A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways.

Uncontrolled inflammation is a leading cause of various chronic diseases. Cinnamaldehyde (CA) is a major bioactive compound isolated from the essential oil of the leaves of Cinnamomum osmophloeum kaneh that exhibits anti-inflammatory activity; however, the use of CA is limited by its cytotoxicity. Here, we synthesized three CA derivatives and identified 4-hydroxycinnamaldehyde-galactosamine (HCAG) as a low toxicity anti-inflammatory compound in vitro (HCAG IC50 ≫ 1600 µM; CA IC50=40 µM) and in vivo. HCAG reduced pro-inflammatory mediator expression in LPS-activated macrophages by inhibiting MAPK and PKC-α/δ phosphorylation, decreasing ROS generation and reducing NF-κB activation. HCAG also reduced NLRP3 inflammasome-derived IL-1ß secretion by inhibiting the ATP-mediated phosphorylation of AKT and PKC-α/δ. In a mouse model of LPS-induced renal inflammation, we observed reduced albuminuria and a mild degree of glomerular proliferation, glomerular sclerosis and periglomerular inflammation in the HCAG-treated mice compared with the vehicle-treated mice. The underlying mechanisms for these renoprotective effects involved: (1) inhibited NLRP3 inflammasome activation; (2) decreased superoxide anion levels and apoptosis; and (3) suppressed activation of NF-κB and related downstream inflammatory mediators.

Iron carbonyl cluster-incorporated Cu(I) NHC complexes in homocoupling of arylboronic acids: an effective [TeFe3(CO)9](2-) ligand.

A new type of TeFe3(CO)9-incorporated dicopper NHC complex was obtained directly from one-pot reactions. By the introduction of the cluster anion [TeFe3(CO)9](2-) and NHCs as the ligands, these di-Cu(i)-based complexes exhibited pronounced catalytic activities toward the homocoupling of arylboronic acids with low Cu loadings and high yields (up to 98%).

Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1.

Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1ß (IL-1ß) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1ß secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1ß secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1ß secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1ß secretion through the NLRP3 inflammasome.

Copper-incorporated mono- and di-TeRu5 metal carbonyl complexes: syntheses, structures, and an unusual skeletal arrangement.

Two sandwich-type Cu3Cl- or Cu2{Te2Ru4(CO)10}-bridging di-TeRu5 clusters, [{TeRu5(CO)14}2Cu3Cl](2-) () and [{TeRu5(CO)14}2Cu2{Te2Ru4(CO)10}](4-) (), were obtained from the reaction of [TeRu5(CO)14](2-) with 1 equiv. of [Cu(MeCN)4][BF4] in CH2Cl2 or THF at 0 °C, respectively, depending on the solvents. The chloride-abstracted was structurally characterized to have two TeRu5 cores that were linked by a Cu3Cl moiety with two Cu-Cu bonds. If the reaction was carried out in a molar ratio of 1 : 2 at 0 or 30 °C in CH2Cl2, the structural isomers [TeRu5(µ-CO)2(CO)12(CuMeCN)2] () and [TeRu5(µ-CO)3(CO)11Cu2(MeCN)2] () were produced, respectively, as the major product. Cluster displayed a TeRu5 core with two adjacent Ru3 triangles each capped by a µ3-Cu(MeCN) fragment, while contained a TeRu5 core with one triangle Ru3 plane capped by a Cu2(MeCN)2 fragment with two Cu atoms covalently bonded. Upon heating, the isomerization of into proceeded to undergo an unusual skeletal arrangement of Cu(MeCN) and migration of CO, with the TeRu5 core remaining intact. An electrochemical study revealed that and each exhibited only one oxidation while cluster had two consecutive oxidations, suggesting significant electronic communication between the two TeRu5 metal cores in via the Cu3 moiety. This work describes the facile synthesis of a series of semiconducting Cux-bridging Te-Ru carbonyl clusters, in which the incorporation of the Cux fragments has significantly influenced their resulting structures, rearrangements, and electronic properties, which was further elucidated by DFT calculations.

Vapochemically and mechanochemically reversible polymerization/depolymerization of S-Fe-Cu carbonyl clusters.

A reversible vapochemical and mechanochemical solid-state transformation between a dppe-linked SFe3Cu2-based cluster [{(µ3-S)Fe3(CO)9}Cu2(dppe)] (2) and its 1D polymer [{(µ4-S)Fe3(CO)9}Cu2(dppe)(MeCN)2]n (3) was demonstrated, in which polymer 3 exhibited semi-conducting properties with an energy gap of 1.69 eV.

Lipopolysaccharide/adenosine triphosphate-mediated signal transduction in the regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1ß secretion.

