Bioactivity Determination of Native and Variant Forms of Therapeutic Interferons

The traditional antiviral assays for the determination of interferon potency are reported to have considerable variability between and within assays. Although several reporter gene assays based on interferon-inducible promoter activities have been reported, data from comprehensive validation studies are lacking and few studies have been conducted to analyze the variant forms of interferons, which could have undesirable clinical implications. Here, a reporter gene assay employing a HEK293 cell line stably transfected with luciferase gene under the control of interferon-stimulated response element promoter was developed and validated. The assay was found to be more sensitive, with a larger detection range than the antiviral assay. Several cytokines tested did not interfere with the test, suggesting the assay possesses a certain degree of selectivity. Moreover, the robustness of the assay was demonstrated by minimal variations in the results generated by different analysts and cell passage number (up to 52 passages). Finally, the method was employed to analyze several interferon variants (interferon-α 2a) and we found that the aggregated form has completely lost its potency; while a modest loss of bioactivity in oxidized interferon was observed (approx. 23%), the deamidated form essentially retained its activity

An improved method to measure 12C/13C\rm ^{12}C/^{13}C and 14N/15N\rm ^{14}N/^{15}N abundance ratios: revisiting CN isotopologues in the Galactic outer disk

The variations of elemental abundance and their ratios along the Galactocentric radius result from the chemical evolution of the Milky Way disks. The $\rm ^{12}C/^{13}C$ ratio in particular is often used as a proxy to determine other isotopic ratios, such as $\rm ^{16}O/^{18}O$ and $\rm ^{14}N/^{15}N$. Measurements of $\rm ^{12}CN$ and $\rm ^{13}CN$ (or $\rm C^{15}N$) -- with their optical depths corrected via their hyper-fine structure lines -- have traditionally been exploited to constrain the Galactocentric gradients of the CNO isotopic ratios. Such methods typically make several simplifying assumptions (e.g. a filling factor of unity, the Rayleigh-Jeans approximation, and the neglect of the cosmic microwave background) while adopting a single average gas phase. However, these simplifications introduce significant biases to the measured $\rm ^{12}C/^{13}C$ and $\rm ^{14}N/^{15}N$. We demonstrate that exploiting the optically thin satellite lines of $\rm ^{12}CN$ constitutes a more reliable new method to derive $\rm ^{12}C/^{13}C$ and $\rm ^{14}N/^{15}N$ from CN isotopologues. We apply this satellite-line method to new IRAM 30-m observations of $\rm ^{12}CN$, $\rm ^{13}CN$, and $\rm C^{15}N$ $N=1\to0$ towards 15 metal-poor molecular clouds in the Galactic outer disk ($R_{\rm gc} >$ 12 kpc), supplemented by data from the literature. After updating their Galactocentric distances, we find that $\rm ^{12}C/^{13}C$ and $\rm ^{14}N/^{15}N$ gradients are in good agreement with those derived using independent optically thin molecular tracers, even in regions with the lowest metallicities. We therefore recommend using optically thin tracers for Galactic and extragalactic CNO isotopic measurements, which avoids the biases associated with the traditional method.Comment: 41 pages, 29 figures, accepted by MNRAS. Meeting materials related to this work at https://box.nju.edu.cn/d/5035a574e236408eab94

Carbon-Chain Molecules in Molecular Outflows and Lupus I Region--New Producing Region and New Forming Mechanism

Using the new equipment of the Shanghai Tian Ma Radio Telescope, we have searched for carbon-chain molecules (CCMs) towards five outflow sources and six Lupus I starless dust cores, including one region known to be characterized by warm carbon-chain chemistry (WCCC), Lupus I-1 (IRAS 15398-3359), and one TMC-1 like cloud, Lupus I-6 (Lupus-1A). Lines of HC3N J=2-1, HC5N J=6-5, HC7N J=14-13, 15-14, 16-15 and C3S J=3-2 were detected in all the targets except in the outflow source L1660 and the starless dust core Lupus I-3/4. The column densities of nitrogen-bearing species range from 10$^{12}$ to 10$^{14}$ cm$^{-2}$ and those of C$_3$S are about 10$^{12}$ cm$^{-2}$. Two outflow sources, I20582+7724 and L1221, could be identified as new carbon-chain--producing regions. Four of the Lupus I dust cores are newly identified as early quiescent and dark carbon-chain--producing regions similar to Lup I-6, which together with the WCCC source, Lup I-1, indicate that carbon-chain-producing regions are popular in Lupus I which can be regard as a Taurus like molecular cloud complex in our Galaxy. The column densities of C3S are larger than those of HC7N in the three outflow sources I20582, L1221 and L1251A. Shocked carbon-chain chemistry (SCCC) is proposed to explain the abnormal high abundances of C3S compared with those of nitrogen-bearing CCMs. Gas-grain chemical models support the idea that shocks can fuel the environment of those sources with enough $S^+$ thus driving the generation of S-bearing CCMs.Comment: 7 figures, 8 tables, accepted by MNRA

