SUMMARYIron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy.

Two-dimensional (2D) membranes exhibit exceptional properties in molecular separation and transport, which reveals their potential use in various applications. However, ion sieving with 2D membranes is severely restrained due to intercalation-induced swelling.Here, we describe how to efficiently stabilize the lamellar architecture using Keggin Al 13 polycations as pillars in a Ti 3 C 2 T x membrane. More importantly, interlayer spacing can be easily adjusted with angstrom precision over a wide range (2.7−11.2 Å) to achieve selective and tunable ion sieving. A membrane with narrow d-spacing demonstrated enhanced selectivity for monovalent ions. When applied in a forward osmosis desalination process, this membrane exhibited high NaCl exclusion (99%) with a fast water flux (0.30 L m −2 h −1 bar −1 ). A membrane with wide d-spacing showed notable selectivity, which was dependent on the cation valence. When it was applied to acid recovery from iron-based industrial wastewater, the membrane showed good H + /Fe 2+ selectivity, which makes it a promising substitute for traditional polymeric membranes. Thus, we introduce a possible route to construct 2D membranes with appropriate structures to satisfy different ion-sieving requirements in diverse environment-, resource-, and energy-related applications. KEYWORDS: Ti 3 C 2 T x membrane, interlayer spacing, Al 13 Keggin ions, tunable ion sieving, desalination

The intestinal invasion of pathogenic microorganisms can have serious health consequences. Recent evidence has shown that the N6-methyladenosine (m6A) mRNA modification is closely associated with innate immunity; however, the underlying mechanism is poorly understood. Here, we examined the function and mechanism of m6A mRNA modification and the YTH domain-containing protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) in the innate immune response against bacterial pathogens in the intestine. Ribo-seq and m6A-seq analyses revealed that YTHDF1 directs the translation of Traf6 mRNA, which encodes tumor necrosis factor receptor-associated factor 6, thereby regulating the immune response via the m6A modification near the transcript's stop codon. Furthermore, we identified a unique mechanism by which the P/Q/N-rich domain in YTHDF1 interacts with the DEAD domain in the host factor DDX60, thereby regulating the intestinal immune response to bacterial infection by recognizing the target Traf6 transcript. These results provide novel insights into the mechanism by which YTHDF1 recognizes its target and reveal YTHDF1 as an important driver of the intestinal immune response, opening new avenues for developing therapeutic strategies designed to modulate the intestinal immune response to bacterial infection.

A high-resolution imaging x-ray crystal spectrometer is described for implementation on the EAST tokamak to provide spatially and temporally resolved data on the ion temperature, electron temperature and poloidal plasma rotation. These data are derived from observations of the satellite spectra of helium-like argon, Ar XVII, which is the dominant charge state for electron temperatures in the range from 0.4 to 3.0 keV and which is accessible to EAST. Employing a novel design, which is based on the imaging properties of spherically bent crystals, the spectrometers will provide spectrally and spatially resolved images of the plasma for all experimental conditions, which include ohmically heated discharges as well as plasmas with rf and neutral-beam heating. The experimental setup and initial experimental results are presented.