tbuckley/cabot-search huggingface dataset:
Response to CaO et al., “Commentary: Response to ‘Risk of fungal infection in patients with psoriasis receiving biologics: a retrospective single-center cohort study’”
Authors: Yoshihito Minami, Junichiro Hiruma, Kazuharu Harada, Kazuki Fujimori, Risa Suzuki, Miho Mori, Masahiro Okura, Namiko Abe, Kazutoshi Harada, Yukari Okubo
Journal: Journal of the American Academy of Dermatology (2025)
KRAS Mutants Confer Platinum Resistance by Regulating ALKBH5 Post-translational Modifications in Lung Cancer
Authors: Fang Yu, Shikan Zheng, Chunjie Yu, Sanhui Gao, Zuqi Shen, Rukiye Nar, Zhexin Liu, Shuang Huang, Lizi Wu, Tongjun Gu, Zhijian Qian
Journal: Journal of Clinical Investigation (2025)

Constitutively active mutations of KRAS are prevalent in non-small cell lung cancer (NSCLC). However, the relationship between these mutations and resistance to platinum-based chemotherapy and the underlying mechanisms remain elusive. In this study, we demonstrated that KRAS mutants confer resistance to platinum in NSCLC. Mechanistically, KRAS mutants mediate platinum resistance in NSCLC cells by activating ERK/JNK signaling, which inhibits ALKBH5 m6A demethylase activity by regulating post-translational modifications (PTMs) of ALKBH5. Consequently, the KRAS mutant leads to a global increase in m6A methylation of mRNAs, particularly DDB2 and XPC, which are essential for nucleotide excision repair. This methylation stabilized the mRNA of these two genes, thus enhancing NSCLC cells' ability to repair platinum-induced DNA damage and avoid apoptosis, thereby contributing to drug resistance. Furthermore, blocking KRAS-mutant-induced m6A methylation, either by overexpressing a SUMOylation-deficient mutant of ALKBH5, or by inhibiting METTL3 pharmacologically, significantly sensitizes KRAS-mutant NSCLC cells to platinum drugs in vitro and in vivo. Collectively, our study uncovers a previously unrecognized mechanism that mediates KRAS mutant-induced chemoresistance in NSCLC cells by activating DNA repair through the modulation of the ERK/JNK/ALKBH5 PTMs-induced m6A modification in DNA damage repair-related genes.
High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients
Authors: Ling Cai, Nia G. Hammond, Alpaslan Tasdogan, Massar Alsamraae, Chendong Yang, Robert B. Cameron, Peiran Quan, Ashley Solmonson, Wen Gu, Panayotis Pachnis, Mayher Kaur, Brianna K. Chang, Qin Zhou, Christopher T. Hensley, Quyen N. Do, Luiza Martins Nascentes Melo, Jessalyn M. Ubellacker, Akash Kaushik, Maia G. Clare, Isabel N. Alcazar, Katarzyna Kurylowicz, Joseph D. Marcuccilli, Gabriele Allies, Andrea Kutritz, Joachim Klode, Vijayashree Ramesh, Thomas J. Rogers, Aparna D. Rao, Hannah E. Crentsil, Hong Li, Fang Brister, Phyllis McDaniel, Xiaohong Xu, Bret M. Evers, Lauren G. Zacharias, Jessica Sudderth, Jian Xu, Thomas P. Mathews, Dwight Oliver, John D. Minna, John Waters, Sean J. Morrison, Kemp H. Kernstine, Brandon Faubert, Ralph J. DeBerardinis
Journal: Cancer Discovery (2025)

