Enhanced Neuroprotective Effects by Inter-Ischemia Hypothermia in Cerebral Stroke

Background and Purpose. Studies have shown that inter-ischemia hypothermia is able to reduce the size of myocardial infarctions and improve their clinical outcomes. The present study determined whether inter-ischemia hypothermia induced by pharmacological approach induced stronger neuroprotection in ischemic brains. Methods. Adult male Sprague-Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (inter-ischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the groups, brain damage was evaluated using infarct volume and neurological deficits. In addition, mRNA expressions of NADPH oxidase subunits and glucose transporter subtypes were determined by real-time PCR. ROS production was measured by Flow cytometry assay at the same time points. Results: In both hypothermia groups, cerebral infarct volumes and neurological deficits were reduced. ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by inter-ischemia hypothermia at 24 h. Conclusion: Inter-ischemia hypothermia and inter-reperfusion hypothermia after stroke induced neuroprotection by reducing oxidative injury, while neuroprotion was more effective with inter-ischemia hypothermia. This study provides a new avenue and reference for a stronger neuroprotective hypothermia before vascular recanalization in stroke patients

Redshifting galaxies from DESI to JWST CEERS: Correction of biases and uncertainties in quantifying morphology

Observations of high-redshift galaxies with unprecedented detail have now been rendered possible with JWST. However, accurately quantifying their morphology remains uncertain due to potential biases and uncertainties. To address this issue, we used a sample of 1816 nearby DESI galaxies, with a mass range of $10^{9.75-11.25}M_{\odot}$, to compute artificial images of galaxies of the same mass located at $0.75\leq z\leq 3$ and observed at rest-frame optical wavelength in CEERS. We analyzed the effects of cosmological redshift on the measurements of Petrosian radius ($R_p$), half-light radius ($R_{50}$), asymmetry ($A$), concentration ($C$), axis ratio ($q$), and S\'ersic index ($n$). Our results show that $R_p$ and $R_{50}$, calculated using non-parametric methods, are slightly overestimated due to PSF smoothing, while $R_{50}$, $q$, and $n$ obtained through model fitting does not exhibit significant biases. We improve the computation of $A$ by incorporating a more accurate noise effect removal procedure. Due to PSF asymmetry, there is a minor overestimation of $A$ for intrinsically symmetric galaxies. However, for intrinsically asymmetric galaxies, PSF smoothing dominates and results in an underestimation of $A$, an effect that becomes more significant with higher intrinsic $A$ or at lower resolutions. Moreover, PSF smoothing also leads to an underestimation of $C$, which is notably more pronounced in galaxies with higher intrinsic $C$ or at lower resolutions. We developed functions based on resolution level, defined as $R_p/$FWHM, for correcting these biases and the associated statistical uncertainties. Applying these corrections, we measured the bias-corrected morphology for the simulated CEERS images and we find that the derived quantities are in good agreement with their intrinsic values -- except for $A$, which is robust only for angularly large galaxies where $R_p/{\rm FWHM}\geq 5$.Comment: 21 pages, 17 figures; A&A in pres

Enhanced fermentative performance under stresses of multiple lignocellulose-derived inhibitors by overexpression of a typical 2-Cys peroxiredoxin from Kluyveromyces marxianus

Additional file 1: Figure S1. Construction of overexpressing vector and subsequent verification. a) The schematic of overexpressing vector containing KmTPX1 gene and its own promoter. b) PCR and restriction enzyme digestion verification with a band of 1042 bp. c) Relative abundance of KmTPX1 overexpression in SC-His medium by real-time quantitative PCR technology

Hypothermia in Stroke Therapy: Systemic versus Local Application

Presently, there are no effective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective benefits of hypothermia, and surface-cooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and efficacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identifies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well

Quantifying the Escape of Ly α at z ≈ 5–6: A Census of Ly α Escape Fraction with H α -emitting Galaxies Spectroscopically Confirmed by JWST and VLT/MUSE

