Publications by authors named "Linjie Guo"

50 Publications

A Nanoradiomics Approach for Differentiation of Tumors Based on Tumor-Associated Macrophage Burden.

Contrast Media Mol Imaging 2021 14;2021:6641384. Epub 2021 Jun 14.

Edward B. Singleton Department of Radiology, Texas Children's Hospital, Houston, TX, USA.

Objective: Tumor-associated macrophages (TAMs) within the tumor immune microenvironment (TiME) of solid tumors play an important role in treatment resistance and disease recurrence. The purpose of this study was to investigate if nanoradiomics (radiomic analysis of nanoparticle contrast-enhanced images) can differentiate tumors based on TAM burden.

Materials And Methods: In vivo studies were performed in transgenic mouse models of neuroblastoma with low ( = 11) and high ( = 10) tumor-associated macrophage (TAM) burden. Animals underwent delayed nanoparticle contrast-enhanced CT (n-CECT) imaging at 4 days after intravenous administration of liposomal-iodine agent (1.1 g/kg). CT imaging-derived conventional tumor metrics (tumor volume and CT attenuation) were computed for segmented tumor CT datasets. Nanoradiomic analysis was performed using a PyRadiomics workflow implemented in the quantitative image feature pipeline (QIFP) server containing 900 radiomic features (RFs). RF selection was performed under supervised machine learning using a nonparametric neighborhood component method. A 5-fold validation was performed using a set of linear and nonlinear classifiers for group separation. Statistical analysis was performed using the Kruskal-Wallis test.

Results: N-CECT imaging demonstrated heterogeneous patterns of signal enhancement in low and high TAM tumors. CT imaging-derived conventional tumor metrics showed no significant differences ( > 0.05) in tumor volume between low and high TAM tumors. Tumor CT attenuation was not significantly different ( > 0.05) between low and high TAM tumors. Machine learning-augmented nanoradiomic analysis revealed two RFs that differentiated ( < 0.002) low TAM and high TAM tumors. The RFs were used to build a linear classifier that demonstrated very high accuracy and further confirmed by 5-fold cross-validation.

Conclusions: Imaging-derived conventional tumor metrics were unable to differentiate tumors with varying TAM burden; however, nanoradiomic analysis revealed texture differences and enabled differentiation of low and high TAM tumors.
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http://dx.doi.org/10.1155/2021/6641384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216795PMC
June 2021

Remote Photothermal Control of DNA Origami Assembly in Cellular Environments.

Nano Lett 2021 07 16;21(13):5834-5841. Epub 2021 Jun 16.

The Interdisciplinary Research Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

In situ synthesis of DNA origami structures in living systems is highly desirable due to its potential in biological applications, which nevertheless is hampered by the requirement of thermal activation procedures. Here, we report a photothermal DNA origami assembly method in near-physiological environments. We find that the use of copper sulfide nanoparticles (CuS NPs) can mediate efficient near-infrared (NIR) photothermal conversion to remotely control the solution temperature. Under a 4 min NIR illumination and subsequent natural cooling, rapid and high-yield (>80%) assembly of various types of DNA origami nanostructures is achieved as revealed by atomic force microscopy and single-molecule fluorescence resonance energy transfer analysis. We further demonstrate the in situ assembly of DNA origami with high location precision in cell lysates and in cell culture environments.
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http://dx.doi.org/10.1021/acs.nanolett.1c01821DOI Listing
July 2021

Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture.

Angew Chem Int Ed Engl 2021 06 24;60(26):14438-14445. Epub 2021 May 24.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Direct delivery of exogenous non-coding nucleic acids into living cells has attracted intense interest in biological applications. However, the cell entry efficiency and target capture ability remain to be improved. Herein, we report a method for compartmenting the nucleic acids on the surface of poly-adenine-based spherical nucleic acids (polyA-SNAs) for efficient capture of oncogenic microRNAs (miRNAs) in living cells. We find that polyA-SNAs exhibit high cell entry efficiency, which is insensitive to the configuration of the anti-miRNA sequences. By programming the length of polyAs, we precisely engineered the spatial configuration of the anti-miRNA sequences in polyA-SNAs. Compartmentalized polyA-SNAs bind to miRNAs with improved capture ability as compared to densely compacted SNAs. We further demonstrate that polyA-SNAs serve as high-efficacy miRNA sponges for capturing oncogenic miRNAs both in living cells and in mice. The efficient inhibition of miRNAs results in significant suppression of tumor growth.
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http://dx.doi.org/10.1002/anie.202017039DOI Listing
June 2021

Successful endoscopic submucosal dissection of a large juvenile polyp in the stomach of an infant.

