Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair by Min-ah Kim, Banseok Kim, Jihyeon Jeon, Jonghyun Lee, Hyeji Jang, Minjae Baek, Sang-Uk Seo, Dongkwan Shin, Anindya Dutta, Kyung Yong Lee

“…Loss-of-function experiments were performed in multiple human cancer cell lines using siRNA-mediated knockdown or CRISPR-Cas9 gene knockout. Cell viability assays were conducted to evaluate resistance to PARP inhibitors. …”
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Mouse ZGRF1 helicase facilitates DNA repair and maintains efficient fertility by Ernest Wee Kiat Lim, Smaragda Kompocholi, André Brannvoll, K. Stine V. Bagge, Jennifer R. Gruhn, Javier Martin-Gonzalez, Eliene Albers, Ian D. Hickson, Andrés López-Contreras, Michael Lisby

“…In the absence of ZGRF1, the rates of tumorigenesis and tumour-free survival in Eμ-Myc and Trp53 knockout mice remained largely unaffected. These findings suggest a potential role for ZGRF1 in the proliferation of specific cancer types, highlighting avenues for further research in other cancer models. …”
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Mast Cell Degranulation Decreases Lipopolysaccharide-Induced Aortic Gene Expression and Systemic Levels of Interleukin-6 In Vivo by Jason M. Springer, Vineesh V. Raveendran, Mingcai Zhang, Ryan Funk, Donald D. Smith, Mehrdad Maz, Kottarappat N. Dileepan

“…The inhibition of LPS-induced increase in serum IL-6 levels by mast cell degranulation was not seen in H1R knockout mice which suggests that mast cell-derived histamine acting through H1R may participate in the regulatory process. …”
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The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner by Tomoko Okuyama, Takahiro Tsuno, Ryota Inoue, Setsuko Fukushima, Mayu Kyohara, Anzu Matsumura, Daisuke Miyashita, Kuniyuki Nishiyama, Yusuke Takano, Yu Togashi, Makiko Meguro-Horike, Shin-ichi Horike, Tatsuya Kin, A.M. James Shapiro, Hiromi Yanagisawa, Yasuo Terauchi, Jun Shirakawa

“…Fbln5 expression was increased upon glucose stimulation in β-cells of mouse and human islets. β-Cell-specific Fbln5-knockout (βFbln5KO) mice exhibit significantly reduced β-cell proliferation in vivo but not in vitro. …”
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TC2N maintains stem cell-like characteristics to accelerate lung carcinogenesis by blockade of dual specificity protein phosphatase 3 by Jing Gu, Yang-fan Lv, Ji-ying Xia, Fu-hai Bai, Ji Gong, Guang-qiang Pan, Bo Liu, Lu Huang, Qiao-nan Guo, Xiang-lin Hao

“…Methods TC2N-engineered mice model was used to assess the effect of TC2N knockout on normal lung and urethane-induced carcinogenesis. …”
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P2Y2 Receptor Induces L. amazonensis Infection Control in a Mechanism Dependent on Caspase-1 Activation and IL-1β Secretion by Maria Luiza Thorstenberg, Monique Daiane Andrade Martins, Vanessa Figliuolo, Claudia Lucia Martins Silva, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva

“…The antiparasitic effects triggered by P2Y2 activation were not observed when cells were pretreated with a caspase-1 inhibitor (Z-YVAD-FMK) or in macrophages from caspase-1/11 knockout mice (CASP-1,11−/−). We also found that UTP treatment induced IL-1β secretion in wild-type (WT) infected macrophages but not in cells from CASP-1,11−/− mice, suggesting that caspase-1 activation by UTP triggers IL-1β secretion in L. amazonensis-infected macrophages. …”
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Aspergillus fumigatus Influences Gasdermin-D-Dependent Pyroptosis of the Lung via Regulating Toll-Like Receptor 2-Mediated Regulatory T Cell Differentiation by Wei Yan, Yi-si Zhao, Ke Xie, Yu Xing, Fang Xu

“…Compared with that of wild-type mice, the fungal burden in the lung of TLR2-deficient mice was reduced and the knockout of TLR2 changed the expression of GSDMD, IL-1α, and IL-1β in A. fumigatus. …”
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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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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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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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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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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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