Oxychloridoselenites( iv ) with cubane-derived anions and stepwise chlorine-to-oxygen exchange

The novel oxychloridoselenites(IV) [BMIm][Se$_3$Cl$_{13}$] (1), [BMIm][Se$_4$Cl$_{15}$O] (2), [BMIm]$_2$[Se$_4$Cl$_{14}$O$_2$] (3), [BMPyr]$_2$[Se$_4$Cl$_{14}$O$_2$] (4), [BMPyr]$_2$[Se$_6$Cl$_{18}$O$_4$] (5), [BMIm]$_2$[SeCl$_4$O] (6), [BMPyr]$_2$[Se$_2$Cl$_6$O$_2$] (7), and [BMPyr]$_2$[Se$_6$Cl$_{14}$O$_6$] (8) are prepared by ionic-liquid-based synthesis. Accordingly, SeCl$_4$, SeO$_2$ (1–6), and/or SeOCl$_2$ (7,8) as the starting materials are reacted in [BMIm]Cl or [BMPyr]Cl as ionic liquid (BMIm: 1-butyl-3-methylimidazolium, BMPyr: 1-butyl-1-methylpyrrolidinium; partially with AlCl$_3$ in addition). Generally, the composition and structure of title compounds can be derived from the tetrameric, heterocubane-type (SeCl$_4$)$_4$ as the initial building unit. Thus, chlorine is successively exchanged by oxygen from 1 to 8. Moreover, the four edge-sharing (SeCl$_6$) octahedra in (SeCl$_4$)$_4$ are increasingly dismantled, ending with a [SeCl$_4$O]$^{2−}$ anion as a single pseudo-octahedron in 6. Based on the weakly coordinating ionic liquid, it is possible to selectively obtain the different species via synthesis near room temperature (20–80 °C). The oxychloridoselenite anions [Se$_4$Cl$_{15}$O]$^−$, [Se$_4$Cl$_{14}$O$_2$]$^{2−}$, [Se$_6$Cl$_{18}$O$_4$]$^{2−}$, and [Se$_6$Cl$_{14}$O$_6$]$^{2−}$ are obtained for the first time. The title compounds are characterized by X-ray structure analysis based on single crystals and powders as well as by infrared spectroscopy and thermal analysis

Second-harmonic-generation of [(Se,Te)Cl3_{3}]+^{+} [GaCl4_{4}]–^{–} with aligned ionic tetrahedra

[SeCl$_{3}$][GaCl$_{4}$] (1) and [TeCl$_{3}$][GaCl$_{4}$] (2) are prepared via Lewis-acid–base reaction of SeCl$_{4}$ or TeCl$_{4}$ with GaCl$_{3}$ at 50 °C (1) and 140 °C (2) in quantitative yield. The ionic compounds contain pseudo-tetrahedral [SeCl$_{3}$]$^{+}$/[TeCl$_{3}$]$^{+}$ cations with a prominent stereochemically active electron lone pair at Se(IV)/Te(IV) as well as tetrahedral [GaCl$_{4}$]$^{–}$ anions. Both compounds crystallize in the polar chiral space group P1 with an unidirectional alignment of all tetrahedral building units. They can be considered as the first examples of a much larger group of ionic compounds [MX$_{3}$]$^{+}$[M′X$_{4}$]$^{–}$ (M, M′: metal or main-group element, X: halogen) showing nonlinear optical effects. Material characterization is performed by X-ray structure analysis based on single crystals and powder samples, thermogravimetry, optical spectroscopy, infrared and Raman spectroscopy. Second harmonic generation (SHG) is observed with intensities about 3-times stronger than for potassium dihydrogen phosphate (KDP) in the visible spectral regime with narrow-band-gap materials (2.8, 3.2 eV). Density functional theory calculations are employed to complement the experimental findings, interpret the Raman spectra, visualize the stereochemically active lone electron pair, and compute the SHG tensor

Genomic characterization of an NDM-9-producing Acinetobacter baumannii clinical isolate and role of Glu152Lys substitution in the enhanced cefiderocol hydrolysis of NDM-9

Here, we characterized the first French NDM-9-producing Acinetobacter baumannii isolate. A. baumannii 13A297, which belonged to the STPas25 (international clone IC7), was highly resistant to β-lactams including cefiderocol (MIC >32 mg/L). Whole genome sequencing (WGS) using both Illumina and Oxford Nanopore technologies revealed a 166-kb non-conjugative plasmid harboring a blaNDM-9 gene embedded in a Tn125 composite transposon. Complementation of E. coli DH5α and A. baumannii CIP70.10 strains with the pABEC plasmid carrying the blaNDM-1 or blaNDM-9 gene, respectively, resulted in a significant increase in cefiderocol MIC values (16 to >256-fold), particularly in the NDM-9 transformants. Interestingly, steady-state kinetic parameters, measured using purified NDM-1 and NDM-9 (Glu152Lys) enzymes, revealed that the affinity for cefiderocol was 3-fold higher for NDM-9 (Km = 53 μM) than for NDM-1 (Km = 161 μM), leading to a 2-fold increase in catalytic efficiency for NDM-9 (0.13 and 0.069 μM−1.s−1, for NDM-9 and NDM-1, respectively). Finally, we showed by molecular docking experiments that the residue 152 of NDM-like enzymes plays a key role in cefiderocol binding and resistance, by allowing a strong ionic interaction between the Lys152 residue of NDM-9 with both the Asp223 residue of NDM-9 and the carboxylate group of the R1 substituent of cefiderocol

Sequential emergence of colistin and rifampicin resistance in an OXA-72- producing outbreak strain of Acinetobacter baumannii

International audienc

Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of 2 layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population