Endoscopy 2020 Dec 3. Epub 2020 Dec 3.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1055/a-1300-0865DOI Listing
December 2020

Detection of multiple lesions of gastrointestinal tract for endoscopy using artificial intelligence model: a pilot study.

Surg Endosc 2020 Nov 13. Epub 2020 Nov 13.

West China Hospital, Sichuan University, Department of Gastroenterology, Chengdu, China.

Background: This study was aimed to develop a computer-aided diagnosis (CAD) system with deep-learning technique and to validate its efficiency on detecting the four categories of lesions such as polyps, advanced cancer, erosion/ulcer and varices at endoscopy.

Methods: A deep convolutional neural network (CNN) that consists of more than 50 layers were trained with a big dataset containing 327,121 white light images (WLI) of endoscopy from 117,005 cases collected from 2012 to 2017. Two CAD models were developed using images with or without annotation of the training dataset. The efficiency of the CAD system detecting the four categories of lesions was validated by another dataset containing consecutive cases from 2018 to 2019.

Results: A total of 1734 cases with 33,959 images were included in the validation datasets which containing lesions of polyps 1265, advanced cancer 500, erosion/ulcer 486, and varices 248. The CAD system developed in this study may detect polyps, advanced cancer, erosion/ulcer and varices as abnormality with the sensitivity of 88.3% and specificity of 90.3%, respectively, in 0.05 s. The training datasets with annotation may enhance either sensitivity or specificity about 20%, p = 0.000. The sensitivities and specificities for polyps, advanced cancer, erosion/ulcer and varices reached about 90%, respectively. The detect efficiency for the four categories of lesions reached to 89.7%.

Conclusion: The CAD model for detection of multiple lesions in gastrointestinal lumen would be potentially developed into a double check along with real-time assessment and interpretation of the findings encountered by the endoscopists and may be a benefit to reduce the events of missing lesions.
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http://dx.doi.org/10.1007/s00464-020-08150-xDOI Listing
November 2020

Endoscopic submucosal dissection with additional radiotherapy in the treatment of T1a esophageal squamous cell cancer: randomized controlled Trial.

Endoscopy 2020 12 15;52(12):1066-1074. Epub 2020 Jul 15.

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Endoscopic submucosal dissection (ESD) is effective for treating T1a early esophageal squamous cell carcinoma (ESCC). However, occasional recurrences are inevitable. This trial was designed to clarify the efficacy of combining ESD with additional radiotherapy in the treatment of T1a ESCC.

Methods: Between January 2015 and September 2018, patients with early ESCC (T1aN0M0) following ESD were randomly assigned (1:1) to the radiotherapy group or non-radiotherapy group. Patients in the radiotherapy group received a median radiation dose of 59.4 Gy within 2 months after ESD. In the non-radiotherapy group, patients underwent regular follow-up only. Recurrence-free survival, cancer-specific survival, overall survival, and complications were evaluated.

Results: 70 patients completed the per-protocol treatment. Three patients in the non-radiotherapy group experienced intraluminal mucosal recurrence compared with none in the radiotherapy group. No local lymph node or distant metastases occurred in either group. The 3-year cumulative recurrence-free survival was 100 % in the radiotherapy group and 85.3 % in the non-radiotherapy group ( = 0.04; hazard ratio 0.08, 95 % confidence interval [CI] 0.01 - 0.86). However, there was no significant difference in RFS between the treatments within the T1a invasion subgroups ( > 0.05). No patient died in either group. Mucosal defects of more than three-quarters of the esophageal circumference were positively correlated with stenosis ( < 0.01; odds ratio 23.26, 95 %CI 4.04 - 133.86). No severe radiation toxicities were recorded.

Conclusions: Radiotherapy after ESD might be a safe and effective optional therapeutic strategy to prevent recurrence of T1a ESCC.
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http://dx.doi.org/10.1055/a-1198-5232DOI Listing
December 2020

Programming Switchable Transcription of Topologically Constrained DNA.

J Am Chem Soc 2020 06 5;142(24):10739-10746. Epub 2020 Jun 5.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200240, China.

