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We present the optical spectroscopic evolution of SN~2023ixf seen in sub-night cadence spectra from 1.18 to 14 days after explosion. We identify high-ionization emission features, signatures of interaction with material surrounding the progenitor star, that fade over the first 7 days, with rapid evolution between spectra observed within the same night. We compare the emission lines present and their relative strength to those of other supernovae with early interaction, finding a close match to SN~2020pni and SN~2017ahn in the first spectrum and SN~2014G at later epochs. To physically interpret our observations we compare them to CMFGEN models with confined, dense circumstellar material around a red supergiant progenitor from the literature. We find that very few models reproduce the blended \\NC{} emission lines observed in the first few spectra and their rapid disappearance thereafter, making this a unique diagnostic. From the best models, we find a mass-loss rate of \\(10^{-3}-10^{-2}\\) \\mlunit{}, which far exceeds the mass-loss rate for any steady wind, especially for a red supergiant in the initial mass range of the detected progenitor. These mass-loss rates are, however, similar to rates inferred for other supernovae with early circumstellar interaction. Using the phase when the narrow emission features disappear, we calculate an outer dense radius of circumstellar material \\(R_\\mathrm{CSM, out}\\sim5\\times10^{14}~\\mathrm{cm}\\) and a mean circumstellar material density of \\(\\rho=5.6\\times10^{-14}~\\mathrm{g\\,cm^{-3}}\\). This is consistent with the lower limit on the outer radius of the circumstellar material we calculate from the peak \\Halpha{} emission flux, \\(R_\\text{CSM, out}\\gtrsim9\\times10^{13}~\\mathrm{cm}\\).

We present five far- and near-ultraviolet spectra of the Type II plateau supernova, SN 2022acko, obtained 5, 6, 7, 19, and 21 days after explosion, all observed with the Hubble Space Telescope/Space Telescope Imaging Spectrograph. The first three epochs are earlier than any Type II plateau supernova has been observed in the far-ultraviolet revealing unprecedented characteristics. These three spectra are dominated by strong lines, primarily from metals, which contrasts with the relatively featureless early optical spectra. The flux decreases over the initial time series as the ejecta cools and line-blanketing takes effect. We model this unique dataset with the non-local thermodynamic equilibrium radiation transport code CMFGEN, finding a good match to the explosion of a low mass red supergiant with energy Ekin = 6 x 10^50 erg. With these models we identify, for the first time, the ions that dominate the early UV spectra. We also present optical photometry and spectroscopy, showing that SN 2022acko has a peak absolute magnitude of V = -15.4 mag and plateau length of ~115d. The spectra closely resemble those of SN 2005cs and SN 2012A. Using the combined optical and UV spectra, we report the fraction of flux redwards of the uvw2, U, B, and V filters on days 5, 7, and 19. We also create a spectral time-series of Type II supernovae in the ultraviolet, demonstrating the rapid decline of UV flux over the first few weeks of evolution. Future observations of Type II supernovae will continue to explore the diversity seen in the limited set of high-quality UV spectra.

SN 2023ixf was discovered in M101 within a day of explosion and rapidly classified as a Type II supernova with flash features. Here we present ultraviolet (UV) spectra obtained with the Hubble Space Telescope 14, 19, 24, and 66 days after explosion. Interaction between the supernova ejecta and circumstellar material (CSM) is seen in the UV throughout our observations in the flux of the first three epochs and asymmetric Mg II emission on day 66. We compare our observations to CMFGEN supernova models that include CSM interaction (\\(\\dot{M}<10^{-3}\\) M\\(_{\\odot}\\) yr\\(^{-1}\\)) and find that the power from CSM interaction is decreasing with time, from \\(L_{\\rm sh}\\approx5\\times10^{42}\\) erg s\\(^{-1}\\) to \\(L_{\\rm sh}\\approx1\\times10^{40}\\) erg s\\(^{-1}\\) between days 14 and 66. We examine the contribution of individual atomic species to the spectra on days 14 and 19, showing that the majority of the features are dominated by iron, nickel, magnesium, and chromium absorption in the ejecta. The UV spectral energy distribution of SN 2023ixf sits between that of supernovae which show no definitive signs of CSM interaction and those with persistent signatures assuming the same progenitor radius and metallicity. Finally, we show that the evolution and asymmetric shape of the Mg II \\(\\lambda\\lambda\\) 2796, 2802 emission are not unique to SN 2023ixf. These observations add to the early measurements of dense, confined CSM interaction, tracing the mass-loss history of SN 2023ixf to \\(\\sim33\\) yr prior to the explosion and the density profile to a radius of \\(\\sim5.7\\times10^{15}\\) cm. They show the relatively short evolution from a quiescent red supergiant wind to high mass loss.

