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Property–structure reconfigurable nanoparticles (NPs) provide additional flexibility for effectively and flexibly manipulating light at the nanoscale. This has facilitated the development of various multifunctional and high-performance nanophotonic devices. Resonant NPs based on dielectric active materials, especially phase change materials, are particularly promising for achieving reconfigurability. However, the on-demand control of the properties, especially the morphology, in individual dielectric resonant NP remains a significant challenge. In this study, we present an all-optical approach for one-step fabrication of Ge2Sb2Te5(GST) hemispherical NPs, integrated active reversible phase-state switching, and morphology reshaping. Reversible optical switching is demonstrated, attributed to reversible phase-state changes, along with unidirectional modifications to their scattering intensity resulting from morphology reshaping. This novel technology allows the precise adjustment of each structural pixel without affecting the overall functionality of the switchable nanophotonic device. It is highly suitable for applications in single-pixel-addressable active optical devices, structural color displays, and information storage, among others.

Tandem mass spectrometry (MS/MS) is widely employed for the analysis of complex proteomic samples. While protein sequence database searching and spectral library searching are both well-established peptide identification methods, each has shortcomings. Protein sequence databases lack fragment peak intensity information, which can result in poor discrimination between correct and incorrect spectrum assignments. Spectral libraries usually contain fewer peptides than protein sequence databases, which limits the number of peptides that can be identified. Notably, few post-translationally modified peptides are represented in spectral libraries. This is because few search engines can both identify a broad spectrum of PTMs and create corresponding spectral libraries. Also, programs that generate spectral libraries using deep learning approaches are not yet able to accurately predict spectra for the vast majority of PTMs. Here, we address these limitations through use of a hybrid search strategy that combines protein sequence database and spectral library searches to improve identification success rates and sensitivity. This software uses Global PTM Discovery (G-PTM-D) to produce spectral libraries for a wide variety of different PTMs. These features, along with a new spectrum annotation and visualization tool, have been integrated into the freely available and open-source search engine MetaMorpheus.

IMPORTANCE: High-intensity statin use after myocardial infarction (MI) varies by patient characteristics, but little is known about differences in use by hospital or region. OBJECTIVE: To explore the relative strength of associations of region and hospital and patient characteristics with high-intensity statin use after MI. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis used Medicare administrative claims and enrollment data to evaluate fee-for-service Medicare beneficiaries 66 years or older who were hospitalized for MI from January 1, 2011, through June 30, 2015, with a statin prescription claim within 30 days of discharge. Data were analyzed from January 4, 2017, through May 12, 2019. EXPOSURES: Beneficiary characteristics were abstracted from Medicare data. Hospital characteristics were obtained from the 2014 American Hospital Association Survey and Hospital Compare quality metrics. Nine regions were defined according to the US Census. MAIN OUTCOMES AND MEASURES: Intensity of the first statin claim after discharge characterized as high (atorvastatin calcium, 40-80 mg, or rosuvastatin calcium, 20-40 mg/d) vs low to moderate (all other statin types and doses). Trends in high-intensity statins were examined from 2011 through 2015. Associations of region and beneficiary and hospital characteristics with high-intensity statin use from January 1, 2014, to June 15, 2015, were examined using Poisson distribution mixed models. RESULTS: Among the 139 643 fee-for-service beneficiaries included (69 968 men [50.1%] and 69 675 women [49.9%]; mean [SD] age, 76.7 [7.5] years), high-intensity statin use overall increased from 23.4% in 2011 to 55.6% in 2015, but treatment gaps persisted across regions. In models considering region and beneficiary and hospital characteristics, region was the strongest correlate of high-intensity statin use, with 66% higher use in New England than in the West South Central region (risk ratio [RR], 1.66; 95% CI, 1.47-1.87). Hospital size of at least 500 beds (RR, 1.15; 95% CI, 1.07-1.23), medical school affiliation (RR, 1.11; 95% CI, 1.05-1.17), male sex (RR, 1.10; 95% CI, 1.07-1.13), and patient receipt of a stent (RR, 1.35; 95% CI, 1.31-1.39) were associated with greater high-intensity statin use. For-profit hospital ownership, patient age older than 75 years, prior coronary disease, and other comorbidities were associated with lower use. CONCLUSIONS AND RELEVANCE: This study’s findings suggest that geographic region is the strongest correlate of high-intensity statin use after MI, leading to large treatment disparities.

The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown. Here we reveal that the E3 ubiquitin ligase Speckle-type BTB–POZ protein (SPOP) restrains the inflammatory activation of HSCs. In the absence of Spop, systemic inflammation proceeded in an unresolved manner, and the sustained response in the HSCs resulted in a lethal phenotype reminiscent of hyper-inflammatory syndrome or sepsis. Our proteomic studies decipher that SPOP restricted inflammation by ubiquitinating the innate signal transducer myeloid differentiation primary response protein 88 (MYD88). These findings unearth an HSC-intrinsic post-translational mechanism that is essential for reestablishing homeostasis after emergency hematopoiesis. Aifantis and colleagues identify the E3 ubiquitin ligase SPOP as a negative regulator of ‘emergency hematopoiesis’ in bone marrow hematopoietic stem progenitor cells.

ABSTRACTUreaplasmaspecies commonly colonize the adult urogenital tract and are implicated in invasive diseases of adults and neonates. Factors that permit the organisms to cause chronic colonization or infection are poorly understood. We sought to investigate whether host innate immune responses, specifically, antimicrobial peptides (AMPs), are involved in determining the outcome of Ureaplasmainfections. THP-1 cells, a human monocytoid tumor line, were cocultured with Ureaplasma parvumand U. urealyticum. Gene expression levels of a variety of host defense genes were quantified by real-time PCR. In vitroantimicrobial activities of synthetic AMPs against Ureaplasmaspp. were determined using a flow cytometry-based assay. Chromosomal histone modifications in host defense gene promoters were tested by chromatin immunoprecipitation (ChIP). DNA methylation status in the AMP promoter regions was also investigated. After stimulation with U. parvumand U. urealyticum, the expression of cell defense genes, including the AMP genes (DEFB1, DEFA5, DEFA6, and CAMP), was significantly downregulated compared to that of TNFAand IL-8, which were upregulated. In vitroflow cytometry-based antimicrobial assay revealed that synthetic peptides LL-37, hBD-3, and hBD-1 had activity against Ureaplasmaspp. Downregulation of the AMP genes was associated with chromatin modification alterations, including the significantly decreased histone H3K9 acetylation with U. parvuminfection. No DNA methylation status changes were detected upon Ureaplasmainfection. In conclusion, AMPs have in vitroactivity against Ureaplasmaspp., and suppression of AMP expression might be important for the organisms to avoid this aspect of the host innate immune response and to establish chronic infection and colonization.