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We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

We present the results of a James Webb Space Telescope NIRCam and NIRSpec investigation into the young massive star cluster (YMC) population of NGC 3256, the most cluster-rich luminous infrared galaxy in the Great Observatories All Sky LIRG Survey. We detect 3061 compact YMC candidates with a signal-to-noise ratio ≥3 at F150W, F200W, and F335M. Based on yggdrasil stellar population models, we identify 116/3061 sources with F150W – F200W > 0.47 and F200W – F355M > −1.37 colors, suggesting that they are young ( t ≤ 5 Myr), dusty ( A _V = 5−15), and massive ( M _⊙ > 10 ^5 ). This increases the sample of dust-enshrouded YMCs detected in this system by an order of magnitude relative to previous Hubble Space Telescope studies. With NIRSpec integral field unit pointings centered on the northern and southern nucleus, we extract the Pa α and 3.3 μ m polycyclic aromatic hydrocarbon (PAH) equivalent widths for eight bright and isolated YMCs. Variations in both the F200W – F335M color and 3.3 μ m PAH emission with the Pa α line strength suggest a rapid dust clearing ( 0) correspond to sources with E ( B − V ) > 3, which are typically missed in UV-optical studies. This underscores the importance of deep near-infrared imaging for finding and characterizing these very young and dust-embedded sources.

Abstract The Philippine blue sponge, Xestospongia sp., is a potential source of natural products for pharmaceutical use. However, knowledge on different aspects of its biology and ecology is still lacking, and improvement on biomass production through mariculture is still needed. In this study, we conducted ecological surveys and open sea mariculture trials of the Philippine blue sponge. The ecological surveys conducted were abundance and size–frequency surveys, as well as monitoring of wild blue sponge colonies. Mariculture trials were done by monitoring explant health and survival using different farming methods and consistent observation of various factors (i.e., predation, biofouling, maintenance effort, presence of disease). We also compared growth rates of explants and wild colonies. Colonies were highly abundant, and all size classes were wellrepresented in stations characterised by previous studies to have low water movement and high nutrient levels. These pieces of information were critical in selecting the sites for establishing mariculture setups. We additionally demonstrated the survival and growth of explants using artificial substrates made of polyvinyl chloride pipes. Several factors affecting sponge survival and health included predation, biofouling, habitat, and maintenance effort. We observed a higher growth rate of sponge explants compared with wild colonies. This study provides novel information on the ecology of the Philippine blue sponge and highlights the process of establishing an open sea mariculture setup for biomass production, which can potentially lead to increased production of biomedically important chemicals.

Measurements of oxygen abundance throughout galaxies provide insight to the formation histories and ongoing processes. Here we present a study of the gas-phase oxygen abundance in the H ii regions and diffuse gas of the nearby starburst dwarf galaxy, IC 10. Using the Keck Cosmic Web Imager at W. M. Keck Observatory, we map the central region of IC 10 from 3500 to 5500 Å. The auroral [O III ] 4363 Å line is detected with a high signal-to-noise ratio in 12 of 46 H II regions observed, allowing for direct measurement of the oxygen abundance, yielding a median and standard deviation of $12+\mathrm{log}({\rm{O}}/{\rm{H}})=8.37\pm 0.25$ . We investigate trends between these directly measured oxygen abundances and other H II region properties, finding weak negative correlations with the radius, velocity dispersion, and luminosity. We also find weak negative correlations between the oxygen abundance and the derived quantities of turbulent pressure and ionized gas mass, and a moderate correlation with the derived dynamical mass. Strong line, R _23 abundance estimates are used in the remainder of the H II regions and on a resolved spaxel-by-spaxel basis. There is a large offset between the abundances measured with R _23 and the auroral line method. We find that the R _23 method is unable to capture the large range of abundances observed via the auroral line measurements. The extent of this variation in the measured abundances further indicates a poorly mixed interstellar medium in IC 10, which is not typical of dwarf galaxies and may be partly due to the ongoing starburst, accretion of pristine gas, or a late stage merger.

We present the CO(1–0) maps of 28 infrared-bright galaxies from the Great Observatories All-Sky Luminous Infrared Galaxy Survey (GOALS) taken with the Combined Array for Research in Millimeter Astronomy (CARMA). We detect 100 GHz continuum in 16 of the 28 CARMA GOALS galaxies, which trace both active galactic nuclei (AGNs) and compact star-forming cores. The GOALS galaxies show a variety of molecular gas morphologies, though in the majority of cases the average velocity fields show a gradient consistent with rotation. We fit the full continuum spectral energy distributions (SEDs) of each of the sources using either magphys or SED3FIT (if there are signs of an AGN) to derive the total stellar mass, dust mass, and SFRs of each object. We adopt a value determined from luminous and ultraluminous infrared galaxies (LIRGs and ULIRGs) of α _CO = ${1.5}_{-0.8}^{+1.3}$ M _⊙ (K km s ^−1 pc ^2 ) ^−1 , which leads to more physical values for f _mol and the gas-to-dust ratio. Mergers tend to have the highest gas-to-dust ratios. We assume the cospatiality of the molecular gas and star formation and plot the CARMA GOALS sample on the Schmidt–Kennicutt relation, where we find that they preferentially lie above the line set by normal star-forming galaxies. This hyper-efficiency is likely due to the increased turbulence in these systems, which decreases the freefall time compared to star-forming galaxies, leading to “enhanced” star formation efficiency. Line wings are present in a non-negligible subsample (11/28) of the CARMA GOALS sources and are likely due to outflows driven by AGNs or star formation, gas inflows, or additional decoupled gas components.