We present far- and near-ultraviolet (UV) spectra of the Type II supernovae (SNe) SN~2023ixf from days 199 to 722 and SN~2024ggi at days 41 and 232. Both supernovae show broad, blueshifted, and asymmetric UV emission lines with an initial maximum velocity of \\(\\sim9000\\,km\\,s^{-1}\\) and narrow unresolved emission in CIV. We compare the optical and UV emission-line profiles, showing that they evolve from two distinct velocity profiles to a single profile tracing the UV emission. We interpret this as shock power from interaction with circumstellar material coming to dominate over the radioactive-decay power from the inner ejecta. Comparing our observations to radiative transfer models with injected shock power, we find SN~2024ggi is best matched by \\(P_{\\mathrm{shock, abs}}=1\\times10^{41}\\,erg\\,s^{-1}\\) at day 40, SN~2023ixf at day 300 and SN~2024ggi at day 200 are best matched by \\(P_{\\mathrm{shock,abs}}=1\\times10^{40}\\,erg\\,s^{-1}\\), and SN~2023ixf at day 600 is best matched by \\(P_{\\mathrm{shock,abs}}=5\\times10^{39}\\,erg\\,s^{-1}\\). From these models, we find the mass-loss rate of both supernovae increased just before explosion. For SN~2023ixf our mass-loss rates go from \\(4\\times10^{-5}\\,M_{\\odot}\\,yr^{-1}\\) at 600 yr before explosion to \\(2\\times10^{-2}\\,M_{\\odot}\\,yr^{-1}\\) at 15 yr prior to explosion. For SN~2024ggi, we find a mass-loss rate of \\(9\\times10^{-5}\\,M_{\\odot}\\,yr^{-1}\\) at 150 yr before explosion and \\(1\\times10^{-3}\\,M_{\\odot}\\,yr^{-1}\\) at 30 yr before explosion.

We present comprehensive optical observations of SN~2021gmj, a Type II supernova (SN~II) discovered within a day of explosion by the Distance Less Than 40~Mpc (DLT40) survey. Follow-up observations show that SN~2021gmj is a low-luminosity SN~II (LL~SN~II), with a peak magnitude \\(M_V = -15.45\\) and Fe~II velocity of \\(\\sim 1800 \\ \\mathrm{km} \\ \\mathrm{s}^{-1}\\) at 50 days past explosion. Using the expanding photosphere method, we derive a distance of \\(17.8^{+0.6}_{-0.4}\\)~Mpc. From the tail of the light curve we obtain a radioactive nickel mass of \\(0.014 \\pm 0.001\\) M\\(_{\\odot}\\). The presence of circumstellar material (CSM) is suggested by the early-time light curve, early spectra, and high-velocity H\\(\\alpha\\) in absorption. Analytical shock-cooling models of the light curve cannot reproduce the fast rise, supporting the idea that the early-time emission is partially powered by the interaction of the SN ejecta and CSM. The inferred low CSM mass of 0.025 M\\(_{\\odot}\\) in our hydrodynamic-modeling light curve analysis is also consistent with our spectroscopy. We observe a broad feature near 4600 \\AA, which may be high-ionization lines of C, N, or/and He~II. This feature is reproduced by radiation-hydrodynamic simulations of red supergiants with extended atmospheres. Several LL~SNe~II show similar spectral features, implying that high-density material around the progenitor may be common among them.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (~0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at ~2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified >18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand–receptor interactions. Data on >800,000 single cells and ~260 million transcripts can be accessed at http://nanostring.com/CosMx-dataset . Hundreds of RNAs and proteins are imaged in fixed tissue at subcellular resolution.

Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.

Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017-2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2-3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7-22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

The human genome contains approximately 800 G protein-coupled receptors (GPCRs), all characterized by a common 7-transmembrane domain architecture. Here, we show that PKD1, an 11-transmembrane protein with a noncanonical transient receptor potential (TRP) channel architecture, functions as a GPCR with unique biochemical properties. PKD1 acts as a WNT-activated receptor, directly coupling to heterotrimeric Gα i1-3 subunits to inhibit cellular cAMP accumulation. While PKD1 contains both ligand-binding and G protein recruitment sites, PKD2, an associating TRP channel subunit, chaperones PKD1 to the plasma membrane to operate as a GPCR. This represents a striking departure from classical GPCR architecture and expands the functional repertoire of the TRP channel family. Given that mutations in either PKD1 or PKD2 are linked to autosomal dominant polycystic kidney disease, a multisystemic disorder marked by elevated cAMP levels, our results provide molecular insights into disease pathogenesis and highlight potential new therapeutic avenues for this debilitating and costly condition. The human genome contains approximately 800 G proteincoupled receptors (GPCRs), all characterized by a common 7-transmembrane domain architecture. Here, the authors show that PKD1, an 11-transmembrane protein with a noncanonical transient receptor potential (TRP) channel architecture, functions as a GPCR with unique biochemical properties.

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. This study presents the genomes of 2,101 emm28 Streptococcus pyogenes invasive strains, of which 492 were transcriptionally profiled, and 50 were assessed for virulence. GWAS, eQTL analysis, and study of isogenic mutant strains identified an intergenic region that alters global transcript profiles and bacterial virulence.