Genomic DNA is compacted via chromatin condensation in mammalian cells, and transcription of such topologically constrained DNA to messenger RNA is under strict spatiotemporal regulation. Nevertheless, control of DNA topology has been poorly explored in transcription and gene transfection. Here we report the construction of topologically ordered (TO-) prokaryotic genes composed of linear DNA templates appended with a T7 promoter sequence with the use of DNA self-assembly. We find that TO-DNA maintains the transcription activity whereas the activity is critically dependent on the configuration of the T7 promoter in a folded DNA nanostructure. By prescribing the position and the intactness of the T7 promoter, we can dynamically activate or repress transcription in response to specific DNA key strands in a Boolean logic manner. Bioorthogonal switchable transcription is realized with the insertion of multiple genes in a TO-DNA. Further, implementing TO-DNA in living bacteria leads to switchable transcription of fluorescent RNA aptamers for light-up cell imaging. Hence, the design of TO-DNAs provides a means for shape-dependent gene delivery, enriching the toolbox of genetic engineering and synthetic biology.
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http://dx.doi.org/10.1021/jacs.0c01962DOI Listing
June 2020

Golgi Alpha-Mannosidase II as a Novel Biomarker Predicts Prognosis in Clear Cell Renal Cell Carcinoma.

Oncol Res Treat 2020 13;43(6):264-275. Epub 2020 May 13.

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.

Objective: Golgi alpha-mannosidase II (GM II) is one of the crucial enzymes in the process of N-glycan processing. The aim of our study was to examine the clinical significance of GM II in patients with clear cell renal cell carcinoma (ccRCC).

Methods: Quantitative reverse transcription polymerase chain reaction analysis and immunohistochemical staining were used to analyze GM II expression in patients with ccRCC. The clinical data of 62 patients with ccRCC were collected to analyze the clinical significance of GM II. The clinical significance among GM II expression, clinicopathological staging, and histological grade of ccRCC was explored. Survival analyses were performed to identify the relevance between the expression of GM II and the overall survival of patients with ccRCC. A uni-/multivariate Cox regression model was used to detect risk factors affecting the prognosis of patients with ccRCC. Subsequently, the proliferation and migration of ccRCC cells were detected after transfecting with GM II-short hairpin RNA (shRNA).

Results: The results of these comparisons suggested that GM II expression of ccRCC tissues was dramatically higher than that of para-carcinoma tissues (p < 0.05). GM II expression in the high-differentiation group was lower than that in the median- and low-differentiation groups (p < 0.05). GM II expression in stage I and II tissues was lower than that in stage III and IV tissues (p < 0.05). The expression levels of GM II in the group without lymph node metastasis were lower than those in the group with lymph node metastasis (p < 0.05). Survival analysis indicated that patients with ccRCC with high GM II expression generally had decreased overall survival. Uni-/multivariate Cox model analyses further suggested an association between GM II expression and prognosis of patients with breast cancer. High GM II expression is a potential and independent prognostic biomarker in ccRCC. The inhibition of GM II by transfecting with GM II-shRNA could reduce the proliferation and migration of ccRCC.

Conclusion: GM II expression in human ccRCC tissues was upregulated compared with that found in normal human renal tissue, and GM II may promote the progression and migration of ccRCC. Furthermore, the GM II gene may be used as a promising tumor marker for the diagnosis and prognosis of ccRCC.
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http://dx.doi.org/10.1159/000505931DOI Listing
September 2020

Encoding quantized fluorescence states with fractal DNA frameworks.

Nat Commun 2020 05 4;11(1):2185. Epub 2020 May 4.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200024, Shanghai, China.

Signal amplification in biological systems is achieved by cooperatively recruiting multiple copies of regulatory biomolecules. Nevertheless, the multiplexing capability of artificial fluorescent amplifiers is limited due to the size limit and lack of modularity. Here, we develop Cayley tree-like fractal DNA frameworks to topologically encode the fluorescence states for multiplexed detection of low-abundance targets. Taking advantage of the self-similar topology of Cayley tree, we use only 16 DNA strands to construct n-node (n = 53) structures of up to 5 megadalton. The high level of degeneracy allows encoding 36 colours with 7 nodes by site-specifically anchoring of distinct fluorophores onto a structure. The fractal topology minimises fluorescence crosstalk and allows quantitative decoding of quantized fluorescence states. We demonstrate a spectrum of rigid-yet-flexible super-multiplex structures for encoded fluorescence detection of single-molecule recognition events and multiplexed discrimination of living cells. Thus, the topological engineering approach enriches the toolbox for high-throughput cell imaging.
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http://dx.doi.org/10.1038/s41467-020-16112-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198603PMC
May 2020

Programming Cell-Cell Communications with Engineered Cell Origami Clusters.