We use deep Spitzer mid-infrared spectroscopic maps of radial strips across three nearby galaxies with well-studied metallicity gradients (M101, NGC 628, and NGC 2403) to explore the physical origins of the observed deficit of polycyclic aromatic hydrocarbons (PAHs) at subsolar metallicity (i.e., the PAH–metallicity relation or PZR). These maps allow us to trace the evolution of all PAH features from 5–18 μ m as metallicity decreases continuously from solar ( Z _⊙ ) to 0.2 Z _⊙ . The total PAH-to-dust luminosity ratio remains relatively constant until reaching a threshold of ∼ 2/3 Z _⊙ , below which it declines smoothly but rapidly. The PZR has been attributed to preferential destruction of the smallest grains in the hard radiation environments found at low metallicity. In this scenario, a decrease in emission from the shortest-wavelength PAH features is expected. In contrast, we find a steep decline in long-wavelength power below Z _⊙ , especially in the 17 μ m feature, with the shorter-wavelength PAH bands carrying an increasingly large fraction of power at low metallicity. We use newly developed grain models to reproduce the observed PZR trends, including these variations in fractional PAH feature strengths. The model that best reproduces the data employs an evolving grain size distribution that shifts to smaller sizes as metallicity declines. We interpret this as a result of inhibited grain growth at low metallicity, suggesting continuous replenishment in the interstellar medium is the dominant process shaping the PAH grain population in galaxies.

We present new observations of the central 1 kpc of the M82 starburst obtained with the James Webb Space Telescope near-infrared camera instrument at a resolution θ ∼ 0.″05–0.″1 (∼1–2 pc). The data comprises images in three mostly continuum filters (F140M, F250M, and F360M), and filters that contain [Fe ii ] (F164N), H _2 v = 1 → 0 (F212N), and the 3.3 μ m polycyclic aromatic hydrocarbon (PAH) feature (F335M). We find prominent plumes of PAH emission extending outward from the central starburst region, together with a network of complex filamentary substructures and edge-brightened bubble-like features. The structure of the PAH emission closely resembles that of the ionized gas, as revealed in Paschen α and free–free radio emission. We discuss the origin of the structure, and suggest the PAHs are embedded in a combination of neutral, molecular, and photoionized gas.

The enormous increase in mid-IR sensitivity and spatial and spectral resolution provided by the JWST spectrographs enables, for the first time, detailed extragalactic studies of molecular vibrational bands. This opens an entirely new window for the study of the molecular interstellar medium in luminous infrared galaxies (LIRGs). We present a detailed analysis of rovibrational bands of gas-phase CO, H _2 O, C _2 H _2 , and HCN toward the heavily obscured eastern nucleus of the LIRG VV 114, as observed by NIRSpec and the medium resolution spectrograph on the Mid-InfraRed Instrument (MIRI MRS). Spectra extracted from apertures of 130 pc in radius show a clear dichotomy between the obscured active galactic nucleus (AGN) and two intense starburst regions. We detect the 2.3 μ m CO bandheads, characteristic of cool stellar atmospheres, in the star-forming regions, but not toward the AGN. Surprisingly, at 4.7 μ m, we find highly excited CO ( T _ex ≈ 700–800 K out to at least rotational level J = 27) toward the star-forming regions, but only cooler gas ( T _ex ≈ 200 K) toward the AGN. We conclude that only mid-infrared pumping through the rovibrational lines can account for the equilibrium conditions found for CO and H _2 O in the deeply embedded starbursts. Here, the CO bands probe regions with an intense local radiation field inside dusty young massive star clusters or near the most massive young stars. The lack of high-excitation molecular gas toward the AGN is attributed to geometric dilution of the intense radiation from the bright point source. An overview of the relevant excitation and radiative transfer physics is provided in an appendix.

We present new JWST NIRSpec integral field spectroscopy (IFS) data for the luminous infrared galaxy NGC 7469, a nearby (70.6 Mpc) active galaxy with a Seyfert 1.5 nucleus that drives a highly ionized gas outflow and a prominent nuclear star-forming ring. Using the superb sensitivity and high spatial resolution of the JWST instrument NIRSpec IFS, we investigate the role of the Seyfert nucleus in the excitation and dynamics of the circumnuclear gas. Our analysis focuses on the [Fe ii ], H _2 , and hydrogen recombination lines that trace the radiation/shocked-excited molecular and ionized interstellar medium around the active galactic nucleus (AGN). We investigate gas excitation through H _2 /Br γ and [Fe ii ]/Pa β emission line ratios and find that photoionization by the AGN dominates within the central 300 pc of the galaxy except in a small region that shows signatures of shock-heated gas; these shock-heated regions are likely associated with a compact radio jet. In addition, the velocity field and velocity dispersion maps reveal complex gas kinematics. Rotation is the dominant feature, but we also identify noncircular motions consistent with gas inflows as traced by the velocity residuals and the spiral pattern in the Pa α velocity dispersion map. The inflow is 2 orders of magnitude higher than the AGN accretion rate. The compact nuclear radio jet has enough power to drive the highly ionized outflow. This scenario suggests that the inflow and outflow are in a self-regulating feeding–feedback process, with a contribution from the radio jet helping to drive the outflow.

We present results from the Quasar hosts Unveiled by high Angular Resolution Techniques survey studying the circumgalactic medium (CGM) by observing rest-frame UV emission lines Ly α , C iv , and He ii around two radio-loud quasars, 3C 9 ( z = 2.02) and 4C 05.84 ( z = 2.32), using the Keck Cosmic Web Imager. We detect large-scale Ly α nebulae around both quasars with projected diameters ∼100 kpc, with spatially resolved, embedded 15–30 kpc He ii and C iv nebulae around both quasars as well as kinematically distinct He ii and C iv nebulae at a physical separation of ∼15 kpc from both quasars. Observations of H α , H β , and [O iii ] emission using Keck MOSFIRE spectroscopically confirm that the Ly α nebulae extend to companion galaxies and that these quasars are in a protogroup/protocluster environment. We confirm that the He ii and C iv emission is kinematically and spatially coincident with the companion galaxies. We estimate the virial masses of the companion galaxies, their metallicities, and star formation rates, and investigate the sources of ionization. We measure the dynamical mass of the host dark matter halos and estimate that the dark matter halos of these systems will grow to a mass of 2 × 10 ^14 M _⊙ (3C 9) and 2 × 10 ^13 M _⊙ (4C 05.84) by z = 0. The combined CGM and companion galaxies observations indicate Ly α substructure can indicate the presence of companion galaxies in the CGM.

