We considered the gelation and its relaxation mechanism of a shear-induced bentonite / heptaethylene oleyl ether (abbreviated as C18:1E7) aqueous suspension based on the analysis of Rheo-SALS. When ...bentonite / C18:1E7 aqueous suspension formed the shake-gel, the concentration of bentonite was greater than or equal to the critical concentration of c* = 1.3 wt% where hydrodynamic interactions occur. The relationship between the time ts when the shear thickening occurs and the bentonite / surfactant concentration (c - cs) can be described by the first-order reaction equation, and ts can be further reduced with the applied shearing.
The gel formation time and the relaxation time were affected by the shear hysteresis. We found that the formation and the relaxation (breakdown) of gels comprising bentonite particles did not follow the same pathway. Thus, Shear induced gel formation is due to the percolation transition by the infinite network structure in which the anisotropic orientation of bentonite particles grows. In contrast, the relaxation (breakdown) of the gel proceeds by the isotropic diffusion of individual bentonite particles forming the network structure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We show that the Nakai–Moishezon ampleness criterion holds for real line bundles on complete schemes. As applications, we treat the relative Nakai–Moishezon ampleness criterion for real line bundles ...and the Nakai–Moishezon ampleness criterion for real line bundles on complete algebraic spaces. The main ingredient of this paper is Birkar’s characterization of augmented base loci of real divisors on projective schemes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is ...particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice. The expression of astrocytes and microglia was increased in the ACC of nerve-ligated mice, which was reversed by intracerebroventricular (i.c.v) treatment with the microglia inhibitor minocycline. Then, we examined the effect of minocycline on mechanical allodynia in nerve-ligated mice. I.c.v. and intra-ACC treatment with minocycline partially inhibited mechanical allodynia in the nerve-ligated mice. The expression of phosphorylated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit at Ser831, but not at Ser845, was increased in the ACC of the nerve-ligated mice compared to sham-operated mice, which was attenuated by minocycline administration. These results suggest that the activation of microglia in the ACC is involved in the development of hyperalgesia in mice with neuropathic pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigated the relationship between the concentration of nanosized fibers and the rheological and the rheo-optic behaviors of CNF suspensions containing unfibrillated fibers prepared by a wet ...refinement system (Water Jet System). The CNF suspensions behaved as a gel in which entropic elasticity was dominant, and the entanglement among fibers would be enhanced with the nanosized fiber volume fraction. The aggregates of the nanosized fibers elongated in the flow direction and deformed into elliptical shape with the applied shearing. However, the effect of these shape changes of the aggregates was barely observed on the viscosity curve. We speculate that this is due to Newtonian flow of the unfibrillated fibers (> 25% by volume) playing a significant role in the overall flow behavior of the CNF suspensions. In conclusion, for the CNF suspensions containing poorly nanosized fibers, we speculated that the nanosized and unfibrillated fibers were largely responsible for the linear response under micro-deformation and the nonlinear response such as under shear flow, respectively.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Astrocytes play a key role in the maintenance of synaptic transmission by producing L‐lactate via the astrocyte‐neuron lactate shuttle (ANLS). Astrocyte activation in the spinal cord is involved in ...the expression of neuropathic pain. We investigated the role of the ANLS in the spinal cord on hyperalgesia in neuropathic pain in mice. Specific activation of dorsal horn astrocytes induced mechanical hyperalgesia, which was attenuated by α‐cyano‐4‐hydroxycinnamate (4‐CIN), an inhibitor of monocarboxylate transporters that deliver L‐lactate from astrocytes to neurons. Intrathecal L‐lactate administration lowered the mechanical nociceptive threshold, which was attenuated by pretreatment with 4‐CIN and isosafrole (a lactate dehydrogenase inhibitor), but not gliotoxin. Intrathecal L‐lactate administration significantly upregulated c‐Fos and cofilin phosphorylation, which was reversed by 4‐CIN. The lowered mechanical nociceptive threshold was significantly attenuated by intrathecal fluorocitrate (an astrocyte‐specific Krebs cycle inhibitor), 4‐CIN, and isosafrole treatment. Thus, these results suggested that, in neuropathic pain, mechanical hyperalgesia was maintained by excessive L‐lactate supplied by activated astrocytes via an aberrant ANLS.
Main Points
Our results indicated that selective astrocyte activation induced mechanical hyperalgesia by enhancing the neuronal supply of L‐lactate.
In addition, neuropathic pain was ameliorated by L‐lactate inhibition.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Glycerol is the main side product in the biodiesel manufacturing process, and the development of glycerol valorization methods would indirectly contribute the sustainable biodiesel production and ...decarbonization. Transformation of glycerol to optically active C3 units would be one of the attractive routes for glycerol valorization. We herein present the asymmetric sulfonylative desymmetrization of glycerol by using a CuCN/(
,
)-PhBOX catalyst system to provide an optically active monosulfonylated glycerol in high efficiency. A high degree of enantioselectivity was achieved with a commercially available chiral ligand and an inexpensive carbonate base. The optically active monosulfonylated glycerol was successfully transformed into a C3 unit attached with differentially protected three hydroxy moieties. In addition, the synthetic utility of the present reaction was also demonstrated by the transformation of the monosulfonylated glycerol into an optically active synthetic ceramide, sphingolipid E.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Processed aconite root (PA, the root of Aconitum carmichaeli, Ranunculaceae) is a crude drug used in traditional Chinese or Japanese kampo medicine to generate heat in the body and to treat pain ...associated with coldness. Oxaliplatin (L-OHP) is a platinum-based anticancer drug that frequently causes acute and chronic peripheral neuropathies, including cold and mechanical hyperalgesia.
