Deletion of CD137 Ligand Exacerbates Renal and Cutaneous but Alleviates Cerebral Manifestations in Lupus by Anselm Mak, Anselm Mak, Anselm Mak, Bhushan Dharmadhikari, Bhushan Dharmadhikari, Nien Yee Kow, Thomas Paulraj Thamboo, Qianqiao Tang, Qianqiao Tang, Lik Wei Wong, Sreedharan Sajikumar, Hiu Yi Wong, Hiu Yi Wong, Herbert Schwarz, Herbert Schwarz

“…Lupus-prone C57BL/6lpr−/− (B6.lpr) mice were crossed to C57BL/6.CD137L−/− mice to obtain CD137L-deficient B6.lpr [double knock out (DKO)] mice. We investigated the extent of survival, glomerulonephritis, skin lesions, cerebral demyelination, immune deviation and long-term synaptic plasticity among the two mouse groups. …”
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Metabolomic Reprogramming of C57BL/6-Macrophages during Early Infection with <i>L. amazonensis</i> by Maricruz Mamani-Huanca, Sandra Marcia Muxel, Stephanie Maia Acuña, Lucile Maria Floeter-Winter, Coral Barbas, Ángeles López-Gonzálvez

“…In this work, we aimed to analyze metabolic networks of bone marrow-derived macrophages from C57BL/6 mice infected with <i>Leishmania amazonensis</i> wild type (<i>La</i>-WT) or arginase knocked out (<i>La</i>-arg⁻), using the untargeted Capillary Electrophoresis-Mass Spectrometry (CE-MS) approach to assess metabolomic profile. …”
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CDK5 destabilizes PD-L1 via chaperon-mediated autophagy to control cancer immune surveillance in hepatocellular carcinoma by Guoqiang Zhang, Jie Wang, Yu Du, Lei Lv, Yixin Wu, Ruonan Zhang, Ze Yu, Yihan Wang, Yixiao Jiang, Ting Le, Ziqi Li, Haijie Ma

“…Despite the impact on post-translational modifications of PD-L1 being substantial, its significance in resistance to HCC immunotherapy remains poorly defined.Methods Cyclin-dependent kinase 5 (CDK5) expression was knocked down in HCC cells, CDK5 and PD-L1 protein levels were examined by Western blot. …”
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FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma by Zhenguo Cai, Zhenguo Cai, Yanjuan Duan, Wen Li, Zhuohang Liu, Zijun Gong, Sheng Hong, Xu He, Xinyang Xuanyuan, Youdong Chen, Xinling Bi, Wuqing Wang

“…The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. …”
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FGF21 does not require adipocyte AMP-activated protein kinase (AMPK) or the phosphorylation of acetyl-CoA carboxylase (ACC) to mediate improvements in whole-body glucose homeostasi... by Emilio P. Mottillo, Eric M. Desjardins, Andreas M. Fritzen, Vito Z. Zou, Justin D. Crane, Julian M. Yabut, Bente Kiens, Derek M. Erion, Adhiraj Lanba, James G. Granneman, Saswata Talukdar, Gregory R. Steinberg

“…Additionally, HFD-fed mice with knock-in mutations on the AMPK phosphorylation sites of acetyl-CoA carboxylase (ACC)1 and ACC2 (DKI mice) along with wild-type (WT) controls received long-acting FGF21 for two weeks. …”
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Exogenous Liposomal Ceramide-C6 Ameliorates Lipidomic Profile, Energy Homeostasis, and Anti-Oxidant Systems in NASH by Francesca Zanieri, Ana Levi, David Montefusco, Lisa Longato, Francesco De Chiara, Luca Frenguelli, Sara Omenetti, Fausto Andreola, Tu Vinh Luong, Veronica Massey, Juan Caballeria, Constantino Fondevila, Sriram S Shanmugavelandy, Todd Fox, Giuseppe Mazza, Josepmaria Argemi, Ramon Bataller, Lauren Ashley Cowart, Mark Kester, Massimo Pinzani, Krista Rombouts

“…Importantly, inhibition of de novo ceramide biosynthesis or knock-down of ceramide synthases reverse some of the pathology of NASH. …”
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Artemisinin Confers Neuroprotection against 6-OHDA-Induced Neuronal Injury In Vitro and In Vivo through Activation of the ERK1/2 Pathway by Qin Li, Shuai Li, Jiankang Fang, Chao Yang, Xia Zhao, Qing Wang, Wenshu Zhou, Wenhua Zheng

“…In addition, the protective effect of artemisinin was significantly reduced when the ERK pathway was blocked using the ERK pathway inhibitor PD98059 or when the expression of ERK was knocked down using sgRNA. These results indicate the essential role of ERK in the protective effect of artemisinin. …”
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Rag GTPase-mediated regulation of mTORC1 by nutrients is necessary for neonatal autophagy and survival by Efeyan, Alejo, Zoncu, Roberto, Chang, Steven, Gumper, Iwona, Snitkin, Harriet, Kirak, Oktay, Sabatini, David D., Wolfson, Rachel Laura, Sabatini, David

“…Cell-based studies showed that mTORC1 senses amino acids through the RagA–D family of GTPases (also known as RRAGA, B, C and D), but their importance in mammalian physiology is unknown. Here we generate knock-in mice that express a constitutively active form of RagA (RagA[superscript GTP]) from its endogenous promoter. …”
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COP27 Climate Change Conference: Urgent Action Needed for Africa and the World by Lukoye Atwoli, Gregory Erhabor, Aiah Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Robert Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski

“…The acute and chronic impacts of the climate crisis create problems like poverty, infectious disease, forced migration, and conflict that spread through globalised systems.6,15 These knock-on impacts affect all nations. COVID-19 served as a wake-up call to these global dynamics and it is no coincidence that health professionals have been active in identifying and responding to the consequences of growing systemic risks to health. …”
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Simulation On Atkinson-Miller Cycle Engine Of Four Stroke Two-Wheel Vehicle For Light Operating Condition by Subramonian, Sobana Raj

“…However, three dimensional analysis of the Atkinson-Miller cycle found the engine to experience fuel knocking for compression ratio above 11:1. Consequently, the stand alone operation of Atkinson-Miller cycle is insufficient. …”
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SMAD4-Dependent Signaling Pathway Involves in the Pathogenesis of TGFBR2-Related CE-like Phenotype by Yen-Chiao Wang, Olivia Betty Zolnik, Chia-Yang Liu

“…The purpose of this study is to elucidate whether the SMAD4-dependent signaling pathway is involved in the TGFBR2-related CE-like pathogenesis. (2) Methods: <i>Smad4</i> was designed to be conditionally knocked out from keratocytes. Novel triple transgenic mice, <i>Kera^rtTA; Tet-O-Cre; Smad4^flox/flox</i> (<i>Smad4^kera-cko</i>), were administered with doxycycline (Dox). …”
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Restoration of Lepr in β cells of Lepr null mice does not prevent hyperinsulinemia and hyperglycemia by Anna M. D'souza, Timothy J. Kieffer

“…Materials and methods: We used a mouse model in which endogenous expression of Lepr was disrupted by a loxP-flanked transcription blocker (LeprloxTB/loxTB), but was restored by Cre recombinase knocked into the Ins1 gene, which is specifically expressed in β cells (Ins1Cre). …”
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A combination of genomics and transcriptomics provides insights into the distribution and differential mRNA expression of type VI secretion system in clinical Klebsiella pneumoniae by Wanzhen Li, Xiaolan Huang, Dan Li, Xiaofen Liu, Xiaoying Jiang, Xingchen Bian, Xin Li, Jing Zhang

“…Afterward, we utilized the predominant sequence type 11 (ST11) K. pneumoniae HS11286 to investigate the effect of knocking out T6SS marker genes hcp or vgrG. Transcriptome analysis identified a total of 1,298 co-upregulated and 1,752 co-downregulated differentially expressed genes in both mutants. …”
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MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways by Vinod Kumar Verma, Syed Sultan Beevi, Rekha A. Nair, Aviral Kumar, Ravi Kiran, Liza Esther Alexander, Lekha Dinesh Kumar

“…Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation. …”
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OTU7B Modulates the Mosquito Immune Response to Beauveria bassiana Infection via Deubiquitination of the Toll Adaptor TRAF4 by Yanhong Wang, Mengmeng Chang, Mao Wang, Yannan Ji, Xiaomei Sun, Alexander S. Raikhel, Zhen Zou

“…Our study identified a fungal-induced deubiquitinase, OTU7B, which, when knocked out, promotes the translocation of the NF-κB factor Rel1 into the nucleus and confers enhanced resistance to fungal infection. …”
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Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation by Hong Zhu, Feng Xiao, Yao Xiao, Yun Guo, Xuesong Shan, Zhe Zhang, Lieliang Zhang, Hua Guo

“…Methods In an in vivo animal model, specific targeting of astrocytic CB2R was achieved by injecting CB2R-specific adenovirus (or fork head box g1(foxg1) adenovirus) to knock down CB2R or administering CB2R agonists, inhibitors, etc., in the substantia nigra pars compacta (SNc) of mice. …”
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Nanoparticles Mediated circROBO1 Silencing to Inhibit Hepatocellular Carcinoma Progression by Modulating miR-130a-5p/CCNT2 Axis by Meng H, Li R, Xie Y, Mo Z, Zhai H, Zhang G, Liang G, Shi X, Zhou B

“…More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice.Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. …”
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GCN5L1 regulates pulmonary surfactant production by modulating lamellar body biogenesis and trafficking in mouse alveolar epithelial cells by Wenqin Xu, Xiaocui Ma, Qing Wang, Jingjing Ye, Nengqian Wang, Zhenzhen Ye, Tianbing Chen

“…Morphology of the lamellar body was analyzed through transmission electron microscopy (TEM), Lysotracker staining, and BODIPY phosphatidylcholine labeling. Results Knocking out GCN5L1 in MLE-12 significantly decreased the release of surfactant proteins and lipids. …”
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Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels by Moritz Schüssler, Kerstin Schott, Nina Verena Fuchs, Adrian Oo, Morssal Zahadi, Paula Rauch, Baek Kim, Renate König

“…We report BLaER1 cells as a novel human macrophage HIV-1 infection model combined with CRISPR/Cas9 knock-in (KI) introducing specific mutations into the SAMHD1 locus to study mutations in a physiological context. …”
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Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema by Yan Xue, Xueting Wang, Baolan Wan, Dongzhi Wang, Meiqi Li, Kang Cheng, Qianqian Luo, Dan Wang, Yapeng Lu, Li Zhu

“…The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence. …”
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