Publications by authors named "J W Sun"

33,465 Publications

Microbiota-derived metabolite Indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice.

Brain Behav Immun 2022 Aug 9. Epub 2022 Aug 9.

Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, microbiota-derived Indoles via tryptophan metabolism prevented Aβ accumulation and Tau hyperphosphorylation, restored synaptic plasticity, and then promoted the cognitive and behavioral ability of APP/PS1 mice. The imbalanced compositions of Indoles-producing bacteria with tryptophan deficiency were found in male APP/PS1 mice, but the molecular mechanisms remained unclear. Our current study revealed that Indoles (including indole, indole-3-acetic acid and indole-3-propionic acid) upregulated the production of aryl hydrocarbon receptor (AhR), inhibited the activation of the NF-κB signal pathway as well as the formation of the NLRP3 inflammasome, reduced the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β and IL-18, alleviating the inflammatory response of APP/PS1 mice. These findings demonstrated the roles of Indoles-producing bacteria in activating the AhR pathway to regulate neuroinflammation of AD through gut microbiota-derived Indoles, which implied a novel way for AD treatment.
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http://dx.doi.org/10.1016/j.bbi.2022.08.003DOI Listing
August 2022

Effects of aging on environmental behavior of plastic additives: Migration, leaching, and ecotoxicity.

Sci Total Environ 2022 Aug 9:157951. Epub 2022 Aug 9.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

Microplastics (MPs), an emerging pollutant, are of global concern due to their wide distribution and large quantities. In addition to MPs themselves, various additives within MPs (such as plasticizers, flame retardants, antioxidants and heavy metals) may also have harmful effects on the environment. Most of these additives are physically bound to plastics and can therefore be leached from the plastic and released into the environment. Aging of MPs in the actual environment can affect the migration and release of additives, further increasing the ecotoxicological risk of additives to organisms. This work reviews the functions of several commonly used additives in MPs, and summarizes the representative characterization methods. Furthermore, the migration and leaching of additives in the human environment and marine environment are outlined. As aging promotes the internal chain breaking of MPs and the increase of specific surface area, it in turn stimulates the release of additives. The hazards of additive exposure have been elucidated, and various studies from the laboratory have shown that more toxic additives such as phthalates and brominated flame retardants can disrupt a variety of biological processes in organisms, including metabolism, skeletal development and so on. Increase of MPs ecological risk caused by the leaching of toxic additives is discussed, especially under the effect of aging. This study presents a systematic summary of various functional and environmental behaviors of additives in plastics, using weathering forces as the main factor, which helps to better assess the environmental impact and potential risks of MPs.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157951DOI Listing
August 2022

Pan-cancer landscape of T-cell exhaustion heterogeneity within the tumor microenvironment revealed a progressive roadmap of hierarchical dysfunction associated with prognosis and therapeutic efficacy.

EBioMedicine 2022 Aug 9;83:104207. Epub 2022 Aug 9.

School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China. Electronic address:

Background: T cells form the major component of anti-tumor immunity. A deeper understanding of T cell exhaustion (TEX) heterogeneity within the tumor microenvironment (TME) is key to overcoming TEX and improving checkpoint blockade immunotherapies in the clinical setting.

Methods: We conducted a comprehensive pan-cancer analysis of TEX subsets from 9564 tumor samples across 30 bulk solid cancer types. Pan-cancer TEX subtypes were identified using literature-derived hierarchical TEX-specific developmental pathway signatures. The potential multi-omics and clinical features involved in TEX heterogeneity were determined.

Findings: Our study yielded a dynamic, progressive roadmap and a hierarchical dysfunction landscape regarding TEX within the TME. In total, we identified five pan-cancer TEX subtypes, revealing tissue/cancer type-specific TEX patterns in low immunogenic tumors. By contrast, highly immunogenic tumors tend to harbor high frequencies of progenitor TEX subsets. In addition, the TEX profile also revealed distinct prognoses, intrinsic molecular subtype distribution, immune microenvironment and multi-omics features among the cancers. Network analysis identified four previously unknown TEX-associated cancer genes (tolloid-like 1, myosin heavy chain 111, P2Y receptor family member 8 and protein kinase D2), the possible association with anti-PD-1 immunotherapy response was validated using a single-cell dataset. Finally, a machine learning-based gene signature was developed to model the hierarchical TEX stages, verified in single-cell and immunotherapy patient cohorts.