Suthershinii G,1,&ast; Weiling Amanda Tan,2,&ast; Ainsley Ryan Yan Bin Lee,2 Matthew Zhixuan Chen3 1Department of Biological Sciences, National University of Singapore, Singapore, Singapore; 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 3Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore&ast;These authors contributed equally to this workCorrespondence: Matthew Zhixuan Chen, Division of Geriatric Medicine, Department of Medicine, National University Hospital, 1E Kent Ridge Road, Tower Block, Level 10 Department of Medicine, 119228, Singapore, Tel +65 6779 5555, Email zhixuan_matthew_chen@nuhs.edu.sgBackground: Chronic heart failure (CHF) is a debilitating condition that affects millions worldwide. It is accompanied by a myriad of adverse consequences, such asdiminishing of quality of life and deterioration of mental health. Caregivers play a pivotal role in helping CHF patients manage their conditions and symptoms, as a result the physical, mental and emotional state of caregivers have a direct impact on CHF patients and the management of this condition.Purpose: This systematic review aims to synthesize data about the effectiveness of behavioral interventions targeted at patients with chronic heart failure (CHF) and/or informal caregivers of CHF patients to improve overall management and treatment of CHF in the population.Patients and Methods: Three databases were searched for published studies and studies that included evaluated outcomes of interventions that targeted CHF patients or informal caregivers. All randomized controlled trials, trials of either experimental or quasi-experimental design were included. Studies that only involved formal caregivers, patient populations of adolescents/young adults and patients with non-chronic conditions were excluded.Results: Across the 21 included studies, no study reported a significant improvement in all three domains of quality of life (QoL), depression and loneliness of caregivers while only three studies reported a significant improvement in two outcomes. Within each domain, heterogeneity in measures limited quantitative pooling.Conclusion: This review provides data on the efficacy of interventions targeted at CHF patients and/or informal caregivers. It also highlights successful interventions and its features. Following this, additional resources need to be invested and directed towards implementing these interventions.Keywords: caregiver burden, chronic care, multidisciplinary care, psychosocial

An altered expression of miR-143-3p has been previously reported in prostate cancer where it is purported to play a tumor suppressor role. Evidence from other cancers suggests miR-143-3p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key biological process required for metastasis. However, in prostate cancer the interaction between miR-143-3p and EMT-associated mechanisms remains unclear. Therefore, this paper investigated the link between miR-143-3p and EMT in prostate cancer using in vitro and in silico analyses. PCR detected that miR-143-3p expression was significantly decreased in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) data showed a significant downregulation of miR-143-3p in prostate cancer, correlating with pathological markers of advanced disease. Functional enrichment analysis confirmed the significant association of miR-143-3p and its target genes with EMT. The EMT-linked gene AKT1 was subsequently shown to be a novel target of miR-143-3p in prostate cancer cells. The in vitro manipulation of miR-143-3p levels significantly altered the cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Further TCGA PRAD analysis suggested miR-143-3p tumor expression may be a useful predictor of disease recurrence. In summary, this is the first study to report that miR-143-3p overexpression in prostate cancer may inhibit EMT by targeting AKT1. The findings suggest miR-143-3p could be a useful diagnostic and prognostic biomarker for prostate cancer.

We present JWST Mid-InfraRed Instrument/Medium-Resolution Spectrometer (MIRI/MRS) observations of an infrared luminous disk galaxy, FLS1, at z ∼ 0.54. With a lookback time of 5 Gyr, FLS1 is chronologically at the midpoint between the peak epoch of star formation and the present day. The MRS data provide maps of the atomic fine structure lines [Ar ii ]6.99, [Ar iii ]8.99, [Ne ii ]12.81, and [Ne iii ]15.55 μ m, polycyclic aromatic hydrocarbon (PAH) features at 3.3, 6.2, and 11.3 μ m, and the warm molecular gas indicators H _2 S(5) and H _2 S(3); all these emission features are spatially resolved. We find that the PAH emission is more extended along the northern side of the galaxy when compared to the well-studied star formation tracer [Ne ii ]. The H _2 rotational lines, which are shock indicators, are strongest and most extended on the southern side of the galaxy. [Ar ii ] is the second brightest fine structure line detected in FLS1 and we show that it is a useful kinematic probe that can be detected with JWST out to z ∼ 3. Velocity maps of [Ar ii ] show a rotating disk with signs of turbulence. Our results provide an example of how spatially resolved mid-infrared spectroscopy can allow us to better understand the star formation and interstellar medium conditions in a galaxy halfway back to the peak epoch of galaxy evolution.

