Inhibitory mechanism of 3-hydroxypropionaldehyde accumulation in 1,3-propanediol synthesis with Klebsiella pneumoniae

3-Hydroxypropionaldehyde accumulation may cause the cessation of 1,3-propanediol sustained production with glycerol by Klebsiella pneumoniae. The impeller tip speed shift from higher to lower speed at glycerol excess or the pulsed glycerol feeding could lead to an abrupt increase of the 3- hydroxypropionaldehyde concentration (up to 10 mmol/l) in 10 min. The intracellular consequence of the 3-hydroxypropionaldehyde accumulation has not yet been elucidated. The rapid accumulation of 3- hydroxypropionaldehyde relying on the impeller tip speed shift was employed to investigate the influences of 3-hydroxypropionaldehyde to the activities of nine key enzymes related to glycerol metabolism, CO2 and O2 levels in off-gas, cell growth and 1,3-propanediol synthesis. Compared with that at 1.19 mmol/l 3-hydroxypropionaldehyde in broth, the residual enzymatic activities of the nine key enzymes ranged from 9.44 to 74.68% in the cultures at 7.5 mmol/l 3-hydroxypropionaldehyde in broth. The inhibitions of cell growth and the 1,3-propanediol synthesis were unnoticeable at the low level of 3- hydroxypropionaldehyde. By contrast, the CO2 and O2 levels changes in off-gas response to the 3- hydroxypropionaldehyde accumulation were less than 15 min. These results suggest that 3- hydroxypropionaldehyde inhibited the growth and metabolism of K. pneumoniae in a more complicated manner.Keywords: Fermentation, glycerol, 3-hydroxypropionaldehyde, Klebsiella pneumoniae, 1,3-propanediol

Tear proteomic analysis of Sjogren syndrome patients with dry eye syndrome by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry

We examined the tear film proteome of patients with Sjögren's syndrome (SS) and dry eye syndrome (group A), patients with dry eye symptoms (group B) and normal volunteers (group C). Tear samples were pooled from 8 subjects from each group and were subjected to two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry (2D-nano-LC-MS/MS). The tear breakup time for group A was significantly reduced compared with group B and C (P < 0.001). Group A (Schirmer I test, 2.13 +/- 2.38 mm/5 min) had markedly lower tear volume than group B (5.94 +/- 4.75 mm/5 min) and C (14.44 +/- 6.57 mm/5 min) (P < 0.001). Group A had significantly higher normalized tear protein content (1.8291 +/- 0.2241 mu g/mm) than group B (1.0839 +/- 0.1120 mu g/mm) (P = 0.001) and C (0.2028 +/- 0.0177 mu g/mm) (P = 0.001). The 2D-nano-LC-MS/MS analysis identified a total of 435 proteins, including 182 (54.8%),247 (74.4%) and 278 (83.7%) in group A, B, and C, respectively, with 56 (16.7%) proteins including defensin alpha 1, clusterin and lactotransferrin unique to group A. In conclusion, dry eye syndrome in SS patients is associated with an altered proteomic profile with dysregulated expression of proteins involved in a variety of important cellular process including inflammation, immunity, and oxidative stress

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Evidence for the direct two-photon transition from ψ(3686) to J/ψ

published_or_final_versio

Enhanced Microwave Absorption Properties of Intrinsically Core/shell Structured La0.6Sr0.4MnO3Nanoparticles

The intrinsically core/shell structured La0.6Sr0.4MnO3nanoparticles with amorphous shells and ferromagnetic cores have been prepared. The magnetic, dielectric and microwave absorption properties are investigated in the frequency range from 1 to 12 GHz. An optimal reflection loss of −41.1 dB is reached at 8.2 GHz with a matching thickness of 2.2 mm, the bandwidth with a reflection loss less than −10 dB is obtained in the 5.5–11.3 GHz range for absorber thicknesses of 1.5–2.5 mm. The excellent microwave absorption properties are a consequence of the better electromagnetic matching due to the existence of the protective amorphous shells, the ferromagnetic cores, as well as the particular core/shell microstructure. As a result, the La0.6Sr0.4MnO3nanoparticles with amorphous shells and ferromagnetic cores may become attractive candidates for the new types of electromagnetic wave absorption materials

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

published_or_final_versio

Cyclen-Based Cationic Lipids for Highly Efficient Gene Delivery towards Tumor Cells

Gene therapy has tremendous potential for both inherited and acquired diseases. However, delivery problems limited their clinical application, and new gene delivery vehicles with low cytotoxicity and high transfection efficiency are greatly required.In this report, we designed and synthesized three amphiphilic molecules (L1-L3) with the structures involving 1, 4, 7, 10-tetraazacyclododecane (cyclen), imidazolium and a hydrophobic dodecyl chain. Their interactions with plasmid DNA were studied via electrophoretic gel retardation assays, fluorescent quenching experiments, dynamic light scattering and transmission electron microscopy. The in vitro gene transfection assay and cytotoxicity assay were conducted in four cell lines.Results indicated that L1 and L3-formed liposomes could effectively bind to DNA to form well-shaped nanoparticles. Combining with neutral lipid DOPE, L3 was found with high efficiency in gene transfer in three tumor cell lines including A549, HepG2 and H460. The optimized gene transfection efficacy of L3 was nearly 5.5 times more efficient than that of the popular commercially available gene delivery agent Lipofectamine 2000™ in human lung carcinoma cells A549. In addition, since L1 and L3 had nearly no gene transfection performance in normal cells HEK293, these cationic lipids showed tumor cell-targeting property to a certain extent. No significant cytotoxicity was found for the lipoplexes formed by L1-L3, and their cytotoxicities were similar to or slightly lower than the lipoplexes prepared from Lipofectamine 2000™.Novel cyclen-based cationic lipids for effective in vitro gene transfection were founded, and these studies here may extend the application areas of macrocyclic polyamines, especially for cyclen

β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development

Abstract β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD