Publications by authors named "Tianliang Li"

50 Publications

Acidity-Activatable Dynamic Nanoparticles Boosting Ferroptotic Cell Death for Immunotherapy of Cancer.

Adv Mater 2021 Jun 25:e2101155. Epub 2021 Jun 25.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.

Immunotherapy shows promising therapeutic potential for long-term tumor regression. However, current cancer immunotherapy displays a low response rate due to insufficient immunogenicity of the tumor cells. To address these challenges, herein, intracellular-acidity-activatable dynamic nanoparticles for eliciting immunogenicity by inducing ferroptosis of the tumor cells are engineered. The nanoparticles are engineered by integrating an ionizable block copolymer and acid-liable phenylboronate ester (PBE) dynamic covalent bonds for tumor-specific delivery of the ferroptosis inducer, a glutathione peroxidase 4 inhibitor RSL-3. The nanoparticles can stably encapsulate RSL-3 inside the hydrophobic core via π-π stacking interaction with the PBE groups at neutral pH (pH = 7.4), while releasing the payload in the endocytic vesicles (pH = 5.8-6.2) by acidity-triggered cleavage of the PBE dynamic covalent bonds. Furthermore, the nanoparticles can perform acid-activatable photodynamic therapy by protonation of the ionizable core, and significantly recruit tumor-infiltrating T lymphocytes for interferon gamma secretion, and thus sensitize the tumor cells to RSL-3-inducible ferroptosis. The combination of nanoparticle-induced ferroptosis and blockade of programmed death ligand 1 efficiently inhibits growth of B16-F10 melanoma tumor and lung metastasis of 4T1 breast tumors, suggesting the promising potential of ferroptosis induction for promoting cancer immunotherapy.
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http://dx.doi.org/10.1002/adma.202101155DOI Listing
June 2021

Demalonylation of DDX3 by Sirtuin 5 promotes antiviral innate immune responses.

Theranostics 2021 24;11(15):7235-7246. Epub 2021 May 24.

Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

: Hosts defend against viral infection by sensing viral pathogen-associated molecular patterns and activating antiviral innate immunity through TBK1-IRF3 signaling. However, the underlying molecular mechanism remains unclear. : SiRNAs targeting Sirt1-7 were transfected into macrophages to screen the antiviral function. deficient mice or macrophages were subjected to viral infection to assess and function of Sirt5 by detecting cytokines, viral replicates and survival rate. Immunoprecipitation, WesternBlot and luciferase reporter assay were used to reveal molecular mechanism. : In this study, we functionally screened seven Sirtuin family members, and found that Sirtuin5 (Sirt5) promotes antiviral signaling and responses. deficiency leads to attenuated antiviral innate immunity and upon viral infection by decreasing TBK1-IRF3 activation and type I IFN production. Sirt5 overexpression increased antiviral innate immunity. Mechanism investigation revealed that Sirt5 interacts with DDX3 and demalonylates DDX3, which is critical for TBK1-IRF3 activation. Mutation of the demalonylation lysine sites (K66, K130, and K162) of DDX3 increased transcription. Furthermore, the acetylation on lysine 118 of DDX3 positively regulated transcription, whereas Sirt5 could not deacetylate this site. : Sirt5 promotes anti- RNA and DNA virus innate immune responses by increasing TBK1 signaling through demalonylating DDX3, which identifies a novel regulatory pathway of antiviral innate immune response.
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http://dx.doi.org/10.7150/thno.52934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210596PMC
May 2021

Ultrasound-assisted CF-filled PLGA nanobubbles for enhanced FGF21 delivery and improved prophylactic treatment of diabetic cardiomyopathy.

Acta Biomater 2021 Aug 12;130:395-408. Epub 2021 Jun 12.

Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, PR China.; Department of Ultrasound in Medicine, Shanghai Eighth People's Hospital, 8 Caobao Road, Shanghai 200235, PR China. Electronic address:

Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment. Fibroblast growth factor 21 (FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of FGF21 in DCM, an effective drug delivery system is urgently required. In this study, perfluoropropane (CF) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-emulsion evaporation and FGF21 was efficiently absorbed ([email protected]) via the electrostatic incorporation effect. [email protected] could effectively deliver FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared [email protected] could efficiently load FGF21 after doping with the cationic polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with CF, [email protected] could be used for distribution monitoring through ultrasound imaging. Moreover, [email protected] significantly downregulated the expression of ANP, CTGF, and caspase-3 mRNA via the action of LFUS owing to increased FGF21 release, therefore exhibiting enhanced inhibition of myocardial hypertrophy, apoptosis, and interstitial fibrosis in DCM mice. In conclusion, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. STATEMENT OF SIGNIFICANCE: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments. Fibroblast growth factor 21 (FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of FGF21 in DCM. In this study, perfluoropropane (C3F8) and polyethylenimine (PEI)-doped poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with FGF21 ([email protected]) were developed for the prophylactic treatment of DCM. [email protected] could effectively deliver the FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that [email protected] combined with LFUS could significantly down-regulate the expressions of ANP, CTGF, and caspase-3 mRNA, and as a result, it prevented the myocardial hypertrophy, apoptosis, and interstitial fibrosis of DCM mice. Overall, we established an effective protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.
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http://dx.doi.org/10.1016/j.actbio.2021.06.015DOI Listing
August 2021

Correlation between monocyte to high-density lipoprotein ratio and major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

Pak J Med Sci 2021 May-Jun;37(3):885-889

Jian An, Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan 030024, China.

Objective: To investigate the correlation between monocyte to high-density lipoprotein ratio (MHR) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).

Methods: In this retrospective study, 120 ACS patients who received PCI in our hospital from September 2014 to August 2019 were selected and divided into MACE group and normal discharge (ND) group. Their clinical data were collected, and MHR values were compared. Logistic regression analysis was conducted to analyze the correlations between various factors and ACS. The correlation between MHR and Gensini score was subjected to Pearson's analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of MHR for MACE.

Results: Hypertension degree, white cell count, Gensini score, MHR and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), apolipoprotein A1 (ApoA1), ApoB, lipoprotein (a) [LP(a)] and uric acid (UA) in MACE group were significantly higher than those in ND group (P<0.05). HDLC, ApoA1, TC, MHR, LDLC and ApoB were independent risk factors for MACE of ACS patients after PCI (P<0.05). There was a positive correlation between MHR and Gensini score (r=0.832, P<0.05), and the optimal cutoff value of MHR for diagnosing MACE was 9.45.

Conclusion: Serum MHR is positively correlated with Gensini score in ACS patients after PCI, which can be used as an independent predictor for MACE in hospital.
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http://dx.doi.org/10.12669/pjms.37.3.3469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155411PMC
June 2021

Engineering Oxaliplatin Prodrug Nanoparticles for Second Near-Infrared Fluorescence Imaging-Guided Immunotherapy of Colorectal Cancer.

Small 2021 04 10;17(13):e2007882. Epub 2021 Mar 10.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.

Colorectal cancer (CRC) ranks as the third common and the fourth lethal cancer type worldwide. Immune checkpoint blockade therapy demonstrates great efficacy in a subset of metastatic CRC patients, but precise activation of the antitumor immune response at the tumor site is still challenging. Here a versatile prodrug nanoparticle for second near-infrared (NIR-II) fluorescence imaging-guided combinatory immunotherapy of CRC is reported. The prodrug nanoparticles are constructed with a polymeric oxaliplatin prodrug (PBOXA) and a donor-spacer-acceptor-spacer-donor type small molecular fluorophore TQTCD. The later displays large Stokes shift (>300 nm), fluorescence emission over 1000 nm, and excellent photothermal conversion performance for NIR-II fluorescence imaging-guided photothermal therapy (PTT). The prodrug nanoparticles show seven times higher intratumoral OXA accumulation than free oxaliplatin. TQTCD-based PTT and PBOXA-induced chemotherapy trigger immunogenic cell death of the tumor cells and elicit antitumor immune response in a spatiotemporally controllable manner. Further combination of the prodrug nanoparticle-based PTT/chemotherapy with programmed death ligand 1 blockade significantly promotes intratumoral infiltration of the cytotoxic T lymphocytes and eradicates the CRC tumors. The NIR-II fluorescence imaging-guided immunotherapy may provide a promising approach for CRC treatment.
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http://dx.doi.org/10.1002/smll.202007882DOI Listing
April 2021

Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer.

Adv Sci (Weinh) 2021 Feb 4;8(4):2002746. Epub 2021 Jan 4.

State Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China.

The low immunogenicity, insufficient infiltration of T lymphocytes, and dismal response to immune checkpoint blockade therapy pose major difficulties in immunotherapy of pancreatic cancer. Photoimmunotherapy by photodynamic therapy (PDT) can induce an antitumor immune response by triggering immunogenic cell death in the tumor cells. Notwithstanding, PDT-driven oxygen consumption and microvascular damage can further aggravate hypoxia to exaggerates glycolysis, leading to lactate accumulation and immunosuppressive tumor microenvironment. Herein, a supramolecular prodrug nanoplatform codelivering a photosensitizer and a prodrug of bromodomain-containing protein 4 inhibitor (BRD4i) JQ1 for combinatory photoimmunotherapy of pancreatic cancer are demonstrated. The nanoparticles are fabricated by host-guest complexation between cyclodextrin-grafted hyaluronic acid (HA-CD) and adamantine-conjugated heterodimers of pyropheophorbide a (PPa) and JQ1, respectively. HA can achieve active tumor targeting by recognizing highly expressed CD44 on the surface of pancreatic tumors. PPa-mediated PDT can enhance the immunogenicity of the tumor cells and promote intratumoral infiltration of the cytotoxic T lymphocytes. Meanwhile, JQ1 combats PDT-mediated immune evasion through inhibiting expression of c-Myc and PD-L1, which are key regulators of tumor glycolysis and immune evasion. Collectively, this study presents a novel strategy to enhance photoimmunotherapy of the pancreatic cancer by provoking T cells activation and overcoming adaptive immune resistance.
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http://dx.doi.org/10.1002/advs.202002746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887571PMC
February 2021

Nanobiomaterial-based vaccination immunotherapy of cancer.

Biomaterials 2021 03 5;270:120709. Epub 2021 Feb 5.

State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cancer immunotherapies including cancer vaccines, immune checkpoint blockade or chimeric antigen receptor T cells have been exploited as the attractive treatment modalities in recent years. Among these approaches, cancer vaccines that designed to deliver tumor antigens and adjuvants to activate the antigen presenting cells (APCs) and induce antitumor immune responses, have shown significant efficacy in inhibiting tumor growth, preventing tumor relapse and metastasis. Despite the potential of cancer vaccination strategies, the therapeutic outcomes in preclinical trials are failed to promote their clinical translation, which is in part due to their inefficient vaccination cascade of five critical steps: antigen identification, antigen encapsulation, antigen delivery, antigen release and antigen presentation to T cells. In recent years, it has been demonstrated that various nanobiomaterials hold great potential to enhance cancer vaccination cascade and improve their antitumor performance and reduce the off-target effect. We summarize the cutting-edge advances of nanobiomaterials-based vaccination immunotherapy of cancer in this review. The various cancer nanovaccines including antigen peptide/adjuvant-based nanovaccines, nucleic acid-based nanovaccines as well as biomimetic nanobiomaterials-based nanovaccines are discussed in detail. We also provide some challenges and perspectives associated with the clinical translation of cancer nanovaccines.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120709DOI Listing
March 2021

Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy.

Nat Microbiol 2021 03 18;6(3):366-379. Epub 2021 Jan 18.

Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.

Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes-an intracellular bacterial pathogen-suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca (mtCa) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa uptake through the mtCa uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host-microbial interactions.
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http://dx.doi.org/10.1038/s41564-020-00843-2DOI Listing
March 2021

Gasdermin D restricts Burkholderia cenocepacia infection in vitro and in vivo.

Sci Rep 2021 01 13;11(1):855. Epub 2021 Jan 13.

Department of Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State University, Columbus, OH, USA.

Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes mice survival in response to certain bacterial infections. However, the role of GSDMD during B. cenocepacia infection is not yet determined. Our in vitro study shows that GSDMD restricts B. cenocepacia replication within macrophages independent of its role in cell death through promoting mitochondrial reactive oxygen species (mROS) production. mROS is known to stimulate autophagy, hence, the inhibition of mROS or the absence of GSDMD during B. cenocepacia infections reduces autophagy which plays a critical role in the restriction of the pathogen. GSDMD promotes inflammation in response to B. cenocepacia through mediating the release of inflammasome dependent cytokine (IL-1β) and an independent one (CXCL1) (KC). Additionally, different B. cenocepacia secretory systems (T3SS, T4SS, and T6SS) contribute to inflammasome activation together with bacterial survival within macrophages. In vivo study confirmed the in vitro findings and showed that GSDMD restricts B. cenocepacia infection and dissemination and stimulates autophagy in response to B. cenocepacia. Nevertheless, GSDMD promotes lung inflammation and necrosis in response to B. cenocepacia without altering mice survival. This study describes the double-edged functions of GSDMD in response to B. cenocepacia infection and shows the importance of GSDMD-mediated mROS in restriction of B. cenocepacia.
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http://dx.doi.org/10.1038/s41598-020-79201-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807041PMC
January 2021

Author Correction: Integrin CD11b attenuates colitis by strengthening Src-Akt pathway to polarize anti-inflammatory IL-10 expression.

Sci Rep 2020 Nov 10;10(1):19885. Epub 2020 Nov 10.

National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-76696-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655800PMC
November 2020

Reaction Force Mapping by 3-Axis Tactile Sensing With Arbitrary Angles for Tissue Hard-Inclusion Localization.

IEEE Trans Biomed Eng 2021 01 21;68(1):26-35. Epub 2020 Dec 21.

Although robot-assisted diagnosis and minimally invasive surgery (MIS) brings distinct benefits, deficient multi-dimensional force feedback remains a noteworthy limitation and challenge in MIS. Aiming for a comprehensive high-fidelity perception of tissue-instrument interactions, we present a Fiber Bragg Grating (FBG)-based 3-axis tactile sensing for surface reaction force mapping, identification and localization of tissue hard-inclusion. The tactile sensing probe consists of five optical fibers inscribed with FBGs and a force-sensitive 3D printed deformable body. All fibers are suspended inside the deformable body in a parallel manner, leading to the direct compression or tension of each FBG. Such configuration can effectively avoid the chirping failure of FBG compared with the pasting FBG-based sensors. A linearized difference model is proposed to calibrate the 3-axis force detection and enhance the resistance to nonlinear interferences. Hard-inclusion identification experiments with varied hard-inclusion sizes and depths have been implemented through discrete palpation and dragging palpation modes. Results indicate that the probe can effectively identify the presence and location of these small hard-inclusions from the force mapping. Furthermore, lengthy vessels embedded in the phantom can be accurately identified through dragging palpation with an arbitrary contact angle. Another novelty of the probe is the reconstruction of the surface profile of a non-planar tissue, which further allows hard-inclusion identification and 3D localization. Ex-vivo tissue palpation on a porcine kidney further validates the effectiveness and feasibility of the probe to map surface reaction forces and localize the hard-inclusions intraoperatively.
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http://dx.doi.org/10.1109/TBME.2020.2991209DOI Listing
January 2021

A bioinspired analogous nerve towards artificial intelligence.

Nat Commun 2020 01 14;11(1):268. Epub 2020 Jan 14.

School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

A bionic artificial device commonly integrates various distributed functional units to mimic the functions of biological sensory neural system, bringing intricate interconnections, complicated structure, and interference in signal transmission. Here we show an all-in-one bionic artificial nerve based on a separate electrical double-layers structure that integrates the functions of perception, recognition, and transmission. The bionic artificial nerve features flexibility, rapid response (<21 ms), high robustness, excellent durability (>10,000 tests), personalized cutability, and no energy consumption when no mechanical stimulation is being applied. The response signals are highly regionally differentiated for the mechanical stimulations, which enables the bionic artificial nerve to mimic the spatiotemporally dynamic logic of a biological neural network. Multifunctional touch interactions demonstrate the enormous potential of the bionic artificial nerve for human-machine hybrid perceptual enhancement. By incorporating the spatiotemporal resolution function and algorithmic analysis, we hope that bionic artificial nerves will promote further development of sophisticated neuroprosthetics and intelligent robotics.
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http://dx.doi.org/10.1038/s41467-019-14214-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959309PMC
January 2020

Siglec-G Deficiency Ameliorates Hyper-Inflammation and Immune Collapse in Sepsis via Regulating Src Activation.

Front Immunol 2019 7;10:2575. Epub 2019 Nov 7.

Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Hyper-inflammation during acute phase and sequential hypo-inflammation during immunosuppressive phase in macrophages/monocytes lead to multiorgan failure syndrome and immune collapse of sepsis, in which toll-like receptor (TLR)-triggered inflammatory responses play a major role. Here, we reported that deficiency attenuated TLR4-triggered pro-inflammatory cytokine production and increased anti-inflammatory cytokine [interleukin-10 [IL-10]] production and at both acute and immunosuppressive phases. deficiency also protected mice from lipopolysaccharide (LPS)-induced sepsis with less inflammation in the lung and less tissue destruction in the spleen. Siglec-G inhibited proto-oncogene tyrosine-protein kinase Src (Src) activation via recruiting and activating tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP1) through immunoreceptor tyrosine-based inhibitory motif (ITIM) domain. Src could inhibit TLR4-induced inflammatory cytokines and promote anti-inflammatory cytokine IL-10. Mechanical investigation showed that Src could interact with and phosphorylate STAT3. Src could also promote HIF1α degradation through activating GSK3β. Our study reveals that Siglec-G orchestrates TLR-induced inflammation, which outlines that blocking Siglec-G or activating Src may be a promising strategy for both acute and chronic inflammatory diseases.
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http://dx.doi.org/10.3389/fimmu.2019.02575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859834PMC
September 2020

Correction to: The methyltransferase PRMT6 attenuates antiviral innate immunity by blocking TBK1-IRF3 signaling.

Cell Mol Immunol 2020 Feb;17(2):192

National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41423-019-0337-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000675PMC
February 2020

Combined transcriptome sequencing reveals the photoperiod insensitivity mechanism of oats.

Plant Physiol Biochem 2020 Jan 12;146:133-142. Epub 2019 Nov 12.

Zhangjiakou Academy of Agricultural Sciences, Zhangjiakou, 075000, China. Electronic address:

Avena sativa L. is the most important cultivated oat species worldwide. Although photoperiod-insensitive oat varieties exist, the molecular mechanisms underlying their photoperiod sensitivity are poorly understood. This study investigated the effects of day length on the fioral transition of oats and the mechanisms underlying oat photoperiod insensitivity. Photoperiod-sensitive and photoperiod-insensitive varieties, including gp012, were used in shading experiments, and the developing leaves and main shoot apices (MSAs) of the HONGQI2 and gp012 varieties were used for sequencing. Leaves and MSAs were collected in 2016, and their transcriptomes were sequenced. The photoperiod-insensitive varieties headed under both short-day and long-day conditions, while the photoperiod-sensitive varieties headed only under long-day conditions. A total of 60673 transcript sequences were obtained, 7932 of which were differentially expressed; 3194 and 4738 transcripts were differentially expressed in the leaves and MSAs, respectively. A total of 25793 transcripts were classified into 123 pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The carbon metabolism pathways were dominant, followed by ribosome and protein processing in the endoplasmic reticulum. In addition, 203 transcripts were classified into the circadian rhythm pathway. Compared with the expression of pseudo-response regulator protein 37 (PRR37) in photoperiod-sensitive varieties, that in photoperiod-insensitive varieties was upregulated. Among the differentially expressed transcripts (DETs), 8 MADS-box genes were identified. PRR37 is a key regulator of oat photoperiod insensitivity. The obtained transcriptome dataset may provide a reference for analyzing oat transcript expression, and the results should be used as a reference for oat breeding and production.
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http://dx.doi.org/10.1016/j.plaphy.2019.11.015DOI Listing
January 2020

A modular approach for cytosolic protein delivery: metal ion-induced self-assembly of gold nanoclusters as a general platform.

Nanoscale 2019 Nov;11(46):22237-22242

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.

We developed a versatile and modular method for cytosolic protein delivery through metal ion-induced co-assembly of gold nanoclusters and proteins into supramolecular assemblies. The versatility and high efficiency of this strategy to assemble and deliver various proteins into living cells were demonstrated. Importantly, the activity of proteins was maintained during the delivery. This modular approach provides an exciting and promising new nano-platform for cytosolic protein delivery.
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http://dx.doi.org/10.1039/c9nr07334eDOI Listing
November 2019

Matrix metalloproteinase-2-targeted superparamagnetic [email protected] nanoprobes for dual-mode imaging and photodynamic therapy.

