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The effect of fatty acids with different aliphatic chain lengths on the accelerated vulcanization reaction of isoprene rubber was investigated through the generation of new intermediates composed of dinuclear bridging bidentate zinc/carboxylate complexes. Using the combination of in situ time-resolved Fourier-transform infrared spectroscopy and in situ time-resolved zinc K-edge X-ray absorption fine structure spectroscopy, the essential complex structure of the intermediates formed during the vulcanization reaction of isoprene rubber was determined to be independent of the aliphatic chain length of fatty acids. However, the reactivity of arachidic acid with ZnO was found to be low, which prolonged the induction period and curing time, and slowed down the curing rate in the vulcanization of isoprene rubber. These results help to understand the complicated vulcanization reaction of rubber, especially natural rubber, which inherently contains various fatty acids. The results obtained in this study are important for developing well-designed high-performance natural rubber products in the future., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.

Introduction: Several studies have recently pointed out the role of many inflammatory mediators in the progression of diabetes complications. We had previously demonstrated that mRNA expression of platelet-activating factor receptor (PAFR) in peripheral blood mononuclear cells (PBMCs) was associated with urinary albumin to creatinine ratio (ACR) and forearm flow-mediated dilatation in patients with type 2 diabetes. In an attempt to elucidate this association, patients were followed up for 1 year., Materials and Methods: We recruited 95 patients from the hospital outpatient clinic, among whom 86 were followed up for 1 year (normoalbuminuria: 40 patients, microalbuminuria: 25 patients, macroalbuminuria: 21 patients). We then measured their baseline and 12 month characteristics and collected blood samples to extract PBMCs and measure gene expressions., Results: Despite higher mRNA expression of PAFR in PBMCs among patients with macroalbuminuria, the rise in its value was not associated with biomarkers of nephropathy, while baseline values were not associated with progression of nephropathy. Moreover, changes in mRNA expression of PAFR were correlated with changes in ACR in all patients ( r  = 0.225, p  = 0.037) and estimated glomerular filtration rate in patients with macroalbuminuria ( r  =  - 0.438, p  = 0.047) during the follow-up period., Conclusion: Our findings indicate that even though no causal relationship exists between diabetic nephropathy and elevated expression of PAFR in PBMCs, their close association signifies the presence of another common mechanism that could induce both events. Given these findings, the PAF/PAFR interaction could clarify corresponding mechanisms involved in diabetic complications., Competing Interests: Conflict of interestThe authors declare no conflict of interest associated with this manuscript., (© The Japan Diabetes Society 2019.)

The patient was a 48-year-old woman. She consulted our hospital with a chief complaint of vomiting. Colonoscopy showed stenosis and edematous mucosa, and biopsy was performed. Histological examination demonstrated the lesion to be colonic metastasis of breast cancer, invasive lobular carcinoma. Although colorectal metastasis of breast cancer has a poor prognosis and chemotherapy is considered as the main treatment modality, hormone therapy is also a treatment option depending on the condition.

We evaluated the anxiolytic effect of γ-oryzanol (GORZ) and elucidated the molecular mechanisms involved in its inhibition of behavioral test-induced anxiety. Behavioral tests were conducted on day 13, and mice were subjected to 30 min of acute restraint stress treatment (ARST) before sacrifice on day 16. In other group, behavioral tests were conducted on day 13 and 14 after ARST. 0.5% GORZ significantly weakened the effect of behavioral stress, but not the effect of strong ARST. GORZ downregulated ARST-induced cFos levels in the cerebral cortex. In conclusion, GORZ has potential ant-anxiety effect in the treatment of weak behavioral test-induced stress., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

