The dilemma of X-linked agammaglobulinemia carriers by Federica Pulvirenti, MD, PhD, Cinzia Milito, MD, PhD, Francesco Cinetto, MD, PhD, Giulia Garzi, MD, Germano Sardella, MD, Giuseppe Spadaro, MD, Francesca Lippi, MD, Valentina Guarnieri, MD, Bianca Laura Cinicola, MD, Maria Carrabba, MD, PhD, Daniele Guadagnolo, MD, Giovanna Fabio, MD, Baldassarre Martire, MD, Caterina Cancrini, MD, PhD, Giulia Lanzoni, MD, Andrea Finocchi, MD, PhD, Gigliola Di Matteo, MD, PhD, Eva Pompilii, MD, Simona Ferrari, BD, PhD, Isabella Quinti, MD, PhD

“…Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking. …”
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Effect of SY009, a novel SGLT1 inhibitor, on the plasma metabolome and bile acids in patients with type 2 diabetes mellitus by Haoyi Yang, Yuwen Zhang, Yuxin Hong, Yuan Wei, Yuning Zhu, Lei Huang, Yuanxun Yang, Runbin Sun, Runbin Sun, Runbin Sun, Juan Li, Juan Li, Juan Li

“…We conducted untargeted and targeted metabolomics analyses on plasma samples from the phase Ib clinical study.ResultsUntargeted metabolomics revealed that, after SY009 treatment, there were differences in metabolic pathways, including primary bile acid biosynthesis; biosynthesis of unsaturated fatty acid; steroid hormone biosynthesis; purine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis. In particular, the increase in bile acid-related metabolites in the 2 mg BID group was significantly greater than that in the placebo group, and unsaturated fatty acid-related metabolites decreased in both the 2 mg BID group and the placebo group, but there was no significant difference between the two groups. …”
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ROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2 by Dan Li, Wenjie Zhang, Ruiheng Wang, Shufeng Xie, Yixin Wang, Wanxin Guo, Zixuan Huang, Chaoqun Lu, Liang Shan, Han Liu, Lifang Ma, Xumin Hou, Zhenshu Xu, Jiayi Wang

“…This study investigated the potential of combining receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeting CAR-T cells with ferroptosis inducers to promote ferroptosis of tumor cells and enhance anti-tumor efficacy. …”
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Cloning, Characterization and Expression Regulation in Response to High-Temperature Stress of TRAF7 Gene in the Sea Cucumber Apostichopus japonicus by Yanfeng ZHAO, Meijie LIAO, Jianlong GE, Jinjin WANG, Yingeng WANG, Xiaojun RONG, Bin LI, Yanting TAN

“…It had 41, 20, and 3 serine, threonine, and tyrosine phosphorylation sites, respectively, and the N-terminus of the protein had 3 asparagine glycosylation sites. …”
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RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer by Charlotte K. Kindt, Sidse Ehmsen, Sidse Ehmsen, Sidse Ehmsen, Sofie Traynor, Benedetta Policastro, Nikoline Nissen, Mie K. Jakobsen, Monique F. Hundebøl, Lene E. Johansen, Martin Bak, Elsa Arbajian, Johan Staaf, Henrik J. Ditzel, Henrik J. Ditzel, Henrik J. Ditzel, Carla L. Alves

“…High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored.MethodsTo identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. …”
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Solid Predominant Histology and High Podoplanin Expression in Cancer-Associated Fibroblast Predict Primary Resistance to Osimertinib in EGFR-Mutated Lung Adenocarcinoma by Yuji Uehara, MD, Hiroki Izumi, MD, PhD, Tetsuro Taki, MD, PhD, Tetsuya Sakai, MD, PhD, Hibiki Udagawa, MD, PhD, Eri Sugiyama, MD, PhD, Shigeki Umemura, MD, PhD, Yoshitaka Zenke, MD, PhD, Shingo Matsumoto, MD, PhD, Kiyotaka Yoh, MD, PhD, Shoko Kubota, MD, PhD, Keiju Aokage, MD, PhD, Naoya Sakamoto, MD, PhD, Shingo Sakashita, MD, PhD, Motohiro Kojima, MD, PhD, Michiko Nagamine, MD, PhD, Yukio Hosomi, MD, PhD, Masahiro Tsuboi, MD, PhD, Koichi Goto, MD, PhD, Genichiro Ishii, MD, PhD