Abstract In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, 13C-labeled nutrients were intraoperatively infused into more than 90 patients with surgically resectable pulmonary lesions, and metabolic properties of resected tumors were correlated with survival. In NSCLCs infused with 13C-glucose, high 13C enrichment in tricarboxylic acid (TCA) cycle intermediates conferred a HR of 3.8 for early death, typically with metastasis. To test whether these features reflect requirements for metastasis, we generated patient-derived xenografts that spontaneously metastasize to multiple organs. Treatment with an electron transport chain (ETC) inhibitor reduced glucose-derived TCA cycle labeling but did not suppress subcutaneous tumor growth. However, ETC blockade reduced the abundance of circulating cancer cells and suppressed xenograft metastatic burden in distant organs. Our data demonstrate that isotope labeling can identify metabolic properties associated with metastasis in patients and that blocking the ETC suppresses metastasis in mice. Significance: Intraoperative 13C-glucose infusions in patients with NSCLC show that tumors with high labeling of TCA cycle intermediates progress rapidly, resulting in metastasis and early death. Blocking this pathway suppresses metastasis of human NSCLC cells in mice.
Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST
Authors: Hans-Georg Sprenger, Melanie J Mittenbühler, Yizhi Sun, Jonathan G Van Vranken, Sebastian Schindler, Abhilash Jayaraj, Sumeet A Khetarpal, Amanda L Smythers, Ariana Vargas-Castillo, Anna M Puszynska, Jessica B Spinelli, Andrea Armani, Tenzin Kunchok, Birgitta Ryback, Hyuk-Soo Seo, Kijun Song, Luke Sebastian, Coby O'Young, Chelsea Braithwaite, Sirano Dhe-Paganon, Nils Burger, Evanna L Mills, Steven P Gygi, Joao A Paulo, Haribabu Arthanari, Edward T Chouchani, David M Sabatini, Bruce M Spiegelman
Journal: Cell Metabolism (2025)
Interplay of m6A RNA methylation and gut microbiota in modulating gut injury
Authors: Haixia Wang, Juanjuan Han, Xin-An Zhang
Journal: Gut Microbes (2025)

The gut microbiota undergoes continuous variations among individuals and across their lifespan, shaped by diverse factors encompassing diet, age, lifestyle choices, medication intake, and disease states. These microbial inhabitants play a pivotal role in orchestrating physiological metabolic pathways through the production of metabolites like bile acids, choline, short-chain fatty acids, and neurotransmitters, thereby establishing a dynamic "gut-organ axis" with the host. The intricate interplay between the gut microbiota and the host is indispensable for gut health, and RNA N6-methyladenosine modification, a pivotal epigenetic mark on RNA, emerges as a key player in this process. M6A modification, the most prevalent internal modification of eukaryotic RNA, has garnered significant attention in the realm of RNA epigenetics. Recent findings underscore its potential to influence gut microbiota diversity and intestinal barrier function by modulating host gene expression patterns. Conversely, the gut microbiota, through its impact on the epigenetic landscape of host cells, may indirectly regulate the recruitment and activity of RNA m6A-modifying enzymes. This review endeavors to delve into the biological functions of m6A modification and its consequences on intestinal injury and disease pathogenesis, elucidating the partial possible mechanisms by which the gut microbiota and its metabolites maintain host intestinal health and homeostasis. Furthermore, it also explores the intricate crosstalk between them in intestinal injury, offering a novel perspective that deepens our understanding of the mechanisms underlying intestinal diseases.
Treatment of Relapsed/Refractory <scp>AML</scp>—Novel Treatment Options Including Immunotherapy
Authors: Catherine Gutierrez Moore, Anthony Stein, Amir T. Fathi, Vinod Pullarkat
Journal: American Journal of Hematology (2025)

ABSTRACT Acute myeloid leukemia is a molecularly heterogenous disease caused by the rapid expansion and impaired differentiation of malignant myeloid progenitors. Overall, outcomes remain poor, and more than half of patients develop relapsed or refractory disease after front‐line therapy. Allogeneic hematopoietic stem cell transplant (HCT) remains the best chance for cure for eligible patients, and the development of novel therapies including BCL2, FLT3, IDH1/2 and menin inhibitors, which are efficacious yet generally more tolerable, have enabled better bridging to prompt HCT. Despite the early success of targeted therapies, more generalized and efficacious therapeutic approaches remain in need, and numerous targeted immunotherapeutic agents (including CAR‐T, bispecific and trispecific antibody therapies) are currently under investigation.
Maintenance Therapy in <scp>AML</scp>: What Is the Future Potential?
Authors: Hannah Goulart, Andrew H. Wei, Tapan M. Kadia
Journal: American Journal of Hematology (2025)

