NOX4 modulates breast cancer progression through cancer cell metabolic reprogramming and CD8+ T cell antitumor activity by Yingying Xiong, Yiming Weng, Shan Zhu, Jian Qin, Jia Feng, Xiaopeng Jing, Chao Luo, Wei Gong, Rui Sun, Min Peng

“…Although NADPH oxidase 4 (NOX4) has been implicated in various oncogenic processes, its exact function in breast cancer progression, metabolic reprogramming, and immune modulation remains unclear.MethodsWe used murine 4T1 and EO771 breast cancer models to generate NOX4 knockout (KO) cell lines via CRISPR/Cas9. In vitro assays (cell proliferation, colony formation, wound healing, and Seahorse metabolic analyses) and in vivo orthotopic tumor studies assessed the impact of NOX4 loss. …”
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Disturbed shear stress promotes atherosclerosis through TRIM21‐regulated MAPK6 degradation and consequent endothelial inflammation by Feng Wang, Shu‐Yu Wang, Yue Gu, Shuai Luo, Ai‐Qun Chen, Chao‐Hua Kong, Wen‐Ying Zhou, Li‐Guo Wang, Zhi‐Mei Wang, Guang‐Feng Zuo, Xiao‐Fei Gao, Jun‐Jie Zhang, Shao‐Liang Chen

“…ApoE−/−MAPK6flox/floxTEKCre mice finally confirmed that conditional MAPK6 knockout resulted in endothelial inflammation and significant increases in plaque areas. …”
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Deficiency of ATF3 facilitates both angiotensin II‐induced and spontaneously formed aortic aneurysm and dissection development by activating cGAS–STING pathway by Yifan Du, Poyi Hu, Xiangchao Ding, Dashuai Wang, Jingjing Luo, Sheng Le, Lingyun Ren, Manhua Chen, Ping Ye, Jiahong Xia

“…VSMC‐specific ATF3 conditional knockout (Atf3 cKO) mice showed notable enlargement, dissection and rupture in both thoracic and abdominal aortic regions after exposure to Ang II. …”
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TMEM135 deficiency improves hepatic steatosis by suppressing CD36 in a SIRT1-dependent manner by Arun Chhetri, Channy Park, Hyunsoo Kim, Laxman Manandhar, Chagtsalmaa Chuluunbaatar, Jaetaek Hwang, Xiaofan Wei, Gyuho Jang, Batching Chinbold, Hyug Moo Kwon, Sang-wook Lee, Raekil Park

“…Methods: We used in vivo, ex vivo, and in vitro models of steatosis. TMEM135 knockout (TMEM135KO) and wild type (WT) mice were fed a high-fat diet (HFD) to induce hepatic steatosis. …”
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ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis by Jinxing Lv, Tiantian Wu, Jiajia Xue, Cong Shen, Wenxin Gao, Xia Chen, Yueshuai Guo, Mingxi Liu, Jun Yu, Xiaoyan Huang, Bo Zheng

“…Subsequent investigations unveiled that Asb1 knockout (Asb1-KO) mice encountered excessive oxidative stress and decreased hydrogen sulfide (H2S) levels in their testes, and severe sperm DNA damage. …”
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The short-chain fatty acid receptors Gpr41/43 regulate bone mass by promoting adipogenic differentiation of mesenchymal stem cells by Friederike Behler-Janbeck, Anke Baranowsky, Timur A. Yorgan, Michelle Y. Jaeckstein, Anna Worthmann, Marceline M. Fuh, Karthikeyan Gunasekaran, Gisa Tiegs, Michael Amling, Thorsten Schinke, Joerg Heeren

“…For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. …”
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O-GlcNAcylation attenuates ischemia-reperfusion-induced pulmonary epithelial cell ferroptosis via the Nrf2/G6PDH pathway by Liuqing Yang, Hexiao Tang, Jin Wang, Dawei Xu, Rui Xuan, Songping Xie, Pengfei Xu, Xinyi Li

“…Thus, we generated Ogt1-conditional knockout mice and found that Ogt1 deficiency aggravated ferroptosis, as evidenced by lipid reactive oxygen species (lipid ROS), malondialdehyde (MDA), Fe2+, as well as alterations in critical protein expression glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). …”
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Epitranscriptome profiles reveal participation of the RNA methyltransferase gene OsMTA1 in rice seed germination and salt stress response by Yingbo Li, Ming Yin, Juan Wang, Xiuqin Zhao, Jianlong Xu, Wensheng Wang, Binying Fu