The importance of the two-dimensional (2D) visualization of validity for nanomechanical mapping in atomic force microscopy (AFM) for sulphur cross-linked rubber is emphasized for accurately interpreting the nanoscale physical properties on the surface of the soft material. The " R -factor," evaluated to be the difference between the experimental and theoretical force-deformation curves, was considered to be the reliability index of the AFM analysis for all data points on the sample surface. A small R -factor corresponds to high accuracy. The advantage of the R -factor mapping method is demonstrated using nanomechanical mapping data of the inhomogeneous isoprene rubber network by the Johnson-Kendall-Roberts and the Derjaguin, Muller, and Toporov contact mechanics models. The 2D R -factor mapping clearly and correctly supported the roles of sulphur cross-linking reagents to control the network morphology of vulcanizates. Additionally, the blanket effect, which is induced by the rubber layer on the hard part and influences experimental force-deformation curves, is firstly proposed in this study. Nanomechanical mapping with 2D reliability indexes is expected to contribute to an advance in AFM studies on soft matter such as rubber materials, leading to a more accurate understanding of the structural characteristics of the rubber networks. Thus, this validity confirmation method is necessary for developing rubber science and technology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the presence of a substoichiometric amount of a tert-butoxy radical precursor, the reaction of alkylamines with sulfonylarenes was found to give α-arylated alkylamines through homolytic aromatic substitution, where a radical chain is operative.

A linear combination fitting in sulfur K-edge X-ray absorption near edge structure (S-XANES) measurements reveals each fraction of monosulfidic, disulfidic and polysulfidic linkages in solvent extracted sulfur cross-linked isoprene rubbers. The sulfidic linkage of a disulfidic type is found for the first time to be dominant when zinc stearate and N -(1,3-benzothiazol-2-ylsulfanyl)cyclohexanamine are used as the activator and accelerator, respectively, for the sulfur cross-linking reaction at 140 °C. The presence of the bridging bidentate zinc/stearate complex as an intermediate for the sulfur cross-linking reaction is supposed to induce the generation of abundant disulfidic linkages in the rubber networks. This unexpected observation is of use for the material design of high performance rubber products with anti-aging and thermal stabilities. S-XANES is a powerful tool that was used to reveal the characteristics of the sulfur cross-linking of rubber. These results will contribute to the development of rubber science and technology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The circadian system controls the behavior and multiple physiological functions. In mammals, the suprachiasmatic nucleus (SCN) acts as the master pacemaker and regulates the circadian clocks of peripheral tissues. The SCN receives information regarding the light-dark cycle and is thus synchronized to the external 24-hour environment. In contrast, peripheral clocks, such as the liver clock, receive information from the SCN and other factors; in particular, food intake which leads to insulin secretion induces strong entrainment of the liver clock. On the other hand, the liver clock of insulin-depleted mice treated with streptozotocin (STZ) has been shown to be entrained by scheduled feeding, suggesting that insulin is not necessary for entrainment of the liver clock by feeding. In this study, we aimed to elucidate additional mechanism on entraining liver clock by feeding a protein-only diet and/or amino-acid administration which does not increase insulin levels. We demonstrated that protein-only diet and cysteine administration elicit entrainment of the liver clock via glucagon secretion and/or insulin-like growth factors (IGF-1) production. Our findings suggest that glucagon and/or IGF-1 production are additional key factors in food-induced entrainment., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.

In mammals, the central clock (the suprachiasmatic nuclei, SCN) is entrained mainly by the light-dark cycle, whereas peripheral clocks in the peripheral tissues are entrained/synchronized by multiple factors, including feeding patterns and endocrine hormones such as glucocorticoids. Clock-mutant mice (Clock/Clock), which have a mutation in a core clock gene, show potent phase resetting in response to light pulses compared with wild-type (WT) mice, owing to the damped and flexible oscillator in the SCN. However, the phase resetting of the peripheral clocks in Clock/Clock mice has not been elucidated. Here, we characterized the peripheral clock gene synchronization in Clock/Clock mice by daily injections of a synthetic glucocorticoid (dexamethasone, DEX) by monitoring in vivo PER2::LUCIFERASE bioluminescence. Compared with WT mice, the Clock/Clock mice showed significantly decreased bioluminescence and peripheral clock rhythms with decreased amplitudes and delayed phases. In addition, the DEX injections increased the amplitudes and advanced the phases. In order to examine the robustness of the internal oscillator, T-cycle experiments involving DEX stimulations with 24- or 30-h intervals were performed. The Clock/Clock mice synchronized to the 30-h T-cycle stimulation, which suggested that the peripheral clocks in the Clock/Clock mice had increased synchronizing ability upon DEX stimulation, to that of circadian and hour-glass type oscillations, because of weak internal clock oscillators.

