Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt.

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.

The multiple arrays of a PD1-derived peptide on chromatin specifically bind to PD-L1 and induce doxorubicin resistance in cancer cell lines.

Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) have been extensively studied to block the activation of the PD-1 axis immune checkpoint pathway on T cells. However, recent evidence suggests that PD-1-independent PD-L1 pathways in cancer cells and macrophages are important in cellular proliferation and survival of those cell types but the underlying mechanism is little understood. To recapitulate the binding of multiple PD-1 to the high levels of PD-L1 expression on cancer cell membranes, recombinant histones carrying a PD-1 receptor-derived peptide (PDR) were prepared and used to assemble a PDR-displayed nucleosome array. PDR-displayed chromatin showed physiologically spaced nucleosomes, unaffected by N-terminal histone tails and biotinylated DNA modifications. PDR-displayed chromatin exhibited selective binding to the breast cancer cell line with high PD-L1 expression, MDA-MB-231, where saturated binding occurred within 3 h, comparable to well-known antigen-antibody reactions. Notably, PDR-displayed chromatin enhanced resistance to doxorubicin in PD-L1-overexpressed cancer cells, revealing a PD-L1 level-dependent effect on cell survival upon chemotherapy. Our study sheds light on the potential of PDR-displayed chromatin as a tool to induce chemoresistance in cancer cells without employing anti-PD-L1 antibodies or soluble PD-1 receptors. Further investigation into the underlying signaling pathways and therapeutic applications is warranted, positioning PDR-displayed chromatin as a valuable tool for understanding PD-L1-mediated intracellular signaling pathways in cancer cells with high PD-L1 expression.

Complete Genome Sequence of Stenotrophomonas maltophilia Siphophage Summit.

Stenotrophomonas maltophilia is an opportunistic pathogen exhibiting resistance to multiple antimicrobials. This study reports the complete genome of an S. maltophilia siphophage, Summit. Its genome of 95,728 bp has 148 protein-coding genes and 5 tRNAs, including 1 predicted suppressor tRNA. Possible target genes for the suppressor tRNA are not identified.

Biomechanical Energy Harvesters Based on Ionic Conductive Organohydrogels via the Hofmeister Effect and Electrostatic Interaction.

The recent use of cryoprotectant replacement method for solving the easy drying problem of hydrogels has attracted increasing research interest. However, the conductivity decrease of organohydrogels due to the induced insulating solvent limited their electronic applications. Herein, we introduce the Hofmeister effect and electrostatic interaction to generate hydrogen and sodium bonds in the hydrogel. Combined with its double network, an effective charge channel that will not be affected by the solvent replacement, is therefore built. The developed organohydrogel-based single-electrode triboelectric nanogenerator (OHS-TENG) shows low conductivity decrease (one order) and high output (1.02-1.81 W/m2), which is much better than reported OHS-TENGs (2-3 orders, 41.2-710 mW/m2). Moreover, replacing water with glycerol in the hydrogel enables the device to exhibit excellent long-term stability (four months) and temperature tolerance (-50-100 °C). The presented strategy and mechanism can be extended to common organohydrogel systems aiming at high performance in electronic applications.

Complete Genome Sequence of Streptomyces Siphophage Sycamore.

Streptomyces sp. strain Mg1 is a competitive soil-dwelling bacterium that secretes antibiotics that inhibit growth of Bacillus subtilis Here, we present the genome sequence of Sycamore, a 44,694-bp Streptomyces sp. Mg1 siphophage with 66 predicted protein-coding genes, that is similar to phage genome sequences in the Lomovskayavirus genus.

A Bis-Indole-Derived NR4A1 Antagonist Induces PD-L1 Degradation and Enhances Antitumor Immunity.

PD-L1 is expressed in tumor cells and its interaction with PD-1 plays an important role in evading immune surveillance; this can be overcome using PD-L1 or PD-1 immunotherapy antibodies. This study reports a novel approach for targeting PD-L1. In human breast cancer cell lines and 4T1 mouse mammary tumor cells, PD-L1 expression was regulated by the nuclear receptor NR4A1/Sp1 complex bound to the proximal germinal center (GC)-rich region of the PD-L1 gene promoter. Treatment of breast cancer cells with bis-indole-derived NR4A1 antagonists including 1,1-bis(3'-indolyl)-1-(3-chloro-4-hydroxy-5-methoxyphenyl)methane (Cl-OCH3) decreased expression of PD-L1 mRNA, promoter-dependent luciferase activity, and protein. In in vivo studies using a syngeneic mouse model bearing orthotopically injected 4T1 cells, Cl-OCH3 decreased tumor growth and weight and inhibited lung metastasis. Cl-OCH3 also decreased expression of CD3+/CD4+/CD25+/FoxP3+ regulatory T cells and increased the Teff/Treg ratio. Therefore, the potent anticancer activities of NR4A1 antagonists are also accompanied by enhanced antitumor immunity in PD-L1-expressing triple-negative breast cancer and thus represent a novel class of drugs that mimic immunotherapy. SIGNIFICANCE: These findings show that the orphan nuclear receptor NR4A1 controls PD-L1 expression and identify a chemical probe capable of disrupting this regulatory axis.