We present James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec) integral field spectroscopy of the nearby luminous infrared galaxy NGC 7469. We take advantage of the high spatial/spectral resolution and wavelength coverage of JWST/NIRSpec to study the 3.3 μ m neutral polycyclic aromatic hydrocarbon (PAH) grain emission on ∼200 pc scales. A clear change in the average grain properties between the star-forming ring and the central AGN is found. Regions in the vicinity of the AGN, with [Ne iii ]/[Ne ii ] > 0.25, tend to have larger grain sizes and lower aliphatic-to-aromatic (3.4/3.3) ratios, indicating that smaller grains are preferentially removed by photodestruction in the vicinity of the AGN. PAH emission at the nucleus is weak and shows a low 11.3/3.3 PAH ratio. We find an overall suppression of the total PAH emission relative to the ionized gas in the central 1 kpc region of the AGN in NGC 7469 compared to what has been observed with Spitzer on 3 kpc scales. However, the fractional 3.3 μ m–to–total PAH power is enhanced in the starburst ring, possibly due to a variety of physical effects on subkiloparsec scales, including recurrent fluorescence of small grains or multiple photon absorption by large grains. Finally, the IFU data show that while the 3.3 μ m PAH-derived star formation rate (SFR) in the ring is 27% higher than that inferred from the [Ne ii ] and [Ne iii ] emission lines, the integrated SFR derived from the 3.3 μ m feature would be underestimated by a factor of 2 due to the deficit of PAHs around the AGN, as might occur if a composite system like NGC 7469 were to be observed at high redshift.

We present James Webb Space Telescope (JWST) imaging of NGC 7469 with the Near-Infrared Camera and the Mid-InfraRed Instrument. NGC 7469 is a nearby, z = 0.01627, luminous infrared galaxy that hosts both a Seyfert Type-1.5 nucleus and a circumnuclear starburst ring with a radius of ∼0.5 kpc. The new near-infrared (NIR) JWST imaging reveals 66 star-forming regions, 37 of which were not detected by Hubble Space Telescope (HST) observations. Twenty-eight of the 37 sources have very red NIR colors that indicate obscurations up to A _v ∼ 7 and a contribution of at least 25% from hot dust emission to the 4.4 μ m band. Their NIR colors are also consistent with young (

We present the results of a James Webb Space Telescope NIRCam investigation into the young massive star cluster (YMC) population in the luminous infrared galaxy VV 114. We identify 374 compact YMC candidates with signal-to-noise ratios ≥ 3, 5, and 5 at F150W, F200W, and F356W, respectively. A direct comparison with our HST cluster catalog reveals that ∼20% of these sources are undetected at optical wavelengths. Based on yggdrasil stellar population models, we identify 17 YMC candidates in our JWST imaging alone with F150W – F200W and F200W – F356W colors suggesting they are all very young, dusty ( A _V = 5–15), and massive (10 ^5.8 < M _⊙ < 10 ^6.1 ). The discovery of these “hidden” sources, many of which are found in the “overlap” region between the two nuclei, quadruples the number of t < 3 Myr clusters and nearly doubles the number of t < 6 Myr clusters detected in VV 114. Now extending the cluster age distribution ( ${dN}/d\tau \propto {\tau }^{\gamma }$ ) to the youngest ages, we find a slope of γ = −1.30 ± 0.39 for 10 ^6 < τ (yr) < 10 ^7 , which is consistent with the previously determined value from 10 ^7 < τ (yr) < 10 ^8.5 , and confirms that VV 114 has a steep age distribution slope for all massive star clusters across the entire range of cluster ages observed. Finally, the consistency between our JWST- and HST-derived age distribution slopes indicates that the balance between cluster formation and destruction has not been significantly altered in VV 114 over the last 0.5 Gyr.

Selecting the first galaxies at z > 7 − 10 from JWST surveys is complicated by z < 6 contaminants with degenerate photometry. For example, strong optical nebular emission lines at z < 6 may mimic JWST/NIRCam photometry of z > 7–10 Lyman-break galaxies (LBGs). Dust-obscured 3 < z < 6 galaxies in particular are potentially important contaminants, and their faint rest-optical spectra have been historically difficult to observe. A lack of optical emission line and continuum measures for 3 < z < 6 dusty galaxies now makes it difficult to test their expected JWST/NIRCam photometry for degenerate solutions with NIRCam dropouts. Toward this end, we quantify the contribution by strong emission lines to NIRCam photometry in a physically motivated manner by stacking 21 Keck II/NIRES spectra of hot, dust-obscured, massive ( $\mathrm{log}{M}_{* }/{M}_{\odot }\gtrsim 10\mbox{--}11$ ) and infrared (IR) luminous galaxies at z ∼ 1–4. We derive an average spectrum and measure strong narrow (broad) [O iii ] _5007 and H α features with equivalent widths of 130 ± 20 Å (150 ± 50 Å) and 220 ± 30 Å (540 ± 80 Å), respectively. These features can increase broadband NIRCam fluxes by factors of 1.2 − 1.7 (0.2–0.6 mag). Due to significant dust attenuation ( A _V ∼ 6), we find H α +[N ii ] to be significantly brighter than [O iii ]+H β and therefore find that emission-line dominated contaminants of high − z galaxy searches can only reproduce moderately blue perceived UV continua of S _λ ∝ λ ^β with β > − 1.5 and z > 4. While there are some redshifts ( z ∼ 3.75) where our stack is more degenerate with the photometry of z > 10 LBGs at λ _rest ∼ 0.3–0.8 μ m , redder filter coverage beyond λ _obs > 3.5 μ m and far-IR/submillimeter follow-up may be useful for breaking the degeneracy and making a crucial separation between two fairly unconstrained populations, dust-obscured galaxies at z ∼ 3–6 and LBGs at z > 10.