The circadian rhythm controls many physiological functions, such as feeding, motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern can entrain the peripheral circadian clock, whereas peripheral clock systems can control the absorption distribution, metabolism and excretion of nutrients, suggesting mutual interactions between circadian clocks and nutrition/food. The interactions were so-called by "chrono-nutrition", and bigger meals for breakfast were good for entrainment of peripheral clock and protection of obesity. Similar to chrono-nutrition the timing of exercise ("chrono-exercise") is important for both entrainment signals and energy expenditure. Evening exercise and/or feeding then exercise was good timing exercise for protection of obesity. Taken all, it is suggested that timing of feeding and exercise is now one of key factors for metabolic syndrome.

A 69-year-old man who has mitral stenosis concomitantly with dilated cardiomyopathy underwent mitral valve replacement. The preoperative left ventricular ejection fraction was 23%. Preoperative dobutamine stress echocardiography showed poor response. High dose fentanyl was administered for induction and maintenance of general anesthesia, and blood pressure was kept with vasoconstrictors. Circulatory assist with milrinone and intraaortic balloon pumping after the cardiopulmonary bypass enabled us to obtain stable hemodynamics.

A patient developed prolonged apnea after emergency cesarean section. The patient was a 38-year-old primiparous woman with myoma uteri and her body weight was 44.8 kg. She received intravenous magnesium sulfate 1 g x hr(-1) as tocolytic agent for threatened premature delivery. We performed rapid sequence induction of anesthesia with thiopental 250 mg and rocuronium 50 mg because she was suspected of full stomach. After the intubation, we did not administer any muscle relaxants during the operation. After the operation which was finished in 65 minutes, the effect of rocuronium remained for more than 100 minutes after its administration probably due to hypermagnesemia. Rocuronium shows rapid onset, and several studies indicate that it can be used for rapid sequence induction instead of suxamethonium. But rocuronium should be used carefully and its effect should be monitored in a patient with hypermagnesemia.

Cellulase production was investigated in a culture of a strain of Acremonium cellulolyticus. The medium components were optimized for the improvement of cellulase production. The maximum production of cellulolytic enzymes was obtained in a medium containing (grams per liter) 50 Solka Floc, 5 (NH4)2SO4, 24 KH2PO4, 4.7 potassium tartrate hemihydrate, 1.2 MgSO4.7H2O, 1 Tween 80, 4 urea, 0.01 ZnSO4.7H2O, 0.01 MnSO4.6H2O, and 0.01 CuSO4.7H2O, with a pH of 4.0. In the flask culture, 15.5 filter paper units (FPU)/mL of maximum cellulase activity was obtained, 17.42 FPU/mL in a 7-L bioreactor, and 13.08 FPU/mL in a 50-L scale bioreactor for 4-8 d at 30 degrees C. Average production rates were 1.94 FPU/mL.d in flasks, 2.86 FPU/mL.d in the 7-L bioreactor, and 2.56 FPU/mL.d in the 50-L bioreactor. Cellulase production on a small scale was successfully reproduced in the 50-L pilot scale bioreactor. Saccharification activity from A. cellulolyticus was compared with cellulolytic enzymes produced by other strains. The A. cellulolyticus culture broth had a comparable saccharification yield in comparison with those of other Trichoderma enzymes (GC220 or Cellulosin T2) under the same total cellulase activity. Its saccharification yield (percent of released reducing sugar to used dried substrate) was 60%, and its glucose content was 83%.