ABSTRACT Over the last decade, there have been significant advancements in the treatment for patients with acute myeloid leukemia (AML) including the addition of novel, targeted agents to intensive or nonintensive chemotherapy regimens. However, despite this, the majority of patients will still ultimately relapse and long‐term survival remains poor. While the use of maintenance therapy has emerged as a potential strategy to maintain more durable remissions and improve overall survival, the optimal use of these therapies has not yet been clearly defined. In this review, we provide a comprehensive overview of the evolution of maintenance strategies in AML and present a commentary on the future of maintenance therapy, including the pressing, unmet needs in this field.
Frontline Therapy of <scp>AML</scp> in the Fit and Younger Population—Incorporating Molecularly Targeted Agents
Authors: Keith W. Pratz, Harry P. Erba
Journal: American Journal of Hematology (2025)

ABSTRACT Backbone therapy for acute myeloid leukemia for younger adults has for 50 years been based on a combination of cytarabine and anthracycline. Over the past 10 years the addition of several targeted agents has been found to improve the outcomes of subsets of AML with particular molecular changes. In this review we will examine the data generated to date on the addition of agents targeting CD33, FLT3, IDH, and BCL2 to standard high intensity therapies. We will also review the potential for future studies evaluating the application of highly active lower intensity therapies developed in older adults to patients considered “fit for high intensity induction.” Lastly, we review the data around the role of stem cell transplant in the modern targeted era.
Phase I clinical trial to assess safety and efficacy of Oraxol, a novel oral paclitaxel chemotherapy agent, in patients with previously treated metastatic breast cancer
Authors: Yunfang Yu, Ying Wang, Luhui Mao, Suiwen Ye, Xiuping Lai, Junyi Chen, Yiwen Zhang, Jieqiong Liu, Junyan Wu, Tao Qin, Herui Yao
Journal: MedComm (2025)

Abstract Oraxol, a novel oral paclitaxel chemotherapy agent, has emerged as a potential alternative for treating metastatic breast cancer (MBC). However, its safety and efficacy remain uncertain due to insufficient evidence supporting it. This open‐label, single‐arm, phase I trial was designed to assess the pharmacokinetics, safety, and preliminary antitumor activity of Oraxol in previously treated MBC. The primary objective was to investigate the pharmacokinetics of Oraxol, while secondary endpoints included assessing safety, tolerability, and antitumor activity. Twenty‐four patients (median age, 53 years) were enrolled, and pharmacokinetic analysis showed consistent and reproducible absorption of Oraxol. Note that 96% patients experienced treatment‐related adverse events (TRAEs) and no deaths attributed to TRAEs. The overall response rate was 34.8%, including 34.8% achieving partial response and 56.5% having stable disease. The median follow‐up was 45.7 months, with median progression‐free survival (PFS) of 3.41 months and median overall survival of 17.80 months. Notably, among patients with triple‐negative breast cancer, the disease control rate was 100%, and the median PFS was 8.90 months, which notably exceeded the outcomes observed in other subtypes. Oraxol significantly alters metabolism and correlates with response and survival. In conclusion, Oraxol exhibited promising antitumor efficacy and manageable safety profiles in MBC patients.
Histidine triad nucleotide‐binding protein 2 attenuates doxorubicin‐induced cardiotoxicity through restoring lysosomal function and promoting autophagy in mice
Authors: Hao Jiang, Jinyan Zhang, Daile Jia, Liwei Liu, Jinfeng Gao, Beijian Zhang, Zhen Dong, Xiaolei Sun, Wenlong Yang, Tiantong Ou, Suling Ding, Luna He, Yiqin Shi, Kai Hu, Aijun Sun, Junbo Ge
Journal: MedComm (2025)