The James Webb Space Telescope provides an unprecedented opportunity for unbiased surveys of Hα-emitting galaxies at z > 4 with the NIRCam's wide-field slitless spectroscopy (WFSS). In this work, we present a census of Lyα escape fraction (f esc,Lyα ) of 165 star-forming galaxies at z = 4.9–6.3, utilizing their Hα emission directly measured from FRESCO NIRCam/WFSS data. We search for Lyα emission of each Hα-emitting galaxy in the Very Large Telescope/MUSE data. The overall f esc,Lyα measured by stacking is 0.090 ± 0.006. We find that f esc,Lyα displays a strong dependence on the observed UV slope (β obs) and E(B − V), such that the bluest galaxies (β obs ∼ −2.5) have the largest escape fractions (f esc,Lyα ≈ 0.6), indicative of the crucial role of dust and gas in modulating the escape of Lyα photons. f esc,Lyα is less well related to other parameters, including the UV luminosity and stellar mass, and the variation in f esc,Lyα with them can be explained by their underlying coupling with E(B − V) or β obs. Our results suggest a tentative decline in f esc,Lyα at z ≳ 5, implying increasing intergalactic medium attenuation toward higher redshift. Furthermore, the dependence of f esc,Lyα on β obs is proportional to that of the ionizing photon escape fraction (f esc,LyC), indicating that the escape of Lyα and ionizing photon may be regulated by similar physical processes. With f esc,Lyα as a proxy to f esc,LyC, we infer that UV-faint (M UV > −16) galaxies contribute >70% of the total ionizing emissivity at z = 5–6. If these relations hold during the epoch of reionization, UV-faint galaxies can contribute the majority of UV photon budget to reionize the Universe

Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta

Dermal immature adipocytes fightagainstStaphylococcusaureusinfectionby secreting antimicrobial peptidesduring adipogenesis. Zhang et al.demonstrate that activation of the TGF-bpathway suppresses the adipogenicpotential of dermal fibroblasts andtherefore leads to an age-dependent lossof antimicrobial protection fromdermal fat. 皮下脂肪细胞作为皮肤的最后一道防线，有很重要的免疫抗菌功能，分化中脂肪细胞释放大量抗菌肽，这是一种人自源抗生素，能有效地抑制细菌生长。但这一重要的宿主天然免疫功能在发育和老化过程中如何被调控还不为人知。研究人员发现，老化过程中皮肤脂肪丢失是和真皮成纤维细胞（dermal fibroblasts）失去脂肪分化能力密切相关的。真皮成纤维细胞是皮肤深处的特化细胞，可以产生结缔组织并帮助皮肤从损伤中恢复。【Abstract】Dermal fibroblasts (dFBs) resist infection by locallydifferentiating into adipocytes and producing cathe-licidin antimicrobial peptide in response toStaphylo-coccusaureus(S.aureus). Here, we show thatneonatal skin was enriched with adipogenic dFBsand immature dermal fat that highly expressed cath-elicidin. The pool of adipogenic and antimicrobialdFBs declined after birth, leading to an age-depen-dent loss of dermal fat and a decrease in adipogene-sis and cathelidicin production in response to infec-tion. Transforming growth factor beta (TGF-b),which acted on uncommitted embryonic and adultdFBs and inhibited their adipogenic and antimicro-bial function, was identified as a key upstream regu-lator of this process. Furthermore, inhibition of theTGF-breceptor restored the adipogenic and antimi-crobial function of dFBs in culture and increasedresistance of adult mice toS.aureusinfection. Theseresults provide insight into changes that occur in theskin innate immune system between the perinataland adult periods of life.This work was supported by NIH grant R01-AR069653 to L.Z. and R.L.G. and NIH grants R01-AI083358, R01-AR052728, and U19-AI117673 to R.L.G. M.V.P. is supported by a Pew Charitable Trust grant, NIH grants U01-AR073159 and R01-AR067273, National Science Foundation (NSF) grant DMS1763272, and Simons Foundation grant 594598 (to Qing Nie). C.F.G.J. is supported by NSF-GRFP grant DGE-1321846 and MBRS-IMSD training grant GM055246. Y.Z. is supported by NIH grant R01-AI107027. 该项目研究得到了厦门大学双一流启动基金的支持