Interpretation: Our study provided a TEX-derived system that can be applied for the immune subtyping of cancers and may have implications for the further optimization of personalized cancer immunotherapy.

Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 62072341 and 61973240). The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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http://dx.doi.org/10.1016/j.ebiom.2022.104207DOI Listing
August 2022

Hybrid Hydrogels from Nongelling Polymers Using a Fibrous Peptide Hydrogelator at Low Concentrations.

Langmuir 2022 Aug 12. Epub 2022 Aug 12.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.

Nature-made hydrogels typically combine a wide range of multiscale fibers into biological composite networks, which offer an adaptive property. Inspired by nature, we report a facile approach to construct hybrid hydrogels from a range of natural or commercially available synthetic nongelling polymers (, poly(ethylene glycol), poly(acrylic acid), carboxylated cellulose nanocrystal, and sodium alginate) at a concentration as low as 0.53 wt % using a nonionic fibrous peptide hydrogelator. Through simply mixing the peptide hydrogelator with a polymer aqueous solution, stable hybrid hydrogels can be formed with the concentration of hydrogelator at ∼0.05 wt %. The gel strength of the resulting hydrogels can be effectively modulated by the concentration, molecular weight, and terminal group of the polymer. We further demonstrate that the molecular interactions between the peptide hydrogelator and the polymer are very crucial for the formation of hybrid hydrogel, which synergically induce the gelation at considerably low concentrations. A peptide hydrogelator can be easily obtained by aminolysis of alkyl-oilgo(γ-benzyl-l-glutamate) samples. Live/Dead assays indicate low cytotoxicity of the hybrid hydrogel toward HeLa cells. Combining the low-cost, scalable synthesis, and biocompatibility, the prepared peptide hydrogelator presents a potential candidate to expand the scope of polymer hydrogels for biomedical applications and also shows considerable commercial significance.
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http://dx.doi.org/10.1021/acs.langmuir.2c01758DOI Listing
August 2022

Imaging Findings of Thoracic Lymphatic Abnormalities.

Radiographics 2022 Aug 12:220040. Epub 2022 Aug 12.

From the Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115.

The lymphatic system plays an important role in balancing fluid compartments in the body. It is disrupted by various disease processes in the thorax, including injury to the thoracic lymphatic duct after surgery, as well as malignancy and heart failure. Because of the small size of lymphatic vessels, imaging of the lymphatics is relatively difficult, and effective imaging methods are still being optimized and developed. The standard of reference for lymphatic imaging has been conventional lymphangiography for several decades. Other modalities such as CT, noncontrast or contrast-enhanced MRI, and lymphoscintigraphy can also demonstrate lymphatic abnormalities and help in treatment planning. Imaging findings associated with lymphatic abnormalities can be seen in the pulmonary parenchyma, pleural space, and mediastinum. In the pulmonary parenchyma, common findings include interlobular septal thickening as well as reversal of lymphatic flow with intravasation of contrast material into pulmonary lymphatics. In the pleural space, findings include chylous pleural effusion and occasionally nonchylous pleural effusion. In the mediastinum, thoracic duct leak, plexiform thoracic duct, lymphatic malformations, and lymphangiectasis may occur. Management of chylothorax includes conservative or medical treatment, surgery, and interventional radiology procedures. The authors discuss thoracic lymphatic anatomy, imaging manifestations of lymphatic abnormalities in the various anatomic compartments, and interventional radiology treatment of chylothorax. Radiologists should be familiar with these imaging findings for diagnosis and to help guide appropriate management. RSNA, 2022.
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http://dx.doi.org/10.1148/rg.220040DOI Listing
August 2022
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