Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells by Anthony M. Battram, Joan Mañé-Pujol, David F. Moreno, Aina Oliver-Caldés, Judit Carpio, Oriol Cardus, Luis Gerardo Rodríguez-Lobato, Álvaro Urbano-Ispizua, Carlos Fernández de Larrea

“…To improve long-term efficacy, we used CRISPR/CRISPR-associated protein 9-mediated gene editing to ablate the expression of the transcription factor Blimp-1. Blimp-1 knockout (KO) CAR T cells displayed a memory-like phenotype compared with control (Mock) CAR T cells, but had reduced effector function, with a striking loss of granzyme B. …”
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SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis by Chaoxiang Du, Yunfan Hu, Xinyu Yang, Zhe Zhang, Jianmin Gu, Tao Zhang, Renfeng Wang, Shaoyuan Zhang, Lijie Tan, Guiping Yu

“…Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. …”
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SRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway by Yuwen Gong, Dongyang Gao, Yibo Shi, Guangrui Fan, Xiaoquan Yu, Enguang Yang, Hui Cheng, Junqiang Tian, Hui Ding, Shanhui Liu, Shengjun Fu, Yan Tao, Yuan Shui, Liang Cheng, Lanlan Li, Zhiping Wang

“…This phenomenon was effectively reversed by knockout of SRC and inhibition of SRC activity by the SRC inhibitor, eCF506. …”
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Direct engulfment of synapses by overactivated microglia due to cadmium exposure and the protective role of Nrf2 by Siyao Li, Mingdan You, Chengjie Chen, Jingqi Fu, Yuanyuan Xu, Jingbo Pi, Yi Wang

“…Nrf2 is deeply implicated in the status of microglial activation; therefore, we also investigated whether it is involved in the above process. Nrf2 knockout mice and wild-type mice were used to explore prolonged Cd exposure-induced synaptic damages, learning-memory impairments, and microglial activation. …”
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Screening and identification of host signaling pathways for alleviating influenza-induced production of pro-inflammatory cytokines, IP-10, IL-8, and MCP-1, using a U937 cell-based... by Si Chen, Si Chen, Yang Yu, Yue Su, Xiaoqin Lian, Lefang Jiang, Zhuogang Li, Mingxin Zhang, Yarou Gao, Haonan Zhang, Xingjian Zhu, Jiaxin Ke, Xulin Chen

“…The lung injury from influenza virus infection can be mitigated by suppressing or inhibiting these cytokines through knockout, knockdown, or targeted intervention approaches. …”
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Isoxazole-based molecules restore NK cell immune surveillance in hepatocarcinogenesis by targeting TM4SF5 and SLAMF7 linkage by Ji Eon Kim, Hyun Su Kim, Wonsik Kim, Eun Hae Lee, Soyeon Kim, Taewoo Kim, Eun-Ae Shin, Kyung-hee Pyo, Haesong Lee, Seo Hee Jin, Jae-Ho Lee, Soo-Min Byeon, Dong Joo Kim, Jinwook Jeong, Jeongwon Lee, Minjae Ohn, Hyojung Lee, Su Jong Yu, Dongyun Shin, Semi Kim, Jun Yeob Yoo, Seung-Chul Lee, Young-Ger Suh, Jung Weon Lee

“…In mouse xenograft models, TSI treatment abrogated HCC development by increasing the abundance and dispersion of Slamf7-positive cells in liver tissues, recapitulating the phenotype of Tm4sf5-knockout mice and indicating TSI-mediated restoration of NK cell surveillance. …”
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TRAF2 and RIPK1 redundantly mediate classical NFκB signaling by TNFR1 and CD95-type death receptors by Jennifer Wagner, David Vredevoogd, Xin Yu, Dong Lu, Daniel S. Peeper, Heike M. Hermanns, Jin Wang, Harald Wajant, Daniela Siegmund

