We report herein the synthesis and structural and chemical characterization of six new compounds consisting of 6-aminonicotinate (6ani) ligands and first-row transition metal ions, namely, Mn2( mu ...-6ani)2(H2O)8(6ani)2 (1), Co(6ani)(bipy)2(H2O)3(6ani).5H2O (2), M( mu -6ani)(6ani)(H2O)3.2H2O MII = Co (3), Ni (4), and M( mu -6ani)2.H2O MII = Co (5), Cu (6) (where bipy = 4,4'-bipyridine). Compounds 1 and 2 consist of isolated dimeric and monomeric entities held together by supramolecular interactions governed by 6ani free anions. The rigid and low symmetry of 6ani ligands, in addition to their coordination as terminal and bridging ligands to octahedral metal geometries, gives rise to chiral 1D chains of compounds 3 and 4. 2D sql layers are formed (5 and 6) when 6ani ligands act as ligands bridging the metal ions, which precludes the presence of water molecules in the framework. Despite the wide structural diversity observed, all architectures share the occurrence of magnetically isolated 3d metal ions, given the poor exchange achieved through 6ani bridges, as confirmed by dc susceptibility measurements and DFT calculations. Dynamic ac susceptibility measurements reveal best-in-class field-induced slow magnetic relaxation behaviour in Co-based compounds with easy-plane magnetic anisotropy. The effective energy barriers (Ueff) of 39.6 K and 18.7 K for 3 and 5, respectively, estimated using the Arrhenius law are remarkably high among CoII-SIM coordination polymers reported so far.
Infections with Clostridioides difficile (formerly Clostridium difficile) have increased in incidence, morbidity, and mortality over the past decade. Preventing infections is becoming increasingly ...important, as frontline antibiotics become less effective and frequently induce recurrence by disrupting intestinal microbiota. The clinically most advanced vaccine approaches prevent symptoms once C. difficile infection is established by inducing immunity to secreted clostridial cytotoxins. However, they do not inhibit bacterial colonization and thereby favor asymptomatic carriage. Synthetic oligosaccharides resembling the C. difficile surface glycans PS-I, PS-II, and PS-III are immunogenic and serve as basis for colonization-preventing vaccines. Here, we demonstrate that glycoconjugate vaccine candidates based on synthetic oligosaccharides protected mice from infections with two different C. difficile strains. Four synthetic antigens, ranging in size from disaccharides to hexasaccharides, were conjugated to CRM197, which is a carrier protein used in commercial vaccines. The vaccine candidates induced glycan-specific antibodies in mice and substantially limited C. difficile colonization and colitis after experimental infection. The glycoconjugates ameliorated intestinal pathology more substantially than a toxin-targeting vaccine. Colonization of the gut by C. difficile was selectively inhibited while intestinal microbiota remained preserved. Passive transfer experiments with anti-PS-I serum revealed that protection is mediated by specific antiglycan antibodies; however, cell-mediated immunity likely also contributed to protection in vivo. Thus, glycoconjugate vaccines against C. difficile are a complementary approach to toxin-targeting strategies and are advancing through preclinical work.
Introduction
We report the case of a fatal hemorrhagic varicella primary infection in an immunocompetent man and whole-genome characterization of the virus for the investigation of biomarkers of ...virulence.
Case
A 38-year-old patient born in Nigeria presented to the emergency department with abdominal pain and subsequently developed fatal hemorrhagic disease without skin rash. Extensive laboratory tests including serology and PCR for arenaviruses, bunyaviruses and ebolaviruses were negative. Varicella-zoster virus (VZV) PCR of sera, liver and spleen tissue samples from autopsy revealed the presence of VZV DNA. Primary infection by varicella-zoster virus with hemorrhagic manifestations was diagnosed after virological testing. The VZV genome was sequenced using a mWGS approach. Bioinformatic analysis showed 53 mutations across the genome, 33 of them producing non-synonymous variants affecting up to 14 genes. Some of them, such as ORF11 and ORF 62, encoded for essential functions related to skin or neurotropism. To our knowledge, the mutations reported here have never been described in a VZV causing such a devastating outcome.
Discussion
In immunocompetent patients, viral factors should be considered in patients with uncommon symptoms or severe diseases. Some relevant mutations revealed by using whole genome sequencing (WGS) directly from clinical samples may be involved in this case and deserves further investigation.
Conclusion
Differential diagnosis of varicella-zoster virus in immunocompetent adults should be considered among patients with suspected VHF, even if the expected vesicular rash is not present at admission and does not arise thereafter. Whole genome sequencing of strains causing uncommon symptoms and/or mortality is needed for epidemiological surveillance and further characterization of putative markers of virulence. Additionally, this report highlights the recommendation for a VZV vaccination policy in non-immunized migrants from developing countries.
Solvothermally promoted assembly of the multifunctional 3‐amino‐4‐hydroxybenzoic acid ligand with the corresponding Eu salt gives rise to the formation of a porous metal‐organic framework with the ...general formula {Eu5L6(OH)3(H2O)3 ⋅ 5DMF}n (1) that has been tested as heterogeneous catalyst for the cyanosilylation of a broad scope of ketones in solvent‐free conditions, using the lowest catalyst loading of 0.5 mol% ever reported, and exhibiting no leak and high recyclability.
MOF for cyanosilylation: A new Europium MOF has been synthesized, characterized and its electrophoretic and catalytic behavior thoroughly studied. The new MOF system has demonstrated a negative surface charge at basic conditions that in the cyanosilylation of ketones (17 examples) and aldehydes (3 examples) afforded outstanding catalytic performance using the most reduced catalyst loading described in the literature and full recyclability at least during the first seven cycles.
We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ...ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6-37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.
We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. ...The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).
Timeline of significant events. *Serum, urine, vaginal swab, cervicovaginal lavage and endocervical swab. CHKV, chikungunya virus; CSF, cerebrospinal fluid; Ct, amplification cycle threshold; CT, computed tomography; DENV, dengue virus; MRI, magnetic resonance imaging; RT-PCR, real-time PCR; US, ultrasound; ZIKV, Zika virus. Display omitted
Herein, to the best of our knowledge, the first heterobimetallic Y/Eu porous metal–organic framework (MOF), based on 3-amino-4-hydroxybenzoic acid (H2L) ligand, with the following formulae ...{Y3.5Eu1.5L6(OH)3(H2O)3·12DMF}n (in advance, namely Y/Eu-MOF), is described. The three-dimensional structure has been synthesized by solvothermal routes and thoroughly characterized, by means of single crystal X-ray diffraction, powder X-ray diffraction, electronic microscopy, ICP-AES, electrophoretic mobility, and FTIR spectra. Intriguingly, the porous nature allows for coordinated solvent molecules displacement, yielding unsaturated metal centers, which can act as a Lewis acid catalyst. This novel supramolecular entity has been tested in cyanosilylation and hydroboration reactions on carbonyl substrates of a diverse nature, exhibiting an extraordinary activity.
l-lactate formation occurs via the reduction of pyruvate catalyzed by lactate dehydrogenase. l-lactate removal takes place via its oxidation into pyruvate, which may be oxidized or converted into ...glucose. Pyruvate oxidation involves the cooperative effort of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. In addition, pyruvate may undergo reversible transamination to alanine by alanine aminotransferase. Enzymes involved in l-lactate metabolism are crucial to diabetes pathophysiology and therapy. Elevated plasma alanine aminotransferase concentration has been associated with insulin resistance. Polymorphisms in the G6PC2 gene have been associated with fasting glucose concentration and insulin secretion. In diabetes patients, pyruvate dehydrogenase is down-regulated and the activity of pyruvate carboxylase is diminished in the pancreatic islets. Inhibitors of fructose 1,6-bisphosphatase are being investigated as potential therapy for type 2 diabetes. In addition, enzymes implicated in l-lactate metabolism have revealed to be important in cancer cell homeostasis. Many human tumors have higher LDH5 levels than normal tissues. The LDHC gene is expressed in a broad range of tumors. The activation of PDH is a potential mediator in the body response that protects against cancer and PDH activation has been observed to reduce glioblastoma growth. The expression of PDK1 may serve as a biomarker of poor prognosis in gastric cancer. Mitochondrial DNA mutations have been detected in a number of human cancers. Genes encoding succinate dehydrogenase have tumor suppressor functions and consequently mutations in these genes may cause a variety of tumors.
The Assignment of the Absolute Configuration by NMR Using Chiral Derivatizing Agents: A Practical Guide briefly explains the theoretical aspects necessary for understanding the methodology of new ...research in the field of Nuclear magnetic resonance spectroscopy (NMR), dedicating most of its space to covering the practical aspects of the assignment, with examples and spectra taken from the authors' own experiments. Upper-level undergraduates, graduate students, and chemical researchers will find this guide useful for their studies and practice.
The already reported monomeric complex Co(SDZ)2bpy (1) and the new ternary complex Co(SDZ)2(6MQ)2 (2) (SDZ = sulfadiazine, bpy = 2,2′‐bipyridine, and 6MQ = 6‐methoxyquinoline) have been synthesized ...in order to study their magnetic properties. X‐ray diffraction studies indicate that in both compounds the SDZ acts as a bidentate ligand coordinating through the sulfonamide and the pyrimidine N atoms giving rise to a CoN6 coordination sphere. The complexes have been characterized based on elemental analyses, FTIR, UV/Vis spectroscopy, and thermogravimetric analysis (TGA, only for 2). Compounds 1 and 2 have been characterized magnetically, and they show slow relaxation of the magnetization below 9 and 6 K, respectively.
Two monomeric cobalt complexes, Co(SDZ)2bpy and Co(SDZ)2(6MQ)2 (SDZ = sulfadiazine, bpy = 2,2′‐bipyridine, and 6MQ = 6‐methoxyquinoline), have been prepared and characterized. X‐ray diffraction studies indicate that in both compounds SDZ acts as a bidentate ligand coordinating through the sulfonamide and the pyrimidine N atoms. The complexes show slow relaxation of the magnetization below 9 and 6 K.
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