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Carbon monoxide (CO) exerts various protective effects on the body. Drugs known as CORMs (CO-releasing molecules) can continuously release small doses of CO into diseased tissues and cells. Transition metals interact strongly with the carbonyl group, and coordination compounds bearing carbonyl groups are a promising class of CORMs. This study investigates the octahedral coordination of Fe2+ and Fe3+ compounds with carbonyl groups (to give Fen+[CO]6) and subsequent substitutions with Cl−, Br−, NH3, and H2O, to understand how these ligands interfere in the M-CO bond. The geometry optimization calculations were performed with the methods BP86 and B3LYP and the atomic basis set def2-TZVP. The molecular orbitals and the properties derived from the electronic density based on QTAIM were analyzed. Coordination with ligands increased the influence of the metal atomic basin on the Fe-C bond, especially for the Fe2+ compounds, and the Cl− and Br− ligands led to lower local ionization energies at the Fe-C bonds. Trans effects were also observed in the QTAIM real functions: Fe-C bond distances were shorter when C was in trans position to a ligand. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) exerts various protective effects on the body. Drugs known as CORMs (CO-releasing molecules) can continuously release small doses of CO into diseased tissues and cells. Transition metals interact strongly with the carbonyl group, and coordination compounds bearing carbonyl groups are a promising class of CORMs. This study investigates the octahedral coordination of Fe2+ and Fe3+ compounds with carbonyl groups (to give Fen+[CO]6) and subsequent substitutions with Cl−, Br−, NH3, and H2O, to understand how these ligands interfere in the M-CO bond. The geometry optimization calculations were performed with the methods BP86 and B3LYP and the atomic basis set def2-TZVP. The molecular orbitals and the properties derived from the electronic density based on QTAIM were analyzed. Coordination with ligands increased the influence of the metal atomic basin on the Fe-C bond, especially for the Fe2+ compounds, and the Cl− and Br− ligands led to lower local ionization energies at the Fe-C bonds. Trans effects were also observed in the QTAIM real functions: Fe-C bond distances were shorter when C was in trans position to a ligand. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP 3/28 ), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP 3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP 3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation., Competing Interests: Competing interests: Y.H., L.Y., E.Z. and J.Y. are inventors on patents relating to this study filed by the University of California, Los Angeles. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The cellular and mechanistic bases underlying endothelial regeneration of adult large vessels have proven challenging to study. Using a reproducible in vivo aortic endothelial injury model, we characterized cellular dynamics underlying the regenerative process through a combination of multi-color lineage tracing, parabiosis, and single-cell transcriptomics. We found that regeneration is a biphasic process driven by distinct populations arising from differentiated endothelial cells. The majority of cells immediately adjacent to the injury site re-enter the cell cycle during the initial damage response, with a second phase driven by a highly proliferative subpopulation. Endothelial regeneration requires activation of stress response genes including Atf3, and aged aortas compromised in their reparative capacity express less Atf3. Deletion of Atf3 reduced endothelial proliferation and compromised the regeneration. These findings provide important insights into cellular dynamics and mechanisms that drive responses to large vessel injury., (Published by Elsevier Inc.)