Abstract Doxorubicin (DOX) is an effective chemotherapy drug widely used against various cancers but is limited by severe cardiotoxicity. Mitochondria–lysosome interactions are crucial for cellular homeostasis. This study investigates the role of histidine triad nucleotide‐binding protein 2 (HINT2) in DOX‐induced cardiotoxicity (DIC). We found that HINT2 expression was significantly upregulated in the hearts of DOX‐treated mice. Cardiac‐specific Hint2 knockout mice exhibited significantly worse cardiac dysfunction, impaired autophagic flux, and lysosomal dysfunction after DOX treatment. Mechanistically, HINT2 deficiency reduced oxidative phosphorylation complex I activity and disrupted the nicotinamide adenine dinucleotide NAD + /NADH ratio, impairing lysosomal function. Further, HINT2 deficiency suppressed sterol regulatory element binding protein 2 activity, downregulating transcription factor A mitochondrial, a critical regulator of complex I. Nicotinamide mononucleotide (NMN) supplementation restored lysosomal function in vitro, while cardiac‐specific Hint2 overexpression using adeno‐associated virus 9 or adenovirus alleviated DIC both in vivo and in vitro. These findings highlight HINT2 as a key cardioprotective factor that mitigates DIC by restoring the NAD + /NADH ratio, lysosomal function, and autophagy. Therapeutic strategies enhancing HINT2 expression or supplementing NMN may reduce cardiac damage and heart failure caused by DOX.
Exosomes: a double‐edged sword in cancer immunotherapy
Authors: Jiayi Chen, Siyuan Hu, Jiayi Liu, Hao Jiang, Simiao Wang, Zhaogang Yang
Journal: MedComm (2025)

Abstract Over the past few decades, immunotherapy has emerged as a powerful strategy to overcome the limitations of conventional cancer treatments. The use of extracellular vesicles, particularly exosomes, which carry cargoes capable of modulating the immune response, has been extensively explored as a potential therapeutic approach in cancer immunotherapy. Exosomes can deliver their cargo to target cells, thereby influencing their phenotype and immunomodulatory functions. They exhibit either immunosuppressive or immune‐activating characteristics, depending on their internal contents. These exosomes originate from diverse cell sources, and their internal contents can vary, suggesting that there may be a delicate balance between immune suppression and stimulation when utilizing them for immunotherapy. Therefore, a thorough understanding of the molecular mechanisms underlying the role of exosomes in cancer progression is essential. This review focuses on the molecular mechanisms driving exosome function and their impact on the tumor microenvironment (TME), highlighting the intricate balance between immune suppression and activation that must be navigated in exosome‐based therapies. Additionally, it underscores the challenges and ongoing efforts to optimize exosome‐based immunotherapies, thereby making a significant contribution to the advancement of cancer immunotherapy research.
Low versus high peripheral oxygen saturation directed oxygen therapy in critically ill patients: a multicenter randomized controlled trial
Authors: Xiaobo Yang, Xuehui Gao, Xiang Zheng, Xu Zhao, Yanli Liu, Lu Zhang, Junli Sun, Peng Wang, Zhengqin Xu, Ronghua Hu, Hongbin Li, Hong Qi, Yin Yuan, Wei Chen, Jie Liu, Guangqing Huang, Li Yu, Fengsheng Cao, Keke Xin, Min Yu, Xiaoyun Liu, Li Zhang, Siyuan Chang, Xiaojing Zou, Hong Liu, Zhaohui Fu, Huaqing Shu, Yuan Yu, Jiqian Xu, Shiying Yuan, You Shang
Journal: MedComm (2025)

Abstract Whether low peripheral oxygen saturation (SpO 2 ) directed oxygen therapy is associated with lower mortality in critically ill patients needs further exploration. Adult critically ill patients from 11 intensive care units in China were screened. Participants were randomly assigned to the low SpO 2 (90%–95%) group or the high SpO 2 (≥96%) ‐group. The primary outcome was 28‐day all‐cause mortality. The secondary outcomes were hours free from ventilators and from renal replacement therapy (RRT) within 14 days. Note that 857 patients in the low SpO 2 group and 849 in the high SpO 2 group were included. In the low SpO 2 group versus the high SpO 2 group, the time‐weighted average of the fraction of inspired oxygen (FiO 2 ) was significantly lower (33.5 ± 9.7% vs. 39.6 ± 9.3%, p &lt; 0.001), and so was the time‐weighted average of SpO 2 (95.9 ± 1.8% vs. 98.0 ± 1.9%, p &lt; 0.001). Within 28 days after randomization, 172 (20.1%) in the low SpO 2 group and 193 (22.7%) in the high SpO 2 group died ( p = 0.180). Ventilator‐free time and RRT‐free time were not significantly different within 14 days. In critically ill patients, low SpO 2 directed oxygen therapy did not decrease 28‐day mortality, 14‐day ventilator‐free time, or 14‐day RRT‐free time.
Controlled release of MIF siRNA and GDNF protein from a photocurable scaffold efficiently repairs spinal cord injury
Authors: Yan Gao, Kaiyu Wang, Yi Wu, Shan Wu, Pingchuan Ma, Jin Zhang, Jingmei Li, Guobo Shen, Ke Men
Journal: MedComm (2025)

