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| Open AccessHomodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation
CCAAT/enhancer binding protein α (C/EBPα) regulates myeloid differentiation, and its dysregulation contributes to acute myeloid leukaemia progress. Here the authors show that homodimer-mediated phosphorylation of C/EBPα-p42 modulates acute myeloid leukaemia cell differentiation by liquid-liquid phase separation.
- Dongmei Wang
- , Tao Sun
- & Chunyan Ji
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Article
| Open AccessPregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions
The increase in detoxification gene expression is a common transcriptome marker for longevity interventions. Here, the authors show that nomilin extends lifespan and healthspan in animals through activation of PXR regulated detoxification functions.
- Shengjie Fan
- , Yingxuan Yan
- & Cheng Huang
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Article
| Open AccessTranslational reprogramming as a driver of antimony-drug resistance in Leishmania
Leishmania is a unicellular protozoan that has limited transcriptional control. Here, the authors show that translational control is a major mechanism of antimony drug resistance in Leishmania. They observe a dramatic translatome reprogramming during development of resistance to the drug and report translational control as a major driver of antimony-resistant phenotypes.
- Sneider Alexander Gutierrez Guarnizo
- , Elena B. Tikhonova
- & Zemfira N. Karamysheva
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Article
| Open AccessRNAi-mediated rheostat for dynamic control of AAV-delivered transgenes
Here the authors propose an RNA interference-based switch for dynamic control of AAV transgene expression. In this approach, transgene expression may be silenced by RNAi and subsequently recovered using REVERSIR oligonucleotides.
- Megha Subramanian
- , James McIninch
- & Vasant Jadhav
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Article
| Open AccessGraphdiyne oxide nanosheets display selective anti-leukemia efficacy against DNMT3A-mutant AML cells
DNA methyltransferase 3A, a mutated gene associated with hematologic malignancies in age-related clonal haematopoiesis lacks targeted therapies. Here, the authors screen carbon nanomaterials and find graphdiyne oxide binds to mutant cells and disrupts cellular processes with a therapeutic effect in vitro and in vivo.
- Qiwei Wang
- , Ying Liu
- & Pengxu Qian
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Article
| Open AccessDesign of a two-dimensional interplanar heterojunction for catalytic cancer therapy
Chemodynamic therapy relies on Fenton or Fenton-like reactions to produce hydroxyl radical in the tumor region. Here the authors design a two-dimensional interplanar heterojunction with in situ hydroxyl radical generation under ultrasound irradiation, showing anti-cancer activity in preclinical models.
- Yong Kang
- , Zhuo Mao
- & Xiaoyuan Ji
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Article
| Open AccessGut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort
Here, the authors present results of the Estonian Microbiome Project, which combines metagenomics and electronic health data from 2500 individuals, expanding microbiome-host interactions in particular with regards to effects of long-term antibiotic usage on the microbiome across diseases.
- Oliver Aasmets
- , Kertu Liis Krigul
- & Elin Org
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| Open AccessReversible modulation of circadian time with chronophotopharmacology
The circadian clock is an internal mechanism that controls various physiological processes, such as the sleep-wake cycle, but its precise regulation is challenging. Here, the authors develop a visible light-responsive inhibitor of casein kinase I which controls the period and phase of cellular and tissue circadian rhythms in a reversible manner.
- Dušan Kolarski
- , Carla Miró-Vinyals
- & Ben L. Feringa
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Article
| Open AccessThe effect of generic market entry on antibiotic prescriptions in the United States
Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.
- Cecilia Kållberg
- , Jemma Hudson
- & Ramanan Laxminarayan
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Article
| Open AccessGLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer
Triple negative breast cancer is a deadly form of breast cancer with limited therapeutic options. Here the authors show the efficacy of GLUT1 pharmacological inhibition against a subset of tumors expressing RB1, thereby identifying RB1 protein level as a biomarker of sensitivity to anti-GLUT1 therapy.
- Qin Wu
- , Wail ba-alawi
- & Cheryl H. Arrowsmith
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Article
| Open AccessBiomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors
Hypoxic tumors are resistant to dynamic therapy, limiting potential treatment options. Here, the authors describe a nanoflower where oxidase mimicking PtCo nanoparticles are decorated with catalase mimicking MnO2 to reverse tumor hypoxia and generate reactive oxygen species for dynamic therapy.
- Zhenzhen Wang
- , Yan Zhang
- & Xiaogang Qu