“…Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. …”
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Integrated hepatic transcriptomics and metabolomics identify Pck1 as a key factor in the broad dysregulation induced by vehicle pollutants by Gajalakshmi Ramanathan, Yuqi Zhao, Rajat Gupta, Siri Langmo, May Bhetraratana, Fen Yin, Will Driscoll, Jerry Ricks, Allen Louie, James A. Stewart, Timothy R. Gould, Timothy V. Larson, Joel Kaufman, Michael E. Rosenfeld, Xia Yang, Jesus A. Araujo

“…Methods Apolipoprotein E knockout (ApoE KO) mice were exposed to DE or filtered air (FA) for two weeks, or DE for two weeks followed by FA for 1 week. …”
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CMPK2 promotes NLRP3 inflammasome activation via mtDNA‐STING pathway in house dust mite‐induced allergic rhinitis by YaoMing Zheng, YaDong Xie, JiaYing Li, YuJie Cao, Min Li, Qing Cao, MiaoMiao Han, HongFei Lou, YiLai Shu, Hui Xiao, HuaBin Li

“…Remarkably, depletion of mtDNA or inhibition of STING signalling reduced HDM‐induced NLRP3 inflammasome activation in HNEPCs. In vivo, genetic knockout of CMPK2 or STING alleviated NLRP3 inflammasome activation and ameliorated clinical symptoms of AR in mice. …”
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Tau oligomers impair memory and synaptic plasticity through the cellular prion protein by Claudia Balducci, Franca Orsini, Milica Cerovic, Marten Beeg, Beatrice Rocutto, Letizia Dacomo, Antonio Masone, Eleonora Busani, Ilaria Raimondi, Giada Lavigna, Po-Tao Chen, Susanna Leva, Laura Colombo, Chiara Zucchelli, Giovanna Musco, Nicholas M. Kanaan, Marco Gobbi, Roberto Chiesa, Luana Fioriti, Gianluigi Forloni

“…To investigate whether PrPC mediates TauO detrimental activities, we compared their effects on memory and synaptic plasticity in wild type (WT) and PrPC knockout (Prnp 0/0) mice. Intracerebroventricular injection of TauOs significantly impaired recognition memory in WT but not in Prnp 0/0 mice. …”
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Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes by Wanyi Huang, Wei He, Yue Huang, Yongping Tang, Ming Chen, Lianbei Sun, Zuwei Yang, Tianyi Hou, Huimin Liu, Haoyu Chen, Tianpeng Wang, Na Li, Yaqiong Guo, Lihua Xiao, Yaoyu Feng

“…They have additional subtelomeric insulinase and MEDLE genes. In interferon-γ knockout mice, three monkey isolates show differences in infectivity and induce higher and longer oocyst shedding than a reference C. parvum isolate. …”
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A KSHV RNA-binding protein promotes FOS to inhibit nuclease AEN and transactivate RGS2 for AKT phosphorylation by Vladimir Majerciak, Beatriz Alvarado-Hernandez, Yanping Ma, Shivalee Duduskar, Alexei Lobanov, Maggie Cam, Zhi-Ming Zheng

“…FOS dimerizes with JUN as a transcription factor AP-1 involved in cell proliferation, differentiation, and transformation. Knockout of the ORF57 gene from the KSHV genome led BAC16-iSLK cells incapable of FOS expression in KSHV lytic infection. …”
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Bubbling insights: unveiling the true sophorolipid biosynthetic pathway by Starmerella bombicola by Sophie L. K. W. Roelants, Stijn Bovijn, Elvira Bytyqi, Nicolas de Fooz, Goedele Luyten, Martijn Castelein, Thibo Van de Craen, Zhoujian Diao, Karolien Maes, Tom Delmulle, Maarten De Mol, Sofie L. De Maeseneire, Bart Devreese, Wim K. Soetaert