“…Introduction: Resistance to EGFR tyrosine kinase inhibitors is influenced by tumor-intrinsic and -extrinsic factors. …”
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Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection by Song Dong, PhD, Bingfa Yan, PhD, Si-Yang Liu, PhD, Xuan Gao, PhD, Hui-Zhao Hong, MD, Hong-Ji Li, MD, Wei Gao, PhD, Hong-Hong Yan, PhD, Si-Yang Maggie Liu, PhD, Hai-Yan Tu, PhD, Yi Pan, PhD, Qing Zhou, PhD, Xue-Ning Yang, PhD, Xue-Feng Xia, PhD, Xin Yi, PhD, Wen-Zhao Zhong, PhD, Yi-Long Wu, MD, Jia-Tao Zhang, PhD

“…Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. …”
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Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma by Daniel Pölöske, Helena Sorger, Anna Schönbichler, Elvin D. deAraujo, Heidi A. Neubauer, Anna Orlova, Sanna H. Timonen, Diaaeldin I. Abdallah, Aleksandr Ianevski, Heikki Kuusanmäki, Marta Surbek, Elisabeth Heyes, Thomas Eder, Christina Wagner, Tobias Suske, Martin L. Metzelder, Michael Bergmann, Maik Dahlhoff, Florian Grebien, Roman Fleck, Christine Pirker, Walter Berger, Emir Hadzijusufovic, Wolfgang R. Sperr, Lukas Kenner, Peter Valent, Tero Aittokallio, Marco Herling, Satu Mustjoki, Patrick T. Gunning, Richard Moriggl

“…Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. …”
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Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation–Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE) by Chee Khoon Lee, PhD, Bin-Chi Liao, MD, Shalini Subramaniam, MMed (Clin Epi), Chao-Hua Chiu, MD, Antony J. Mersiades, MMed (Clin Epi), Chao-Chi Ho, MD, PhD, Chris Brown, MBiostats, Chun-Liang Lai, MD, PhD, Brett G.M. Hughes, M.B.B.S. (Hons), Tsung-Ying Yang, MD, PhD, Ken O’Byrne, MD, Yung-Hung Luo, MD, PhD, Sonia Yip, PhD, Ching-Liang Ho, MD, Victoria Bray, PhD, Wu-Chou Su, MD, PhD, Melissa Moore, PhD, Wei-Lien Feng, MS, Ya-Ying Bai, MS, Kate Ford, MHSc, Michelle M. Cummins, PhD, Martin R. Stockler, MSc (Clin Epi), Benjamin J. Solomon, PhD, Thomas John, PhD, James Chih-Hsin Yang, MD, PhD

“…We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in EGFR-mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs). Methods: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. …”
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Effect of Xingbi Gel Nasal Drops on Rats with Allergic Rhinitis Based on the Nasal Mucosa-Hippocampus Neuroimmune Mechanism by FAN Xueqi, QIU Caixia, YAN Shuiping, ZHUANG Xiangli, AI Si, GUO Lihua, ZHENG Jian

“…The AR rat behavioral scoring criteria was used to evaluate rhinitis behavior of rats; Morris water maze test was used to evaluate learning and memory function of rats; enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of immunoglobulin E (IgE) and transforming growth factor-β1 (TGF-β1); hematoxylin-eosin (HE) staining was used to observe pathological changes of nasal mucosa and eosinophil (EOS) count; immunohistochemistry method was used to detect expression levels of non-receptor tyrosine kinases Fyn, substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in the hippocampus; and real-time polymerase chain reaction (RT-PCR) was used to detect mRNA transcription levels of Fyn, SP, VIP and NPY in the hippocampus.Results(1) Behavioral scores of rhinitis: compared with the normal group, behavioral scores of rhinitis were significantly higher in the model group, the traditional Chinese medicine group and the western medicine group before treatment (<italic>P</italic>&lt;0.05). …”
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Potential Antidepressant Effects of Omeprazole Introduced Through Network Analysis and Systems Biology Should Be Interpreted with Caution in the Clinical Environment by Seyed-Ali Mostafavi

