Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes

AimTo evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes.MethodsWomen (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups.ResultsBlood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment (P < 0.05), and there was no statistical difference in the blood glucose levels, biochemical index and HOMA-IR between the two groups (P > 0.05). The CER levels did not differ statistically between the two groups (P > 0.05). Both the cost and the incidence of drug side effects during solution injection were lower in the observation group than in the control group after 24 weeks of treatment (P < 0.05).ConclusionBoth Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe.Clinical trial registrationhttps://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026514

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

Efficacy of polyethylene glycol loxenatide versus insulin glargine on glycemic control in patients with type 2 diabetes: a randomized, open-label, parallel-group trial

Objective: This trial aimed to evaluate the glycemic control of polyethylene glycol loxenatide measured with continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM), with the hypothesis that participants given PEG-Loxe would spend more time in time-in-range (TIR) than participants were given insulin glargine after 24 weeks of treatment.Methods: This 24-week, randomized, open-label, parallel-group study was conducted in the Department of Endocrine and Metabolic Diseases, Longhu Hospital, Shantou, China. Participants with T2DM, who were ≥45 years of age, HbA1c of 7.0%–11.0%, and treated at least 3 months with metformin were randomized (1:1) to receive PEG-Loxe or insulin glargine. The primary endpoint was TIR (blood glucose range: 3.9–10.0 mmol/L) during the last 2 weeks of treatment (weeks 22–24).Results: From March 2020 to April 2022, a total of 107 participants with T2DM were screened, of whom 78 were enrolled into the trial (n = 39 per group). At the end of treatment (weeks 22–24), participants given PEG-Loxe had a greater proportion of time in TIR compared with participants given insulin glargine [estimated treatment difference (ETD) of 13.4% (95% CI, 6.8 to 20.0, p < 0.001)]. The tight TIR (3.9–7.8 mmol/L) was greater with PEG-Loxe versus insulin glargine, with an ETD of 15.6% (95% CI, 8.9 to 22.4, p < 0.001). The time above range (TAR) was significantly lower with PEG-Loxe versus insulin glargine [ETD for level 1: −10.5% (95% CI: −14.9 to −6.0), p < 0.001; ETD for level 2: −4.7% (95% CI: −7.9 to −1.5), p = 0.004]. The time below range (TBR) was similar between the two groups. The mean glucose was lower with PEG-Loxe versus insulin glargine, with an ETD of −1.2 mmol/L (95% CI, −1.9 to −0.5, p = 0.001). The SD of CGM glucose levels was 1.88 mmol/L for PEG-Loxe and 2.22 mmol/L for insulin glargine [ETD -0.34 mmol/L (95% CI: −0.55 to −0.12), p = 0.002], with a similar CV between the two groups.Conclusion: The addition of once-weekly GLP-1RA PEG-Loxe to metformin was superior to insulin glargine in improving glycemic control and glycemic variability evaluated by CGM in middle-aged and elderly patients with T2DM

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

Spitzer + VLTI-GRAVITY Measure the Lens Mass of a Nearby Microlensing Event

We report the lens mass and distance measurements of the nearby microlensing event TCP J05074264+2447555. We measure the microlens parallax vector ${\pi}_{\rm E}$ using Spitzer and ground-based light curves with constraints on the direction of lens-source relative proper motion derived from Very Large Telescope Interferometer (VLTI) GRAVITY observations. Combining this ${\pi}_{\rm E}$ determination with the angular Einstein radius $\theta_{\rm E}$ measured by VLTI GRAVITY observations, we find that the lens is a star with mass $M_{\rm L} = 0.495 \pm 0.063~M_{\odot}$ at a distance $D_{\rm L} = 429 \pm 21~{\rm pc}$. We find that the blended light basically all comes from the lens. The lens-source proper motion is $\mu_{\rm rel,hel} = 26.55 \pm 0.36~{\rm mas\,yr^{-1}}$, so with currently available adaptive-optics (AO) instruments, the lens and source can be resolved in 2021. This is the first microlensing event whose lens mass is unambiguously measured by interferometry + satellite parallax observations, which opens a new window for mass measurements of isolated objects such as stellar-mass black holes.Comment: 3 Figures and 6 Tables Submitted to AAS Journa

Spitzer + VLTI-GRAVITY Measure the Lens Mass of a Nearby Microlensing Event

We report the lens mass and distance measurements of the nearby microlensing event TCP J05074264+2447555 (Kojima-1). We measure the microlens parallax vector π_E using Spitzer and ground-based light curves with constraints on the direction of lens-source relative proper motion derived from Very Large Telescope Interferometer (VLTI) GRAVITY observations. Combining this π_E determination with the angular Einstein radius θ_E measured by VLTI-GRAVITY observations, we find that the lens is a star with mass M_L = 0.495±0.063 M⊙ at a distance D_L = 429 ± 21 pc. We find that the blended light basically all comes from the lens. The lens-source proper motion is Μ_(rel,hel) = 26.55±0.36 mas yr⁻¹, so with currently available adaptive-optics instruments, the lens and source can be resolved in 2021. This is the first microlensing event whose lens mass is unambiguously measured by interferometry + satellite-parallax observations, which opens a new window for mass measurements of isolated objects such as stellar-mass black holes

JADES: Resolving the Stellar Component and Filamentary Overdense Environment of HST-Dark Submillimeter Galaxy HDF850.1 at z=5.18z=5.18

HDF850.1 is the brightest submillimeter galaxy (SMG) in the Hubble Deep Field. It is known as a heavily dust-obscured star-forming galaxy embedded in an overdense environment at $z = 5.18$. With nine-band NIRCam images at 0.8-5.0 $\mu$m obtained through the JWST Advanced Deep Extragalactic Survey (JADES), we detect and resolve the rest-frame UV-optical counterpart of HDF850.1, which splits into two components because of heavy dust obscuration in the center. The southern component leaks UV and H$\alpha$ photons, bringing the galaxy $\sim$100 times above the empirical relation between infrared excess and UV continuum slope (IRX-$\beta_\mathrm{UV}$). The northern component is higher in dust attenuation and thus fainter in UV and H$\alpha$ surface brightness. We construct a spatially resolved dust attenuation map from the NIRCam images, well matched with the dust continuum emission obtained through millimeter interferometry. The whole system hosts a stellar mass of $10^{11.0\pm0.1}\,\mathrm{M}_\odot$ and star-formation rate of $10^{3.0\pm0.2}\,\mathrm{M}_\odot\,\mathrm{yr}^{-1}$, placing the galaxy at the massive end of the star-forming main sequence at this epoch. We further confirm that HDF850.1 resides in a complex overdense environment at $z=5.17-5.30$, which hosts another luminous SMG at $z=5.30$ (GN10). The filamentary structures of the overdensity are characterized by 109 H$\alpha$-emitting galaxies confirmed through NIRCam slitless spectroscopy at 3.9-5 $\mu$m, of which only eight were known before the JWST observations. Given the existence of a similar galaxy overdensity in the GOODS-S field, our results suggest that $50\pm20$% of the cosmic star formation at $z=5.1-5.5$ occur in protocluster environments.Comment: 44 pages, 16 figures, 2 tables. Resubmitted to ApJ after including the first-round referee's comment

JADES: Resolving the Stellar Component and Filamentary Overdense Environment of Hubble Space Telescope (HST)-dark Submillimeter Galaxy HDF850.1 at z = 5.18

© 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/HDF850.1 is the brightest submillimeter galaxy (SMG) in the Hubble Deep Field. It is known as a heavily dust-obscured star-forming galaxy embedded in an overdense environment at z = 5.18. With nine-band NIRCam images at 0.8–5.0 μm obtained through the JWST Advanced Deep Extragalactic Survey, we detect and resolve the rest-frame UV–optical counterpart of HDF850.1, which splits into two components because of heavy dust obscuration in the center. The southern component leaks UV and Hα photons, bringing the galaxy ∼100 times above the empirical relation between infrared excess and UV continuum slope (IRX–β UV). The northern component is higher in dust attenuation and thus fainter in UV and Hα surface brightness. We construct a spatially resolved dust-attenuation map from the NIRCam images, well matched with the dust continuum emission obtained through millimeter interferometry. The whole system hosts a stellar mass of 1010.8±0.1 M ⊙ and star formation rate (SFR) of 102.8±0.2 M ⊙ yr−1, placing the galaxy at the massive end of the star-forming main sequence at this epoch. We further confirm that HDF850.1 resides in a complex overdense environment at z = 5.17–5.30, which hosts another luminous SMG at z = 5.30 (GN10). The filamentary structures of the overdensity are characterized by 109 Hα-emitting galaxies confirmed through NIRCam slitless spectroscopy at 3.9–5 μm, of which only eight were known before the JWST observations. Given the existence of a similar galaxy overdensity in the GOODS-S field, our results suggest that 50% ± 20% of the cosmic star formation at z = 5.1–5.5 occur in protocluster environments.Peer reviewe

The JWST Advanced Deep Extragalactic Survey: Discovery of an Extreme Galaxy Overdensity at z = 5.4 with JWST/NIRCam in GOODS-S

© 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We report the discovery of an extreme galaxy overdensity at $z = 5.4$ in the GOODS-S field using JWST/NIRCam imaging from JADES and JEMS alongside JWST/NIRCam wide field slitless spectroscopy from FRESCO. We identified potential members of the overdensity using HST+JWST photometry spanning $\lambda = 0.4-5.0\ \mu\mathrm{m}$. These data provide accurate and well-constrained photometric redshifts down to $m \approx 29-30\,\mathrm{mag}$. We subsequently confirmed $N = 81$ galaxies at $5.2 < z < 5.5$ using JWST slitless spectroscopy over $\lambda = 3.9-5.0\ \mu\mathrm{m}$ through a targeted line search for $\mathrm{H} \alpha$ around the best-fit photometric redshift. We verified that $N = 42$ of these galaxies reside in the field while $N = 39$ galaxies reside in a density around $\sim 10$ times that of a random volume. Stellar populations for these galaxies were inferred from the photometry and used to construct the star-forming main sequence, where protocluster members appeared more massive and exhibited earlier star formation (and thus older stellar populations) when compared to their field galaxy counterparts. We estimate the total halo mass of this large-scale structure to be $12.6 \lesssim \mathrm{log}_{10} \left( M_{\mathrm{halo}}/M_{\odot} \right) \lesssim 12.8$ using an empirical stellar mass to halo mass relation, which is likely an underestimate as a result of incompleteness. Our discovery demonstrates the power of JWST at constraining dark matter halo assembly and galaxy formation at very early cosmic times.Peer reviewe