We investigated the effects of PA on L-OHP-induced peripheral neuropathies and identified the active ingredient within PA extract.
L-OHP was intraperitoneally injected into mice, and PA boiled water extract was orally administered. Cold and mechanical hyperalgesia were evaluated using the acetone test and the von Frey filament method, respectively. Dorsal root ganglion (DRG) neurons were isolated from normal mice and cultured with L-OHP with or without PA extract. Cell viability and neurite elongation were evaluated.
PA extract significantly attenuated cold and mechanical hyperalgesia induced by L-OHP in mice. In cultured DRG neurons, L-OHP reduced cell viability and neurite elongation in a dose-dependent manner. Treatment with PA extract significantly alleviated the L-OHP-induced reduction of neurite elongation, while the cytotoxicity of L-OHP was not affected. Using activity-guided fractionation, we isolated neoline from PA extract as the active ingredient. Neoline significantly alleviated L-OHP-induced reduction of neurite elongation in cultured DRG neurons in a concentration-dependent manner. Moreover, subcutaneous injection of neoline attenuated cold and mechanical hyperalgesia in L-OHP-treated mice. PA extract and neoline did not show sedation and motor impairment.
The present study indicates that PA and its active ingredient neoline are promising agents to alleviate L-OHP-induced neuropathic pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We have developed a novel rheo-optical measurement system based on two-dimensional polarization analysis, which can evaluate the rheological properties and structure of a complex fluid ...simultaneously. To assess the utility of the system, we used it to investigate the relationship between yield behavior and structural evolution in a TEMPO-oxidized cellulose nanofiber (T-CNF) suspension, which is a yield-stress fluid that has been actively studied in recent years. To analyze the structural evolution of a T-CNF suspension, stress-ramp tests were conducted. A two-step yield behavior was observed, and distributions of retardation and orientation axis varied dramatically with increasing shear stress. In particular, different distributions were observed in the three regions: after the first yield point, before the second yield point, and after the second yield point. In experiments with a low-concentration T-CNF suspension that exhibits no yield behavior, the retardation increased monotonically with increasing shear stress, and its distribution was uniform. It was demonstrated that the yield behavior and related structures can be analyzed from these results. More detailed structural mechanisms require various rheological tests using the developed system. However, the present insights demonstrate the valuable information provided by the developed rheo-optical measurement system, contributing essential knowledge for applications in various fields.
Chemotherapy is an important first-line treatment for oesophageal squamous cell carcinoma (ESCC). However, there are few secondary options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, ...enhances the cytotoxicity of various anticancer drugs and has been used to treat advanced ovarian and breast cancers. This study examined the effect of olaparib on the cytotoxicity of anticancer drugs in ESCC cell lines.
ESCC KYSE70 and KYSE140 cells were grown in Dulbecco's modified Eagle's medium and treated with 5-fluorouracil (5-FU), cisplatin, docetaxel, doxorubicin, SN-38, or temozolomide without or with olaparib.
Olaparib enhanced the cytotoxicity of all tested anticancer drugs and increased the effects of cisplatin, doxorubicin, SN-38, and temozolomide synergistically. These anticancer drugs caused the accumulation of phospho-histone H2AX Ser139 (γH2AX), a biomarker of DNA damage, and olaparib increased this accumulation.
PARP inhibitors may potentiate the anticancer activity of DNA-damaging agents in ESCC patients synergistically.
Venous thromboembolism often develops after surgery and childbirth, resulting in death in some cases. Although early deep vein thrombosis (DVT) detection can predict pulmonary thromboembolism, there ...is no early screening method for DVT in pregnant women. Lack of consensus regarding significance or setting and cut-off value interpretation of D-dimer levels further impedes venous thromboembolism screening in pregnant women. This study aimed to examine the utility of third-trimester serum D-dimer levels as a screening test for DVT during pregnancy and to determine the frequency of asymptomatic DVT using lower-limb compression ultrasonography.
This single-center retrospective study included 497 pregnant women who underwent elective cesarean section at term in our hospital between January 2013 and December 2019. Serum D-dimer levels were preoperatively measured at 32-37 weeks' gestation. The presence or absence of DVT in patients with serum D-dimer levels ≥ 3.0 µg/ml, the cut-off value, was examined using compression ultrasonography. In all patients, the presence or absence of clinical venous thrombosis (symptoms such as lower-limb pain, swelling, and heat sensation) was examined within 4 postoperative weeks. The Royal College of Obstetricians and Gynecologists Guideline 2015 was referred to determine risk factors for the onset of venous thrombosis during pregnancy. Among those, we examined the risk factors for DVT that result in high D-dimer levels during pregnancy.
The median age and body mass index were 35 (20-47) years and 21.2 (16.4-41.1) kg/m
, respectively. Further, the median gestational age and D-dimer levels were 37 weeks and 2.1 (0.2-16.0) µg/ml, respectively. Compression ultrasonography was performed on 135 (26.5%) patients with a D-dimer level ≥ 3.0 µg/ml, with none of the patients showing DVT. All patients were followed up for 4 postoperative weeks, with none presenting with venous thromboembolism. Multivariate analysis showed that hypertensive disorders of pregnancy are an independent risk factor for venous thromboembolism that causes high D-dimer levels (odds ratio: 2.48, 95% confidence interval: 1.05-6.50, P = 0.04).
There may be low utility in screening for DVT using D-dimer levels in the third trimester. Further, prepartum asymptomatic DVT has a low frequency, indicating the low utility of compression ultrasonography.
Institutional Review Board of Tottori University Hospital (IRB no. 20A149 ).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK