PD-L1/TLR7 dual-targeting nanobody-drug conjugate mediates potent tumor regression via elevating tumor immunogenicity in a host-expressed PD-L1 bias-dependent way by Wei Huang, Ji Zhou, Jia Li, Yakun Wan, Chao Hu, Meng Liu, Pan Xu, Feng Tang, Jianhua Sun, Xiaolu Yu, Yiru Long, Binfan Chen, Yongliang Tong, Mengwen Shan, Xiaomin Jia, Henglei Lu, Runqiu Chen, Jin Ren, Guangyi Jin, Likun Gong

“…Toll-like receptors (TLRs) establish the link between innate and adaptive immunity, which can assist T-cell activation and serve as promising targets for combination to enhance ICB therapy. Here, we aimed to improve efficacy for anti-programmed death ligand 1 (PD-L1) therapy by developing a PD-L1/TLR7 dual-targeting nanobody-drug conjugate (NDC), based on the PD-L1 nanobodies and TLR7 agonist we developed.Methods PD-L1 nanobodies were obtained by phage display screening and identified through T-cell activation bioassay, in vivo imaging and quantitative biodistribution study. …”
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Physiological accumulation of lipid droplets in the newborn liver during breastfeeding is driven by TLR4 ligands by Wanderson Ferreira da Silva Júnior, Karen Marques de Oliveira Costa, Hortência Maciel Castro Oliveira, Maísa Mota Antunes, Kassiana Mafra, Brenda Naemi Nakagaki, Pedro Sérgio Corradi da Silva, Júlia Duarte Megale, Sarah Campos de Sales, Douglas Carvalho Caixeta, Mário Machado Martins, Robinson Sabino-Silva, Cristina Maria Pinto de Paula, Luiz Ricardo Goulart, Rafael Machado Rezende, Gustavo Batista Menezes

“…The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. …”
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Single-cell multiomics reveal divergent effects of DNMT3A- and TET2-mutant clonal hematopoiesis in inflammatory response by Wazim Mohammed Ismail, Jenna A. Fernandez, Moritz Binder, Terra L. Lasho, Minsuk Kim, Susan M. Geyer, Amelia Mazzone, Christy M. Finke, Abhishek A. Mangaonkar, Jeong-Heon Lee, Liguo Wang, Kwan Hyun Kim, Vernadette A. Simon, Fariborz Rakhshan Rohakthar, Amik Munankarmy, Seul Kee Byeon, Susan M. Schwager, Jonathan J. Harrington, Melissa R. Snyder, Keith D. Robertson, Akhilesh Pandey, Eric D. Wieben, Nicholas Chia, Alexandre Gaspar-Maia, Mrinal M. Patnaik

“…Although individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated. Here, we make use of a natural inflammatory response occurring during coronavirus disease 2019 (COVID-19), to understand the association of these mutations with inflammatory morbidity (acute respiratory distress syndrome [ARDS]) and mortality. …”
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Clonal hematopoiesis in patients with autoimmune thrombocytopenia: an international multicenter study by Bruno Fattizzo, Alfredo Marchetti, Alessandro Bosi, Carmelo Gurnari, Juri Alessandro Giannotta, Giacinto Luca Pedone, Elena Rossi, Valentina Carrai, Andrea Guido, Filippo Brioschi, Monica Carpenedo, Monica Crugnola, Domenica Caramazza, Livia Leuzzi, Monia Marchetti, Gabriele Merati, Simona Malato, Fabrizio Vianello, Andrea Patriarca, Hussein Awada, Marta Bortolotti, Marta Canzi, Niccolò Bolli, Marco Capecchi, Frederick Chen, Andrea Artoni, Jaroslaw P. Maciejewski, Wilma Barcellini

“…Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. …”
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Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting by Anaïs Cardon, Thomas Guinebretière, Chuang Dong, Laurine Gil, Sakina Ado, Pierre-jean Gavlovsky, Martin Braud, Richard Danger, Christoph Schultheiß, Aurélie Doméné, Perrine Paul-Gilloteaux, Caroline Chevalier, Laura Bernier, Jean-Paul Judor, Cynthia Fourgeux, Astrid Imbert, Marion Khaldi, Edouard Bardou-Jacquet, Laure Elkrief, Adrien Lannes, Christine Silvain, Matthieu Schnee, Florence Tanne, Fabienne Vavasseur, Lucas Brusselle, Sophie Brouard, William W. Kwok, Jean-François Mosnier, Ansgar W. Lohse, Jeremie Poschmann, Mascha Binder, Jérôme Gournay, Sophie Conchon, Pierre Milpied, Amédée Renand

“…Abstract Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. …”
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Micronutrient levels of global tropical reef fish communities differ from fisheries capture by Conor Waldock, Eva Maire, Camille Albouy, Vania Andreoli, Maria Beger, Thomas Claverie, Katie L. Cramer, David A. Feary, Sebastian C. A. Ferse, Andrew Hoey, Nicolas Loiseau, M. Aaron MacNeil, Matthew McLean, Camille Mellin, Simon Ahouansou Montcho, Maria Lourdes Palomares, Santiago de laPuente, Mark Tupper, Shaun Wilson, Laure Velez, Jessica Zamborain‐Mason, Dirk Zeller, David Mouillot, Loïc Pellissier

