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The structural determination of natural products (NPs) can be arduous because of sample heterogeneity. This often demands iterative purification processes and characterization of complex molecules that may be available only in miniscule quantities. Microcrystal electron diffraction (microED) has recently shown promise as a method to solve crystal structures of NPs from nanogram quantities of analyte. However, its implementation in NP discovery remains hampered by sample throughput and purity requirements, akin to traditional NP-discovery workflows. In the methods described herein, we leverage the resolving power of transmission electron microscopy (TEM) and the miniaturization capabilities of deoxyribonucleic acid (DNA) microarray technology to address these challenges through the establishment of an NP screening platform, array electron diffraction (ArrayED). In this workflow, an array of high-performance liquid chromatography (HPLC) fractions taken from crude extracts was deposited onto TEM grids in picoliter-sized droplets. This multiplexing of analytes on TEM grids enables 1200 or more unique samples to be simultaneously inserted into a TEM instrument equipped with an autoloader. Selected area electron diffraction analysis of these microarrayed grids allows for the rapid identification of crystalline metabolites. In this study, ArrayED enabled structural characterization of 14 natural products, including four novel crystal structures and two novel polymorphs, from 20 crude extracts. Moreover, we identify several chemical species that would not be detected by standard mass spectrometry (MS) or ultraviolet-visible (UV/vis) spectroscopy and crystal forms that would not be characterized using traditional methods.

Comparison of biosynthetic gene clusters (BGCs) found in devastating plant pathogens and biocontrol fungi revealed an uncharacterized and conserved polyketide BGC. Genome mining identified the associated metabolite to be treconorin, which has a terpene-like, trans-fused 5,7-bicyclic core that is proposed to derive from a (4 + 3) cycloaddition. The core is esterified with d-glucose, which derives from the glycosidic cleavage of a trehalose ester precursor. This glycomodification strategy is different from the commonly observed glycosylation of natural products.

Although increasing attention has been paid to the importance of different forms of capital in graduate employability, few studies have investigated the contribution of capital to the employability of international graduates in the host labor market. This study aimed to explore how six forms of capital (human, social, cultural, psychological, identity, and agentic) contribute to the employability of Chinese international graduates in Australia. This study deploys Bourdieusian theories and a capitals-based approach as complementary theoretical frameworks. A mixed-methods approach was used in this study. Data were first collected via an online survey (N = 203) and then through in-depth interviews (N = 14). The quantitative results showed that cultural capital made the highest self-perceived contribution to employability, whereas social capital made the lowest contribution. The qualitative findings revealed that capital not only helped the participants obtain employment but also enhanced their wellbeing, sustainable employment, and professional growth. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the impact of demographics, including gender, race, ethnicity, and preferred language, on regional visual field (VF) loss and progression in glaucoma., Methods: Multivariable linear mixed regressions were performed to determine the impact of race, ethnicity, and preferred language on regional VF loss with adjustment for age and gender. Regional VF loss was defined by pointwise total deviation values and VF loss patterns quantified by an unsupervised machine learning method termed archetypal analysis. All cross-sectional and longitudinal analyses were performed both without and with adjustment for VF mean deviation, which represented overall VF loss severity. P values were corrected for multiple comparisons., Results: All results mentioned had corrected P values less than 0.05. Asian and Black patients showed worse pointwise VF loss than White patients with superior hemifield more affected. Patients with a preferred language other than English demonstrated worse pointwise VF loss than patients with English as their preferred language. Longitudinal analyses revealed Black patients showed worse VF loss/year compared to White patients. Patients with a preferred language other than English demonstrated worse VF loss/year compared to patients preferring English., Conclusions: Blacks and non-English speakers have more severe VF loss, with superior hemifield being more affected and faster VF worsening., Translational Relevance: This study furthered our understanding of racial, ethnic, and socioeconomic disparities in glaucoma outcomes. Understanding the VF loss burden in different racial, ethnic, and socioeconomic groups may guide more effective glaucoma screening and community outreach efforts. This research could help reduce vision loss and improve quality of life in disproportionately affected populations by guiding public health efforts to promote glaucoma awareness and access to care.

We aimed to determine whether additional molecular and microbiological evaluations of methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients newly identified as nasal carriers were useful for control strategies and whether longitudinal testing during the same or repeat hospitalization changed MRSA status. Nasal swabs from patients positive by Xpert MRSA PCR and not known to be colonized in the previous year were cultured for S. aureus. Isolates were tested for resistance to a variety of antibiotics, including high-level mupirocin resistance (HLMR) and low-level mupirocin resistance (LLMR) and the presence of genes mecA and mupA and those for Panton-Valentine leukocidin (PVL), USA300, and USA400. Repeat nasal screens during the 6-month study were tested for continued presence of MRSA. Among 130 patients, cultures revealed MRSA in 85 (65.4%), methicillin-susceptible S. aureus in 19 (14.6%), and no growth in 26 (20%). MRSA isolates were USA300 positive in 13/85 (15.3%) and LLMR in 8/85 (9.4%) patients. No isolates were HLMR or mupA positive. mecA dropout was detected in 9/130 (6.9%) patients. The rate of subsequent MRSA infections in USA300-positive versus -negative patients was not different. MRSA nasal status remained concordant in 69/70 (98.6%) patients who had follow-up testing. The findings do not support expanding MRSA surveillance to include routine detection of genes for USA300, PVL, or mupA, all of which were either of low frequency or not significantly associated with MRSA infection risk in our population of newly identified nasal carriers. Repeat nasal screening for MRSA during the same or subsequent hospitalizations over 6 months could also be deferred, reducing costs associated with screening.