catena-Poly[[[diaqua­nickel(II)]-μ-pyrazine-2-carboxyl­ato-silver(I)-μ-pyrazine-2-carboxyl­ato] nitrate dihydrate]

In the polymeric complex of the title compound, {[AgNi(C5H3N2O2)2(H2O)2]NO3·2H2O}n, the AgI ion displays an angular coordination geometry with two N atoms from pyrazine-2-carboxyl­ate ligands, and the NiII ion is hexa­coordinated by two O atoms from two water mol­ecules, two O and two N atoms from pyrazine-2-carboxyl­ate ligands in a distorted octa­hedral geometry. In the crystal, the AgI and NiII ions lie on a mirror plane and an inversion centre, respectively. The complex chains, the nitrate ions and the uncoordinated water mol­ecules are linked together through O—H⋯O hydrogen bonds and weak Ag⋯O inter­actions [2.619 (17)–2.749 (17) Å] into a three-dimensional network

Mechanisms of TGFβ inhibition of LUNG endodermal morphogenesis: The role of TβRII, Smads, Nkx2.1 and Pten

AbstractTransforming growth factor-beta is a multifunctional growth factor with roles in normal development and disease pathogenesis. One such role is in inhibition of lung branching morphogenesis, although the precise mechanism remains unknown. In an explant model, all three TGFβ isoforms inhibited FGF10-induced morphogenesis of mesenchyme-free embryonic lung endoderm. Inhibition of budding by TGFβ was partially abrogated in endodermal explants from Smad3−/− or conditional endodermal-specific Smad4Δ/Δ embryonic lungs. Endodermal explants from conditional TGFβ receptor II knockout lungs were entirely refractive to TGFβ-induced inhibition. Inhibition of morphogenesis was associated with dedifferentiation of endodermal cells as documented by a decrease in key transcriptional factor, NKX2.1 protein, and its downstream target, surfactant protein C (SpC). TGFβ reduced the proliferation of wild-type endodermal cells within the explants as assessed by BrdU labeling. Gene expression analysis showed increased levels of mRNA for Pten, a key regulator of cell proliferation. Conditional, endodermal-specific deletion of Pten overcame TGFβ's inhibitory effect on cell proliferation, but did not restore morphogenesis. Thus, the mechanisms by which TGFβ inhibits FGF10-induced lung endodermal morphogenesis may entail both inhibition of cell proliferation, through increased Pten, as well as inhibition or interference with morphogenetic mediators such as Nkx2.1. Both of the latter are dependent on signaling through TβRII

4-[(Z)-(2-Fur­yl)(2-naphthyl­amino)methyl­ene)]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one

The title compound, C25H19N3O2, crystallizes as discrete mol­ecules which are well ordered through one intra­molecular N—H⋯O hydrogen bond. Structural analysis indicates that the mol­ecules exist as the amine–one form

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis.

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. RESULTS: Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. CONCLUSIONS: Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells

The upholding of multilateralism idea and the efforts done by stakeholders

Multilateralism is the practice of promoting trade among several countries through agreements concerning quantity and price of commodities, as the Common Market, and sometimes, restrictive tariffs and goods from outsiders. In this paper, the difference of perception between the Westerns and the Asians on the idea of multilateralism would be looked into in details.Also, this paper highlighted a few points that include the relationship between the stakeholders and the force driving the upholding of multilateralism. Information on this topic are gathered by doing research on published and unpublished materials that dated back to the early formation of the idea so as to support the reliability of this research. In a nutshell, this research paper is highly informative in the field of multilateralism

Effect of YiShenJianPi recipe on semen quality and sperm mitochondria in mice with oligoasthenozoospermia induced by tripterygium glycosides

Background：Kidney tonifying - spleen strengthening method being one of the modalities for treatment of astheno-oligozoospermia is currently commonly used in the clinical setting. To investigate the mechanism of YiShenJianPi (YSJP) Recipe, used in Traditional Chinese Medicine to benefit “the kidney” and strengthen “the spleen”.Materials and Methods: Oligoasthenozoospermia, male BALB/c mice were randomly divided into normal control, disease model, positive control, low-dosage and high-dosage groups. Oligoasthenozoospermia was induced by tripterygium glucosides intragastric administration before treatment started.Through using computer-aided sperm analysis to test the changes in sperm quality, utilizing flow cytometry to test the percentage of sperm with normal mitochondrial transmembrane potential (JC-1 + %), utilizing X-ray microscopy to observe epididymal sperm ultra-microstructure placing special emphasis and photographing the differences in mitochondria of the flagellum region.Results: Compared with DM, sperm quality of the treated mice was significantly better (P<0.05, respectively). Compared with PC, the LD group had significantly better quality sperms, while the parameters in the HD group were numerically better. Compared with NC, all other groups had significantly lower percentage of sperms with normal mitochondrial membrane potential. In PC, LD and HD groups, the percentage of sperms with normal mitochondrial membrane potential was significantly higher than that of D. The 9+9+2 mitochondrial sheath structure was complete in NC but damaged in DM. In the treatment groups, this structure was fairly clear.Conclusion: YSJP improved semen quality with oligoasthenozoospermia by improving sperm mitochondrial membrane potential and restoring sperm mitochondrial ultrastructure.Keywords: traditional Chinese medicine, oligoasthenozoospermia, semen quality, mitochondrial membrane potential, mitochondrial ultrastructur

