Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder by Kira Furlano, Henning Plage, Sebastian Hofbauer, Sarah Weinberger, Bernhard Ralla, Annika Fendler, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Martina Kluth, Maximilian Lennartz, Niclas C. Blessin, Andreas H. Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Stefan Koch, Nico Adamini, Sarah Minner, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Henrik Zecha

“…One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression‐based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis. …”
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piR-26441 inhibits mitochondrial oxidative phosphorylation and tumorigenesis in ovarian cancer through m6A modification by interacting with YTHDC1 by Jing Yuan, Bu-Min Xie, Yu-Meng Ji, Hai-Juan Bao, Jie-Lin Wang, Jia-Chen Cheng, Xiang-Chun Huang, Yang Zhao, Shuo Chen

“…Furthermore, piR-26441 directly binds to and upregulates the expression of YTHDC1 in OC cells. piR-26441 also increased m6A levels, thereby interacting with YTHDC1 to destabilize the mRNA of TSFM. The resultant TSFM loss reduced mitochondrial complex I activity and mitochondrial OXPHOS, leading to mitochondrial dysfunction in OC cells, increased reactive oxygen species levels, and thus, DNA damage and apoptosis in OC cells, thereby inhibiting OC progression. …”
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Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway by Yan Li, Hong Wang, Xiaoyang Li, Yuan He, Huiquan Liu, Dong Han, Ting Mei, Yixuan Li, Zilong Xu, Xiaoying Wei, Jianguo Wang, Peijie Zhou, Yuwen Wang, Ziye Li, Junhao Ning, Anlin Wang, Jingjing Cheng, Dong Qian

“…To further validate our findings, we established subcutaneous and orthotopic mouse HCC models with tumor-intrinsic Pgam5 deficiency and analyzed tumor-infiltrating immune cells by flow cytometry and single-cell RNA sequencing. Mechanistically, we established an in vitro co-culture system and analyzed proteomics data to find out the bridge between tumor cell PGAM5 and tumor-associated macrophages (TAMs) in the microenvironment. …”
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Mechanosensor YAP mediates bone remodeling via NF-κB p65 induced osteoclastogenesis during orthodontic tooth movement by Jie Deng, Yu-Ning Zhang, Ru-Shui Bai, Ting-Ting Yu, Yi Zhao, Hao Liu, Yun-Fan Zhang, Tian-Min Xu, Bing Han

“…Time-course analysis revealed two YAP activity peaks on day1 and 14, contrasting with one peak of type I collagen expression on day14. In addition, RNA-sequencing highlighted increased nuclear factor kappa B (NF-κB) signaling, mineral absorption, and osteoclast differentiation at day-1 and 3. …”
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Dysfunction of ATP7B Splicing Variant Caused by Enhanced Interaction With COMMD1 in Wilson DiseaseSummary by Donghu Zhou, Huaduan Zi, Xiaoxi Yang, Xiaojin Li, Yanmeng Li, Anjian Xu, Bei Zhang, Wei Zhang, Xiaojuan Ou, Jidong Jia, Jian Huang, Hong You

“…Methods: The splicing assay and RNA pull-down were performed to explore the mechanism of the aberrant splicing. …”
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Targeting BRD4 ameliorates experimental emphysema by disrupting super-enhancer in polarized alveolar macrophage by Difei Li, Xing Shi, Yuqiong Yang, Yao Deng, Dandan Chen, Shuyu Chen, Jinyong Wang, Guanxi Wen, Zhenyu Liang, Fengyan Wang, Jiaqi Gao, Yuanyuan Liu, Danna Wang, Ruifang Liang, Haizhao Xu, Rongchang Chen, Shanze Chen, Lingwei Wang

“…In vivo, BRD4 inhibitor JQ1 and degrader ARV-825 were intraperitoneally administrated into emphysema mice to assess their effects on lung emphysema and inflammation. In vitro, RNA-seq and CUT&Tag assay of BRD4 and H3K27ac were applied for elucidating how BRD4 regulates macrophage polarization. …”
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Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis by Patricia Ruiz-Limón, Patricia Ruiz-Limón, Patricia Ruiz-Limón, Natalia Mena-Vázquez, Natalia Mena-Vázquez, Isabel Moreno-Indias, Isabel Moreno-Indias, Isabel Moreno-Indias, Jose Manuel Lisbona-Montañez, Jose Manuel Lisbona-Montañez, Jose Manuel Lisbona-Montañez, Arkaitz Mucientes, Arkaitz Mucientes, Sara Manrique-Arija, Sara Manrique-Arija, Sara Manrique-Arija, Rocío Redondo-Rodriguez, Rocío Redondo-Rodriguez, Laura Cano-García, Laura Cano-García, Francisco J. Tinahones, Francisco J. Tinahones, Francisco J. Tinahones, Francisco J. Tinahones, Antonio Fernández-Nebro, Antonio Fernández-Nebro, Antonio Fernández-Nebro

