[5-Chloro-2-hy­droxy-N′-(2-oxidobenzyl­idene)benzohydrazidato]dimethyl­tin(IV)

In the title compound, [Sn(CH3)2(C14H9ClN2O3)], the SnIV ion is coordinated by one N and two O atoms from the tridentate 5-chloro-2-hy­droxy-N′-(2-oxidobenzyl­idene)benzohydrazidate (L) ligand and two methyl groups in a distorted trigonal–bipyramidal geometry. In the ligand, the hy­droxy group is involved in an intra­molecular O—H⋯N hydrogen bond and the two aromatic rings form a dihedral angle of 5.5 (1)°. In the crystal, weak inter­molecular C—H⋯O hydrogen bonds and π–π inter­actions between the aromatic rings [centroid–centroid distance = 3.816 (3) Å] link the mol­ecules into centrosymmetric dimers

Metallothionein mediates leukocyte chemotaxis

BACKGROUND: Metallothionein (MT) is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. RESULTS: In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis. CONCLUSION: These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure

3-Hy­droxy-N′-[(E)-3-pyridyl­methyl­idene]-2-naphtho­hydrazide

The title compound, C17H13N3O2, displays an E configuration about the C=N bond. The mean planes of the pyridine and benzene rings make a dihedral angle of 31.2 (2)°. An intra­molecular O—H⋯O hydrogen bond is observed. In the crystal, inter­molecular N—H⋯N hydrogen bonding links the mol­ecules into a chain along [101]

Photoredox-catalyzed reaction as a powerful tool for rapid natural product Gem -dimethylation modification: discovery of potent anti-cancer agents with improved druggability

Tylophorine has diverse biological activities; however, the stability, solubility, and central nervous system toxicity have severely limited use of tylophorine. The gem -dimethyl group is an organic chemistry functional group that consists of two methyl groups bonded to the same carbon atom. This feature has gained significant attention in medicinal chemistry due to its unique properties and potential applications in drug design. We applied a new photoredox methodology to tylophorine modification, resulting in a series of gem-dimethyl tylophorine analogues. Among the analogues, compound 4b demonstrated promising activity against a wide range of tumor cell lines and exhibited significantly improved drug-like properties, including enhanced solubility and stability. Compound 4b showed an exceptional inhibitory effect (7.8 nM) against a C481S mutation-induced ibrutinib-resistant non-Hodgkin’s lymphoma cell line, as well as primary tumor cell lines obtained from patients. Importantly, compound 4b exhibited significantly reduced anti-proliferative activity against the normal cell line tested, indicating the potential for an enhanced therapeutic window for compound 4b . Based on these early-stage data, we believe that our study provides a solid foundation for the development of new therapeutic agents for potential drug-resistant cancer treatment in the near future

Clonal replacement of epidemic KPC-producing Klebsiella pneumoniae in a hospital in China

Abstract Background Klebsiella pneumoniae is a frequent nosocomial pathogen causing difficult-to-treat infections worldwide. The prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-KP) is increasing in China. The aim of this study was to investigate the molecular epidemiology of KPC-KP in a nosocomial outbreak. Methods Fifty-four KPC-KP isolates were consecutively collected between November 2013 and August 2014 during a KPC-KP outbreak in a tertiary care hospital in Beijing, China. Antimicrobial susceptibility was determined by agar dilution. Carbapenemase, extended-spectrum β–lactamase, 16S rRNA methylase, AmpC β-lactamase, and plasmid-mediated quinolone resistance determinants were detected by PCR amplification. The genetic relatedness of isolates was analyzed by pulsed-field gel electrophoresis and multi-locus sequence typing. Results All isolates belonged to ST11 except one isolate which was identified as a new sequence type (ST2040). PFGE profile of genomic DNA revealed seven clusters, of which cluster A and C dominated the KPC-KP outbreak and cluster A was replaced by cluster C during the outbreak. PFGE of genomic DNA, S1-PFGE of plasmids, replicon typing, and drug resistant characteristics showed that clonal spread occurred during the outbreak. When compared with isolates within cluster A, all isolates in cluster C harbored rmtB and showed higher level of resistance to cefepime, amikacin, tobramycin, and tigecycline. Conclusion We reported a nosocomial outbreak of KPC-KP with clonal replacement and a new sequence type (ST2040) of KP. High degree of awareness and surveillance of KPC-KP should be given to avoid potential outbreaks, especially in ICU wards

Alternating Direction Method of Multipliers for Generalized Low-Rank Tensor Recovery

Low-Rank Tensor Recovery (LRTR), the higher order generalization of Low-Rank Matrix Recovery (LRMR), is especially suitable for analyzing multi-linear data with gross corruptions, outliers and missing values, and it attracts broad attention in the fields of computer vision, machine learning and data mining. This paper considers a generalized model of LRTR and attempts to recover simultaneously the low-rank, the sparse, and the small disturbance components from partial entries of a given data tensor. Specifically, we first describe generalized LRTR as a tensor nuclear norm optimization problem that minimizes a weighted combination of the tensor nuclear norm, the l1-norm and the Frobenius norm under linear constraints. Then, the technique of Alternating Direction Method of Multipliers (ADMM) is employed to solve the proposed minimization problem. Next, we discuss the weak convergence of the proposed iterative algorithm. Finally, experimental results on synthetic and real-world datasets validate the efficiency and effectiveness of the proposed method