J Am Chem Soc 2020 05 28;142(19):8800-8808. Epub 2020 Apr 28.

Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200024, China.

Cells existing in the form of clusters often exhibit distinct physiological functions from their monodispersed forms, which have a close association with tissue and organ development, immunoresponses, and cancer metastasis. Nevertheless, the ability to construct artificial cell clusters as in vitro models for probing and manipulating intercellular communications remains limited. Here we design DNA origami nanostructure (DON)-based biomimetic membrane channels to organize cell origami clusters (COCs) with controlled geometric configuration and cell-cell communications. We demonstrate that programmable patterning of homotypic and heterotypic COCs with different configurations can result in three distinct types of intercellular communications: gap junctions, tunneling nanotubes, and immune/tumor cell interactions. In particular, the organization of T cells and cancer cells with a prescribed ratio and geometry can program in vitro immunoresponses, providing a new route to understanding and engineering cancer immunotherapy.
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http://dx.doi.org/10.1021/jacs.0c01580DOI Listing
May 2020

DNA Nanoribbon-Templated Self-Assembly of Ultrasmall Fluorescent Copper Nanoclusters with Enhanced Luminescence.

Angew Chem Int Ed Engl 2020 07 12;59(29):11836-11844. Epub 2020 May 12.

Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China.

Fluorescent copper nanoclusters (CuNCs) have been widely used in chemical sensors, biological imaging, and light-emitting devices. However, individual fluorescent CuNCs have limitations in their capabilities arising from poor photostability and weak emission intensities. As one kind of aggregation-induced emission luminogen (AIEgen), the formation of aggregates with high compactness and good order can efficiently improve the emission intensity, stability, and tunability of CuNCs. Here, DNA nanoribbons, containing multiple specific binding sites, serve as a template for in situ synthesis and assembly of ultrasmall CuNCs (0.6 nm). These CuNC self-assemblies exhibit enhanced luminescence and excellent fluorescence stability because of tight and ordered arrangement through DNA nanoribbons templating. Furthermore, the stable and bright CuNC assemblies are demonstrated in the high-sensitivity detection and intracellular fluorescence imaging of biothiols.
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http://dx.doi.org/10.1002/anie.202003905DOI Listing
July 2020

DNA Origami-Enabled Engineering of Ligand-Drug Conjugates for Targeted Drug Delivery.

Small 2020 04 19;16(16):e1904857. Epub 2020 Mar 19.

School of Chemistry and Chemical Engineering and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligand-modified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody for drug conjugation in ADC. Doxorubicin (Dox) is then loaded to DON through intercalation to dsDNA. This platform features in spatially controllable organization of targeting ligands and high drug loading capacity. With this nanocomposite, selective delivery of Dox to the PSMA+ cancer cell line LNCaP is readily achieved. The consequent therapeutic efficacy is critically dependent on the numbers of targeting ligand assembled on DON. This target-specific and biocompatible drug delivery platform with high maximum tolerated doses shows immense potential for developing novel nanomedicine.
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http://dx.doi.org/10.1002/smll.201904857DOI Listing
April 2020

Open peroral endoscopic myotomy for refractory benign esophageal stricture.

Endoscopy 2020 08 29;52(8):E271-E272. Epub 2020 Jan 29.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1055/a-1089-7551DOI Listing
August 2020

Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.

Cancer Immunol Res 2020 03 17;8(3):309-320. Epub 2020 Jan 17.

Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)-expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function and can improve the antitumor properties of T cells. We explored whether transgenic expression of IL15 and/or IL21 enhanced glypican-3-CAR (GPC3-CAR) T cells' antitumor properties against HCC. We previously optimized the costimulation in GPC3-CARs and selected a second-generation GPC3-CAR incorporating a 4-1BB costimulatory endodomain (GBBz) for development. Here, we generated constructs encoding IL15, IL21, or both with GBBz (15.GBBz, 21.GBBz, and 21.15.GBBz, respectively) and examined the ability of transduced T cells to kill, produce effector cytokines, and expand in an antigen-dependent manner. We performed gene-expression and phenotypic analyses of GPC3-CAR T cells and CRISPR-Cas9 knockout of the gene. Finally, we measured GPC3-CAR T-cell antitumor activity in murine xenograft models of GPC3 tumors. The increased proliferation of 21.15.GBBz T cells was at least in part dependent on the upregulation and maintenance of TCF-1 (encoded by ) and associated with a higher percentage of stem cell memory and central memory populations after manufacturing. T cells expressing 21.15.GBBz had superior and expansion and persistence, and the most robust antitumor activity These results provided preclinical evidence to support the clinical evaluation of 21.15.GPC3-CAR T cells in patients with HCC.
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http://dx.doi.org/10.1158/2326-6066.CIR-19-0293DOI Listing
March 2020

Abnormal submucosal artery mimicking submucosal tumor in the sigmoid colon.

