Porphyromonas gingivalis Lipopolysaccharides Promote Proliferation and Migration of Human Vascular Smooth Muscle Cells through the MAPK/TLR4 Pathway

Atherosclerosis is a major cause of mortality worldwide. The initial change in atherosclerosis is intimal thickening due to muscle cell proliferation and migration. A correlation has been observed between periodontal disease and atherosclerosis. Here, we investigated the proliferation and migration of human aortic smooth muscle cells (HASMCs) using Porphyromonas gingivalis-derived LPS (Pg-LPS). To elucidate intracellular signaling, toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) of HASMCs were knocked down, and the role of these molecules in Pg-LPS-stimulated proliferation and migration was examined. The role of mitogen-activated protein kinase (MAPK) in HASMC proliferation and migration was further elucidated by MAPK inhibition. Pg-LPS stimulation increased the proliferation and migration of HASMCs and activated the TLR4/MyD88 pathway. TLR4 knockdown inhibited Pg-LPS stimulated HASMCs proliferation and migration. Pg-LPS stimulation led to the phosphorylation of P38 MAPK, JNK, and ERK, and MyD88 knockdown inhibited the phosphorylation of P38 MAPK and JNK but not ERK. P38 MAPK and SAPK/JNK inhibition did not suppress the proliferation of HASMCs upon Pg-LPS stimulation, but ERK inhibition significantly inhibited proliferation. SAPK/JNK and ERK inhibition suppressed Pg-LPS-stimulated migration of HASMCs. In conclusion, our findings suggest that Pg-LPS may promote atherosclerosis via the activation of MAPK through TLR4.     

Identification of genus Nitrosovibrio, ammonia-oxidizing bacteria, by comparison of N-terminal amino acid sequences of phosphoglycerate kinase

Nitrosospira, Nitrosolobus, and Nitrosovibrio, three genera of ammonia-oxidizing bacteria (AOB), are morphologically distinct from each other (Nitrosospira: spiral, Nitrosolobus: lobate, Nitrosovibrio: slender curved rods). However, these three genera cannot be classified using the phylogenetic tree based on 16S rDNA sequences. Phosphoglycerate kinase (PGK) was purified from 10 AOB strains as an index for identification, and its enzymatic properties were investigated. No distinction could be made between these three genera of AOB, because there was no notable difference in the molecular weight, K(m), or other properties of their PGKs. However, the N-terminal amino acid residues of PGK of Pro(P)-1, Ile(I)-6 and Asp(D)-12 have sequences characteristic of genus Nitrosovibrio (three strains) in four AOB genera. Therefore, it is proved possible to use the differences in the sequence to identify individual strains of the genus Nitrosovibrio.     

Solar to chemical conversion using metal nanoparticle modified microcrystalline silicon thin film photoelectrode

Microcrystalline silicon (μc-Si:H) thin films, which are prospective low-cost semiconductor materials, are used as photoelectrodes for the direct conversion of solar energy to chemical energy. An n-type microcrystalline cubic silicon carbide layer and an intrinsic μc-Si:H layer are deposited on glassy carbon substrates using the hot-wire cat-CVD method. The μc-Si:H electrodes are modified with platinum nanoparticles through electroless displacement deposition. The electrodes produce hydrogen gas and iodine via photoelectrochemical decomposition of hydrogen iodide with no external bias under solar illumination. Surface modification with platinum nanoparticles and surface termination with iodine improve the conversion efficiency.     

Acceleration or Suppression of α-Phase Precipitation Using Isothermal ω Phase in Ti-20 at.pct Nb Alloy

Homogeneous precipitation of a fine α phase in the β matrix of Ti alloys is a promising method for obtaining a highly strengthened Ti-based alloy. Isothermal ω particles are known to be the nucleation sites for fine α-phase precipitation, but an understanding of the kinetics of α-phase formation on isothermal ω particles is still lacking. This study aimed to reveal the effect of isothermal ω particles on α-phase precipitation onset time. Two-step isothermal aging of a Ti-20 at.pct Nb alloy after solid solution treatment at 1273 K (1000 °C) was carried out. The first step of the aging at 633 K (360 °C) involved the formation of isothermal ω particles in the β matrix. This was followed by a second aging step at 673 K, 723 K, and 773 K (400 °C, 450 °C, and 500 °C) for α-phase precipitation. Suppression of α-phase nucleation on the isothermal ω particles occurred at 673 K (400 °C), whereas acceleration of α-phase nucleation on the isothermal ω particles was observed at 723 K and 773 K (450 °C and 500 °C). Thermodynamic stability of the isothermal ω particles and solute partitioning were controlling factors for the α-phase precipitation kinetics.     