“…The gut microbiota was analyzed using 16S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2, and its functionality was inferred through PICRUSt. …”
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E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration by Michela Tozzi, Alessia Fiore, Sara Travaglione, Francesca Marcon, Gabriella Rainaldi, Elena Angela Pia Germinario, Ilenia Laterza, Simona Donati, Daniele Macchia, Massimo Spada, Omar Leoni, Maria Cristina Quattrini, Donatella Pietraforte, Sofia Tomasoni, Filippo Torrigiani, Ranieri Verin, Paola Matarrese, Lucrezia Gambardella, Francesca Spadaro, Maria Carollo, Agostina Pietrantoni, Francesca Carlini, Concetta Panebianco, Valerio Pazienza, Filomena Colella, Donatella Lucchetti, Alessandro Sgambato, Antonella Sistigu, Federica Moschella, Marco Guidotti, Olimpia Vincentini, Zaira Maroccia, Mauro Biffoni, Roberta De Angelis, Laura Bracci, Alessia Fabbri

“…Immunohistochemistry and immunofluorescence stainings of formalin-fixed paraffin-embedded (FFPE) colon tissue were carried out as well as fecal microbiota composition analysis by 16 S rRNA gene sequencing. Results CNF1 induces the release of reactive oxidizing species and chromosomal instability in non-neoplastic intestinal epithelial cells. …”
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COVID-19 Vaccines Effectiveness and Safety in Trinidad and Tobago: A Systematic Review and Meta-Analysis by Angel Justiz-Vaillant, Kimberly Roopnarine, Shaundell Solomon, Alyssa Phillips, Solange Sandy, Alyssa Subero, Sarah Seepersad, Nicholas Span, Phalmanie Ramnath, Akaasha Ramnarine, Bimala Ramdath, Chelsea Rampaul, Renissa Ramdial, Dana Phagoo, Thalia Ramdhanie, Vinaya Moonilal, Emily-Marie Poliah, Steffan Poonwassie, Karishta Punilal, Sarah Panchoo, Justice Parris, Steven Oudit, Trudy Muir, Johnson Nicholas-Joseph, Bijey Raj Pandit, Sanjeev Pakeerah, Vesham Sookoo, Patrice Richards, Tishia John, Darren Gopaul, Sachin Soodeen, Odette Arozarena-Barbosa, Arlene Williams, Chandrashehkar Unakal, Rodolfo Arozarena Fundora, Reinand Thompson, Patrick Eberechi Akpaka

“…The Pfizer-BioNTech and Moderna vaccines demonstrated the highest efficacy, particularly against COVID-19 variants, while Janssen and Sinopharm were comparatively less effective. mRNA vaccines, such as Pfizer-BioNTech and Oxford-AstraZeneca, were associated with more frequent and severe side effects, including soreness, fever, and cardiovascular issues. …”
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The in vivo metabolic pathway of Deg-AZM and in vitro investigations into the contribution of drug metabolizing enzymes and drug transporters in the drug interactions of Deg-AZM, a... by Xiaoting Gu, Xiaohe Li, Weixue Tian, Chaoyue Zheng, Chaoyue Zheng, Yutian Cai, Yutian Cai, Xiang Xu, Xiang Xu, Conglu Zhao, Conglu Zhao, Hongting Liu, Hongting Liu, Yao Sun, Yao Sun, Zhilin Luo, Zhilin Luo, Shuwen Zhu, Shuwen Zhu, Honggang Zhou, Honggang Zhou, Xiaoyu Ai, Cheng Yang, Cheng Yang

“…A HLM inhibition reaction system was established to evaluate the inhibitory effect of Deg-AZM on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The mRNA expression of human primary hepatocytes incubated with Deg-AZM or not was evaluate the induction of Deg-AZM on CYP1A2, CYP2B6, and CYP3A4.Results44 metabolites of Deg-AZM were identified in rat urine, feces, bile, and plasma, the metabolic pathways included demethylation, monohydroxylation, dihydroxylation, dehydroxidation, hydroreduction, hydrolysis, methylation, glucuronidation and the combination of different metabolic pathways. …”
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Development and evaluation of a CRISPR/Cas12a-based diagnostic test for rapid detection and genotyping of HR-HPV in clinical specimens by Lijuan Yin, Ziqian Zhao, Chunhua Wang, Caihong Zhou, Xiuzhen Wu, Baoxue Gao, Liangyuan Wang, Shuli Man, Xinkuan Cheng, Qiankun Wu, Siqi Hu, Hongxia Fan, Long Ma, Hui Xing, Liang Shen