Authors:
LinJie Guo Bing Hu

Gastrointest Endosc 2020 05 7;91(5):1213-1214. Epub 2020 Jan 7.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1016/j.gie.2020.01.001DOI Listing
May 2020

Detection of Performance of Hybrid Rice Pot-Tray Sowing Utilizing Machine Vision and Machine Learning Approach.

Sensors (Basel) 2019 Dec 3;19(23). Epub 2019 Dec 3.

College of Engineering, South China Agricultural University, Guangzhou 510642, China.

Monitoring the performance of hybrid rice seeding is very important for the seedling production line to adjust the sowing amount of the seeding device. The objective of this paper was to develop a system for the real-time online monitoring of the performance of hybrid rice seeding based on embedded machine vision and machine learning technology. The embedded detection system captured images of pot trays that passed under the illuminant cabinet installed in the seedling production line. This paper proposed an algorithm for fixed threshold segmentation by analyzing the images with the exploratory analysis method. With the algorithm, the grid image and seed image were extracted from the pot tray image. The paper also proposed a method for obtaining pixel coordinates of gridlines from the grid image. Binary images of seeds were divided into small pieces, according to the pixel coordinates of gridlines. Each piece corresponded to a cell on the pot tray. By scanning the contours in each piece of the image to check whether there were seeds in the cell, the number of empty cells was counted and then used to calculate the missing rate of hybrid rice seeding. The seed number sowed in pot trays was monitored while using the machine learning approach. The experimental results demonstrated that it would consume 4.863 s for the device to process an image, which allowed for the detection of the missing rate and seed number in real-time at the rate of 500 trays per hour (7.2 s per tray). The average accuracy of the detection of missing rates of a seedling production line was 94.67%. The average accuracy of the detection of seed numbers was 95.68%.
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http://dx.doi.org/10.3390/s19235332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928799PMC
December 2019

NKT Cells Coexpressing a GD2-Specific Chimeric Antigen Receptor and IL15 Show Enhanced Persistence and Antitumor Activity against Neuroblastoma.

Clin Cancer Res 2019 12 4;25(23):7126-7138. Epub 2019 Sep 4.

Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Purpose: Vα24-invariant natural killer T cells (NKT) are attractive carriers for chimeric antigen receptors (CAR) due to their inherent antitumor properties and preferential localization to tumor sites. However, limited persistence of CAR-NKTs in tumor-bearing mice is associated with tumor recurrence. Here, we evaluated whether coexpression of the NKT homeostatic cytokine IL15 with a CAR enhances the persistence and therapeutic efficacy of CAR-NKTs.

Experimental Design: Human primary NKTs were expanded and transduced with CAR constructs containing an optimized GD2-specific single-chain variable fragment and either the CD28 or 4-1BB costimulatory endodomain, each with or without IL15 (GD2.CAR or GD2.CAR.15). Constructs that mediated robust CAR-NKT cell expansion were selected for further functional evaluation and in xenogeneic mouse models of neuroblastoma.

Results: Coexpression of IL15 with either costimulatory domain increased CAR-NKT absolute numbers. However, constructs containing 4-1BB induced excessive activation-induced cell death and reduced numeric expansion of NKTs compared with respective CD28-based constructs. Further evaluation of CD28-based GD2.CAR and GD2.CAR.15 showed that coexpression of IL15 led to reduced expression levels of exhaustion markers in NKTs and increased multiround tumor cell killing. Following transfer into mice bearing neuroblastoma xenografts, GD2.CAR.15 NKTs demonstrated enhanced persistence, increased localization to tumor sites, and improved tumor control compared with GD2.CAR NKTs. Importantly, GD2.CAR.15 NKTs did not produce significant toxicity as determined by histopathologic analysis.

Conclusions: Our results informed selection of the CD28-based GD2.CAR.15 construct for clinical testing and led to initiation of a first-in-human CAR-NKT cell clinical trial (NCT03294954).
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http://dx.doi.org/10.1158/1078-0432.CCR-19-0421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891170PMC
December 2019

Real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinoma using a deep learning model (with videos).

Gastrointest Endosc 2020 01 21;91(1):41-51. Epub 2019 Aug 21.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.

Background And Aims: We developed a system for computer-assisted diagnosis (CAD) for real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinomas (ESCCs) to assist the diagnosis of esophageal cancer.

Methods: A total of 6473 narrow-band imaging (NBI) images, including precancerous lesions, early ESCCs, and noncancerous lesions, were used to train the CAD system. We validated the CAD system using both endoscopic images and video datasets. The receiver operating characteristic curve of the CAD system was generated based on image datasets. An artificial intelligence probability heat map was generated for each input of endoscopic images. The yellow color indicated high possibility of cancerous lesion, and the blue color indicated noncancerous lesions on the probability heat map. When the CAD system detected any precancerous lesion or early ESCCs, the lesion of interest was masked with color.

Results: The image datasets contained 1480 malignant NBI images from 59 consecutive cancerous cases (sensitivity, 98.04%) and 5191 noncancerous NBI images from 2004 cases (specificity, 95.03%). The area under curve was 0.989. The video datasets of precancerous lesions or early ESCCs included 27 nonmagnifying videos (per-frame sensitivity 60.8%, per-lesion sensitivity, 100%) and 20 magnifying videos (per-frame sensitivity 96.1%, per-lesion sensitivity, 100%). Unaltered full-range normal esophagus videos included 33 videos (per-frame specificity 99.9%, per-case specificity, 90.9%).

Conclusions: A deep learning model demonstrated high sensitivity and specificity for both endoscopic images and video datasets. The real-time CAD system has a promising potential in the near future to assist endoscopists in diagnosing precancerous lesions and ESCCs.
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http://dx.doi.org/10.1016/j.gie.2019.08.018DOI Listing
January 2020

The REGγ-Proteasome Regulates Spermatogenesis Partially by P53-PLZF Signaling.

Stem Cell Reports 2019 09 8;13(3):559-571. Epub 2019 Aug 8.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. Electronic address:

Development of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are poorly explored. Here we found that ablation of REGγ, a proteasome activator, resulted in male subfertility. Analysis of the mouse testes after birth showed there was a decreased number of PLZF spermatogonia and spermatocytes. Molecular analysis found that REGγ loss significantly increased the abundance of p53 protein in the testis, and directly repressed PLZF transcription in cell lines. Of note, allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. In summary, our results identify REGγ-p53-PLZF to be a critical pathway that regulates spermatogenesis and establishes a new molecular link between the proteasome system and male reproduction.
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http://dx.doi.org/10.1016/j.stemcr.2019.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742627PMC
September 2019

Indolent T-cell lymphoproliferative disease with synchronous diffuse large B-cell lymphoma: A case report.

Medicine (Baltimore) 2019 Apr;98(17):e15323

Department of Gastroenterology.

Rationale: Indolent T-cell lymphoproliferative disease (T-LPD) of gastrointestinal tract is a rare recently described disease that seldom progresses. We report a case of T-LPD with synchronous diffuse large B-cell lymphoma (DLBCL) that cause aggravation of disease.

Patient Concerns: A 46-year-old Chinese male presented with intermittent paraumbilical colic pain, bloating, and occasional diarrhea for 10 years. His condition aggravated with partial bowel obstruction recently. The patient was diagnosed as T-LPD initially based on histological result and T-cell receptor-gamma clonal gene rearrangement test. The patient was followed without chemotherapy. His condition stabilized for 1 year and then deteriorated with small intestine perforation.

Diagnosis: The patient was diagnosed as indolent T-LPD and DLBCL finally.

Interventions: The patient had surgery for intestine perforation and received chemotherapy for DLBCL and T-LPD afterward.

Outcomes: At 6 months follow-up, the patient continued to have resolution of his symptoms.

Lessons: Early detection of high-grade transformation of T-LPD or the coexistence of aggressive lymphoma is essential for the patient. DLBCL may coexist in the indolent course of T-LPD. The diagnosis of T-LPD should be made cautiously in case with progressing symptoms such as intestinal obstruction.
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http://dx.doi.org/10.1097/MD.0000000000015323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831179PMC
April 2019

Intramural esophageal dissection during peroral endoscopic myotomy.