Abstract Compared with traditional treatment strategies, siRNA‐based gene therapy combines with protein therapy to offer a new strategy for spinal cord injury (SCI). The siRNA and protein therapy are limited by the large and deep lesion site and local co‐delivery vectors. However, the photocurable scaffold has the properties of injectable, flexible, and biodegradable, which provide a potential formulation for siRNA and protein combined therapy. Here, a photocurable lipid nanoparticle gel (PLNG) scaffold is designed for efficiently sustained and controlled release of the macrophage migration‐inhibitory factor (MIF) targeted siRNA and co‐delivery of GDNF protein for SCI. The GDNF is chemically modified in the scaffold and the prepared GDNF‐PLNG/siRNA scaffold is injectable with easily photocured. This formulation can inhibit inflammation by promoting macrophage M2 polarization and effectively promote primary neuron axon growth. After locally administered with GDNF‐PLNG/siMIF scaffold to SCI mice, the scaffold promoted neuron regeneration by upregulation of neuron cytokine production and inhibited inflammation through the downregulation immune pathway. With the interaction mechanism of GDNF and MIF siRNA, GDNF‐PLNG/siMIF scaffold increases the collagen and integrin expression to promote spinal cord repairing and significantly improve motor function, so that scaffold is a potential candidate gene formulation applied to clinical SCI treatment.
The Marchantia polymorpha pangenome reveals ancient mechanisms of plant adaptation to the environment
Authors: Chloé Beaulieu, Cyril Libourel, Duchesse Lacourt Mbadinga Zamar, Karima El Mahboubi, David J. Hoey, George R. L. Greiff, Jean Keller, Camille Girou, Helene San Clemente, Issa Diop, Emilie Amblard, Baptiste Castel, Anthony Théron, Stéphane Cauet, Nathalie Rodde, Sabine Zachgo, Wiebke Halpape, Anja Meierhenrich, Bianca Laker, Andrea Bräutigam, David J. Hoey, Edwige Moyroud, Alan Wanke, Alessandra Bonfanti, Stefano Gatti, Alexander Summers, Elisabeth Burmeister, Kathy Grube, Andreea Alexa, Nataliia Kuksa, Lauren Gardiner, Martin Balcerowicz, Jemma Salmon, Bryony Yates, Lucie Riglet, Elena Salvi, Peter Szovenyi, Shifeng Cheng, Yasuhiro Tanizawa, Simon Aziz, James H. Leebens-Mack, Jeremy Schmutz, Jenell Webber, Jane Grimwood, Christophe Jacquet, Christophe Dunand, Jessica M. Nelson, Fabrice Roux, Hervé Philippe, Sebastian Schornack, Maxime Bonhomme, Pierre-Marc Delaux
Journal: Nature Genetics (2025)
Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time
Authors: Megha Sehgal, Daniel Almeida Filho, George Kastellakis, Sungsoo Kim, Jinsu Lee, Yang Shen, Shan Huang, Ayal Lavi, Giselle Fernandes, Irene Davila Mejia, Sunaina Soans Martin, Asli Pekcan, Melody Shana Wu, Won Do Heo, Panayiota Poirazi, Joshua T. Trachtenberg, Alcino J. Silva
Journal: Nature Neuroscience (2025)
Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke
Authors: Louis-Philippe Bernier, Jasmin K. Hefendehl, R. Wilder Scott, Lin Wei Tung, Coral-Ann Lewis, Hesham Soliman, Stefan Simm, Lasse Dissing-Olesen, Jan Hofmann, David Guo, Murphy DeMeglio, Fabio M. Rossi, T. Michael Underhill, Brian A. MacVicar
Journal: Nature Neuroscience (2025)
Functional analysis of cancer-associated germline risk variants
Authors: Laura N. Kellman, Poornima H. Neela, Suhas Srinivasan, Zurab Siprashvili, Ronald L. Shanderson, Audrey W. Hong, Deepti Rao, Douglas F. Porter, David L. Reynolds, Robin M. Meyers, Margaret G. Guo, Xue Yang, Yang Zhao, Glenn G. Wozniak, Laura K. H. Donohue, Rajani Shenoy, Lisa A. Ko, Duy T. Nguyen, Smarajit Mondal, Omar S. Garcia, Lara E. Elcavage, Ibtihal Elfaki, Nathan S. Abell, Shiying Tao, Christopher M. Lopez, Stephen B. Montgomery, Paul A. Khavari
Journal: Nature Genetics (2025)
Multiomic single-cell profiling identifies critical regulators of postnatal brain
Authors: Tereza Clarence, Jaroslav Bendl, Xuan Cao, Xinyi Wang, Shiwei Zheng, Gabriel E Hoffman, Alexey Kozlenkov, Aram Hong, Marina Iskhakova, Manoj K Jaiswal, Sarah Murphy, Alexander Yu, Vahram Haroutunian, Stella Dracheva, Schahram Akbarian, John F Fullard, Guo-Cheng Yuan, Donghoon Lee, Panos Roussos
Journal: Nature Genetics (2025)
β-Hydroxybutyrate Facilitates Postinfarction Cardiac Repair via Targeting PHD2
Authors: Cheng Wang, Wenjing Xu, Shushu Jiang, Yichen Wu, Jiangchen Shu, Xinyuan Gao, Kai Huang
Journal: Circulation Research (2025)

