Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK‐001 using a randomized, double‐blind, placebo‐controlled study design by Sibel Ucpinar, Joyce K. Kwan, Joshua D. Hoffman, Mera K. Tilley, Jeffrey A. Douglas, Roman G. Rubio, Ruixiao Lu, Philip A. Nunn, Claire L. Langrish

“…In conclusion, ESK‐001 was generally safe and well‐tolerated in healthy participants, showed linear dose‐dependent PK characteristics, and maximally inhibited TYK2‐dependent pathways with a predictable concentration‐dependent PK/PD relationship. …”
Get full text

Predictors of response and disease course in patients with inflammatory bowel disease treated with biological therapy—the Danish IBD Biobank Project: protocol for a multicentre pro... by Jakob Benedict Seidelin, Andreas Munk Petersen, Johan Burisch, Flemming Bendtsen, Mirabella Zhao, Lone Larsen, Anders Dige, Christian Hvas

“…Samples will undergo transcriptomic, proteomic and microbial DNA analyses. …”
Get full text

Integrated Multi-Omics Profiling Reveals That Highly Pyroptotic MDMs Contribute to Psoriasis Progression Through CXCL16 by Liping Jin, Xiaowen Xie, Mi Zhang, Wu Zhu, Guanxiong Zhang, Wangqing Chen

“…<b>Methods:</b> We integrated 21 transcriptomic datasets (from 2007 to 2020) obtained from the GEO database and two single-cell RNA sequencing datasets to quantify pyroptotic activity using Gene Set Variation Analysis and AUCell algorithms. …”
Get full text

Increased adherence and expression of virulence genes in a lineage of Escherichia coli O157:H7 commonly associated with human infections. by Galeb S Abu-Ali, Lindsey M Ouellette, Scott T Henderson, David W Lacher, James T Riordan, Thomas S Whittam, Shannon D Manning

“…Relative to clade 2, clade 8 strains showed upregulation of major virulence genes, including 29 of the 41 locus of enterocyte effacement (LEE) pathogenicity island genes, which are critical for adherence, as well as Shiga toxin genes and pO157 plasmid-encoded virulence genes. …”
Get full text

USP5 Promotes Head and Neck Squamous Cell Carcinoma Progression via mTOR Signaling Pathway by Ni Xiong, Yue Wang, Junhong Jiang

“…Materials & Methods This work utilized single‐cell transcriptomic analysis with the Scissor algorithm to identify distinct epithelial subpopulations, particularly focusing on the Stress subpopulation that exhibited significant upregulation of USP5. …”
Get full text

QTL mapping provides new insights into emamectin benzoate resistance in salmon lice, Lepeophtheirus salmonis by Armin Sturm, Greta Carmona-Antoñanzas, Joseph L. Humble, Claudia Croton, Sally Boyd, Rapule Mphuti, John B. Taggart, David I. Bassett, Ross D. Houston, Karim Gharbi, James E. Bron, Michaël Bekaert

“…The aim of the present work was to obtain insights into potential EMB resistance mechanisms by identifying genetic and transcriptomic markers associated with EMB resistance. …”
Get full text

RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer by Yongzhou Luo, Wenwen Tian, Da Kang, Linyu Wu, Hailin Tang, Sifen Wang, Chao Zhang, Yi Xie, Yue Zhang, Jindong Xie, Xinpei Deng, Hao Zou, Hao Wu, Huan Lin, Weidong Wei

“…Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. …”
Get full text

Disentangling the Switching Behavior in Functional Connectivity Dynamics in Autism Spectrum Disorder: Insights from Developmental Cohort Analysis and Molecular‐Cellular Association... by Wei Li, Xia Qiu, Jin Chen, Kexuan Chen, Meiling Chen, Yinyan Wang, Wenjie Sun, Jing Su, Yongchang Chen, Xiaobao Liu, Congying Chu, Jiaojian Wang

“…However, whether and how switching behaviors in FCD change in patients with developmental ASD, as well as their cellular and molecular basis, remains unexplored. …”
Get full text

<i>SHROOM3</i> Deficiency Aggravates Adriamycin-Induced Nephropathy Accompanied by Focal Adhesion Disassembly and Stress Fiber Disorganization by Li-Nan Xu, Ying-Ying Sun, Yan-Feng Tan, Xin-Yue Zhou, Tian-Chao Xiang, Ye Fang, Fei Li, Qian Shen, Hong Xu, Jia Rao

“…However, its regulatory role in proteinuric kidney diseases and its mechanistic contributions to podocyte homeostasis remain poorly defined. Here, we analyzed single-cell transcriptomic datasets and the Nephroseq database to delineate <i>SHROOM3</i> expression patterns in proteinuric kidney diseases. …”
Get full text