“…In the present study, we surveyed global m6A methylation in rice seed germination under salt stress and the control (no stress) using an osmta1 mutant and its wild type. Results The knockout of OsMTA1 resulted in a decreased level of m6A methylation and delayed seed germination, together with increased oxidative damage in the osmta1-1 mutant, especially under salt stress, indicating that OsMTA1 performs a crucial function in rice seed germination and salt stress response. …”
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Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients. by Abirami Kugadas, Pietro Artoni, Wanida Ruangsiriluk, Meng Zhao, Natalia Boukharov, Rizwana Islam, Dmitri Volfson, Katayoun Derakhchan

“…Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. …”
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Regulation of human papillomavirus E6 oncoprotein function via a novel ubiquitin ligase FBXO4 by Arushi Vats, Luca Braga, Nezka Kavcic, Paola Massimi, Edoardo Schneider, Mauro Giacca, Laimonis A. Laimins, Lawrence Banks

“…Therefore, to identify these novel ubiquitin ligases, we performed high-throughput human siRNA library screen against ubiquitin ligases in clustered regularly interspaced palindromic repeat (CRISPR)-edited E6AP-knockout human embryonic kidney (HEK) 293 cells, stably expressing green fluorescent protein (GFP)-tagged HPV-18E6. …”
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CDK14 regulates the development and repair of lung by Jian-wei Chen, Yu-xiang Wang, Rong-rong Gao, Lan-yue Ma, Jing Zhong, Jia-xin Yang, Zhao-hua Deng, Yu-yan Li, Xiao-ling Li, Ya-hai Shu, Wen-jing Guo, Zi-yuan Zhou, Xiao Yu Tian, Jinjin Ma, Yang Liu, Qi Chen

“…Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury. Genetic knockout of Cdk14 and the CDK14 covalent inhibitor FMF-04-159-2 resulted in reduction of pulmonary vessel covered area and epithelial cell number, exhibiting increased mortality and more severe lung damage after injury. …”
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METTL1 mediates PKM m7G modification to regulate CD155 expression and promote immune evasion in colorectal cancer by Fang Wang, Chen Yang, Fang Zheng, Yang Yan, Guifang Li, Yanyan Feng, Hejia Xu, Zilong He, Dongyan Cai, Hairong Sun, Xiaowei Qi, Yong Mao

“…In addition, METTL1 knockout mice were studied in vivo with CD155 blockers. …”
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Genetic and pharmacological targeting of HINT2 promotes OXPHOS to alleviate inflammatory responses and cell necrosis in acute pancreatitis by Jiaqi Yao, Yuhong Jiang, Pengcheng Zhang, Yifan Miao, Xiajia Wu, Hang Lei, Zhijun Xie, Yong Tian, Xianlin Zhao, Juan Li, Lv Zhu, Meihua Wan, Wenfu Tang

“…Furthermore, CRISPR/Cas9-mediated HINT2 knockout significantly impaired the protective effects of Emo against AP-induced mitochondrial energy metabolism disorders, inflammatory responses, and acinar cell necrosis. …”
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Serpina3k lactylation protects from cardiac ischemia reperfusion injury by Le Wang, Dandan Li, Fang Yao, Shanshan Feng, Chao Tong, Rongjia Rao, Meiyan Zhong, Xianqiang Wang, Wei Feng, Zhan Hu, Bo Jin, Li Wang, Shengshou Hu, Bingying Zhou

“…Biochemically, lactylation of Serpina3k enhances protein stability. Using Serpina3k knockout mice and mice overexpressing its lactylation-deficient mutant, we find that Serpina3k protects from cardiac injury in a lysine 351 lactylation-dependent manner. …”
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Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH by Gopanandan Parthasarathy, Nanditha Venkatesan, Guneet Singh Sidhu, Myeong Jun Song, Chieh-Yu Liao, Fanta Barrow, Amy Mauer, Tejasav Sehrawat, Yasuhiko Nakao, P. Vineeth Daniel, Debanjali Dasgupta, Kevin Pavelko, Xavier S. Revelo, Harmeet Malhi