BACKGROUND: Acute myocardial infarction (MI) remains one of the major causes of death worldwide, and innovative treatment strategies for MI represent a major challenge in cardiovascular medicine. Caloric restriction (CR) is the most potent nonpharmacological intervention known to prevent age-related disorders and extend lifespan. CR reduces glycolysis and elevates ketone body metabolism. However, whether and how CR or ketone body prevents the progression of MI remains poorly defined. METHODS: Mice treated with CR and β-hydroxybutyrate (β-OHB) underwent MI induced by ligation of the left anterior descending coronary artery. Cardiac function was assessed by echocardiographic measurements. Histological analysis, fluorescence-activated cell sorting, and immunofluorescence were used to assess myocardial neovascularization and macrophage filtration. The interaction and modification of β-OHB on PHD2 were analyzed by molecular docking, cellular thermal shift assay, liquid chromatography with tandem mass spectrometry, and coimmunoprecipitation. Macrophage-specific PHD2 K239R and K385R knock-in mice were used to determine the functional significance of β-OHB/PHD2 axis in vivo. RESULTS: Twelve weeks of CR markedly rescued postinfarction cardiac function by enhancing neovascularization. CR significantly increased circulating and cardiac ketone bodies, including β-OHB and acetoacetate. We identified β-OHB but not acetoacetate selectively targeted macrophages to stimulate VEGF (vascular endothelial growth factor) production in the peri-infarct area to promote neovascularization and cardiac repair. Mechanistically, β-OHB binds to and induces lysine β-hydroxybutyrylation of PHD2 at lysines 239 and 385, thus blocking its function in the hydroxylation of HIF-1α (hypoxia-inducible factor 1α) and resulting in enhanced HIF1α-dependent VEGF transcription and secretion. More importantly, specific PHD2 lys239 and lys385 mutations in macrophages abolished the preventive effects of exogenous β-OHB on MI in mice. CONCLUSIONS: These data reveal a novel regulation of lysine β-hydroxybutyrylation on PHD2 and demonstrate a promising and therapeutic role for β-OHB/PHD2 in effectively accelerating neovascularization and preserving heart function after cardiac ischemia.
Authors’ reply to Zhou et al.
Authors: Martina Uzzo, Helmut Schumacher, Juergen Steffgen, Simone Deutschel, David Jayne, Ingeborg Bajema
Journal: Arthritis & Rheumatology (2025)

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