KMT-2022-BLG-0440Lb: A New q<10−4q < 10^{-4} Microlensing Planet with the Central-Resonant Caustic Degeneracy Broken

We present the observations and analysis of a high-magnification microlensing planetary event, KMT-2022-BLG-0440, for which the weak and short-lived planetary signal was covered by both the KMTNet survey and follow-up observations. The binary-lens models with a central caustic provide the best fits, with a planet/host mass ratio, $q = 0.75$--$1.00 \times 10^{-4}$ at $1\sigma$. The binary-lens models with a resonant caustic and a brown-dwarf mass ratio are both excluded by $\Delta\chi^2 > 70$. The binary-source model can fit the anomaly well but is rejected by the ``color argument'' on the second source. From Bayesian analyses, it is estimated that the host star is likely a K or M dwarf located in the Galactic disk, the planet probably has a Neptune-mass, and the projected planet-host separation is $1.9^{+0.6}_{-0.7}$ or $4.6^{+1.4}_{-1.7}$ au, subject to the close/wide degeneracy. This is the third $q < 10^{-4}$ planet from a high-magnification planetary signal ($A \gtrsim 65$). Together with another such planet, KMT-2021-BLG-0171Lb, the ongoing follow-up program for the KMTNet high-magnification events has demonstrated its ability in detecting high-magnification planetary signals for $q < 10^{-4}$ planets, which are challenging for the current microlensing surveys.Comment: MNRAS accepte

Question of CO’s Ability to Induce HO‑1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

With the recognition of the endogenous signaling roles and pharmacological functions of carbon monoxide (CO), there is an increasing need to understand CO’s mechanism of actions. Along this line, chemical donors have been introduced as CO surrogates for ease of delivery, dosage control, and sometimes the ability to target. Among all of the donors, two ruthenium–carbonyl complexes, CORM-2 and -3, are arguably the most commonly used tools for about 20 years in studying the mechanism of actions of CO. Largely based on data using these two CORMs, there has been a widely accepted inference that the upregulation of heme oxygenase-1 (HO-1) expression is one of the key mechanisms for CO’s actions. However, recent years have seen reports of very pronounced chemical reactivities and CO-independent activities of these CORMs. We are interested in examining this question by conducting comparative studies using CO gas, CORM-2/-3, and organic CO donors in RAW264.7, HeLa, and HepG2 cell cultures. CORM-2 and CORM-3 treatment showed significant dose-dependent induction of HO-1 compared to “controls,” while incubation for 6 h with 250–500 ppm CO gas did not increase the HO-1 protein expression and mRNA transcription level. A further increase of the CO concentration to 5% did not lead to HO-1 expression either. Additionally, we demonstrate that CORM-2/-3 releases minimal amounts of CO under the experimental conditions. These results indicate that the HO-1 induction effects of CORM-2/-3 are not attributable to CO. We also assessed two organic CO prodrugs, BW-CO-103 and BW-CO-111. BW-CO-111 but not BW-CO-103 dose-dependently increased HO-1 levels in RAW264.7 and HeLa cells. We subsequently studied the mechanism of induction with an Nrf2-luciferase reporter assay, showing that the HO-1 induction activity is likely due to the activation of Nrf2 by the CO donors. Overall, CO alone is unable to induce HO-1 or activate Nrf2 under various conditions in vitro. As such, there is no evidence to support attributing the HO-1 induction effect of the CO donors such as CORM-2/-3 and BW-CO-111 in cell culture to CO. This comparative study demonstrates the critical need to consider possible CO-independent effects of a chemical CO donor before attributing the observed biological effects to CO. It is also important to note that such in vitro results cannot be directly extrapolated to in vivo studies because of the increased level of complexity and the likelihood of secondary and/or synergistic effects in the latter

FRET‐Based In‐Cell Detection of Highly Selective Supramolecular Complexes of <i>meso</i> ‐Tetraarylporphyrin with Peptide/BODIPY‐Modified Per‐ <i>O</i> ‐Methyl‐β‐Cyclodextrins

Artificial supramolecular systems capable of self-assembly and that precisely function in biological media are in high demand. Herein, we demonstrate a highly specific host-guest-pair system that functions in living cells. A per-O-methyl-β-cyclodextrin derivative (R8-B-CD Me) bearing both an octaarginine peptide chain and a BODIPY dye was synthesized as a fluorescent intracellular delivery tool. R8-B-CD Me was efficiently taken up by HeLa cells through both endocytosis and direct transmembrane pathways. R8-B-CD Me formed a 2 : 1 inclusion complex with tetrakis(4-sulfonatophenyl)porphyrin (TPPS) as a guest molecule in water, from which fluorescence resonance energy transfer (FRET) from R8-B-CD Me to TPPS was observed. The FRET phenomenon was clearly detected in living cells using confocal microscopy techniques, which revealed that the formed supramolecular R8-B-CD Me /TPPS complex was maintained within the cells. The R8-B-CD Me cytotoxicity assay revealed that the addition of TPPS counteracts the strong cytotoxicity (IC 50 = 16 μM) of the CD cavity due to complexation within the cells. A series of experiments demonstrated the bio-orthogonality of the supramolecular per-O-methyl-β-CD/tetraarylporphyrin hostguest pair in living cells

Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication

International audienceAbstract Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, while the fact that CO accumulation in tissues is the most likely direct cause of mortality is less investigated. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as an effective adjuvant to O 2 ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning

Functional Myoglobin Model Composed of a Strapped Porphyrin/Cyclodextrin Supramolecular Complex with an Overhanging COOH That Increases O(2)/CO Binding Selectivity in Aqueous Solution

International audienceA water-soluble strapped iron(III)tetraarylporphyrin () bearing two propylpyridinium groups at the side chains and a carboxylic acid group at the overhanging position of the strap was synthesized to mimic the function of myoglobin with the distal polar functionality in aqueous solution. forms a stable 1:1 inclusion complex with a per--methylated β-cyclodextrin dimer having a pyridine linker (), providing a hydrophobic environment and a proximal fifth ligand to stabilize the O-complex. The ferrous complex () binds both O and CO in aqueous solution. The O and CO binding affinities ( and ) and half-life time () of the O complex of are 6.3 and 0.021 Torr, and 7 h, respectively, at pH 7 and 25 °C. The control compound without the strap structure () has similar oxygen binding characteristics ( = 8.0 Torr), but much higher CO binding affinity ( = 3.8 × 10 Torr), and longer (30 h). The O and CO kinetics indicate that the strapped structure in inhibits the entrance of these gaseous ligands into the iron(II) center, as evidenced by lower and values. Interestingly, the CO complex of is significantly destabilized (relatively larger ), while the value is much smaller than that of , resulting in significantly increased O/CO selectivity (reduced value, where = / = 320) in compared to ( = 21000)