Enhancing the purity and intrinsic properties of ovine dermal papilla cells through flow cytometry sorting and cellular interactions by Yuan Gou, Tingyan Hu, Lijuan Zhu, Xiaoyang Lv, Yutao Li, Rui Su, Zhenghai Song, Shanhe Wang, Wei Sun

“…Methods We identified sheep DPC membrane-specific genes using single-cell transcriptomic data, validated by immunostaining and flow cytometry. …”
Get full text

A novel mitochondrial quality regulation gene signature for anticipating prognosis, TME, and therapeutic response in LUAD by multi-omics analysis and experimental verification by Lijun Zeng, Sixuan Wu, Zhimin Li, Yuanbin Tang, Yeru Tan, Renji Liang, Yuehua Li

“…Despite advances in LUAD treatment and detection, early diagnostic biomarkers are still lacking, and the roles of MQRGs in LUAD are not well understood. Methods We extensively examined transcriptome and clinical data from TCGA and GEO databases to discover differentially expressed MQRGs. …”
Get full text

Estimation of genetic parameters and genome-wide association study for carcass traits in native chickens by Xianghua Zhu, Houxue Cui, Nanxi Dong, Lu Liu

“…Methods In this study, we performed a genome-wide association study on SW, EW, and thigh muscle weight (ThW), as well as the relative weight of these traits in 565 Sanhuang (SH) chickens. …”
Get full text

Widespread splicing changes in human brain development and aging by Pavel Mazin, Jieyi Xiong, Xiling Liu, Zheng Yan, Xiaoyu Zhang, Mingshuang Li, Liu He, Mehmet Somel, Yuan Yuan, Yi‐Ping Phoebe Chen, Na Li, Yuhui Hu, Ning Fu, Zhibin Ning, Rong Zeng, Hongyi Yang, Wei Chen, Mikhail Gelfand, Philipp Khaitovich

“…Abstract While splicing differences between tissues, sexes and species are well documented, little is known about the extent and the nature of splicing changes that take place during human or mammalian development and aging. …”
Get full text

Effect of immune infiltration intensity on the efficacy of neoadjuvant immunotherapy for esophageal cancer by Yong Zhang, Xinyao Xu, Xinyao Xu, Xiaorong Mu, Xiaorong Mu, Juzheng Wang, Jipeng Zhang, Guangyu Xiang, Jiahe Li, Chunlong Zheng, Huaiyu Wang, Qiang Lu

“…However, the effectiveness of these treatments is limited by immune infiltration in the tumor microenvironment.MethodsWe analyzed single-cell transcriptomic data from 22 patients with resectable ESCC, collected before and after neoadjuvant therapy. …”
Get full text

Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure by Mahboube Ganji-Arjenaki, Zoha Kamali, Soroush Sardari, Martin de Borst, Harold Snieder, Ahmad Vaez, Evangelos Evangelou, Helen R. Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Stéphanie Debette, Jun Ding, Franco Giulianini, Elizabeth G. Holliday, Anne U. Jackson, Ruifang Li -Gao, Wei -Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M. Willems, Jing -Hua Zhao, Philippe Amouyel, John Connell, Renée de Mutsert, Alex S.F. Doney, Martin Farrall, Cristina Menni, Andrew D. Morris, Raymond Noordam, Guillaume Paré, Neil R. Poulter, Denis C. Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E. Arking, Kristin L. Ayers, Caterina M. Barbieri, Chiara Batini, Joshua C. Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I. Boomsma, Erwin P. Bottinger, Peter S. Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C. Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J. Cordell, Gail Davies, Martin H. de Borst, Eco J. de Geus, Ian J. Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B. Ehret, Roberto Elosua, Stefan Enroth, A. Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H. Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J. Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Sarah E. Harris, Catharina A. Hartman, Aki S. Havulinna, Andrew A. Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E. Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo -Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D. Johnson, Peter K. Joshi, Pekka Jousilahti, J. Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D. Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S. Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J. Launer, Benjamin Lehne, Terho Lehtimäki, David C.M. Liewald, Li Lin, Lars Lind, Cecilia M. Lindgren, YongMei Liu, Ruth J.F. Loos, Lorna M. Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P. Morris, Alanna C. Morrison, Peter J. Munson, Mike A. Nalls, Priyanka Nandakumar, Christopher P. Nelson, Teemu Niiranen, Ilja M. Nolte, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Paul F. O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda W.J.H. Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P. Pramstaller, Quang Tri Nguyen, Olli T. Raitakari, Rainer Rettig, Kenneth Rice, Paul M. Ridker, Janina S. Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M. Rose, Jerome I. Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F. Sala, Veikko Salomaa, Nilesh J. Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V. Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M. Starr, David J. Stott, David P. Strachan, Rona J. Strawbridge, Johan Sundström, Morris A. Swertz, Kent D. Taylor, Alexander Teumer, Martin D. Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G. Uitterlinden, Ahmad Vaez, Peter J. van der Most, Cornelia M. van Duijn, Germaine C. Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H. Wild, Gonneke Willemsen, James F. Wilson, Alan F. Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R. Attia, Adam S. Butterworth, Daniel I. Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna M.M. Howson, Markku Laakso, Edward G. Lakatta, Claudia Langenberg, Olle Melander, Dennis O. Mook-Kanamori, Colin N.A. Palmer, Lorenz Risch, Robert A. Scott, Rodney J. Scott, Peter Sever, Tim D. Spector, Pim van der Harst, Nicholas J. Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B. Munroe, Christopher Newton-Cheh, Morris J. Brown, Andres Metspalu, Bruce M. Psaty, Louise V. Wain, Paul Elliott, Mark J. Caulfield