“…The LyzMCre approach was used to generate myeloid cell–specific knockout mice, termed S1pr1 MKO . Littermate S1pr1 loxp/loxp mice were used as wild-type controls. …”
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The zinc receptor, ZnR/GPR39, modulates taste sensitivity by regulating ion secretion in mouse salivary gland by Moran Melamed, Hila Asraf, Noa Livne, Milos Bogdanovic, Anil Shendge, Gilad Shamir, Maayan Mero, Omer Adir, Avi Schroeder, Israel Sekler, Michal Hershfinkel

“…By monitoring transport of NH4+, a surrogate for K+, we revealed that Zn2+ upregulates the Na+/K+ ATPase pump activity in parotid and submandibular salivary gland epithelium from wildtype (WT), but not from ZnR/GPR39 knockout (KO), mice. Since Na+/K+ ATPase activity is crucial for solute transport, we compared saliva composition in WT and ZnR/GPR39 KO mice and found impaired ionic concentration and reduced saliva secretion in ZnR/GPR39 KO mice. …”
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VCP regulates early tau seed amplification via specific cofactors by Sushobhna Batra, Jaime Vaquer-Alicea, Clarissa Valdez, Skyler P. Taylor, Victor A. Manon, Anthony R. Vega, Omar M. Kashmer, Sourav Kolay, Andrew Lemoff, Nigel J. Cairns, Charles L. White, Marc I. Diamond

“…We screened 30 VCP co-factors in HEK293T biosensor cells by genetic knockout or knockdown. Reduction of ATXN3, NSFL1C, UBE4B, NGLY1, and OTUB1 decreased tau seeding, as did NPLOC4, which also uniquely increased soluble tau levels. …”
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Selective expression and significance of ACKR2 in lung aerocytes by Alberto Mantovani, Gianluigi Condorelli, Raffaella Bonecchi, Massimo Locati, Marina Sironi, Roberta Carriero, Francesca Albano, Valeria Mollica Poeta, Lucia Zotti, Alessandra Castagna, Arianna Felicetta, Alessandro Mesaglio, Elisa Zaghen, Arianna Capucetti, Rachele Di Donato, Mattia Laffranchi, Matteo Massara, Silvano Sozzani

“…This study aims to explore the specific cell types expressing ACKR2 and their relative contributions to the protection against lung metastasis.Methods ACKR2 expression was studied by the generation of an inducible and conditional knockout (KO) mouse expressing two reporter genes, luciferase and TdTomato visible by In Vivo Imaging System, flow cytometry and immunofluorescence. …”
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Maternal phthalates exposure promotes neural stem cell differentiation into phagocytic astrocytes and synapse engulfment via IRE1α/XBP1s pathway by Fengzhen Cui, Shiyu Deng, Yan Fu, Tongtong Xu, Shuangshuang Bao, Siyi Wang, Yahang Lin, Xianghui Wang, Faming Zhao, Tingting Zhang, Shunqing Xu, Zhijun Zhang, Wanlu Li, Guo-Yuan Yang, Huanwen Tang, Jixian Wang, Xia Sheng, Yaohui Tang

“…Mechanistically, we find that MBP exposure activates the IRE1α/XBP1s (spliced XBP1) stress response pathway, which regulates key genes involved in astrocyte differentiation (SOX9 and ATF3) and reactivity (C3 and LCN2). Conditional knockout or pharmacological inhibition of IRE1α markedly inhibits NSC differentiation into astrocytes and astrocyte reactivity, attenuates synapse phagocytosis, and improves cognitive function. …”
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Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control by Helena Escuin-Ordinas, Ignacio Melero, Marisol Quintero, Jose Luis Perez-Gracia, Maite Alvarez, Maria E Rodriguez-Ruiz, Miguel F Sanmamed, Paloma Sanchez-Mateos, Inmaculada Rodríguez López, Irantzu Serrano-Mendioroz, Celia Barrio-Alonso, Eneko Garate-Soraluze, Victor Diaz Pascual, Leire Arbea Moreno

“…Depletions of immune cell populations and knockout mice for the IFNAR and BATF-3 genes were used to delineate the immune system requirements for efficacy.Results In cultures of TS/A breast cancer cells, the combination of irradiation and BO-112 showed more prominent features of immunogenic tumor cell death in terms of calreticulin exposure. …”
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