“…Further evaluation suggested that she had a profound deficiency of tyrosine, which is an amino acid necessary for the production of neurotransmitters such as dopamine and norepinephrine which play consequential roles in mood. …”
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VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment by Cheng Cheng, Qingrui Zha, Linmao Sun, Tianming Cui, Xinyu Guo, Changjian Xing, Zhengxiang Chen, Changyong Ji, Shuhang Liang, Shengwei Tao, Junhui Chu, Chenghui Wu, Qi Chu, Xuetian Gu, Ning Zhang, Yumin Fu, Shumin Deng, Yitong Zhu, Jiabei Wang, Yao Liu, Lianxin Liu

“…The accumulated G3P diffuses into the TME and directly interacts with SRC-family tyrosine kinase LCK, a critical component of the T-cell receptor (TCR) signaling pathway in CD8+T cells. …”
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The protective effects of Levilactobacillus brevis FZU0713 on lipid metabolism and intestinal microbiota in hyperlipidemic rats by Xiaoyun Fan, Qing Zhang, Weiling Guo, Qi Wu, Jinpeng Hu, Wenjian Cheng, Xucong Lü, Pingfan Rao, Li Ni, Youting Chen, Lijiao Chen

“…Furthermore, liver metabolomics analysis demonstrated that L. brevis FZU0713 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic rats, especially the levels of some important biomarkers involved in the metabolic pathways of arachidonic acid metabolism, primary bile acid biosynthesis, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, biosynthesis of unsaturated fatty acid, fructose and mannose metabolism, tyrosine metabolism, etc. Additionally, oral administration of L. brevis FZU0713 significantly regulated the mRNA levels of liver genes (including Acat2, Acox1, Hmgcr, Cd36, Srebp-1c and Cyp7a1) involved in lipid metabolism and bile acid homeostasis. …”
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Gut microbiota and plasma metabolites in pregnant mothers and infant atopic dermatitis: A multi-omics studyKey Message by Bingqian Du, MA.Sc, Aga Shama, BA.Sc, Yi Zhang, BA.Sc, Baolan Chen, MA.Sc, Yongqi Bu, BA.Sc, Pei-an Chen, MA.Sc, Chuzhi Lin, BA.Sc, Jie Liu, MA.Sc, Juan Zheng, MA.Sc, Zhenjun Li, MD, PhD, Qingsong Chen, PhD, Yu Sun, PhD, Xi Fu, PhD

“…Short-chain fatty acids (SCFAs) producing microorganisms, including Faecalibacterium, Roseburia, Butyricicoccus, and Ruminococcus, as well as the abundance of phenylalanine, tyrosine, and tryptophan biosynthesis pathway, were enriched in health group (LDA>2 and P < 0.05). …”
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Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator’s Consortium Registry Analysis by Margaret Stalker, MD, Connor B. Grady, MPH, Alex Watts, MS, Wei-Ting Hwang, PhD, Krishna Chandrasekhara, MS, Fangdi Sun, MD, Geoffrey Liu, MD, Devalben Patel, MD, Jorge Nieva, MD, Amanda Herrmann, MD, Kristen Marrone, MD, Vincent K. Lam, MD, Vamsidhar Velcheti, MD, Stephen V. Liu, MD, Gabriela Liliana Bravo Montenegro, MD, William Tompkins, MD, Tejas Patil, MD, Jared Weiss, MD, Kelsey Leigh Miller, MD, William Schwartzman, MD, Jonathan E. Dowell, MD, Khvaramze Shaverdashvili, MD, PhD, Liza Villaruz, MD, Amanda Cass, PharmD, Wade Iams, MD, Dara Aisner, MD, PhD, Charu Aggarwal, MD, MD, D. Ross Camidge, MD, PhD, Lova Sun, MD, Melina E. Marmarelis, MD

