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| http://dx.doi.org/10.1016/j.ccell.2022.05.016 | DOI Listing |
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Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.
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Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
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Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Contemporary osteoporosis treatment often neglects the intricate interactions among immune cells, signaling proteins, and cytokines within the osteoporotic microenvironment. Here, we developed core-shell nanocapsules composed of a cationized lactoferrin core and an alendronate polymer shell. By tuning the size of these nanocapsules and leveraging the alendronate shell, we enabled precise delivery of small interfering RNA targeting the Semaphorin 4D gene (siSema4D) to specific bone sites.
View Article and Find Full Text PDFIntralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.
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Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFIntegrated Two-in-one Strategy for Efficient Neutral Hydrogen Peroxide Electrosynthesis via Phosphorous Doping in 2D Mesoporous Carbon Carriers.
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Donghua University, No.2999, North Renmin Road, Songjiang District, Shanghai, CHINA.
Herein, we demonstrate a two-in-one strategy for efficient neutral electrosynthesis of H2O2 via two-electron oxygen reduction reaction (2e-ORR), achieved by synergistically fine-modulating both the local microenvironment and electronic structure of indium (In) single atom (SA) sites. Through a series of finite elemental simulations and experimental analysis, we highlight the significant impact of phosphorous (P) doping on an optimized 2D mesoporous carbon carrier, which fosters a favorable microenvironment by improving the mass transfer and O2 enrichment, subsequently leading to an increased local pH levels. Consequently, an outstanding 2e-ORR performance is observed in neutral electrolytes, achieving over 95% selectivity for H2O2 across a broad voltage range of 0.
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Department of Neurosurgery, Huanggang Central Hospital of Yangtze University, Huanggang, China.
Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood-brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L.
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