“…Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years. …”
Get full text

Novel and Highly Potent Therapeutic Agent, Trametes Robiniophila Murr (Huaier), Mitigates Pulmonary Vascular Remodeling in Rodents by Huangshu Ye, Yue Zhang, Li Hu, Yuxin Feng, Tianfan Zhu, Qi Meng, Xiaoxuan Sun, Miaojia Zhang, Zhengsheng Mao, Feng Chen, Yanfang Yu, Qiang Wang, Jie Wang

“…Background Pulmonary hypertension (PH) is a critical disease causing right ventricular failure and early death. Conventional single‐pathway treatments are inadequate, highlighting the need for new therapies. …”
Get full text

ITGA4 as a potential prognostic and immunotherapeutic biomarker in human cancer and its clinical significance in gastric cancer: an integrated analysis and validation by Jiaxing Zhang, Jiaxing Zhang, Gang Wang, Jie Liu, Futian Tang, Song Wang, Yumin Li, Yumin Li

“…However, its role across different cancer types is not well understood.MethodsUtilizing multi-omics data, we comprehensively evaluated ITGA4’s expression, clinical relevance, diagnostic and prognostic value, functions, mutations, and methylation status, along with its impact on immunity, mismatch repair (MMR), heterogeneity, stemness, immunotherapy responsiveness, and drug resistance in pan-cancer, with partial validation in gastric cancer (GC) using transcriptomic analysis, single-cell data, western blot (WB), wound-healing assay, flow cytometry and immunohistochemistry (IHC). …”
Get full text

Ileal microbial microbiome and its secondary bile acids modulate susceptibility to nonalcoholic steatohepatitis in dairy goats by Yue Wang, Xiaodong Chen, Sharon A. Huws, Guanghao Xu, Jing Li, Jianrong Ren, Jingyi Xu, Le Luo Guan, Junhu Yao, Shengru Wu

“…Since the ileum is the primary site for BAs reabsorption and return to the liver, we analysed the ileal metagenome and metabolome, liver and serum metabolome, and liver single-nuclei transcriptome of NASH-resistant and susceptible goats together with a mice validation model to explore how ileal microbial BAs metabolism affects liver metabolism and immunity, uncovering the key mechanisms behind varied NASH pathogenesis in dairy goats. …”
Get full text

Radiogenomics of intrahepatic cholangiocarcinoma predicts immunochemotherapy response and identifies therapeutic target by Gu-Wei Ji, Zheng-Gang Xu, Shuo-Chen Liu, Shu-Ya Cao, Chen-Yu Jiao, Ming Lu, Biao Zhang, Yue Yang, Qing Xu, Xiao-Feng Wu, Ke Wang, Yong-Xiang Xia, Xiang-Cheng Li, Xue-Hao Wang

“…Methods We analyzed bulk, single-cell and spatial transcriptomic data comprising 457 ICC patients to identify an immune-related score (IRS), followed by decoding its spatial immune context. …”
Get full text

CRISPR/dCas-mediated counter-silencing: reprogramming dCas proteins into antagonists of xenogeneic silencers by Johanna Wiechert, Biel Badia Roigé, Doris Dohmen-Olma, Hindra, Xiafei Zhang, Roberto G. Stella, Marie A. Elliot, Julia Frunzke

“…Analyzing the system in C. glutamicum strains lacking the XS protein CgpS revealed varying strengths of counteracting CRISPR interference effects based on the target position and strand. Genome-wide transcriptome profiling in single-guide RNA/dCas9 co-expressing C. glutamicum wild-type strains revealed high counter-silencing specificity with minimal off-target effects. …”
Get full text