“…The predominant first EGFR–tyrosine kinase inhibitor was erlotinib (65%) before 2018 and osimertinib (81%) after 2018. …”
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Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice by Wen Yin, Heng Xu, Zhonghao Bai, Yue Wu, Yan Zhang, Rui Liu, Zhangzhao Wang, Bei Zhang, Jing Shen, Hao Zhang, Xin Chen, Danting Ma, Xiaofeng Shi, Lihui Yan, Chang Zhang, Hualiang Jiang, Kaixian Chen, Dean Guo, Wenyan Niu, Huiyong Yin, Weiping J. Zhang, Cheng Luo, Xiangyang Xie

“…Mechanistically, PRDX1 suppresses STAT signaling and protects mitochondrial function by scavenging hydrogen peroxide, and mitigating the oxidation of protein tyrosine phosphatases and lipid peroxidation. We further identify rosmarinic acid (RA) as a potent agonist of PRDX1. …”
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ERBB4 selectively amplifies TGF-β pro-metastatic responses by Peihong Luo, Huanyu Hong, Baoling Zhang, Jie Li, Shuyi Zhang, Chaomin Yue, Jin Cao, Jia Wang, Yuhan Dai, Qingqing Liao, Pinglong Xu, Bing Yang, Xia Liu, Xia Lin, Yi Yu, Xin-Hua Feng

“…Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β′s metastatic response but not its anti-growth response. …”
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A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings by Steven P. Treon, Camille N. Kotton, David J. Park, Giorgia Moranzoni, Camilla K. Lemvigh, Joseph C. Gathe, Tilly A. Varughese, Christopher F. Barnett, Johnny M. Belenchia, Nina M. Clark, Charles M. Farber, Muhammad Bilal Abid, Gulrayz Ahmed, Christopher J. Patterson, Maria L. Guerrera, Jacob D. Soumerai, Vipheaviny A. Chea, Isabel P. Carulli, Jackson Southard, Shuqiang Li, Catherine J. Wu, Kenneth J. Livak, Eric Holmgren, Pil Kim, Carrie Shi, Holly Lin, Vanitha Ramakrishnan, Ying Ou, Scott Olszewski, Lars Rønn Olsen, Derin B. Keskin, Derin B. Keskin, Zachary R. Hunter, Christopher Tankersley, Todd Zimmerman, Binod Dhakal

“…BackgroundCytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)–related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. …”
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Intranigral Administration of β-Sitosterol-β-D-Glucoside Elicits Neurotoxic A1 Astrocyte Reactivity and Chronic Neuroinflammation in the Rat Substantia Nigra by Claudia Luna-Herrera, Irma A. Martínez-Dávila, Luis O. Soto-Rojas, Yazmin M. Flores-Martinez, Manuel A. Fernandez-Parrilla, Jose Ayala-Davila, Bertha A. León-Chavez, Guadalupe Soto-Rodriguez, Victor M. Blanco-Alvarez, Francisco E. Lopez-Salas, Maria E. Gutierrez-Castillo, Bismark Gatica-Garcia, America Padilla-Viveros, Cecilia Bañuelos, David Reyes-Corona, Armando J. Espadas-Alvarez, Linda Garcés-Ramírez, Oriana Hidalgo-Alegria, Fidel De La Cruz-lópez, Daniel Martinez-Fong

“…We injected 6 μg BSSG/1 μL DMSO or vehicle into the left substantia nigra and immunostained with antibodies against tyrosine hydroxylase (TH) together with markers of microglia (OX42), astrocytes (GFAP, S100β, C3), and leukocytes (CD45). …”
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ALDH1L2 drives HCC progression through TAM polarization by Jiajun Li, Chi Zhang, Qingqing Zhou, Qinqin Long, Jiayi Chen, Lili Meng, Wei Tian, Yue Yang, Chao Ge, Yuting Su, Xi-Dai Long, Jun Wu, Hua Tian

“…In addition, ALDH1L2 knockdown enhances the anti-HCC activity of the tyrosine kinase inhibitor sorafenib. Conclusions: These findings provide the first evidence indicating that ALDH1L2 is directly involved in tumor progression by interacting with tumor-associated macrophages through the Jak2/STAT3 signaling pathway and that ALDH1L2 may be a target molecule for HCC therapy. …”
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