As emerging alternatives of legacy perfluoroalkyl substances, perfluorophosphinates (PFPiAs) and perfluorophosphonates (PFPAs) are widely applied in industrial and agricultural fields and are supposed to be large partitioned to soil and highly persistent. It is of particular interest to understand their transfer from roots to shoots and transformation in plants, such as wheat. The results of hydroponic experiments indicated that C6/C6 PFPiA, C8/C8 PFPiA, perfluorooctanophosphonic acid (PFOPA), and perfluorohexaphosphonic acid (PFHxPA) were quickly adsorbed on the epidermis of wheat root (Triticum aestivum L.), which was driven by their hydrophobicity. A small fraction of the accumulated PFPiAs and PFPAs in the wheat root was subjected to absorption via an active process dependent on H+-ATPase. PFHxPA, which has the smallest molecular weight and medium hydrophilicity (log K ow < 4), displayed the strongest absorption efficiency via the water and anion channels and had the highest translocation potential from roots to shoots in wheat. C6/C6 and C8/C8 PFPiAs experienced phase I metabolism in wheat, although at a low rate, to form more persistent PFHxPA and PFOPA, respectively, as well as 1H-perfluorohexane (1H-PFHx) and 1H-perfluorooctane (1H-PFO), which were regulated by cytochrome P450 in wheat root. As a result, exposure to PFPiAs in roots ultimately caused the accumulation of more persistent PFPAs in the above-ground parts of plants, raising concerns on their potential risks on human health.
The creation of micromotors that can convert stored energy to autonomous movement would be of great value in various applications, ranging from chemical sensing to precision water-quality screening and from cleaning clogged arteries to repairing microscopic cracks. Many of micromotors, based on different propulsion mechanisms (e.g., magnetic fields, ultrasound filed, chemical fuels, light, and bubble propulsion), [1][2][3][4][5][6][7][8][9] have been designed and fabricated over the past decade. Generally, they are built of rigid materials [10] to maintain a good maneuverability, but often with limited body compliance and adaptability in confined spaces. [11][12][13] In contrast to the hard Shape-transformable liquid metal (LM) micromachines have attracted the attention of the scientific community over the past 5 years, but the inconvenience of transfer routes and the use of corrosive fuels have limited their potential applications. In this work, a shape-transformable LM micromotor that is fabricated by a simple, versatile ice-assisted transfer printing method is demonstrated, in which an ice layer is employed as a "sacrificial" substrate that can enable the direct transfer of LM micromotors to arbitrary target substrates conveniently. The resulting LM microswimmers display efficient propulsion of over 60 µm s −1 (≈3 bodylength s −1 ) under elliptically polarized magnetic fields, comparable to that of the common magnetic micro/ nanomotors with rigid bodies. Moreover, these LM micromotors can undergo dramatic morphological transformation in an aqueous environment under the irradiation of an alternating magnetic field. The ability to transform the shape and efficiently propel LM microswimmers holds great promise for chemical sensing, controlled cargo transport, materials science, and even artificial intelligence in ways that are not possible with rigid-bodies microrobots.bodied, nature has created a wide range of biological motors with deformable bodies at small scales. They often have strong ability to actively adapt to their environment, thus can perform various demanding tasks in complex environments. Inspired by nature, researchers have begun to explore the design and control shape-transformable micromotors composed of compliant materials [14,15] (e.g., hydrogels, [16] granular media, [17] lowmelting point alloys, [18,19] and electroactive polymers [14] ) to ensure maneuverability, adaptability and agility in practical applications. Liquid metals (LMs) are typical examples of highly extensible and adaptable compliant materials, [20,21] such as Gallium and gallium-containing alloys (e.g., eutectic gallium-indium (EGaIn): 75% gallium and 25% indium; Galinstan: 68.5% gallium, 21.5% indium, and 10% tin). One of the most striking features of these gallium-based liquid metals is the nearly instant formation of a passivating oxide layer on their surface in the present of oxygen. This oxide layer (mainly composed of Ga 2 O 3 ) mechanically stabilizes the liquid metals into nonequilibrium shapes [22] and can be removed ...
MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2.
Magnetically actuated nanomotor, which swims under externally applied magnetic fields, shows great promise for controlled cargo delivery and release in biological fluids. Here, we report an on-demand release of 6-carboxyfluoresceins (FAM), a green fluorescein, from G-quadruplex DNA functionalized magnetically actuated wormlike nanomotors by applying an alternating magnetic field. This field-triggered FAM releasing process can be easily controlled by multiple parameters such as magnetic field, frequency, and exposure time. In addition, the experimental results and the theoretical simulation demonstrate that both a thermal and a nonthermal mechanism are involved in the cargo releasing process.
Nucleophosmin (NPM1) is a ubiquitously expressed nucleolar protein with a wide range of biological functions. In 30% of acute myeloid leukemia (AML), the terminal exon of NPM1 is often found mutated, resulting in the addition of a nuclear export signal and a shift of the protein to the cytoplasm (NPM1c). AMLs carrying this mutation have aberrant expression of the HOXA/B genes, whose overexpression lead to leukemogenic transformation. Here, for the first time, we comprehensively prove NPM1c binds to a subset of active gene promoters in NPM1c AMLs, including well-known leukemia-driving genes – HOXA/B cluster genes and MEIS1. NPM1c sustains the active transcription of key target genes by orchestrating a transcription hub and maintains the active chromatin landscape by inhibiting the activity of histone deacetylases (HDACs). Together, these findings reveal the neomorphic function of NPM1c as a transcriptional amplifier for leukemic gene expression and open up new paradigms for therapeutic intervention.
Epigenetic programs are dysregulated in acute myeloid leukemia (AML) and help enforce an oncogenic state of differentiation arrest. To identify key epigenetic regulators of AML cell fate, we performed a differentiation-focused CRISPR screen in AML cells. This screen identified the histone acetyltransferase KAT6A as a novel regulator of myeloid differentiation that drives critical leukemogenic gene-expression programs. We show that KAT6A is the initiator of a newly described transcriptional control module in which KAT6A-catalyzed promoter H3K9ac is bound by the acetyl-lysine reader ENL, which in turn cooperates with a network of chromatin factors to induce transcriptional elongation. Inhibition of KAT6A has strong anti-AML phenotypes in vitro and in vivo, suggesting that KAT6A small-molecule inhibitors could be of high therapeutic interest for mono-therapy or combinatorial differentiation-based treatment of AML. Significance: AML is a poor-prognosis disease characterized by differentiation blockade. Through a cell-fate CRISPR screen, we identified KAT6A as a novel regulator of AML cell differentiation. Mechanistically, KAT6A cooperates with ENL in a “writer–reader” epigenetic transcriptional control module. These results uncover a new epigenetic dependency and therapeutic opportunity in AML. This article is highlighted in the In This Issue feature, p. 587
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