Design Rationale for CO2 Separation Membranes with Micropatterned Surface Structures.

Here, we report the design rationale of CO2 separation membranes with micropatterned surface structures. Thin film composite (TFC) membranes with micropatterned surface structures were fabricated by spray coating amine-containing hydrogel particles on the top of micropatterned porous support membranes, which were synthesized by a polymerization-induced phase separation process in a micromold (PIPsµM). The pore size of the support membranes was optimized by tuning the proportion of good and poor solvents for the polymerization process so that the microgels would be assembled as a defect-free separation layer. The relationship between the size of the micropatterned structures on the surface of the support membrane and the thickness of the separation layer was optimized to maximize the surface area of the separation layer. The rationally designed micropatterned TFC membrane showed a CO2 permeability (835.8 GPU) proportional to the increase in surface area relative to the flat membrane with a high CO2/N2 selectivity of 58.7. The rational design for micropatterned TFC membranes will enable the development of inexpensive and high-performance functional membranes not only for CO2 separation but also for other applications such as water treatment and membrane reactors.

Photoinduced α-Aminoalkylation of Sulfonylarenes with Alkylamines.

α-Aminoalkylation of sulfonylarenes with alkylamines was found to be induced by photoirradiation. Here various types of alkylamines, such as trialkylamines, dialkylamines, N,N-dialkylanilines and N-alkylanilines as well as sulfonylarenes containing an azole, azine, heterole or benzene ring are available. The reaction proceeds through a homolytic aromatic substitution (HAS) process consisting of addition of an α-aminoalkyl radical to a sulfonylarene and elimination of the sulfonyl radical to give the α-arylalkylamine, where photoirradiation is considered to induce homolysis of sulfonylarenes leading to the generation of α-aminoalkyl radicals that make a radical chain operative.

SEM Observation of the Filter after Administration of Blinatumomab: A Possibility of Leakage during Home Administration Using a Portable Infusion Pump.

Blinatumomab (Blincyto® injection solution) is classified as a bispecific T-cell engaging (BiTE) antibody and is intended for the treatment of relapsed/refractory acute lymphoblastic leukemia. It requires continuous infusion to maintain therapeutic levels. Therefore, it is often administered at home. Monoclonal antibodies, which are administered intravenously, have the potential to leak depending on the nature of the administration devices. Therefore, we investigated device-associated causes of blinatumomab leakage. We observed no apparent changes to the filter and its materials after exposure to the injection solution and surfactant. From scanning electron microscopic images, precipitate on the surface of the filters was observed after physical stimulation of the injection solution. Therefore, physical stimulations should be avoided during the prolonged administration of blinatumomab. In conclusion, the findings of this study assist in the safe administration of antibodies using portable infusion pumps, taking into consideration the composition of drug excipients and the choice of filter type and structure.

[Laparoscopic Proximal Gastrectomy with Supra-Pancreatic Dissection First Approach].

BACKGROUND: In laparoscopic proximal gastrectomy(LPG)with esophago-gastro anastomosis, the key of obtaining good surgical view is how to exclude the stomach from the supra-pancreatic area. METHODS: We could get good surgical view at the supra-pancreatic area with gastro-ptosis by firstly dissecting lesser curvature. Followed by the supra-pancreatic dissection we could efficiently dissect the gastro-splenic ligament from cranial side. We performed this procedure in 20 cases with upper gastric cancer. We evaluate the surgical outcomes of this procedure(S group)comparing to that of the previous procedure in 14 cases(G group). RESULTS: The median operative time in S group was significantly shorter than that in G group (226 min vs 249 min, p=0.02). Other data were similar in 2 groups. CONCLUSIONS: The short-term clinical outcomes of LPG with supra-pancreatic dissection first approach revealed that this technique is safe and feasible.

Effects of organic components in cuttlebone on the morphological and mechanical properties of peroxide cross-linked cuttlebone/natural rubber composites.

