YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6 by Lihua Zhang, Ming Chen, Shenghong Ju, Kai Lu, Bin Xu, Wenchao Li, Saisai Chen, Jianping Wu, Yue Hou, Zonghao You, Chuanjun Shu, Xiaoying Wei, Tiange Wu, Naipeng Shi, Guangyuan Zhang, Shuqiu Chen, Dingxiao Zhang

“…Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid–liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment.Results YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. …”
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Knockout of STE20-type kinase TAOK3 does not attenuate diet-induced NAFLD development in mice by Ying Xia, Emma Andersson, Mara Caputo, Emmelie Cansby, Francesca Sedda, Ferran Font-Gironès, Johan Ruud, Yeshwant Kurhe, Bengt Hallberg, Hanns-Ulrich Marschall, Ingrid Wernstedt Asterholm, Stefano Romeo, Matthias Blüher, Margit Mahlapuu

“…Intracellular lipid accumulation and oxidative/ER stress were analyzed in cultured human and mouse hepatocytes where TAOK3 was knocked down by small interfering RNA. The expression of TAOK3-related STE20-type kinases was quantified in different organs from high-fat diet-fed Taok3 –/– and wild-type mice. …”
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The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specif... by Brooke M. Van Loh, Alexandra M. Yaw, Joseph A. Breuer, Brooke Jackson, Duong Nguyen, Krystal Jang, Fabiola Ramos, Emily V. Ho, Laura J. Cui, Dominique L. M. Gillette, Lorenzo F. Sempere, Michael R. Gorman, Michael R. Gorman, Karen J. Tonsfeldt, Karen J. Tonsfeldt, Pamela L. Mellon, Pamela L. Mellon, Hanne M. Hoffmann, Hanne M. Hoffmann

“…MethodsTo specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre).ResultsWe found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. …”
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Functional characterization of the m⁶A-dependent translational modulator PfYTH.2 in the human malaria parasite by Sinha, Ameya, Baumgarten, Sebastian, Distiller, Amy, McHugh, Emma, Chen, Patty, Singh, Meetali, Bryant, Jessica M., Liang, Jiaqi, Cecere, Germano, Dedon, Peter C., Preiser, Peter Rainer, Ralph, Stuart A., Scherf, Artur

“…Interaction proteomics revealed that PfYTH.2 associates with the translation machinery, including multiple subunits of the eukaryotic initiation factor 3 (eIF3) and poly(A)-binding proteins. Furthermore, knock sideways of PfYTH.2 coupled with ribosome profiling showed that this m6A reader is essential for parasite survival and is a repressor of mRNA translation. …”
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MicroRNA-29a-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting Roundabout homolog 1 in hepatic stellate cells by Hongyan Kong, Qiqin Song, Wenjiang Hu, Shusen Guo, Dandan Xiang, Shuaiwen Huang, Xin Xu, Jinan He, Lanyue Pan, Ran Tao, Haijing Yu, Jiaquan Huang

“…We used MIR29A conditional knock-in mice and mice injected with an miR-29a-3p agomir to investigate the role of miR-29a-3p in schistosomiasis-induced hepatic fibrosis. …”
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SH2 Domain-Containing Phosphatase-SHP2 Attenuates Fibrotic Responses through Negative Regulation of Mitochondrial Metabolism in Lung Fibroblasts by Theodoros Karampitsakos, Apostolos Galaris, Ilianna Barbayianni, Giuseppe DeIuliis, Farida Ahangari, Fotis Sampsonas, Vasilina Sotiropoulou, Vassilis Aidinis, Anton M. Bennett, Jose D. Herazo-Maya, Nikolaos Xylourgidis, Petros Bakakos, Demosthenes Bouros, Naftali Kaminski, Argyrios Tzouvelekis

“…Methods and Results: Primary mouse lung fibroblasts derived from mice carrying a conditional knock-in mutation (D61G/+), rendering the SHP2 catalytic domain constitutively active, had reduced proliferation (1.6-fold, <i>p</i> < 0.05), migration (2-fold, <i>p</i> < 0.05), as well as reduced responsiveness of TGFB-1 induced fibroblasts-to-myofibroblasts differentiation, compared to wild-type ones. …”
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Mutation in the two-component regulator BaeSR mediates cefiderocol resistance and enhances virulence in Acinetobacter baumannii by Xiaochen Liu, Yunjie Chang, Qingye Xu, Wang Zhang, Zhen Huang, Linyue Zhang, Shanshan Weng, Sebastian Leptihn, Yan Jiang, Yunsong Yu, Xiaoting Hua