Abstract Background Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy. Redox factor-1 (Ref-1), a redox signaling protein, regulates the conversion of several transcription factors (TFs), including HIF-1α, STAT3 and NFκB from an oxidized to reduced state leading to enhancement of their DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia. Methods scRNA-seq comparing pancreatic cancer cells expressing less than 20% of the Ref-1 protein was analyzed using left truncated mixture Gaussian model and validated using proteomics and qRT-PCR. The identified Ref-1’s role in mitochondrial function was confirmed using mitochondrial function assays, qRT-PCR, western blotting and NADP assay. Further, the effect of Ref-1 redox function inhibition against pancreatic cancer metabolism was assayed using 3D co-culture in vitro and xenograft studies in vivo. Results Distinct transcriptional variation in central metabolism, cell cycle, apoptosis, immune response, and genes downstream of a series of signaling pathways and transcriptional regulatory factors were identified in Ref-1 knockdown vs Scrambled control from the scRNA-seq data. Mitochondrial DEG subsets downregulated with Ref-1 knockdown were significantly reduced following Ref-1 redox inhibition and more dramatically in combination with Devimistat in vitro. Mitochondrial function assays demonstrated that Ref-1 knockdown and Ref-1 redox signaling inhibition decreased utilization of TCA cycle substrates and slowed the growth of pancreatic cancer co-culture spheroids. In Ref-1 knockdown cells, a higher flux rate of NADP + consuming reactions was observed suggesting the less availability of NADP + and a higher level of oxidative stress in these cells. In vivo xenograft studies demonstrated that tumor reduction was potent with Ref-1 redox inhibitor similar to Devimistat. Conclusion Ref-1 redox signaling inhibition conclusively alters cancer cell metabolism by causing TCA cycle dysfunction while also reducing the pancreatic tumor growth in vitro as well as in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a poor response to current treatment regimens. The multifunctional DNA repair-redox signaling protein Ref-1 has a redox signaling function that activates several transcriptional factors (TFs) including NF-κB (RelA), STAT3, AP-1. These have been implicated in signaling in PDAC and associated with cancer progression and therapy resistance. Numerous studies have shown a role for RelA in PDAC inflammatory responses and therapy resistance, little is known as to how these inflammatory responses are modulated through Ref-1 redox signaling pathways during pancreatic pathogenesis. RelA and STAT3 are two major targets of Ref-1 and are important in PDAC pathogenesis. To decipher the mechanistic role of RelA in response to Ref-1 inhibition, we used PDAC cells (KC3590) from a genetically engineered KrasG12D-driven mouse model that also is functionally deficient for RelA (Parent/Vector) or KC3590 cells with fully functional RelA added back (clone 13; C13). We demonstrated that RelA deficient cells are more resistant to Ref-1 redox inhibitors APX3330, APX2009, and APX2014, and their sensitivity is restored in the RelA proficient cells. Knockdown of STAT3 did not change cellular sensitivity to Ref-1 redox inhibitors in either cell type. Gene expression analysis demonstrated that Ref-1 inhibitors significantly decreased IL-8, FOSB, and c-Jun when functional RelA is present. We also demonstrated that PRDX1, a known Ref-1 redox modulator, contributes to Ref-1 inhibitor cellular response. Knockdown of PRDX1 when functional RelA is present resulted in dramatically increased PDAC killing in response to Ref-1 inhibitors. The enhanced cell killing was not due to increased intracellular ROS production. Although Ref-1 inhibition decreased the NADP/NADPH ratio in the cells, the addition of PRDX1 knockdown did not further this redox imbalance. This data suggests that the mechanism of cell killing following Ref-1 inhibition is at least partially mediated through RelA and not STAT3. Further imbalancing of the redox signaling through disruption of the PRDX1-Ref-1 interaction may have therapeutic implications. Our data further support a pivotal role of RelA in mediating Ref-1 redox signaling in PDAC cells with the KrasG12D genotype and provide novel therapeutic strategies to combat PDAC drug resistance.

James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) images of the luminous infrared (IR) galaxy VV 114 are presented. This redshift ∼0.020 merger has a western component (VV 114W) rich in optical star clusters and an eastern component (VV 114E) hosting a luminous mid-IR nucleus hidden at UV and optical wavelengths by dust lanes. With MIRI, the VV 114E nucleus resolves primarily into bright NE and SW cores separated by 630 pc. This nucleus comprises 45% of the 15 μ m light of VV 114, with the NE and SW cores having IR luminosities, L _IR (8 − 1000 μ m) ∼ 8 ± 0.8 × 10 ^10 L _⊙ and ∼ 5 ± 0.5 × 10 ^10 L _⊙ , respectively, and IR densities, Σ _IR ≳ 2 ± 0.2 × 10 ^13 L _⊙ kpc ^−2 and ≳ 7 ± 0.7 × 10 ^12 L _⊙ kpc ^−2 , respectively—in the range of Σ _IR for the Orion star-forming core and the nuclei of Arp 220. The NE core, previously speculated to have an active galactic nucleus (AGN), has starburst-like mid-IR colors. In contrast, the VV 114E SW core has AGN-like colors. Approximately 40 star-forming knots with L _IR ∼ 0.02–5 × 10 ^10 L _⊙ are identified, 28% of which have no optical counterpart. Finally, diffuse emission accounts for 40%–60% of the mid-IR emission. Mostly notably, filamentary polycyclic aromatic hydrocarbon (PAH) emission stochastically excited by UV and optical photons accounts for half of the 7.7 μ m light of VV 114. This study illustrates the ability of JWST to detect obscured compact activity and distributed PAH emission in the most extreme starburst galaxies in the local universe.

We have used the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) to obtain the first spatially resolved, mid-infrared images of IIZw096, a merging luminous infrared galaxy (LIRG) at z = 0.036. Previous observations with the Spitzer Space Telescope suggested that the vast majority of the total IR luminosity ( L _IR ) of the system originated from a small region outside of the two merging nuclei. New observations with JWST/MIRI now allow an accurate measurement of the location and luminosity density of the source that is responsible for the bulk of the IR emission. We estimate that 40%–70% of the IR bolometric luminosity, or 3–5 × 10 ^11 L _⊙ , arises from a source no larger than 175 pc in radius, suggesting a luminosity density of at least 3–5 × 10 ^12 L _⊙ kpc ^−2 . In addition, we detect 11 other star-forming sources, five of which were previously unknown. The MIRI F1500W/F560W colors of most of these sources, including the source responsible for the bulk of the far-IR emission, are much redder than the nuclei of local LIRGs. These observations reveal the power of JWST to disentangle the complex regions at the hearts of merging, dusty galaxies.