“…To assess whether micronutrient deficiencies could be addressed through specific fisheries management actions, we first require a quantification of the potentially available micronutrients contained in biodiverse reef fish assemblages. Here, we therefore undertake a broad heuristic assessment of available micronutrients on tropical reefs using ensemble species distribution modelling and identify potential mismatches with micronutrients derived from summarising coastal fisheries landings data. …”
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ENO1 promotes PDAC progression by inhibiting CD8+ T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling by Aziguli Tulamaiti, Shu-Yu Xiao, Yan Yang, Musitaba Mutailifu, Xia-Qing Li, Shi-Qi Yin, Hong-Tai Ma, Hong-Fei Yao, Lin-Li Yao, Li-Peng Hu, Jun Li, Shu-Heng Jiang, Zhi-Gang Zhang, Yan-Miao Huo, Dong-Xue Li, Xue-Li Zhang

“…ENO1 was found to be overexpressed in multiple types of cancers. Here, we investigated the role of ENO1 in modulating the PDAC microenvironment.Using bioinformatic analyses, we demonstrated that ENO1 was highly expressed in PDAC patients, which was related to a poor prognosis. …”
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VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment by Cheng Cheng, Qingrui Zha, Linmao Sun, Tianming Cui, Xinyu Guo, Changjian Xing, Zhengxiang Chen, Changyong Ji, Shuhang Liang, Shengwei Tao, Junhui Chu, Chenghui Wu, Qi Chu, Xuetian Gu, Ning Zhang, Yumin Fu, Shumin Deng, Yitong Zhu, Jiabei Wang, Yao Liu, Lianxin Liu

“…However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8+T cells suppression in hepatocellular carcinoma (HCC). …”
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Production of all-triploid derived from gynogenetic homologous diploid crucian carp (♀) × diploid red crucian carp (♂) by Chongqing Wang, Yan Tang, Xiang Luo, Yuxin Zhang, Yue Zhou, Qingwen Xiao, Zhengkun Liu, Xinyi Deng, Xu Huang, Xidan Xu, Xiaowei Xu, Kun Zhang, Qinbo Qin, Shaojun Liu

“…Triploid breeding is vital in aquaculture production. Here, based on the formation of all-female gynogenetic homologous diploid crucian carp (G, 2 n = 100) derived from gynogenesis of the autotetraploid crucian carp (4nRR, 4 n = 200) eggs and without chromosome duplication treatment, a novel triploid fish (3nRR, 3 n = 150) were produced by crossing G and males of red crucian carp (RCC, 2 n = 100). …”
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Peptide P2 targeting Vibrio parahaemolyticus PirB toxins blocks the cytotoxic effects to shrimp Litopenaeus vannamei by Xin Zhang, Ting Chen, Chunhua Ren, Yanhong Wang, Xiao Jiang, Jiasheng Huang, Bo Ma, Boxiang Zhu, Jiayue Yin, Chaoqun Hu, Peng Luo

“…This study aims to screen the PirB binding peptide to rescue the survival rate under VpAHPND infection. Here, the PirB toxin-binding peptides were selected using the random phage peptide library kit, and their biological function was verified by injecting them under VpAHPND challenge. …”
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Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract by Mohammad Jad Moussa, Georges C. Tabet, Arlene O. Siefker‐Radtke, Lianchun Xiao, Nathaniel R. Wilson, Jianjun Gao, Christopher J. Logothetis, Petros Grivas, Byron Lee, Amishi Y. Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M. Tannir, Ashish M. Kamat, Donna E. Hansel, Charles C. Guo, Matthew T. Campbell, Omar Alhalabi

“…ABSTRACT Introduction Small cell neuroendocrine carcinoma of the urinary tract (SCNEC‐URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery. …”
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Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors by Alfred Zippelius, Petra Herzig, Pratiksha Gulati, Christian Klein, Marta Trüb, Kirsten D Mertz, Robert Rosenberg, Viola Heinzelmann-Schwarz, Mark Wiese, Didier Lardinois, Pablo Umana, Marina Natoli, Klas Hatje, Fabian Junker, Zhiwen Jiang, Iakov I Davydov, Markus Germann, Daniel Marbach, Adrian Zwick, Patrick Weber, Stefan Seeber, Lothar Tietze, Laura Codarri-Deak, Henry Kao