Startup,performance, and microbial communities of an anammox reactor inoculated with indigenous sludge for the treatment of high-salinity and mesophilic underground brine

Clean Technologies and Environmental Policy - Anaerobic ammonium oxidation (anammox) has been implemented as a cost-effective nitrogen removal process in wastewater treatment. To apply the process...     

YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development

Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1.     

Intercalation of substituted alkylammonium ions into layered potassium niobate K4Nb6O17

Substituted alkylammonium ions (protonated hydroxy amine and diamine) were intercalated into layered niobate K₄Nb₆O₁₇in order to introduce functional substituents into the interlayer spaces of the niobate. In the case of reaction with 3-hydroxypropylammonium ion, the intercalation compound incorporated the ammonium ions in a bilayer arrangement, by which the hydroxyl substituents were located in the middle of the interlayer spaces to form intermolecular hydrogen bonding. For the intercalation compounds with alkyldiammonium ions, the intercalated alkyldiammonium ions were present in monolayer and oriented transversally with respect to the niobate layers.     

Structural response of organically modified layered niobate K4Nb6O17 to the adsorption of 2,4-dichlorophenol

We investigated structural alteration of organically modified layered hexaniobate K₄Nb₆O₁₇ upon adsorption of 2,4-dichlorophenol. Two adsorbents examined were hexaniobate intercalated with dodecylammonium (C₁₂N) or dioctadecyldimethylammonium (2C₁₈2MeN) ions. The adsorbent modified with the C₁₂N ions was structurally durable for the adsorption of 2,4-dichlorophenol from 0.4 to 10 mmol dm⁻³ aqueous solutions. The adsorbate molecules were accommodated among the pre-intercalated C₁₂N moieties. In contrast, the adsorbent intercalated with the 2C₁₈2MeN ions suffered from structural collapse with the uptake of adsorbate molecules from relatively concentrated solutions (10 mmol dm⁻³), although this sample adsorbed larger amount of 2,4-dichlorophenol than the niobate modified with C₁₂N ions. X-ray diffraction and IR spectroscopy showed that the 2C₁₈2MeN ions were deintercalated with the adsorption. However, liquid chromatography and total organic carbon analysis indicated that the deintercalated organic moiety stayed on the external surface of niobate to form an effective adsorption site of 2,4-dichlorophenol. The “deintercalative adsorption” was ascribed based on UV spectroscopy to a specific interaction between the adsorbate and 2C₁₈2MeN molecules. Such drastic structural response had not been reported for other organically modified layered adsorbents.     

Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds

In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory activity against apomorphine-induced climbing behavior in mice. The results indicate that D2, D3, and D4 receptors have different bulk tolerance (D4 > D3 > D2) for the substituent of the 4-amino group (R1) on the benzamide nuclei and that cyclopropyl-, cyclobutyl-, and cyclopentylcarbonyl groups likely possess adequate bulkiness with respect to D3 and D4 affinity and selectivity over D2 receptors in this series. The results also suggested that the N-substituent (R2) on the pyrrolidin-3-yl group performs an important role in expressing affinity for D2, D3, and D4 receptors and selectivity among the respective subtypes. One of the compounds, (S)-(+)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-[(cyclopropylcarbonyl+ ++) amino]-2-methoxybenzamide (5c) (YM-43611), showed high affinity for D3 and D4 receptors (Ki values of 21 and 2.1 nM, respectively) with 110-fold D4 selectivity and 10-fold D3 preference over D2 receptors and weak or negligible affinity for representative neurotransmitter receptors. Compound 5c displayed potent antipsychotic activity in inhibiting apomorphine-induced climbing behavior in mice (ED50 value, 0.32 mg/kg sc).     

Photochemical behavior of intercalation compounds of layered niobates with methylvilologen

Intercalation compounds of three layered niobates with methylviologen (1, 1'-dimethyl-4,4'-bipyridinium ion) were synthesized and their photochemical behavior was investigated. All the host niobates successfully intercalated methylviologen dications, and there were structural differences among the samples. UV irradiation of the intercalation compounds caused photoinduced electron transfer from the hosts to the guest to form methylviologen radical cations. The radical cations were characterized by their high stability, which had a relation to the structure of the intercalation compounds. Co-intercalation of photochemically inactive ions (K₊ or propylammonium ions) with methylviologen extremely well stabilized the radical cations.