Evaluation of anatomical and visual function for early detection of ethambutol toxicity among tuberculosis patients

AIM: To evaluate if early ethambutol toxicity can be detected by comparing pre - and post - treatment anatomical and visual function using retinal nerve fiber thickness, pattern visual evoked potentials and conventional optic nerve function tests. METHODS:This was a prospective study involving 72 eyes of 36 patients treated with ethambutol according to directly observed treatment short-course(DOTS) strategy in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. The visual acuity and optic nerve function tests were performed by a single investigator. Likewise, Humphrey automated perimetry, optical coherence tomography ( OCT ) measurement of the retinal nerve fibre layer (RNFL) and pattern visual evoked potential (PVEP) were performed by a single technician. The examinations were performed before initiating ethambutol treatment and 3mo after that. RESULTS: There was no change in visual acuity, colour vision, light brightness, red saturation and fundus findings pre and post ethambutol. However, there was a statistically significant deterioration in the mean deviation of the visual field post treatment (P = 0. 010). There were also significant changes on OCT and PVEP, with increased RNFL thickness in all quadrants ( P < 0. 05 ) and PVEP delayed P100 peak latency and amplitude (P<0. 001). CONCLUSION: Ethambutol toxicity is a known complication of tuberculosis treatment. Early detection of this toxicity may prevent severe irreversible visual loss. The use of OCT to detect RNFL thickness and PVEP to assess P100 latency and amplitude can assist in the detection of subclinical anatomical and visual function changes prior to development of abnormalities on conventional optic nerve function tests

Highly Efficient Decomposition of Perfluorocarbons for over 1000 Hours via Active Site Regeneration

Tetrafluoromethane (CF4), the simplest perfluorocarbon (PFC), has the potential to exacerbate global warming. Catalytic hydrolysis is a viable method to degrade CF4, but fluorine poisoning severely restricts both the catalytic performance and catalyst lifetime. In this study, Ga is introduced to effectively assists the defluorination of poisoned Al active sites, leading to highly efficient CF4 decomposition at 600 °C with a catalytic lifetime exceeding 1,000 hours. 27Al and 71Ga magic-angle spinning nuclear magnetic resonance spectroscopy (MAS NMR) showed that the introduced Ga exists as tetracoordinated Ga sites (GaIV), which readily dissociate water to form Ga−OH. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density function theory (DFT) calculations confirmed that Ga−OH assists the defluorination of poisoned Al active sites via a dehydration-like process. As a result, the Ga/Al2O3 catalyst achieved 100 % CF4 decomposition keeping an ultra-long catalytic lifetime and outperforming reported results. This work proposes a new approach for efficient and long-term CF4 decomposition by promoting the regeneration of active sites

De novo Assembly and Transcriptome Characterization of Opisthopappus (Asteraceae) for Population Differentiation and Adaption

Opisthopappus Shih (Asteraceae), an endangered genus endemic to the Taihang Mountains of China, is a high-value ornamental and medicinal plant consisting of two species, Opisthopappus longilobus shih and Opisthopappus taihangensis (Ling) Shih. However, the evolutionary relationships and the taxonomic characteristics between the two species remain unknown. In this study, high-throughput transcriptome sequencing was used to analyze the differential metabolic activity and gene expression and screened special molecular markers for exploring the genetic variation and species differentiation in Opisthopappus Shih. The results showed that 33,974 unigenes with an average size of 801 bp were obtained with optimization of de novo assembly. The comprehensive functional annotation based on Gene Ontology (GO), Cluster of Orthologous Group (COG) and Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG) revealed that these unigenes were mainly related to many physiological, metabolic, and molecular processes. Furthermore, the comparative transcriptome analysis indicated that 3,410 differentially expressed genes were mainly involved in lipid, carbohydrate and amino acid metabolism, xenobiotics biodegradation and metabolism as well as environment adaptation via KEGG. Such as the CYP710A, GST, HSP90A and so on, could be the potential candidate genes for further investigating the molecular mechanism of physiological variations between O. taihangensis and O. longilobus. In addition, the potential 71,804 high quality single nucleotide polymorphisms (SNPs) and 1,444 simple sequence repeats (SSRs) were estimated. Based on the predicted SNP, we have developed eight SNP markers for population genetic analysis in Opisthopappus Shih. A significantly high level of genetic differentiation between the populations of O. longilobus and O. taihangensis were found, and they were clearly grouped into two distinct genetic clusters. These results conformed to the record of Flora Reipublicae Popularis Sinicae (FRPS) and unsupported the taxonomic status in the Flora of China. The transcriptome analysis of Opisthopappus Shih can contribute to in-depth exploring of internal mechanisms in species variation and differentiation based on molecular evidence. With the rich and valuable data resources, the more novel structural, functional, and comparative genomic studies will provide comprehensive insights into the evolutionary relationships between O. taihangensis and O. longilobus