“…Strains over-expressing MFS transporter and MacAB-TolC displayed higher MICs and higher median inhibition concentration (IC50) values, while MICs and IC50 decreased when efflux pump genes were knocked out. In a BaeR mutant with up-regulated csu operon, we observed a higher number of pili, enhanced surface motility, and increased biofilm formation compared to wild-type ATCC 17978. …”
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Expression of the phagocytic receptors αMβ2 and αXβ2 is controlled by RIAM, VASP and Vinculin in neutrophil-differentiated HL-60 cells by Alvaro Torres-Gomez, Alvaro Torres-Gomez, Tara Fiyouzi, Tara Fiyouzi, Claudia Guerra-Espinosa, Beatriz Cardeñes, Irene Clares, Víctor Toribio, Pedro A. Reche, Pedro A. Reche, Carlos Cabañas, Carlos Cabañas, Carlos Cabañas, Esther M. Lafuente, Esther M. Lafuente

“…Finally, reexpression of VASP in the VASP knockout resulted in a complete reversion of the phenotype, as knock-ins restored αM expression. Taken together, our results suggest that RIAM, VASP and Vinculin, are necessary for the correct expression of αMβ2 and αXβ2 during neutrophilic differentiation in the human promyelocytic HL-60 cell line, and strongly point to an involvement of these proteins in the acquisition of a phagocytic phenotype.…”
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Interleukin-34-NF-κB signaling aggravates myocardial ischemic/reperfusion injury by facilitating macrophage recruitment and polarizationResearch in context by Lingfang Zhuang, Xiao Zong, Qian Yang, Qin Fan, Rong Tao

“…Whether IL-34 mediates inflammatory responses and contributes to cardiac remodeling and heart failure post-IR remains unclear. Methods: IL-34 knock-out mice were used to determine the role of IL-34 on cardiac remodeling after IR surgery. …”
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ZEB1 transcription factor promotes immune escape in melanoma by Christophe Caux, Stephane Dalle, Arnaud de la Fouchardière, Laurie Tonon, Maud Plaschka, Valentin Benboubker, Maxime Grimont, Justine Berthet, Jonathan Lopez, Myrtille Le-Bouar, Brigitte Balme, Garance Tondeur, Lionel Larue, Alain Puisieux, Yenkel Grinberg-Bleyer, Nathalie Bendriss-Vermare, Bertrand Dubois, Julie Caramel

“…Mechanistically, we demonstrate that ZEB1 directly represses the secretion of T cell-attracting chemokines, including CXCL10. Finally, Zeb1 knock-out, by promoting CD8+ T cell infiltration, synergizes with anti-PD-1 antibody therapy in promoting tumor regression.Conclusions We identify the ZEB1 transcription factor as a key determinant of melanoma immune escape, highlighting a previously unknown therapeutic target to increase efficacy of immunotherapy in melanoma.Trial registration number NCT02828202.…”
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Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice by Pauline Labbé, Pauline Labbé, Cécile Martel, Cécile Martel, Yan-Fen Shi, Augusto Montezano, Ying He, Marc-Antoine Gillis, Marie-Ève Higgins, Louis Villeneuve, Rhian Touyz, Jean-Claude Tardif, Jean-Claude Tardif, Nathalie Thorin-Trescases, Eric Thorin, Eric Thorin, Eric Thorin

“…Indeed, in adult mice knocked down (KD) for ANGPTL2, we recently reported a mild left ventricular (LV) dysfunction originating from a congenital aortic valve stenosis, demonstrating that ANGPTL2 is essential to cardiac development and function.Hypothesis: Because we originally demonstrated that the KD of ANGPTL2 protected vascular endothelial function via an upregulation of arterial NOX4, promoting the beneficial production of dilatory H2O2, we tested the hypothesis that increased cardiac NOX4 could negatively affect cardiac redox and remodeling and contribute to LV dysfunction observed in adult Angptl2-KD mice.Methods and results: Cardiac expression and activity of NOX4 were higher in KD mice, promoting higher levels of cardiac H2O2 when compared to wild-type (WT) mice. …”
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Production of two SARS-CoV-2 neutralizing antibodies with different potencies in Nicotiana benthamiana by Rachele Frigerio, Carla Marusic, Maria Elena Villani, Chiara Lico, Cristina Capodicasa, Emanuele Andreano, Ida Paciello, Rino Rappuoli, Rino Rappuoli, Anna Maria Salzano, Andrea Scaloni, Selene Baschieri, Marcello Donini

“…Different accumulation levels of mAbJ08-MUT and mAb675 were observed after transient agroinfiltration in Nicotiana benthamiana plants knocked-out for xylosil and fucosil transferases, leading to yields of ~35 and 150 mg/kg of fresh leaf mass, respectively. …”
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FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression by Jie Wang, Chunlin Wang, Anling Hu, Kunlin Yu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Klarke Michael Sample, Xiao Xiao, Wuling Liu, Yaacov Ben-David

“…RNAseq analysis combined with bioinformatic was used to determine the effect of knocking-down UBASH3A and UBASH3B in leukemic cells. …”
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The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH^−/− Mice by Cong Wang, Honglin Ren, Han Wang, Haosong Li, Jian Guo, Yiran Xiao, Yuxi Guo, Mengdi Liu, Fuchun Duan, Pan Hu, Yansong Li, Zengshan Liu, Shiying Lu

“…Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. …”
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LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression by Noah Lubben, Julia K. Brynildsen, Connor M. Webb, Howard L. Li, Cheryl E. G. Leyns, Lakshmi Changolkar, Bin Zhang, Emily S. Meymand, Mia O’Reilly, Zach Madaj, Daniella DeWeerd, Matthew J. Fell, Virginia M. Y. Lee, Dani S. Bassett, Michael X. Henderson

“…Wild-type or LRRK2G2019S knock-in mice were injected with tau fibrils and treated with control diet or diet containing LRRK2 kinase inhibitor MLi-2 targeting the IC50 or IC90 of LRRK2 for 3–6 months. …”
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Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein by Hongyue Li, Yuhang Zhang, Dong Li, Yong-Qiang Deng, Hongde Xu, Chaoyue Zhao, Jiandong Liu, Dan Wen, Jianguo Zhao, Yongchun Li, Yong Wu, Shujun Liu, Jiankai Liu, Junfeng Hao, Fei Yuan, Shuguang Duo, Cheng-Feng Qin, Aihua Zheng

“…Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. …”
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Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex by Yini Zhang, Jianan Tang, Xuemei Wang, Yisi Sun, Tianying Yang, Xiaorong Shen, Xinyue Yang, Huijuan Shi, Xiaoxi Sun, Aijie Xin

“…Methods Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. …”
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Regulation of TGF-<i>β</i>1-Induced EMT by Autophagy-Dependent Energy Metabolism in Cancer Cells by Jin Seok Hwang, Trang Huyen Lai, Mahmoud Ahmed, Trang Minh Pham, Omar Elashkar, Entaz Bahar, Deok Ryong Kim

“…Suppression of autophagy activity by knocking down of <i>BECN1</i> or chloroquine (CQ) treatment inhibited mesenchymal protein expression. …”
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Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma by Yibei Wang, Ziwei Miao, Xiaoxue Qin, Yi Yang, Si Wu, Qi Miao, Beibei Li, Mingyu Zhang, Pengfei Wu, Yun Han, Bo Li

“…To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. …”
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CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations by Ling Tang, Hongming Huang, Yutong Tang, Qing Li, Jue Wang, Dengju Li, Zhaodong Zhong, Ping Zou, Yong You, Yang Cao, Yingjie Kong, Anyuan Guo, Shu Zhou, Huimin Li, Fankai Meng, Yi Xiao, Xiaojian Zhu

“…Methods Internal tandem duplication (ITD) mutations of FLT3 (FLT3/ITD) knock‐in clone and DNMT3A‐R882H mutant clones of SKM‐1 cells were generated using CRISPR/Cas9 and lentiviral transfection, respectively. …”
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