“…Furthermore, we achieved one-tube multiplex detection of 14 HR-HPV types through the use of multiple amplifications and a crRNA pool. The detection sensitivity of this method is 2 copies/μL with no cross-reactivity, and the results can be obtained within 30 minutes. …”
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Weighted Gene Co-Expression Network of Growth Differentiation-Related lncRNAs and mRNAs in Plectropomus leopardus by Jin GAO, Jinye LIU, Fuxiao CHEN, Yongbo WANG, Shuyuan FU

“…High-weight and high-connectivity lncRNAs and mRNAs were screened from the three specific modules to construct a gene interaction network, revealing key genes associated with growth differentiation including psmd6, nmt1, als2, brcc3, kank1, ada12, at131, hdac3, as well as 20 lncRNA transcription factors such as MSTRG.15660, MSTRG.8694, and MSTRG.1896. …”
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Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins by Maria Angelica Freitas-Cortez, Fatemeh Masrorpour, Hong Jiang, Iqbal Mahmud, Yue Lu, Ailing Huang, Lisa K. Duong, Qi Wang, Tiffany A. Voss, Claudia S. Kettlun Leyton, Bo Wei, Wai-Kin Chan, Kevin Lin, Jie Zhang, Efrosini Tsouko, Shonik Ganjoo, Hampartsoum B. Barsoumian, Thomas S. Riad, Yun Hu, Carola Leuschner, Nahum Puebla-Osorio, Jing Wang, Jian Hu, Michael A. Davies, Vinay K. Puduvalli, Cyrielle Billon, Thomas P. Burris, Philip L. Lorenzi, Boyi Gan, James W. Welsh

“…Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry. …”
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Alcohol intake exacerbates experimental autoimmune prostatitis through activating PI3K/AKT/mTOR pathway-mediated Th1 differentiation by Shun Xu, Shun Xu, Shun Xu, Jing Chen, Jing Chen, Jing Chen, Shaoyu Yue, Shaoyu Yue, Shaoyu Yue, Yifan Zhang, Yifan Zhang, Yifan Zhang, Shengyu Zhao, Shengyu Zhao, Shengyu Zhao, Yongtao Hu, Yongtao Hu, Yongtao Hu, Cheng Zhang, Cheng Zhang, Cheng Zhang, Wenrui Guan, Wenrui Guan, Wenrui Guan, Li Zhang, Li Zhang, Li Zhang, Ligang Zhang, Ligang Zhang, Ligang Zhang, Chaozhao Liang, Chaozhao Liang, Chaozhao Liang

“…In contrast, PI3K inhibitor LY294002 and shRNA-PI3K plasmid inhibited PI3K/AKT/mTOR pathway activation, reduced Th1 cell differentiation, and alleviated EAP inflammation severity, respectively.ConclusionOur study is the first to demonstrate that alcohol intake promotes Th1 cell differentiation and exacerbates EAP by activating the PI3K/AKT/mTOR pathway. …”
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Identification of a novel SPTB gene splicing mutation in hereditary spherocytosis: a case report and diagnostic insights by Xiaobing Li, Xiaobing Li, Xiaobing Li, Xiaobing Li, Xiaobing Li, Tingqiang Zhang, Tingqiang Zhang, Tingqiang Zhang, Tingqiang Zhang, Xuemei Li, Li Wang, Li Wang, Li Wang, Li Wang, Qian Li, Qian Li, Qian Li, Qian Li, Qianqian Liu, Qianqian Liu, Qianqian Liu, Qianqian Liu, Chengyin He, Li Zhang, Li Zhang, Li Zhang, Li Zhang, Yongsheng Liu, Yongsheng Liu, Yongsheng Liu, Yongsheng Liu, Junling Tang, Junling Tang, Junling Tang, Junling Tang

“…Genetic testing identified a novel SPTB gene splicing mutation (NM_001355436.2: c.1645-1G>A), inherited maternally, which is predicted to disrupt normal RNA splicing and protein synthesis.DiscussionThe identified SPTB mutation expands the known mutation spectrum of the SPTB gene and highlights its role in the pathogenesis of HS. …”
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Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19 by Andrew I Kim, William Bain, Alison Morris, Barbara Methe, Bryan J McVerry, Georgios D Kitsios, Daniel Kotok, Janet S Lee, Nameer Al-Yousif, Christine E Girard, Jana J Jacobs, Konstantin Golubykh, Hafiz Qurashi, Michael Lu, Saketram Komanduri, Anatoliy Korzhuk, Halimat O Lawal, Nicholas Abourizk, Caitlin Schaefer, Kevin J Mitchell, Catherine M Dietz, Ellen K Hughes, Clara S Brandt, Georgia M Fitzgerald, Robin Joyce, Asmaa S Chaudhry, Jose D Rivera, Shruti Shettigar, Allen Lavina, Samantha R Gillenwater, Anas Hadeh, Faraaz A Shah, Matthew Bittner, Niall Prendergast, John Evankovich, Navitha Ramesh, Cathy Kessinger