Endoscopy 2019 07 12;51(7):E197-E198. Epub 2019 Apr 12.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1055/a-0875-3869DOI Listing
July 2019

Mechanistic insights into environmental and genetic risk factors for systemic lupus erythematosus.

Am J Transl Res 2019 15;11(3):1241-1254. Epub 2019 Mar 15.

Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, Guangdong, China.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems with diverse presentation, primarily affecting women of reproductive age. Various genetic and environmental risk factors are involved in the pathogenesis of SLE, and many SLE susceptibility genes have been identified recently; however, gene therapy is not a viable clinical option at this time. Thus, environmental risks factors, particularly regional characteristics that can be controlled, need to be further investigated. Here, we systematically explored these risk factors, including ultraviolet radiation, seasonal distribution, geographical distribution, and climate factors, and also summarized the mechanisms related to these risk factors. Probable mechanisms were explicated in at least four aspects including inflammatory mediators, apoptosis and autophagy in keratinocytes, epigenetic factors, and gene-environment interactions. This information is expected to provide practical insights into these risk factors in order to benefit patients with SLE and facilitate the development of potential therapeutic strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456562PMC
March 2019

Mechanistic Insights of Chemicals and Drugs as Risk Factors for Systemic Lupus Erythematosus.

Curr Med Chem 2020 ;27(31):5175-5188

Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, 57th South Renmin Road, Zhanjiang 524001, Guangdong, China.

Systemic Lupus Erythematosus (SLE) is a chronic and relapsing heterogenous autoimmune disease that primarily affects women of reproductive age. Genetic and environmental risk factors are involved in the pathogenesis of SLE, and susceptibility genes have recently been identified. However, as gene therapy is far from clinical application, further investigation of environmental risk factors could reveal important therapeutic approaches. We systematically explored two groups of environmental risk factors: chemicals (including silica, solvents, pesticides, hydrocarbons, heavy metals, and particulate matter) and drugs (including procainamide, hydralazine, quinidine, Dpenicillamine, isoniazid, and methyldopa). Furthermore, the mechanisms underlying risk factors, such as genetic factors, epigenetic change, and disrupted immune tolerance, were explored. This review identifies novel risk factors and their underlying mechanisms. Practicable measures for the management of these risk factors will benefit SLE patients and provide potential therapeutic strategies.
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http://dx.doi.org/10.2174/0929867326666190404140658DOI Listing
September 2020

Tube-assisted suction: a novel technique for removing massive food residue during gastroscopy.

Endoscopy 2019 04 18;51(4):E73-E74. Epub 2019 Jan 18.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1055/a-0824-6162DOI Listing
April 2019

Purse-string suture and double percutaneous endoscopic gastrostomies for treating a postoperative duodenal fistula.

Endoscopy 2019 03 11;51(3):E55-E56. Epub 2019 Jan 11.

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1055/a-0800-8286DOI Listing
March 2019

DNA Nanostructure-Programmed Like-Charge Attraction at the Cell-Membrane Interface.

ACS Cent Sci 2018 Oct 25;4(10):1344-1351. Epub 2018 Sep 25.

Division of Physical Biology and Bioimaging Center, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

Cell entry of anionic nano-objects has been observed in various types of viruses and self-assembled DNA nanostructures. Nevertheless, the physical mechanism underlying the internalization of these anionic particles across the negatively charged cell membrane remains poorly understood. Here, we report the use of virus-mimicking designer DNA nanostructures with near-atomic resolution to program "like-charge attraction" at the interface of cytoplasmic membranes. Single-particle tracking shows that cellular internalization of tetrahedral DNA nanostructures (TDNs) depends primarily on the lipid-raft-mediated pathway, where caveolin plays a key role in providing the short-range attraction at the membrane interface. Both simulation and experimental data establish that TDNs approach the membrane primarily with their corners to minimize electrostatic repulsion, and that they induce uneven charge redistribution in the membrane under the short-distance confinement by caveolin. We expect that the nanoscale like-charge attraction mechanism provides new clues for viral entry and general rules for rational design of anionic carriers for therapeutics.
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http://dx.doi.org/10.1021/acscentsci.8b00383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202645PMC
October 2018

IL-21 Selectively Protects CD62L NKT Cells and Enhances Their Effector Functions for Adoptive Immunotherapy.

J Immunol 2018 10 15;201(7):2141-2153. Epub 2018 Aug 15.

Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;

T cells expressing CD19-specific chimeric Ag receptors (CARs) produce high remission rates in B cell lymphoma, but frequent disease recurrence and challenges in generating sufficient numbers of autologous CAR T cells necessitate the development of alternative therapeutic effectors. Vα24-invariant NKTs have intrinsic antitumor properties and are not alloreactive, allowing for off-the-shelf use of CAR-NKTs from healthy donors. We recently reported that CD62L NKTs persist longer and have more potent antilymphoma activity than CD62L cells. However, the conditions governing preservation of CD62L cells during NKT cell expansion remain largely unknown. In this study, we demonstrate that IL-21 preserves this crucial central memory-like NKT subset and enhances its antitumor effector functionality. We found that following antigenic stimulation with α-galactosylceramide, CD62L NKTs both expressed IL-21R and secreted IL-21, each at significantly higher levels than CD62L cells. Although IL-21 alone failed to expand stimulated NKTs, combined IL-2/IL-21 treatment produced more NKTs and increased the frequency of CD62L cells versus IL-2 alone. Gene expression analysis comparing CD62L and CD62L cells treated with IL-2 alone or IL-2/IL-21 revealed that the latter condition downregulated the proapoptotic protein BIM selectively in CD62L NKTs, protecting them from activation-induced cell death. Moreover, IL-2/IL-21-expanded NKTs upregulated granzyme B expression and produced more T1 cytokines, leading to enhanced in vitro cytotoxicity of nontransduced and anti-CD19-CAR-transduced NKTs against CD1d and CD19 lymphoma cells, respectively. Further, IL-2/IL-21-expanded CAR-NKTs dramatically increased the survival of lymphoma-bearing NSG mice compared with IL-2-expanded CAR-NKTs. These findings have immediate translational implications for the development of NKT cell-based immunotherapies targeting lymphoma and other malignancies.
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http://dx.doi.org/10.4049/jimmunol.1800429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143411PMC
October 2018

Preservation of DNA Nanostructure Carriers: Effects of Freeze-Thawing and Ionic Strength during Lyophilization and Storage.

ACS Appl Mater Interfaces 2017 Jun 30;9(22):18434-18439. Epub 2017 May 30.

Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility; CAS Key Laboratory of Interfacial Physics and Technology; Shanghai Institute of Applied Physics, Chinese Academy of Sciences , Shanghai 201800, China.

DNA nanostructures have attracted wide interest in biomedical applications, especially as nanocarriers for drug delivery. Therefore, it is important to ensure the structural integrity of DNA nanostructures under ambient temperature storage. In this study, we examined lyophilization-based preservation of DNA nanostructures by investigating the structural integrity of different DNA nanostructures reconstituted from lyophilization. We demonstrated that lyophilization under appropriate ionic strength is amenable to the storage of DNA nanostructures. Compared with that stored in liquid solution, DNA nanostructure carriers reconstituted from lyophilization showed significantly better structural integrity after an accelerated aging test equivalent to 100-day room-temperature storage.
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http://dx.doi.org/10.1021/acsami.7b04784DOI Listing
June 2017

Ion-Mediated Polymerase Chain Reactions Performed with an Electronically Driven Microfluidic Device.

Angew Chem Int Ed Engl 2016 09 9;55(40):12450-4. Epub 2016 Sep 9.

Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.

The polymerase chain reaction (PCR) is a powerful method for exponentially amplifying very low amounts of target DNA from genetic, clinical, and forensic samples. However, the heating and cooling steps in PCR largely hamper the miniaturization of thermocyclers for on-site detection of pathogens and point-of-care tests. Herein, we devise an ion-mediated PCR (IM-PCR) strategy by exploiting ion-induced DNA denaturation/renaturation cycles. DNA duplexes are effectively denatured in alkaline solutions; whereas, the denatured single-stranded DNA strands readily reform duplexes at neutral pH. By using an integrated microchip that can programmably control the solution pH simply switching the potential in a range of several hundred millivolts, we can trigger IM-PCR at a constant temperature. Analogously to thermal cycling, 30 cycles of pH-induced denaturation/renaturation were used to amplify protein DNA fragments as confirmed by DNA sequencing. We anticipate that this portable, low-cost, and scalable IM-PCR holds great promise for widespread biological, clinical, and environmental applications.
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http://dx.doi.org/10.1002/anie.201606137DOI Listing
September 2016

Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus.

Mediators Inflamm 2016 11;2016:2196986. Epub 2016 Aug 11.

Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.

In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE.
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http://dx.doi.org/10.1155/2016/2196986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997081PMC
June 2017