The nearby, luminous infrared galaxy NGC 7469 hosts a Seyfert nucleus with a circumnuclear star-forming ring and is thus the ideal local laboratory for investigating the starburst–AGN (active galactic nucleus) connection in detail. We present integral-field observations of the central 1.3 kpc region in NGC 7469 obtained with the JWST Mid-InfraRed Instrument. Molecular and ionized gas distributions and kinematics at a resolution of ∼100 pc over the 4.9–7.6 μ m region are examined to study the gas dynamics influenced by the central AGN. The low-ionization [Fe ii ] λ 5.34 μ m and [Ar ii ] λ 6.99 μ m lines are bright on the nucleus and in the starburst ring, as opposed to H _2 S(5) λ 6.91 μ m, which is strongly peaked at the center and surrounding ISM. The high-ionization [Mg v ] line is resolved and shows a broad, blueshifted component associated with the outflow. It has a nearly face-on geometry that is strongly peaked on the nucleus, where it reaches a maximum velocity of −650 km s ^−1 , and extends about 400 pc to the east. Regions of enhanced velocity dispersion in H _2 and [Fe ii ] ∼ 180 pc from the AGN that also show high L (H _2 )/ L (PAH) and L ([Fe ii ])/ L (Pf α ) ratios to the W and N of the nucleus pinpoint regions where the ionized outflow is depositing energy, via shocks, into the dense interstellar medium between the nucleus and the starburst ring. These resolved mid-infrared observations of the nuclear gas dynamics demonstrate the power of JWST and its high-sensitivity integral-field spectroscopic capability to resolve feedback processes around supermassive black holes in the dusty cores of nearby luminous infrared galaxies.

We present James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) integral-field spectroscopy of the nearby merging, luminous infrared galaxy, NGC 7469. This galaxy hosts a Seyfert type-1.5 nucleus, a highly ionized outflow, and a bright, circumnuclear star-forming ring, making it an ideal target to study active galactic nucleus (AGN) feedback in the local universe. We take advantage of the high spatial/spectral resolution of JWST/MIRI to isolate the star-forming regions surrounding the central active nucleus and study the properties of the dust and warm molecular gas on ∼100 pc scales. The starburst ring exhibits prominent polycyclic aromatic hydrocarbon (PAH) emission, with grain sizes and ionization states varying by only ∼30%, and a total star formation rate of 10–30 M _⊙ yr ^−1 derived from fine structure and recombination emission lines. Using pure rotational lines of H _2 we detect 1.2 × 10 ^7 M _⊙ of warm molecular gas at a temperature higher than 200 K in the ring. All PAH bands get significantly weaker toward the central source, where larger and possibly more ionized grains dominate the emission, likely the result of the ionizing radiation and/or the fast wind emerging from the AGN. The small grains and warm molecular gas in the bright regions of the ring however display properties consistent with normal star-forming regions. These observations highlight the power of JWST to probe the inner regions of dusty, rapidly evolving galaxies for signatures of feedback and inform models that seek to explain the coevolution of supermassive black holes and their hosts.

M82 is an archetypal starburst galaxy in the local Universe. The central burst of star formation, thought to be triggered by M82's interaction with other members in the M81 group, is driving a multiphase galaxy-scale wind away from the plane of the disk that has been studied across the electromagnetic spectrum. Here, we present new velocity-resolved observations of the [C ii ] 158 μ m line in the central disk and the southern outflow of M82 using the upGREAT instrument on board SOFIA. We also report the first detections of velocity-resolved (Δ V = 10 km s ^−1 ) [C ii ] emission in the outflow of M82 at projected distances of ≈1–2 kpc south of the galaxy center. We compare the [C ii ] line profiles to observations of CO and H i and find that likely the majority (>55%) of the [C ii ] emission in the outflow is associated with the neutral atomic medium. We find that the fraction of [C ii ] actually outflowing from M82 is small compared to the bulk gas outside the midplane (which may be in a halo or tidal streamers), which has important implications for observations of [C ii ] outflows at higher redshift. Finally, by comparing the observed ratio of the [C ii ] and CO intensities to models of photodissociation regions, we estimate that the far-ultraviolet (FUV) radiation field in the disk is ∼10 ^3.5 G _0 , in agreement with previous estimates. In the outflow, however, the FUV radiation field is 2–3 orders of magnitudes lower, which may explain the high fraction of [C ii ] arising from the neutral medium in the wind.

The surface densities of gas, dust, and stars provide a window into the physics of star formation that, until the advent of high-resolution far-IR/submillimeter observations, has been historically difficult to assess among dusty galaxies. To study the link between IR surface densities and dust properties, we leverage the Atacama Large Millimetre/Submillimetre Array archive to measure the extent of cold dust emission in 15 z ∼ 2 IR-selected galaxies selected on the basis of having available mid-IR spectroscopy from Spitzer. We use the mid-IR spectra to constrain the relative balance between dust heating from star formation and active galactic nuclei (AGNs), and to measure emission from polycylic aromatic hydrocarbons (PAHs), small dust grains that play a key role in the photoelectric heating of gas. In general, we find that dust-obscured star formation at high IR surface densities exhibits similar properties at low and high redshift, namely, local luminous IR galaxies (LIRGs) have comparable PAH luminosity to total dust mass ratios as high- z galaxies, and star formation at z ∼ 0–2 is more efficient at high IR surface densities despite the fact that our sample of high- z galaxies is closer to the main sequence than local LIRGs. High star formation efficiencies are coincident with a decline in the PAH-to-IR luminosity ratio reminiscent of the deficit observed in far-IR fine-structure lines. Changes in the gas and dust conditions arising from high star formation surface densities might help drive the star formation efficiency up. This could help explain the high efficiencies needed to reconcile star formation and gas volume densities in dusty galaxies at cosmic noon.