“…The AT enzyme encoded in the sophorolipid biosynthetic gene cluster is the only described enzyme known to acetylate sophorolipids, while the SBLE enzyme encoded by the SBLE gene is described to catalyze the conversion of (acetylated) acidic sophorolipids into lactonic sophorolipids. A double knockout of both genes was described to result in the generation of bolaform sophorolipids. …”
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Endothelial cell Piezo1 promotes vascular smooth muscle cell differentiation on large arteries by Javier Abello, Ying Yin, Yonghui Zhao, Josh Maurer, Jihui Lee, Cherokee Bodell, Jahmiera Richee, Abigail J. Clevenger, Zarek Burton, Megan E. Goeckel, Michelle Lin, Stephanie Grainger, Carmen M. Halabi, Shreya A. Raghavan, Rajan Sah, Amber N. Stratman

“…Further, endothelial cell (EC)-specific Piezo1 knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. …”
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Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal by Jianrong He, Yuda Cheng, Yan Ruan, Jiali Wang, Yanping Tian, Jiaqi Wang, Fengsheng Wang, Chen Zhang, Yixiao Xu, Lianlian Liu, Meng Yu, Jiangjun Wang, Binyu Zhao, Yue Zhang, Yi Yang, Gaoke Liu, Wei Wu, Ping He, Jiaxiang Xiong, He Huang, Junlei Zhang, Rui Jian

“…Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. …”
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Illuminating a biologics development challenge: systematic characterization of CHO cell-derived hydrolases identified in monoclonal antibody formulations by Melanie Maier, Linus Weiß, Nikolas Zeh, Valerie Schmieder-Todtenhaupt, Alireza Dehghani, Marius Nicolaus Felix, Daniel Heinzelmann, Benjamin Lindner, Moritz Schmidt, Joey Studts, Patrick Schulz, Bernd Reisinger, Kerstin Otte, Matthias Franzreb, Daniel Lakatos, Simon Fischer

“…By means of a highly sensitive liquid chromatography-tandem mass spectrometry method, we investigated seven different mAb products, resulting in the identification of 12 potentially PS-degrading hydrolases, including the strongly PS-degrading lipoprotein lipase (LPL). Using an LPL knockout CHO host cell line, we were able to stably overexpress and purify the remaining candidate hydrolases through orthogonal affinity chromatography methods, enabling their detailed functional characterization. …”
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Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine sett... by Sara Amiranda, Mariangela Succoio, Serenella Anzilotti, Ornella Cuomo, Tiziana Petrozziello, Valentina Tedeschi, Arianna Finizio, Giorgia Mele, Seppo Parkkila, Lucio Annunziato, Giuseppina De Simone, Giuseppe Pignataro, Agnese Secondo, Nicola Zambrano

“…The treatments exerted neuroprotective effects on neurons from Car9 knockout mice. Moreover, administration of the sulfonamide inhibitor to rats subjected to transient middle cerebral artery occlusion decreased infarct volumes and improved neurological deficits. …”
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Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis by Min Hu, Xinyu Meng, Tong Wang, Yifan Wang, Xiaodong Chen, Dongliang Xu, Wei He, Hongjia Zhang, Wenzheng Guo, Bo Jing, Siwei Zhang, Jianhua Xu, Beibei Sun, Xueqian Sun, Tingting Liu, Na Ni, Tongtong Zhang, Wenwen Cui, Xiaoyu Wu, Liping Xia, Feng Yao, Fang Zhang, Jing Du, Jiong Deng

“…We immunized mice with ICD dying tumor cells in prevention, therapy in lung metastasis models, and Gprc5a-knockout (ko) model of lung tumorigenesis. T cells and macrophages isolated from lymph nodes or tumor tissues were analyzed by flow cytometry. …”
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Nucleus-translocated GCLM promotes chemoresistance in colorectal cancer through a moonlighting function by Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

“…Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. …”
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Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic ta... by Qinqing Wu, Qinqing Wu, Lu Ye, Yuwei Wu, Mengyu Zhao, Mengyu Zhao, Jiaxin Lu, Yanping Yu, Yanping Yu, Yixiao Niu, Yixiao Niu, Luxiao Zhang, Peijun Zuo, Peijun Zuo

“…Finally, we used gene knockout techniques to silence the key gene INHBB and explored its biological functions in vitro.ResultsIn our study, by analyzing the expression differences of ARGs, we successfully classified patients with COAD. …”
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