Nanoscale 2019 Oct;11(39):18426-18435

Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, Department of Instrument Science and Technology, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.

This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the [email protected] nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of [email protected] nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the [email protected] nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of [email protected] nanoprobes. Additionally, the [email protected] nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.
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http://dx.doi.org/10.1039/c9nr06774dDOI Listing
October 2019

Carbon-gold hybrid nanoprobes for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy.

Theranostics 2019 24;9(12):3443-3458. Epub 2019 May 24.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, P.R. China.

Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment. In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the [email protected] [email protected] nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze HO located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study and , our fabricated nanoprobes based on carbon-gold hybrid ([email protected] [email protected]) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor. All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics.
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http://dx.doi.org/10.7150/thno.33266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587161PMC
July 2020

Photo-Fenton-like Metal-Protein Self-Assemblies as Multifunctional Tumor Theranostic Agent.

Adv Healthc Mater 2019 08 13;8(15):e1900192. Epub 2019 Jun 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Instrument for Diagnosis and Therapy, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Emerging Fenton-like activity of copper ions has inspired great exploration for tumor microenvironment-activated tumor therapy due to the toxic ·OH production for chemodynamic therapy and extra oxygen generation for photodynamic therapy (PDT). Still, the ·OH produced by copper ions is not satisfied even when copper ions are placed in a low pH environment (pH ≈ 5.0). To amplify its Fenton-like activity, in this work, one kind of Cu -protein self-assemblies (C-m-ABs) loaded with photosensitizer indocyanine green (ICG) is constructed, which can catalyze H O generating more amounts of ·OH under light irradiation once Cu is reduced to Cu by glutathione. Such fantastic phenomena confirms that C-m-ABs can act as a photo-Fenton-like agent. Furthermore, C-m-ABs can dramatically accelerate O generation (catalase activity) to enhance the PDT of ICG. After loading with the anticancer drug doxorubicin, C-m-ABs are further self-assembled into novel nanobelts, which simultaneously exhibit superior photo-heat conversion effects, enhanced r1 relaxation (21.416 s mm ) and stimuli-responsive drug release behaviors. High cytotoxicity in vitro, effective tumor accumulation capacity observed by fluorescence/photoacoustic/magnetic resonance imaging, and enhanced chemo-/photodynamic/photothermal therapeutic performance are achieved. Based on these results, a photo-Fenton-like metal-protein self-assemblies demonstrate great potential for tumor theranostics.
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http://dx.doi.org/10.1002/adhm.201900192DOI Listing
August 2019

An endosomal LAPF is required for macrophage endocytosis and elimination of bacteria.

Proc Natl Acad Sci U S A 2019 06 12;116(26):12958-12963. Epub 2019 Jun 12.

National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 200433 Shanghai, China;

Macrophages can internalize the invading pathogens by raft/caveolae and/or clathrin-dependent endocytosis and elicit an immune response against infection. However, the molecular mechanism for macrophage endocytosis remains elusive. Here we report that LAPF (lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains) is required for caveolae-mediated endocytosis. deficient macrophages have impaired capacity to endocytose and eliminate bacteria. Macrophage-specific -deficient mice are more susceptible to () infection with higher bacterial loads. Moreover, deficiency impairs TLR4 endocytosis, resulting in attenuated production of TLR-triggered proinflammatory cytokines. LAPF is localized to early endosomes and interacts with caveolin-1. Phosphorylation of LAPF by the tyrosine kinase Src is required for LAPF-Src-Caveolin complex formation and endocytosis and elimination of bacteria. Collectively, our work demonstrates that LAPF is critical for endocytosis of bacteria and induction of inflammatory responses, suggesting that LAPF and Src could be potential targets for the control of infectious diseases.
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http://dx.doi.org/10.1073/pnas.1903896116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601291PMC
June 2019

Impact of Short-Term Exposure of AuNCs on the Gut Microbiota of BALB/c Mice.