The Mass-Metallicity Relation of Dwarf Galaxies at the Cosmic Noon in the JWST Era

We present the mass-metallicity relation (MZR) at $z=2-3$ in the stellar mass range of $M_\star\approx 10^{6.5}-10^{9.5}M_\odot$ using 55 dwarf galaxies in the Abell 2744 and SMACS J0723-3732 galaxy cluster fields. These dwarf galaxies are identified and confirmed by deep JWST/NIRISS imaging and slitless grism spectroscopic observations. Taking advantage of the gravitational lensing effect, we extend the previous MZR relation at $z=2-3$ to a much lower mass regime by more than 2.5 orders of magnitude compared with previous studies. We find that the MZR has a shallower slope at the low-mass end ($M_\star<10^{9}M_\odot$) compared to that at the high-mass end ($M_\star>10^{9}M_\odot$), with a slope turnover point at around the stellar mass of $10^9 M_\odot$. This implies that dominating feedback processes in dwarf galaxies may be different from that in galaxies with higher mass. From $z=3$ to $z=2$, the metallicity of the dwarf galaxies is enhanced by $\approx0.1$ dex for a given stellar mass, consistent with the mild evolution found in galaxies with higher mass. Further, we confirm the existence of a 3D relation between the gas-phase metallicity, stellar mass, and star formation rate, i.e., fundamental metallicity relation (FMR), in dwarf galaxies at $z=2-3$. Our derived FMR, which has no significant redshift evolution, can be used as a benchmark to understand the origin of the anti-correlation between SFR and metallicity of dwarf galaxies in the high-redshift Universe.Comment: 16 pages, 4 figures, 1 table, submitted to AAS Journal; welcome comment

Metal-Enriched Neutral Gas Reservoir around a Strongly-lensed, Low-mass Galaxy at z=4z=4 Identified by JWST/NIRISS and VLT/MUSE

Direct observations of low-mass, low-metallicity galaxies at $z\gtrsim4$ provide an indispensable opportunity for detailed inspection of the ionization radiation, gas flow, and metal enrichment in sources similar to those that reionized the Universe. Combining the James Webb Space Telescope (JWST), VLT/MUSE, and ALMA, we present detailed observations of a strongly lensed, low-mass ($\approx 10^{7.6}$ ${\rm M}_\odot$) galaxy at $z=3.98$ (also see Vanzella et al. 2022). We identify strong narrow nebular emission, including CIV $\lambda\lambda1548,1550$, HeII $\lambda1640$, OIII] $\lambda\lambda1661,1666$, [NeIII] $\lambda3868$, [OII] $\lambda3727$, and Balmer series of Hydrogen from this galaxy, indicating a metal-poor HII region ($\lesssim 0.12\ {\rm Z}_\odot$) powered by massive stars. Further, we detect a metal-enriched damped Ly$\alpha$ system (DLA) associated with the galaxy with the HI column density of $N_{\rm{HI}}\approx 10^{21.8}$ cm$^{-2}$. The metallicity of the associated DLA may reach the super solar metallicity (${\gtrsim Z}_\odot$). Moreover, thanks to JWST and gravitational lensing, we present the resolved UV slope ($\beta$) map at the spatial resolution of $\approx 100$ pc at $z=4$, with steep UV slopes reaching $\beta \approx -2.5$ around three star-forming clumps. Combining with low-redshift analogs, our observations suggest that low-mass, low-metallicity galaxies, which dominate reionization, could be surrounded by a high covering fraction of the metal-enriched, neutral-gaseous clouds. This implies that the metal enrichment of low-mass galaxies is highly efficient, and further support that in low-mass galaxies, only a small fraction of ionizing radiation can escape through the interstellar or circumgalactic channels with low column-density neutral gas.Comment: 4 pages, 1 table; submitted to the ApJL; welcome comment