In this erratum we acknowledge EASCO as one of the inspirational mission concepts that helped the development of our original mission concept OSCAR.

Coronal Mass Ejections (CMEs) and Corotating Interaction Regions (CIRs) are major sources of magnetic storms on Earth and are therefore considered to be the most dangerous space weather events. The Observatories of Solar Corona and Active Regions (OSCAR) mission is designed to identify the 3D structure of coronal loops and to study the trigger mechanisms of CMEs in solar Active Regions (ARs) as well as their evolution and propagation processes in the inner heliosphere. It also aims to provide monitoring and forecasting of geo-effective CMEs and CIRs. OSCAR would contribute to significant advancements in the field of solar physics, improvements of the current CME prediction models, and provide data for reliable space weather forecasting. These objectives are achieved by utilising two spacecraft with identical instrumentation, located at a heliocentric orbital distance of 1 AU from the Sun. The spacecraft will be separated by an angle of 68° to provide optimum stereoscopic view of the solar corona. We study the feasibility of such a mission and propose a preliminary design for OSCAR.

In this study, results of the experimental study on the depth profiles of production yields of 206,205,204,203,202Bi radio-nuclei in the natural Pb target irradiated by a 100-MeV proton beam are presented. Irradiation was performed at proton linac facility (KOMAC) in Korea. The target, irradiated by 100-MeV protons, was arranged in a stack consisting of natural Pb, Al, Au foils and Pb plates. The proton beam intensity was determined by activation analysis method using 27Al(p, 3p1n)24Na, 197Au(p, p1n)196Au, and 197Au(p, p3n)194Au monitor reactions and also using dosimetry method by a Gafchromic film. The production yields of produced Bi radio-nuclei in the natural Pb foils and monitor reactions were measured by gamma-ray spectroscopy. Monte Carlo simulations were performed by FLUKA, PHITS, and MCNPX codes and compared with the measurements in order to verify validity of physical models and nuclear data libraries in the Monte Carlo codes. A fairly good agreement was observed between the present experimental data and the simulations by FLUKA, PHITS, and MCNPX. However, physical models and the nuclear data relevant to the end of range of protons in the codes need to be improved.