OBJECTIVE: Reactive oxygen species (ROS) plays a critical role in the regulation of NLRP3 inflammasome activation. However, the ROS-mediated signaling pathways controlling NLRP3 inflammasome activation are not well defined. METHODS: Using lipopolysaccharide (LPS) and adenosine triphosphate (ATP) activated murine macrophages as the testing model, cytokine release and protein expression were quantified by enzyme-linked immunosorbent assay and Western blot, respectively. ROS was scavenged by N-acetyl cysteine; NADPH oxidase, the major source of ROS, was inhibited by diphenyliodonium, apocynin or gp91-phox siRNA transfection; and protein kinase was inhibited by its specific inhibitor. RESULTS: LPS-induced NLRP3 protein expression was regulated through the NADPH oxidase/ROS/NF-κB-dependent, JAK2/PI3-kinase/AKT/NF-κB-dependent, and MAPK-dependent pathways, while ATP-induced caspase-1 activation was regulated through the NADPH oxidase/ROS-dependent pathway. CONCLUSIONS: These results demonstrate that ROS regulates not only the priming stage, but also the activation stage, of NLRP3 inflammasome activation in LPS + ATP-activated macrophages.

Composition and antimicrobial activities of the leaf essential oil of Machilus kusanoi from Taiwan.

The hydrodistillated leaf essential oil of Machilus kusanoi was analyzed to determine its composition and yield. Twenty-three compounds were identified, the main components being beta-caryophyllene (23.3%), beta-eudesmol (17.1%), alpha-terpineol (16.0%), n-dodecanal (14.2%), and n-decanal (10.4%). Sesquiterpene hydrocarbons (28.1%) and non-terpenoids (25.0%) were the predominant groups of compounds. The leaf oil exhibited excellent antimicrobial and anti-wood-decay fungal activities.

Composition, antioxidant and antimicrobial activities of the seed essential oil of Calocedrus formosana from Taiwan.

The hydrodistillated seed essential oil of Calocedrus formosana was analyzed to determine its composition and yield. Twenty-seven compounds were identified, the main ones being alpha-pinene (63.8%), totarol (9.9%) and ferruginol (8.9%). Monoterpene hydrocarbons (73.5%) and oxygenated diterpenes (18.8%) were the predominant groups of compounds. The seed essential oil exhibited excellent antioxidant, antimicrobial and anti-wood-decay fungal activities.

Lead-chromium carbonyl complexes incorporated with group 8 metals: synthesis, reactivity, and theoretical calculations.

The trichromium-lead complex [Pb{Cr(CO)5}3](2-) (1) was isolated from the reaction of PbCl2 and Cr(CO)6 in a KOH/MeOH solution, and the new mixed chromium-iron-lead complex [Pb{Cr(CO)5}{Fe(CO)4}2](2-) (3) was synthesized from the reaction of PbCl2 and Cr(CO)6 in a KOH/MeOH solution followed by the addition of Fe(CO)5. X-ray crystallography showed that 3 consisted of a central Pb atom bound in a trigonal-planar environment to two Fe(CO)4 and one Cr(CO)5 fragments. When complex 1 reacted with 1.5 equiv of Mn(CO)5Br, the Cr(CO)4-bridged dimeric lead-chromium carbonyl complex [Pb2Br2Cr4(CO)18](2-) (4) was produced. However, a similar reaction of 3 or the isostructural triiron-lead complex [Pb{Fe(CO)4}3](2-) (2) with Mn(CO)5Br in MeCN led to the formation of the Fe3Pb2-based trigonal-bipyramidal complexes [Fe3(CO)9{PbCr(CO)5}2](2-) (6) and [Fe3(CO)9{PbFe(CO)4}2](2-) (5), respectively. On the other hand, the Ru3Pb2-based trigonal-bipyramidal complex [Ru3(CO)9{PbCr(CO)5}2](2-) (7) was obtained directly from the reaction of PbCl2, Cr(CO)6, and Ru3(CO)12 in a KOH/MeOH solution. X-ray crystallography showed that 5 and 6 each had an Fe3Pb2 trigonal-bipyramidal core geometry, with three Fe(CO)3 groups occupying the equatorial positions and two PbFe(CO)4 or PbCr(CO)5 units in the axial positions, while 7 displayed a Ru3Pb2 trigonal-bipyramidal geometry with three equatorial Ru(CO)3 groups and two axial PbCr(CO)5 units. The complexes 3-7 were characterized spectroscopically, and their nature, formation, and electrochemistry were further examined by molecular orbital calculations at the B3LYP level of density functional theory.

Chromium-manganese selenide carbonyl complexes: paramagnetic clusters and relevance to C=O activation of acetone.