J Biomed Nanotechnol 2019 Apr;15(4):779-789

The widespread application of nanoparticles causes extensive public concern on their biological safety. However, up to date, few reports have been associated with the impact of metal nanoparticles on gut microbiota . In this study, gold nanoclusters (AuNCs) were orally administered to BALB/c mice for 7 days, and the dynamic effects of AuNCs on gut microbiota were investigated at 0 h, 4 h, 8 h, 1 d, 3 d and 7 d, respectively. Using high-throughput sequencing of V4-V5 regions of the 16S rRNA gene on the Illumina MiSeq platform, we found that gavage of AuNCs did not significantly change the gut microbiota diversity and community at the initial 3 days. Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres, Tenericutes and Actinobacteria were the six most abundant phylum in the control and AuNCs groups. However, the phylum Proteobacteria was significantly increased by AuNCs at 7 d ( < 0.05). At the genus level, were notably decreased while , and were dramatically increased by AuNCs at 7 d ( < 0.05). Taken together, gavage of AuNCs shifted the bacterial composition at 7 d. This is the first research to investigate the toxicity of AuNCs from the perspective of gut microbiota and opens up a new avenue for the safety or toxicity evaluation of AuNCs.
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http://dx.doi.org/10.1166/jbn.2019.2731DOI Listing
April 2019

O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.

Immunity 2019 03 12;50(3):576-590.e6. Epub 2019 Feb 12.

Department of Microbial Infection and Immunity, Infectious Disease Institute, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP). Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation. Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation. Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling. Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
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http://dx.doi.org/10.1016/j.immuni.2019.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426684PMC
March 2019

Chinese association of ultrasound in medicine and engineering, superficial organs and peripheral vessels committee expert consensus on clinical frequently asked questions in breast ultrasonography, June 2018.

J Cancer Res Ther 2018 ;14(7):1463-1468

Department of Ultrasound, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

Ultrasonography, the preferred imaging modality for breast diseases, has merits such as absence of radiation, high diagnostic accuracy, and convenience for follow-up, thus playing an important role in clinical diagnosis and management. The American College of Radiology (ACR) proposed Breast Imaging-Reporting and Data System (BI-RADS ) and has updated for several times. Gradually, the BI-RADS has been accepted and adopted by ultrasound physicians at all levels of hospitals in China, and it has played a certain role in improving the diagnostic level of breast ultrasound in China. In order to standardize breast ultrasound application and raise the status of ultrasound in clinical decision-making of breast diseases, based on the latest edition of ACR BI-RADS Atlas 2013, the committee has reached the "Expert Consensus on Clinical Frequently Asked Questions in Breast Ultrasonography"on a number of controversial Frequently Asked Questions (FAQs) in clinical practice (hereafter referred to as "Consensus"), and will be dedicated to updating the contents of the "Consensus", through further experience in clinical practice and the advent of new information from further studies. This consensus is only for reference purposes for medical personnel, and the processes outlined are not mandatory by law.
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http://dx.doi.org/10.4103/jcrt.JCRT_509_18DOI Listing
February 2019

Incipient fault detection of rolling bearing using maximum autocorrelation impulse harmonic to noise deconvolution and parameter optimized fast EEMD.

ISA Trans 2019 Jun 17;89:256-271. Epub 2018 Dec 17.

School of Advanced Manufacturing Engineering, Chongqing University of Posts and Telecommunications, Chongqing, China.

Incipient Fault Detection of Rolling Bearing with heavy background noise and interference harmonics is a hot topic. In this paper, a new method based on parameter optimized fast EEMD (FEEMD) and Maximum Autocorrelation Impulse Harmonic to Noise Deconvolution (MAIHND) method is proposed for detecting the incipient fault of rolling bearing. Firstly, the FEEMD method with parameters optimization is used to reduce the noise and eliminate the interference harmonics of the fault signal. As a noise assistant improved method, the FEEMD can reduce the mode mixing and enhance the calculation efficiency significantly. Secondly, a new indicator is developed to select the sensitive IMF. Finally, a novel MAIHND method is employed to extract impulse fault feature from the sensitive IMF. Simulation and experiments results indicated that the proposed parameter optimized FEEMD-MAIHND method can effectively identify the weak impulse fault feature of rolling bearing. Moreover, the excellent performance of the proposed indicator for sensitive IMF component selection and MAIHND method is verified.
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http://dx.doi.org/10.1016/j.isatra.2018.12.020DOI Listing
June 2019

O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.