“…Similarly, little is known on the differential effects of dual, compared with single, checkpoint inhibition.Methods We here performed in-depth characterization, including multicolor flow cytometry, single cell RNA sequencing and multiplex supernatant analysis, using tumor single cell suspensions from patients with cancer treated ex vivo with novel bispecific antibodies targeting programmed cell death protein 1 (PD-1) and TIM-3 (PD1-TIM3), PD-1 and LAG-3 (PD1-LAG3), or with anti-PD-1.Results We identified patient samples which were responsive to PD1-TIM3, PD1-LAG3 or anti-PD-1 using an in vitro approach, validated by the analysis of 659 soluble proteins and enrichment for an anti-PD-1 responder signature. …”
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IFNβ drives ferroptosis through elevating TRIM22 and promotes the cytotoxicity of RSL3 by Huiyue Dong, Huiyue Dong, Ling Zhu, Ling Zhu, Jingjing Sun, Jingjing Sun, Qiuyan Chen, Qiuyan Chen, Pengyang Liu, Pengyang Liu, Wei Zhang, Huajing Zeng, Rong Lin, Rong Lin, Zongyang Yu, Zongyang Yu, Jun Lu, Jun Lu, Jun Lu, Jun Lu

“…HT1080 cells, three-dimensional (3D) spheroids, and the xenograft mouse models were treated with IFNβ, RSL3, or IFNβ combination with RSL3 to analyze whether IFNβ enhances RSL3-induced ferroptosis.ResultsHere, we found that IFNβ could promote intracellular Fe2+ and lipid peroxidation levels, and decrease GSH levels in tumor cells. …”
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A Chemically Defined Culture for Tooth Reconstitution by Ziwei Zhang, Hong Hu, Zhiheng Xu, Ce Shan, Hanyi Chen, Kun Xie, Kun Wang, Yifu Wang, Qing Zhu, Yike Yin, Haoyang Cai, Yunqiu Zhang, Zhonghan Li

“…However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established that supports tooth reconstitution, further development with normal anatomy, and prompt response to chemical interference in key developmental signaling pathways, termed as toothoids. …”
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The high-resolution global shipping emission inventory by the Shipping Emission Inventory Model (SEIM) by W. Yi, X. Wang, T. He, H. Liu, Z. Luo, Z. Lv, K. He

“…<p>The high-resolution ship emission inventory serves as a crucial dataset for various disciplines including atmospheric science, marine science, and environmental management. Here, we present a global high-spatiotemporal-resolution ship emission inventory at a resolution of 0.1° <span class="inline-formula">×</span> 0.1° for the years 2013 and 2016–2021, generated by the state-of-the-art Shipping Emission Inventory Model (SEIMv2.2). …”
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Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery by Kaichao Hu, Junrui Ye, Pinglong Fan, Ruifang Zheng, Shasha Wang, Ye Peng, Yuan Ruan, Xu Yan, Zhao Zhang, Shifeng Chu, Naihong Chen

“…Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. …”
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WALLABY Pilot Survey and ASymba: Comparing H i Detection Asymmetries to the SIMBA Simulation by Mathieu Perron-Cormier, Nathan Deg, Kristine Spekkens, Mark L. A. Richardson, Marcin Glowacki, Kyle A. Oman, Marc A. W. Verheijen, Nadine A. N. Hank, Sarah Blyth, Helga Dénes, Jonghwan Rhee, Ahmed Elagali, Austin Xiaofan Shen, Wasim Raja, Karen Lee-Waddell, Luca Cortese, Barbara Catinella, Tobias Westmeier

“…The statistical power of quantitative comparisons of asymmetries such as the one presented here will improve as the WALLABY survey progresses and as simulation volumes and resolutions increase.…”
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Genomic insights into population dynamics and adaptive strategies of the endangered dipterocarp, Hopea chinensis by Wei-Min Xiang, Yu-Ting Jiang, Jie Zou, Yan Deng, Kai Jiang, Kai-Jian Zhang, Xin-Yu Zhou, Kai-Xi Quan, Zi-Wen Han, Wei-Chao Liu, Liang Tang, Yuan-Yuan Li, Simon T. Segar, Yuan-Ye Zhang, Xing-Hua Hu, Rong Wang, Xiao-Yong Chen

“…Despite the perceived conservation priority of these species, we know little about how they became endangered and how they have adapted to marginal habitats. Here, we focused on the population genomics of Hopea chinensis, an endangered species narrowly distributed at the northern limit of dipterocarps, to (1) reveal its demographic history and infer factors contributing to endangered status; (2) evaluate the genetic consequences of its small remnant population; and (3) identify key genes associated with its adaptation. …”
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Differentiation of high risk prostate cancer with a facile urinary exosome detection workflow by Shuai Qiu, Yue Li, Zheng Zhang, Chunchang Li, Haoyu Wang, Ao Chen, Zhi Yan, Yang Liu, Zifei Li, Hua Huang, Yi Liu, Yiqi Seow, Ruibing Chen, Jinhong Guo, Simeng Wen, Jing Tian, Hongtuan Zhang, Ranlu Liu, Gang Han, Baolong Wang, Yong Wang, Yuanjie Niu, HaiFang Yin

“…Summary: Clear differentiation of high-grade and clinically insignificant prostate cancer (PCa) is critical for clinical decision-making. Here, we developed a proprietary urinary exosome isolation approach (EVLatch) and established a facile diagnostic workflow. …”
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NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression by Wenchao Xu, Jianzhou Liu, Qiaofei Liu, Jia Xu, Li Zhou, Zhiyong Liang, Haoran Huang, Bowen Huang, Gary Guishan Xiao, Junchao Guo

“…The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor. …”
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