive rats, which were alleviated by a high dose of vaccarin and captopril. Vaccarin treatment attenuated hypertension, reduced fibrosis markers, NADPH oxidase (NOX)-2, NOX-4, 3-nitrotyrosine, tumor necrosis factor-α, interleukin 1β (IL-1β), and IL-6 protein levels and altered pro-apoptotic protein levels including caspase-3, anti-apoptosis protein B cell lymphoma (Bcl)-2 and Bcl-2 associated X, apoptosis regulator in the right kidney of 2K1C rats. These findings suggest that the protective effects of vaccarin on the right kidney in renovascular hypertension are possibly due to downregulation of fibrosis, inflammatory molecules, oxidative stress, Ang II, and AT1 receptor levels.
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http://dx.doi.org/10.3892/etm.2017.5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772753PMC
January 2018

Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch.

Mol Syst Biol 2010 9;6:350. Epub 2010 Mar 9.

2007 Peking University Team for The International Genetic Engineering Machine Competition (iGEM), Peking University, Beijng, PR China.

Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and 'memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch.
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http://dx.doi.org/10.1038/msb.2010.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858441PMC
August 2010
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