Synthesis of Polycyclic Spirocarbocycles via Acid-Promoted Ring-Contraction/Dearomative Ring-Closure Cascade of Oxapropellanes

We report herein the development of an acid-promoted rearrangement of oxa[4.3.2]propellanes to afford polyaromatic-fused spiro[4.5]carbocycles. DFT calculations suggest that the reaction pathway involves generation of a cyclobutyl cation, ring contraction to the cyclopropylcarbinyl cation, and dearomative ring closure by an internal 2-naphthol moiety. The resulting spirocarbocycles are synthetically valuable, as they could be transformed into two different polycyclic aromatic hydrocarbons via skeletal rearrangement. Syntheses of optically pure spirocarbocycles via a central-to-axial-to-central chirality transfer are also described

Helical Nanographenes Embedded with Contiguous Azulene Units

うねり構造をもつグラフェンナノリボンの精密合成に成功 --非ベンゼノイド構造の新規構築反応を開発--. 京都大学プレスリリース. 2020-07-20.The azulene moiety, composed of contiguous pentagonal and heptagonal rings, is a structural defect that alters the electronic, magnetic, and structural properties of graphenes and graphene nanoribbons. However, nanographenes embedded with an azulene cluster have not been widely investigated because these compounds are difficult to synthesize in their pure form. Herein, azulene-embedded nanographenes bearing a unique cove-type edge were synthesized by a novel synthetic protocol. Experimental and theoretical investigations revealed that this cove edge imparts stable helical chirality, unlike normal cove edges. The in-solution self-association behavior and the structural, electronic, and electrochemical properties were also described in detail

Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia

Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver

Protective effect of tin chloride on rhabdomyolysis-induced acute kidney injury in rats

The heme component of myoglobin plays a crucial role in the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI). Heme oxiganenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism, and its metabolites, iron, biliverdin, and carbon monoxide, have antioxidant properties. Tin chloride (SnCl2) is a kidney specific HO-1 inducer. In this study, we examined whether the induction of HO-1 in the kidney by SnCl2 pretreatment ameliorates RM-AKI in rats and if the effect is due to the degradation of excess renal free heme. We developed an RM-AKI rat (male Sprague-Dawley rats) model by injecting glycerol (Gly) in the hind limbs. RM-AKI rats were pretreated with saline or SnCl2 or additional SnMP (tin mesoporphyrin, a specific HO inhibitor) followed by Gly treatment. Serum blood urea nitrogen (BUN) and creatinine (Crea) were measured as indicators of renal function. Renal free heme level was assessed based on the levels of delta-aminolevulinate synthase (ALAS1), a heme biosynthetic enzyme, and nuclear BTB and CNC homology 1 (Bach1), an inhibitory transcription factor of HO-1. Elevated free heme levels lead to decreases in ALAS1 and nuclear Bach1. After 24 h of Gly injection, serum BUN and Crea levels in saline-pretreated rats were significantly higher than those in untreated control rats. In contrast, SnCl2-pretreated rats showed no significant increase in the indices. However, additional treatment of SnMP abolished the beneficial effect of SnCl2. Renal ALAS1 mRNA levels and renal nuclear Bach1 protein levels in the saline pretreated rats were significantly lower than those in control rats 3 h after Gly injection. In contrast, the levels in SnCl2-pretreated rats were not altered. The findings indicate that SnCl2 pretreatment confers protection against RM-AKI by virtue of HO-1 induction in the renal system, at least in part through excess free heme degradation

Electric spectroscopy of vortex states and dynamics in magnetic disks

Spin-polarized radio frequency (RF) currents and RF-Oersted fields resonantly excite a magnetic vortex core confined in a micron-scale soft magnetic disk. In this study, we measured the rectifying voltage spectra caused by the anisotropic magnetoresistance oscillation due to the gyration of the vortex with different polarity and chirality. The measured spectra are presented such that we can determine the vortex properties and strength of the spin torques and Oersted field accurately and directly through analytical calculation.Comment: 39 pages,1 table, 10 figure

Up-regulation of hepatitis C virus replication by human T cell leukemia virus type I-encoded Tax protein

AbstractCo-infection of hepatitis C virus (HCV) with other blood-borne pathogens such as human T cell leukemia virus (HTLV) is common in highly endemic areas. Clinical evidence showing a correlation between HTLV-I co-infection and rapid progression of HCV-associated liver disease promoted us to investigate the effect of HTLV-I-encoded Tax protein on HCV replication. Reporter assay showed that HCV replicon-encoded luciferase expression was significantly augmented by co-transfection of the Tax-expressing plasmid. Further, HCV RNA replication in replicon cells was increased either by co-culture with cells stably expressing Tax protein (Huhtax) or by culture in the presence of Huhtax-conditioned medium, indicating that Tax could also modulate HCV replication of adjacent cells in a paracrine manner. Additionally, HCV replication in Huhtax exhibited a reduced responsiveness to interferon-α-induced antiviral activity. This study demonstrates the facilitation of HCV replication by Tax protein, which may partially account for severer clinical consequences of HCV-related disease in HCV/HTLV co-infected individuals