Dependence of Chemical Abundance on the Cosmic Ray Ionization Rate in IC 348

Ions (e.g., H$_3^+$, H$_2$O$^+$) have been used extensively to quantify the cosmic-ray ionization rate (CRIR) in diffuse sightlines. However, measurements of CRIR in low-to-intermediate density gas environments are rare, especially when background stars are absent. In this work, we combine molecular line observations of CO, OH, CH, and HCO$^+$ in the star-forming cloud IC~348, and chemical models to constrain the value of CRIR and study the response of the chemical abundances distribution. The cloud boundary is found to have an $A_{\rm V}$ of approximately 4 mag. From the interior to the exterior of the cloud, the observed $^{13}$CO line intensities drop by an order of magnitude. The calculated average abundance of $^{12}$CO (assuming $^{12}$C/$^{13}$C = 65) is (1.2$\pm$0.9) $\times$10$^{-4}$, which increases by a factor of 6 from the interior to the outside regions. The average abundance of CH (3.3$\pm$0.7 $\times$ 10$^{-8}$) is in good agreement with previous findings in diffuse and translucent clouds ($A_{\rm V}$ $<$ 5 mag). However, we did not find a decline in CH abundance in regions of high extinction ($A_{\rm V}\simeq$8 mag) as previously reported in Taurus. By comparing the observed molecular abundances and chemical models, we find a decreasing trend of CRIR as $A_{\rm V}$ increases. The inferred CRIR of $\zeta_{cr}$ = (4.7$\pm$1.5) $\times$ 10$^{-16}$ s$^{-1}$ at low $A_{\rm V}$ is consistent with H$^+_3$ measurements toward two nearby massive stars.Comment: 21 pages, 11 figures. Submitted to Ap

Discovery of a radio lobe in the Cloverleaf Quasar at z = 2.56

The fast growth of supermassive black holes and their feedback to the host galaxies play an important role in regulating the evolution of galaxies, especially in the early Universe. However, due to cosmological dimming and the limited angular resolution of most observations, it is difficult to resolve the feedback from the active galactic nuclei (AGN) to their host galaxies. Gravitational lensing, for its magnification, provides a powerful tool to spatially differentiate emission originated from AGN and host galaxy at high redshifts. Here we report a discovery of a radio lobe in a strongly lensed starburst quasar, H1413+117 or Cloverleaf at redshift $z= 2.56$, based on observational data at optical, sub-millimetre, and radio wavelengths. With both parametric and non-parametric lens models and with reconstructed images on the source plane, we find a differentially lensed, kpc scaled, single-sided radio lobe, located at ${\sim}1.2\,\mathrm{kpc}$ to the north west of the host galaxy on the source plane. From the spectral energy distribution in radio bands, we find that the radio lobe has an energy turning point residing between 1.5 GHz and 8 GHz, indicating an age of 20--50 Myr. This could indicate a feedback switching of Cloverleaf quasar from the jet mode to the quasar mode

Re-visiting the extended Schmidt law: the important role of existing stars in regulating star formation

We revisit the proposed extended Schmidt law (Shi et al. 2011) which points that the star formation efficiency in galaxies depends on the stellar mass surface density, by investigating spatially-resolved star formation rates (SFRs), gas masses and stellar masses of star formation regions in a vast range of galactic environments, from the outer disks of dwarf galaxies to spiral disks and to merging galaxies as well as individual molecular clouds in M33. We find that these regions are distributed in a tight power-law as Sigma_SFR ~(Sigma_star^0.5 Sigma_gas )^1.09, which is also valid for the integrated measurements of disk and merging galaxies at high-z. Interestingly, we show that star formation regions in the outer disks of dwarf galaxies with Sigma_SFR down to 10^(-5) Msun/yr/kpc^2, which are outliers of both Kennicutt-Schmidt and Silk-Elmegreen law, also follow the extended Schmidt law. Other outliers in the Kennicutt-Schmidt law, such as extremely-metal poor star-formation regions, also show significantly reduced deviations from the extended Schmidt law. These results suggest an important role for existing stars in helping to regulate star formation through the effect of their gravity on the mid-plane pressure in a wide range of galactic environments.Comment: 15 pages, 6 figures, 3 tables; ApJ in pres

Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required

Assessing the structure and diversity of fungal community in plant soil under different climatic and vegetation conditions

IntroductionUnderstanding microbial communities in diverse ecosystems is crucial for unraveling the intricate relationships among microorganisms, their environment, and ecosystem processes. In this study, we investigated differences in the fungal community structure and diversity in soils from two contrasting climatic and vegetation conditions: the Xinjiang western China plateau and the Fujian southeastern coastal province.MethodsA total of 36 soil samples collected from two climatic regions were subjected to high-throughput ITS gene sequencing for fungal community analysis. In conjunction soil physicochemical properties were assessed and compared. Analyses included an examination of the relationship of fungal community structure to environmental factors and functional profiling of the community structure was using the FUNGuild pipeline.ResultsOur data revealed rich fungal diversity, with a total of 11 fungal phyla, 31 classes, 86 orders, 200 families, 388 genera, and 515 species identified in the soil samples. Distinct variations in the physicochemical properties of the soil and fungal community structure were seen in relation to climate and surface vegetation. Notably, despite a colder climate, the rhizosphere soil of Xinjiang exhibited higher fungal (α-)diversity compared to the rhizosphere soil of Fujian. β-diversity analyses indicated that soil heterogeneity and differences in fungal community structure were primarily influenced by spatial distance limitations and vegetation type. Furthermore, we identified dominant fungal phyla with significant roles in energy cycling and organic matter degradation, including members of the Sordariomycetes, Leotiomycetes, Archaeosporomycetes, and Agaricomycetes. Functional analyses of soil fungal communities highlighted distinct microbial ecological functions in Xinjiang and Fujian soils. Xinjiang soil was characterized by a focus on wood and plant saprotrophy, and endophytes, whereas in Fujian soil the fungal community was mainly associated with ectomycorrhizal interactions, fungal parasitism, and wood saprotrophy.DiscussionOur findings suggest fungal communities in different climatic conditions adapt along distinct patterns with, plants to cope with environmental stress and contribute significantly to energy metabolism and material cycling within soil-plant systems. This study provides valuable insights into the ecological diversity of fungal communities driven by geological and environmental factors

Effect of Vaccination on Bordetella pertussis Strains, China

Strains in China may differ from those in countries that have long histories of high vaccination coverage