Background: Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge., Methods: Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing seroresponse to GV isolates., Results: Serum from immunocompromised pediatric patients vaccinated with an inactivated JE vaccine showed higher 50% plaque reduction neutralization test (PRNT50) geometric mean titer (GMT) against GIII Nakayama (11,358; 95% CI = 1,790, 29,658), but lower GMTs against GV isolates: GV Muar (499; 95% CI = 0, 2,437), GV 43279 (308; 95% CI = 159, 582), and GV 43413 (231; 95% CI = 108, 738). Similarly, 32 healthy volunteers receiving a live attenuated JE vaccine achieved 100% seroprotection against GIII Nakayama with GMT of 338 (95% CI = 304, 651) at 1 month post-vaccination. However, GMTs against GV isolates were 123 (95% CI = 102, 446) for GV Muar, 81 (95% CI = 63, 168) for GV 43279, and 107 (95% CI = 100, 322) for GV 43413, not achieving 100% seroprotection against these isolates. At 6 months post-vaccination, GMT against Nakayama increased to 696 (95% CI = 409, 2,353), while remaining similar for GV isolates., Conclusions: Our study underscores that current GIII-based vaccines do not provide comparable protection against GV JEVs, impacting individuals in both current and potential endemic regions, as well as travelers to these regions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Northern temperate coniferous forests serve as crucial connectors between boreal and temperate forests, yet they are vulnerable to various stressors such as climate change and human activities. Severe drought poses a significant threat to plant species within these forests, prompting recent research into its impacts. However, many studies lack explicit definitions of post-disturbance vegetation processes and fail to identify potential interactions with disturbance factors, necessitating comprehensive discussions. This study examines the effects of drought on tree growth patterns of the main dominant species in northern temperate regions: Abies nephrolepis and Picea jezoensis, along with two commonly associated Betula ermanii, and Quercus mongolica. Additionally, new disturbance factors in forests inhabited by these species (A. nephrolepis and P. jezoensis) were evaluated based on community classification. The study sites were located in the Mt. Baekdu (Changbai) and South Korea regions, which are positioned at the southern limit of the phytogeographical patterns of target species. Results indicate that A. nephrolepis and P. jezoensis exhibit high levels of recovery and resilience, while B. ermanii and Q. mongolica demonstrate high resistance. Species-specific responses align with drought intensity, with resistance, recovery, and resilience decreasing notably with increasing pre-drought radial growth. South Korean forests, the invasion of the vine species Tripterygium regelii after the death of A. nephrolepis in the overstory vegetation threatens the regeneration of new trees. However, certain environmental factors, such as high rock exposure and dense overstory canopy, limit vine invasion. Based on the results, pre-drought radial growth emerges as a key determinant in how trees respond to drought. Additionally, the results suggest the potential for new disturbances to emerge in forest gaps due to overstory vegetation mortality induced by global warming. These findings contribute to a deeper understanding of increasing drought stress, aid in identifying climate refugia, and inform conservation priorities based on habitat characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Coeliac disease (CeD) is a type of enteropathy characterised by an immune-mediated reaction to ingested gluten, resulting in impaired absorption of nutrients and symptoms such as bloating, abdominal cramping and diarrhoea. Currently, the only treatment for CeD is adherence to a gluten-free diet (GFD). The latest draft guidance from the US Food and Drug Administration recommends that dietitians experienced in CeD management evaluate patients during the screening and treatment period of CeD clinical trials to assess adherence to a GFD. However, there are currently no standardised guidelines on dietary assessment of patients with CeD on a GFD and there is a lack of widespread availability of expertise in this field., Methods: Based on the findings of a literature review conducted between April and September 2023, this article provides an overview of key points to consider in the nutritional and dietary assessment of patients with CeD who are following a GFD, with particular focus on the clinical trial setting., Results: Based on a consensus from dietitians and gastroenterologists experienced in treating patients with CeD, we present specific recommendations for registered dietitians who manage patients with CeD. We also describe the development of a simplified tool for assessment of adherence to a GFD, the Gluten-Free Adherence Survey, based on these recommendations., Conclusions: These guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Background: Most people maintaining a gluten-free diet (GFD) do not have celiac disease (CD). Comorbidities and associated conditions in this population are largely unknown., Aims: This study identified demographics, dietary patterns, and diagnoses for patients prescribed a GFD during hospitalization and compared patients with CD to those without CD., Methods: We performed a retrospective cross-sectional study for hospital admissions with a GFD between Jan 1, 2010 and June 30, 2022, while excluding patients missing demographic data (n = 113). We compared patients with and without a CD diagnosis, including multivariable logistic regression to identify characteristics independently associated with a CD diagnosis., Results: We analyzed 1527 hospitalized patients of all ages. A minority (n = 467, 30.6%) carried a CD diagnosis. Age, sex, body mass index, and Medicare/Medicaid enrollment and additional diagnoses associated with a GFD (e.g., IBS) were not significantly different. The CD cohort was more predominantly white (66.6% vs 58.4%, p = 0.007) and non-Hispanic (62.5% vs. 52.7%, p = 0.001). While hospitalized, patients with CD had fewer additional dietary restrictions (mean 0.33 vs 0.56, p < 0.001) and more frequent micronutrient supplementation (26.6% vs 21.4%, p = 0.03). CD was independently associated with malnutrition (OR 1.86, 95% CI 1.31-2.65) and inversely associated with a vegetarian diet (OR 0.35, 95% CI 0.15-0.81), reduced lactose diet (OR 0.25, 95% CI 0.13-0.50), and Hispanic ethnicity (OR 0.56, 95% CI 0.35-0.90) while controlling for other covariates., Discussion: Two-thirds of hospitalized patients receiving a GFD do not have a diagnosis of CD. Among GFD inpatients, CD is associated with fewer dietary restrictions and independently associated with malnutrition., Competing Interests: Declarations Conflict of interest No conflicts of interest and nothing to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Self-management is pivotal in helping people with their independence and in managing their health conditions more effectively. The PRIDE-app is a novel online intervention, providing support and information for people living with dementia and their families, aimed at increasing self-management and improving quality of life. Knowledge generated will help inform future developments to the app, with the aim of improving its uptake and implementation in services., Methods: A mixed-methods approach incorporating the RE-AIM framework. Recruited 25 people living with dementia, of which 17completed the PRIDE-app intervention over 8 weeks with support from a dementia adviser facilitator. Measures exploring mood, physical well-being, and quality of life were collected at baseline, 3 and 6 months and analysed through modelled analysis. Post-intervention interviews were conducted with participants and facilitators and analysed through thematic analysis., Results: Quantitative results did not show significant improvements in participants' scores. Qualitative data showed that the PRIDE-app motivated people to reconnect socially and set individual goals for activities. Participants and facilitators identified areas for improvements to the app interface and delivery format., Conclusions: This study evaluated the PRIDE-app's reach, effectiveness and adoptability in the independence and quality of life of people living with dementia, as well as how it could be implemented and maintained within services. Pre- and post-intervention scores were inconclusive. Interviews provided positive feedback of the app's influence on peoples' activities and mood., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Air pollutants, such as diesel exhaust particles (DEPs), induce respiratory disease exacerbation with neutrophilic infiltration. Progranulin (PGRN), an epithelial cell and macrophage-derived secretory protein, is associated with neutrophilic inflammation. PGRN is digested into various derivatives at inflammatory sites and is involved in several inflammatory processes. PGRN and its derivatives likely regulate responses to DEP exposure in allergic airway inflammation., Aim: To investigate the role of PGRN and its derivatives in the regulation of responses to DEP exposure in allergic airway inflammation., Methods: A murine model of allergic airway inflammation was generated in PGRN-deficient mice, and they were simultaneously exposed to DEP followed by intranasal administration of full-length recombinant PGRN (PGRN-FL) and a PGRN-derived fragment (FBAC). Inflammatory status was evaluated by bronchoalveolar lavage fluid and histopathologic analyses. Human bronchial epithelial cells were stimulated with DEPs and house dust mites (HDMs), and the effect of FBAC treatment was evaluated by assessing various intracellular signaling molecules, autophagy markers, inflammatory cytokines, and intracellular oxidative stress., Results: DEP exposure exaggerated neutrophilic inflammation, enhanced IL-6 and CXCL15 secretions, and increased oxidative stress in the murine model; this effect was greater in PGRN-deficient mice than in wild-type mice. The DEP-exposed mice with PGRN-FL treatment revealed no change in neutrophil infiltration and higher oxidative stress status in the lungs. On the contrary, FBAC administration inhibited neutrophilic infiltration and reduced oxidative stress. In human bronchial epithelial cells, DEP and HDM exposure increased intracellular oxidative stress and IL-6 and IL-8 secretion. Decreased nuclear factor erythroid 2-related factor 2 (Nrf2) expression and increased phosphor-p62 and LC3B expression were also observed. FBAC treatment attenuated oxidative stress from DEP and HDM exposure., Conclusions: FBAC reduced neutrophilic inflammation exaggerated by DEP exposure in a mouse model of allergic airway inflammation by reducing oxidative stress. PGRN and PGRN-derived proteins may be novel therapeutic agents in attenuating asthma exacerbation induced by air pollutant exposure., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [1,2]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression. Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin + IL-17 + T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector. In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024. Published by Elsevier Inc.)