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m(3) and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m(3)) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m(3)) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m(3) thoron inhalation was lower than that after 500 Bq/m(3) thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m(3) and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m(3) was more effective than that at 2000 Bq/m(3), possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m(3) and AA administration promoted an early recovery from alcohol-induced liver damage

Risk Factors for Delirium after Spine Surgery: An Age-Matched Analysis

Study Design A retrospective cohort study. Purpose To investigate the risk factors for postoperative delirium after spine surgery, excluding older age, which has already been established as a strong risk factor. Overview of Literature More than 30 risk factors have been reported for delirium after spine surgery, making it challenging to identify which factors should be prioritized. We hypothesized that risk factors could not be prioritized to date because the factor of older age is very strong and influenced other factors. To eliminate the influence of older age, we performed an age-matched group comparison analysis for the investigation of other risk factors. Methods This study involved 532 patients who underwent spine surgery. Two patients of the same age without delirium (delirium negative group) were matched to each patient with delirium (delirium positive group). Differences in suspected risk factors for post-operative delirium between the two groups identified from previous reports were analyzed using univariate analysis. Multivariate analysis was performed for factors that showed a significant difference between the two groups in the univariate analysis. Results Fifty-nine (11.1%) of 532 patients developed postoperative delirium after spine surgery. Large amounts of intraoperative bleeding, low preoperative concentration of serum Na, high postoperative (day after surgery) serum level of C-reactive protein, low hematocrit level, low concentration of albumin, and high body temperature were detected as significant risk factors in the univariate analysis. Large amounts of intraoperative bleeding remained a risk factor for postoperative delirium in the multivariate analysis. Conclusions We should pay attention to and take precautions against the occurrence of postoperative delirium after spine surgery in patients of older age or those who experience severe intraoperative bleeding

MAXI GSC observations of a spectral state transition in the black hole candidate XTE J1752-223

We present the first results on the black hole candidate XTE J1752-223 from the Gas Slit Camera (GSC) on-board the Monitor of All-sky X-ray Image (MAXI) on the International Space Station. Including the onset of the outburst reported by the Proportional Counter Array on-board the Rossi X-ray Timing Explorer on 2009 October 23, the MAXI/GSC has been monitoring this source approximately 10 times per day with a high sensitivity in the 2-20 keV band. XTE J1752-223 was initially in the low/hard state during the first 3 months. An anti-correlated behavior between the 2-4 keV and 4-20 keV bands were observed around January 20, 2010, indicating that the source exhibited the spectral transition to the high/soft state. A transient radio jet may have been ejected when the source was in the intermediate state where the spectrum was roughly explained by a power-law with a photon index of 2.5-3.0. The unusually long period in the initial low/hard state implies a slow variation in the mass accretion rate, and the dramatic soft X-ray increase may be explained by a sudden appearance of the accretion disk component with a relatively low innermost temperature (0.4-0.7 keV). Such a low temperature might suggest that the maximum accretion rate was just above the critical gas evaporation rate required for the state transition.Comment: Publication of Astronomical Society of Japan Vol.62, No.5 (2010) [in print

Bright X-ray flares from the BL Lac object Mrk 421, detected with MAXI in 2010 January and February

Strong X-ray flares from the blazar Mrk 421 were detected in 2010 January and February through the 7 month monitoring with the MAXI GSC. The maximum 2 -- 10 keV flux in the January and February flares was measured as 120 +- 10 mCrab and 164 +- 17 mCrab respectively; the latter is the highest among those reported from the object. A comparison of the MAXI and Swift BAT data suggests a convex X-ray spectrum with an approximated photon index of about 2. This spectrum is consistent with a picture that MAXI is observing near the synchrotron peak frequency. The source exhibited a spectral variation during these flares, slightly different from those in the previous observations, in which the positive correlation between the flux and hardness was widely reported. By equating the halving decay timescale in the January flare, $t_{\rm d} \sim 2.5 \times 10^{4}$ s, to the synchrotron cooling time, the magnetic field was evaluated as B = 0.045 G $(\delta/10)^{-1/3}$, where $\delta$ is the jet beaming factor. Assuming that the light crossing time of the emission region is shorter than the doubling rise time, $t_{\rm r} \lesssim 2 \times 10^{4}$ s, the region size was roughly estimated as $R < 6 \times 10^{15}$ cm $(\delta/10)$. These are consistent with the values previously reported. For the February flare, the rise time, $t_{\rm r} < 1.3 \times 10^{5}$ s, gives a loose upper limit on the size as $R < 4 \times 10^{16}$ cm $(\delta/10)$, although the longer decay time $t_{\rm d} \sim 1.4 \times 10^{5}$ s, indicates B = 0.015 G $(\delta/10)^{-1/3}$, which is weaker than the previous results. This could be reconciled by invoking a scenario that this flare is a superposition of unresolved events with a shorter timescale.Comment: 14 pages, 4 figures, accepted for PASJ (Vol. 62 No. 6