Very rare cases of hypersensitivity reactions to various constituents of parenteral nutrition (PN) have been reported in children. Adverse effects associated with PN administration have centered on metabolic, infectious, and mechanical complications. Here we describe three cases of hypersensitivity to components of PN. Case 1 is a 1-mo-old breastfed baby with a diagnosis of acute gastroenteritis associated with an infection with cytomegalovirus. On the second day of PN, 60 min after the initiation of the infusion, the patient had an allergic reaction with an overall diffused rash. On day 4 of PN, the multivitamin solution and the trace element mix were excluded, showing a good tolerance. Case 2 is a 4-y-old girl with a background of stage III neuroblastoma. On day 3 of PN, 15 min after the initiation of the infusion, the patient showed sudden facial edema. On day 5, suspecting the amino acid solution to be the etiology of her reaction, PN was infused with another amino acid preparation, and the patient showed good tolerance. Case 3 is a 10-y-old boy with a diagnosis of an acute peritonitis. Two h after the initiation of the infusion, the patient showed a general wheal rash. He referred a background of fish allergy. Considering that the lipid emulsion used had components from fish oil (SMOF Lipid), a new PN was infused on day 2. The new PN contained a lipid emulsion containing vegetable oil (ClinOleic). The patient showed good tolerance. In conclusion, we consider that, although the hypersensitivity to PN components is infrequent, there is an increase in reports of pediatric cases describing this allergic pathology., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether hypoxia inducible factor (HIF-1α) targeting pharmacological drugs, echinomycin, resveratrol and CdCl2 which inhibit HIF-1α stimulation, and mimosine, which enhances the stability of HIF-1α present antileishmanial properties., Methods: The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis., Results: Resveratrol and CdCl2 reduced the parasite load [IC50, (27.3 ± 2.25) μM and (24.8 ± 0.95) μM, respectively]. The IC50 value of echinomycin was (22.7 ± 7.36) nM and mimosine did not alter the parasite load in primary macrophages. The macrophage viability IC50 values for resveratrol, echinomycin and CdCl2 and mimosine were >40 μM, >100 nM, >200 μM and>2000 μM, respectively. In vivo no differences between cutaneous lesions from control, resveratrol- and echinomycin-treated Balb/c mice were detected., Conclusions: Resveratrol, echinomycin and CdCl2 reduce parasite survival in vitro. The HIF-1α targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies., (Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Background: To determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed., Methods: Ten CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system., Results: An average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1)., Conclusion: The RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis.

Chemically speaking, atomic clusters are very rich, allowing their application in a broad range of technological areas such as developing functional materials, heterogeneous catalysis, and building optical devices. In this work, high level computational chemistry methods were used in a systematic manner to improve the characterization of small clusters formed by boron, silicon, germanium, mixed boron/silicon, and mixed boron/germanium. Calculations were carried out with both ab initio [MP2 and CCSD(T)] and density functional (B3LYP) methods with extended basis sets. The CCSD(T) results were then extrapolated to the complete basis set (CBS) limit. Finally, geometrical parameters, vibrational frequencies, and relative energies were then obtained and compared to data presented in the literature. Graphical Abstract Small boron, silicon and germanium clusters: BmSin and BmGen (m + n = 2-4).

Tetralogy of Fallot (TOF) (OMIM #187500) is the most frequent conotruncal congenital heart defect (CHD) with a range of intra- and extracardiac phenotypes. TBX5 is a transcription factor with well-defined roles in heart and forelimb development, and mutations in TBX5 are associated with Holt-Oram syndrome (HOS) (OMIM#142900). Here we report on the screening of 94 TOF patients for mutations in TBX5, NKX2.5 and GATA4 genes. We identified two heterozygous mutations in TBX5. One mutation was detected in a Moroccan patient with TOF, a large ostium secundum atrial septal defect and complete atrioventricular block, and features of HOS including bilateral triphalangeal thumbs and fifth finger clinodactyly. This patient carried a previously described de novo, stop codon mutation (p.R279X) located in exon 8 causing a premature truncated protein. In a second patient from Italy with TOF, ostium secundum atrial septal defect and progressive arrhythmic changes on ECG, we identified a maternally inherited novel mutation in exon 9, which caused a substitution of a serine with a leucine at amino acid position 372 (p.S372L, c.1115C>T). The mother's clinical evaluation demonstrated frequent ventricular extrasystoles and an atrial septal aneurysm. Physical examination and radiographs of the hands showed no apparent skeletal defects in either child or mother. Molecular evaluation of the p.S372L mutation demonstrated a gain-of-function phenotype. We also review the literature on the co-occurrence of TOF and HOS, highlighting its relevance. This is the first systematic screening for TBX5 mutations in TOF patients which detected mutations in two of 94 (2.1%) patients., (© 2014 Wiley Periodicals, Inc.)