“…Objectives To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes.Setting Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems.Participants 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set.Primary and secondary outcomes We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host–response biomarkers, SARS-CoV-2 RNA load and clinical outcomes.Results Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). …”
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Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients by João Locke Ferreira de Araújo, Átila Duque Rossi, Jessica Maciel de Almeida, Hugo José Alves, Isabela de Carvalho Leitão, Renata Eliane de Ávila, Anna Carla Pinto Castiñeiras, Jéssica da Silva Oliveira, Rafael Mello Galliez, Marlon Daniel Lima Tonini, Débora Souza Faffe, Shana Priscila Coutinho Barroso Barroso, Gustavo Gomes Resende, Cássia Cristina Alves Gonçalves, Terezinha Marta Pereira Pinto Castiñeiras, Amilcar Tanuri, Mauro Martins Teixeira, Renato Santana Aguiar, Cynthia Chester Cardoso, Renan Pedra de Souza

“…This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19. …”
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NSUN5 Facilitates Hepatocellular Carcinoma Progression by Increasing SMAD3 Expression by Hexu Han, Chengcheng zhang, Wenbo Shi, Jiawei Wang, Wenhui Zhao, Yanping Du, Zhibin Zhao, Yifan Wang, Maosong Lin, Lei Qin, Xiaoxue Zhao, Qianqian Yin, Yiyi Liu, Zhongqi Wang, Jing Zhang, Xiaomin You, Guoxiong Zhou, Honghui Wu, Jun Ye, Xianzhong He, Weizhong Tian, Hong Yu, Yin Yuan, Qiang Wang

“…However, the expression of NOP2/Sun RNA methyltransferase 5 (NSUN5) in HCC and its role in mediating EMT remain poorly understood. …”
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Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials by Jingyun Yang, Weiqi Hong, Huashan Shi, Cai He, Hong Lei, Yanan Zhou, Hao Yang, Aqu Alu, Zimin Chen, Yun Yang, Wenhai Yu, Cong Tang, Junbin Wang, Bai Li, Qing Huang, Jiong Li, Li Yang, Wei Wang, Guobo Shen, Jinliang Yang, Zhiwei Zhao, Xiangrong Song, Zhaoming Su, Yuquan Wei, Qiangming Sun, Shuaiyao Lu, Zhenling Wang, Youchun Wang, Guangwen Lu, Weimin Li, Xiawei Wei

“…Tri-Vac also serves as a candidate booster for enhancing immunity after three doses of inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety and immunogenicity in humans, focusing on the primary endpoint of adverse reactions within 7 days and key secondary endpoints including the geometric mean titers (GMTs) of serum neutralizing antibodies within 30 days and 6 months post-vaccination, as well as adverse events within 30 days and serious adverse events within 6 months post-vaccination. …”
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Sex and outcomes of patients with microsatellite instability-high and BRAF V600E mutated metastatic colorectal cancer receiving immune checkpoint inhibitors by Michael Hoffmeister, Hermann Brenner, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Julien Taieb, David Tougeron, Robyn L Ward, Marco Vitellaro, Thierry André, Pierre Laurent-Puig, Jitendra Jonnagaddala, Francesca Bergamo, Raghav Sundar, Claire Gallois, Michael J Overman, Jakob Nikolas Kather, Lisa Salvatore, Romain Cohen, Rossana Intini, Priya Jayachandran, Miriam Koopman, Javier Ros, Marwan Fakih, Vincenzo Nasca, Giacomo Mazzoli, Jeanine M L Roodhart, Filippo Ghelardi, Elena Elez, Durgesh Wankhede, Marta Ligero, Joseph Zhao, Koen Zwart, Jeroen Derksen, Nicholas Hawkins, Javier Carmona

“…Finally, we explored two public microarray and RNA-seq datasets from patients with non-metastatic or metastatic MSI-H CRC to gain translational insights on the association between sex, BRAF status and immune contextures/ICI efficacy.Results Although no differences were observed between females and males either overall or in the BRAF wild-type cohort, male sex was associated with inferior progression-free survival (PFS) and overall survival (OS) in the BRAF mutated cohort (in multivariable models, HR for PFS: 1.79, 95% CI: 1.13 to 2.83, p=0.014, and for OS: 2.33, 95% CI: 1.36 to 3.98, p=0.002). …”
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