Imaging dark matter at the smallest scales with z ≈ 1 lensed stars

Recent observations of caustic-crossing galaxies at redshift 0.7 . z . 1 show a wealth of transient events. Most of them are believed to be microlensing events of highly magnified stars. Earlier work predicts such events should be common near the critical curves (CCs) of galaxy clusters (“near region”), but some are found relatively far away from these CCs (“far region”). We consider the possibility that substructure on milliarcsecond scales (few parsecs in the lens plane) is boosting the microlensing signal in the far region. We study the combined magnification from the macrolens, millilenses, and microlenses (“3M lensing”), when the macromodel magnification is relatively low (common in the far region). After considering realistic populations of millilenses and microlenses, we conclude that the enhanced microlensing rate around millilenses is not sufficient to explain the high fraction of observed events in the far region. Instead, we find that the shape of the luminosity function (LF) of the lensed stars combined with the amount of substructure in the lens plane determines the number of microlensing events found near and far from the CC. By measuring β (the exponent of the adopted power law LF, dN/dL = φ(L) ∝ (1/L)β), and the number density of microlensing events at each location, one can create a pseudoimage of the underlying distribution of mass on small scales. We identify two regimes: (i) positive-imaging regime where β &gt; 2 and the number density of events is greater around substructures, and (ii) negative-imaging regime where β &lt; 2 and the number density of microlensing events is reduced around substructures. This technique opens a new window to map the distribution of dark-matter substructure down to ∼103 M . We study the particular case of seven microlensing events found in the Flashlights program in the Dragon arc (z = 0.725). A population of supergiant stars having a steep LF with β = 2.55+−007256 fits the distribution of these events in the far and near regions. We also find that the new microlensing events from JWST observations in this arc imply a surface mass density substructure of Σ∗ = 54 M pc−2, consistent with the expected population of stars from the intracluster medium. We identify a small region of high density of microlensing events, and interpret it as evidence of a possible invisible substructure, for which we derive a mass of ∼1.3 × 108 M (within its Einstein radius) in the galaxy cluster

A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE): Impact of Galaxies on the CGM Metal Enrichment at z > 6 Using the JWST and VLT

We characterize the multiphase circumgalactic medium and galaxy properties at z = 6.0-6.5 in four quasar fields from the James Webb Space Telescope A SPectroscopic survey of biased halos In the Reionization Era (ASPIRE) program. We use the Very Large Telescope/X-shooter spectra of quasar J0305-3150 to identify one new metal absorber at z = 6.2713 with multiple transitions (OI, MgI, FeII and CII). They are combined with the published absorbing systems in Davies et al. (2023a) at the same redshift range to form of a sample of nine metal absorbers at z = 6.03 to 6.49. We identify eight galaxies within 1000 km s$^{-1}$ and 350 kpc around the absorbing gas from the ASPIRE spectroscopic data, with their redshifts secured by [OIII]($\lambda\lambda$4959, 5007) doublets and H$\beta$ emission lines. Our spectral energy distribution fitting indicates that the absorbing galaxies have stellar mass ranging from 10$^{7.2}$ to 10$^{8.8}M_{\odot}$ and metallicity between 0.02 and 0.4 solar. Notably, the z = 6.2713 system in the J0305-3150 field resides in a galaxy overdensity region, which contains two (tentatively) merging galaxies within 350 kpc and seven galaxies within 1 Mpc. We measure the relative abundances of $\alpha$ elements to iron ([$\alpha$/Fe]) and find that the CGM gas in the most overdense region exhibits a lower [$\alpha$/Fe] ratio. Our modeling of the galaxy's chemical abundance favors a top-heavy stellar initial mass function, and hints that we may be witnessing the contribution of the first generation Population III stars to the CGM at the end of reionization epoch.Comment: 21 pages, 4 figures in the main text. Accepted for publication in ApJ