Cell Host Microbe 2018 12;24(6):791-803.e6

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address:

Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage. However, the role of individual glucose metabolic pathways during viral infection remains largely unknown. Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity. Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation. Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge. Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation. Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
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http://dx.doi.org/10.1016/j.chom.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296827PMC
December 2018

The methyltransferase PRMT6 attenuates antiviral innate immunity by blocking TBK1-IRF3 signaling.

Cell Mol Immunol 2019 10 4;16(10):800-809. Epub 2018 Jul 4.

National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.

Protein arginine methyltransferases (PRMTs) play diverse biological roles and are specifically involved in immune cell development and inflammation. However, their role in antiviral innate immunity has not been elucidated. Viral infection triggers the TBK1-IRF3 signaling pathway to stimulate the production of type-I interferon, which mediates antiviral immunity. We performed a functional screen of the nine mammalian PRMTs for regulators of IFN-β expression and found that PRMT6 inhibits the antiviral innate immune response. Viral infection also upregulated PRMT6 protein levels. We generated PRMT6-deficient mice and found that they exhibited enhanced antiviral innate immunity. PRMT6 deficiency promoted the TBK1-IRF3 interaction and subsequently enhanced IRF3 activation and type-I interferon production. Mechanistically, viral infection enhanced the binding of PRMT6 to IRF3 and inhibited the interaction between IRF3 and TBK1; this mechanism was independent of PRMT6 methyltransferase activity. Thus, PRMT6 inhibits antiviral innate immunity by sequestering IRF3, thereby blocking TBK1-IRF3 signaling. Our work demonstrates a methyltransferase-independent role for PRMTs. It also identifies a negative regulator of the antiviral immune response, which may protect the host from the damaging effects of an overactive immune system and/or be exploited by viruses to escape immune detection.
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http://dx.doi.org/10.1038/s41423-018-0057-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804946PMC
October 2019

Sensitivity Enhancement of FBG-Based Strain Sensor.

Sensors (Basel) 2018 May 17;18(5). Epub 2018 May 17.

School of Mechanical and Electronic Engineering, Wuhan University of Technology, Wuhan 430070, China.

A novel fiber Bragg grating (FBG)-based strain sensor with a high-sensitivity is presented in this paper. The proposed FBG-based strain sensor enhances sensitivity by pasting the FBG on a substrate with a lever structure. This typical mechanical configuration mechanically amplifies the strain of the FBG to enhance overall sensitivity. As this mechanical configuration has a high stiffness, the proposed sensor can achieve a high resonant frequency and a wide dynamic working range. The sensing principle is presented, and the corresponding theoretical model is derived and validated. Experimental results demonstrate that the developed FBG-based strain sensor achieves an enhanced strain sensitivity of 6.2 pm/με, which is consistent with the theoretical analysis result. The strain sensitivity of the developed sensor is 5.2 times of the strain sensitivity of a bare fiber Bragg grating strain sensor. The dynamic characteristics of this sensor are investigated through the finite element method (FEM) and experimental tests. The developed sensor exhibits an excellent strain-sensitivity-enhancing property in a wide frequency range. The proposed high-sensitivity FBG-based strain sensor can be used for small-amplitude micro-strain measurement in harsh industrial environments.
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http://dx.doi.org/10.3390/s18051607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982636PMC
May 2018

Charge-switchable nanocapsules with multistage pH-responsive behaviours for enhanced tumour-targeted chemo/photodynamic therapy guided by NIR/MR imaging.

Nanoscale 2018 May;10(20):9707-9719

Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo-photodynamic therapeutic nanoplatforms. Importantly, the nanocapsule can intelligently switch its surface charge to positive under mildly acidic conditions (pH 6.5) with no release of Ce6 and DOX, which is confirmed by ξ-potential and cumulative release measurements. Moreover, confocal imaging pictures demonstrate that acid-sensitive DOX sealed in nanocapsules is progressively released into the nuclei of MGC-803 cells. These advantages as well as FA-targeting facilitate effective endocytosis and synergistic therapeutic efficacy. Selective tumour accumulation and long tumour retention time are further indicated by NIR/MR in vivo imaging. In addition, excellent therapeutic efficacy combined with chemotherapy (DOX) and photodynamic therapy (PDT) is observed with the tumour eventually ablating at the 15th day. All results demonstrate that the as-prepared nanocapsules hold great potential for clinical cancer theranostics.
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http://dx.doi.org/10.1039/c8nr00994eDOI Listing
May 2018
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