The paramagnetic even-electron cluster, [Et(4)N](2)[Se(2)Cr(3)(CO)(10)], was found to react readily with Mn(CO)(5)Br in acetone to produce two unprecedented mixed chromium-manganese selenide carbonyl complexes, [Et(4)N][Me(2)CSe(2){Mn(CO)(4)}{Cr(CO)(5)}(2)] ([Et(4)N][1]) and [Et(4)N](2)[Se(2)Mn(3)(CO)(10){Cr(CO)(5)}(2)] ([Et(4)N](2)[2]). X-ray crystallographic analysis showed that anion 1 consisted of two Se-Cr(CO)(5) moieties, which were further bridged by one isopropylene group and one Mn(CO)(4) moiety. The dianionic cluster 2 was shown to display a Se(2)Mn(3) square-pyramidal core with each Se atom externally coordinated by one Cr(CO)(5) group. The formation of complex 1, presumably via C=O activation of acetone, was further facilitated by acidification of the reaction of [Et(4)N](2)[Se(2)Cr(3)(CO)(10)] with Mn(CO)(5)Br in acetone. Complex 1 readily transformed into 2 upon treatment with Mn(2)(CO)(10) in a KOH/MeOH/MeCN solution. Cluster 2 was a 51-electron species, which readily converted to the known 49-electron cluster [Se(2)Mn(3)(CO)(9)](2-) upon heating and bubbling with CO. Magnetic studies of the even-electron cluster, [Et(4)N](2)[Se(2)Cr(3)(CO)(10)], and the odd-electron species, [Et(4)N](2)[2] and [PPN](2)[Se(2)Mn(3)(CO)(9)], were determined by the SQUID measurement to have 2, 3, and 1 unpaired electrons, respectively. In addition, the nature and formation of complexes 1 and 2 are discussed, and the magnetic properties and electrochemistry of [Se(2)Cr(3)(CO)(10)](2-), 2, and [Se(2)Mn(3)(CO)(9)](2-) were further studied and elucidated by molecular orbital calculations at the PW91 level of density functional theory.

Composition and antimicrobial activity of the leaf and twig oils of Litsea mushaensis and L. linii from Taiwan.

The hydrodistilled essential oils of the leaves and twigs of Litsea mushaensis and L. linii were analyzed. Sixty-nine and ninety compounds were identified in the leaf and twig oils, respectively, of L. mushaensis. The main components of the leaf oil were beta-eudesmol (24.2%), tau-cadinol (10.2%), alpha-humulene (10.1%), alpha-pinene (9.7%), and trans-beta-ocimene (6.5%), whereas the main components of the twig oil were trans-beta-ocimene (19.5%), alpha-pinene (12.8%) and cis-beta-ocimene (7.7%). With L. linii, 72 and 78 compounds were respectively identified in the leaf and twig oils. The main components of the leaf oil were beta-selinene (15.7%), alpha-selinene (15.5%), beta-caryophyllene (12.2%), alpha-humulene (7.2%), and delta-cadinene (5.6%), and of the twig oil trans-beta-ocimene (20.8%), beta-selinene (11.4%), alpha-cadinol (6.0%), delta-cadinene (5.8%), tau-cadinol (5.4%) and beta-eudesmol (5.2%). L. mushaensis leaf oil was shown to have excellent antimicrobial and anti-wood-decay fungal activity, superior to the other oils.

Image processing for a tactile/vision substitution system using digital CNN.

In view of the parallel processing and easy implementation properties of CNN, we propose to use digital CNN as the image processor of a tactile/vision substitution system (TVSS). The digital CNN processor is used to execute the wavelet down-sampling filtering and the half-toning operations, aiming to extract important features from the images. A template combination method is used to embed the two image processing functions into a single CNN processor. The digital CNN processor is implemented on an intellectual property (IP) and is implemented on a XILINX VIRTEX II 2000 FPGA board. Experiments are designated to test the capability of the CNN processor in the recognition of characters and human subjects in different environments. The experiments demonstrates impressive results, which proves the proposed digital CNN processor a powerful component in the design of efficient tactile/vision substitution systems for the visually impaired people.

Association study for Parkinson's disease and a dopamine transporter gene polymorphism (1215A/G).

The dopamine transporter (DAT) may play a role in the pathogenesis of Parkinson's disease (PD) because dopamine-specific neurotoxins are taken into dopaminergic nerve terminals via the DAT. A recent study has demonstrated that a DAT polymorphism in exon 9 (1215A/G) is associated with susceptibility to PD. This finding was not replicated by another study, however. Therefore, the significance of this association was tested using a Chinese sample population consisting of 102 PD patients and 174 controls, together with the association for onset age. Comparing the two groups, neither the genotypic (p = 0.272) nor allelic frequencies (p = 0.209) were statistically different. Further, the mean onset age was not significantly different for PD patients comparing the DAT genotypes (p = 0.925). Our findings confirm those of the previous negative report and, taken together, suggest that the DAT polymorphism (1215A/G) does not play a major role in the susceptibility to PD. Other DAT genetic variants, and the association of these variants with PD symptomatology or treatment response, may merit further investigation.