The clarification of the role of organic components in cuttlebone particles on the morphological and mechanical properties in terms of the strain-induced crystallization (SIC) of peroxide cross-linked cuttlebone/natural rubber (NR) composites was revealed for the first time in this study. The organic components in cuttlebone particles affected the increased bound rubber layers and the decreased rubber chain orientation due to the formation of interfacial interactions (filler-to-filler and/or filler-to-rubber interactions). During SIC, the presence of organic components in cuttlebone particles did not significantly affect the crystallinity index and crystallite size in cuttlebone/NR composites. The increased moduli in the stress-strain curve resulted from the presence of biofiller, SIC, and organic components in the cuttlebone. Therefore, the presence of organic components in biofiller is an important factor in improving the mechanical properties of green rubber composite materials.

Development of imaging biomarker for esophageal cancer using intravoxel incoherent motion MRI.

BACKGROUND: Intravoxel incoherent motion MRI (IVIM-MRI) can quantify micro-perfusion at the capillary level in the tissue. The purpose of this study is to measure tumor perfusion using IVIM-MRI, and evaluate its value as a biomarker to predict prognosis in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 109 ESCC patients (93 men and 16 women; median age: 72) who underwent IVIM-MRI prior to treatment between February 2018 and August 2020 were retrospectively investigated. Both mean apparent diffusion coefficient (ADC) value and mean perfusion-related parameter (PP) value of the primary tumor were measured using three b values of 0, 400, and 1000 s/mm2 based on the IVIM model. We analyzed associations of these parameters with clinical stage and disease-specific survival (DSS). RESULTS: Lower ADC and PP values of the tumor were significantly associated with the higher clinical T stage (p < 0.0001, p < 0.0001, respectively). In Kaplan-Meier analyses, patients with lower PP value tumors (< 18.94, median) had significantly worse DSS (p < 0.0001), while tumor ADC value did not show a significant correlation with DSS. In a multivariate analysis, PP value of the tumor was an independent prognostic factor for DSS (p = 0.0027). CONCLUSIONS: Quantification of tumor perfusion using IVIM-MRI can be a non-invasive prognostic biomarker of ESCC, reflecting clinical stage and survival.

The Relationship between the Lunar Phase, Menstrual Cycle Onset and Subjective Sleep Quality among Women of Reproductive Age.

The aim of the present study was to investigate the association among lunar cycle, menstrual cycle onset, and subjective sleep quality. Menstrual cycle onset data from the six most recent menstrual cycles were obtained for 529 women (aged 25-39 years) using the smartphone app Luna Luna. We also collected questionnaire survey data on sleep quality from each participant. Overall, there was no association between the onset of menstrual cycle and lunar phase. Interestingly, the proportion of good sleepers with menstrual cycle beginning during the light period was significantly higher than that during the dark period, while the proportion of poor sleepers with menstrual cycle beginning during the dark period was significantly higher than that during the light period. When participants were categorized by the combination of lunar phases (light, dark, neutral periods) in the two most recent menstrual cycle onsets, the "both dark period" group and the "other (light and dark) period" group showed the lowest proportion of good sleepers. Menstrual cycle onset in the dark period was associated with a deterioration in subsequent subjective sleep quality, which was more apparent with consecutive onsets in the dark period or at a rapidly changing lunar phase.

Association between changes in the mRNA expression of platelet-activating factor receptor in peripheral blood mononuclear cells and progression of diabetic nephropathy.

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.

Effect of fatty acids on the accelerated sulfur vulcanization of rubber by active zinc/carboxylate complexes.

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.

[A Case of Gastric Cancer with Necrotic Lymph Node Perforation in the Stomach during Chemotherapy].

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.

Phase resetting of circadian peripheral clocks using human and rodent diets in mouse models of type 2 diabetes and chronic kidney disease.

The expression rhythms of clock genes, such as Per1, Per2, Bmal1, and Rev-erb α, in mouse peripheral clocks, are entrained by a scheduled feeding paradigm. In terms of food composition, a carbohydrate-containing diet is reported to cause strong entrainment through insulin secretion. However, it is unknown whether human diets entrain peripheral circadian clocks. In this study, we used freeze-dried diets for type 2 diabetes (DB) and chronic kidney disease (CKD), as well as low-carbohydrate diets. After 24 h of fasting, PER2::LUC knock-in mice were given access to food for 2 days during inactive periods, and bioluminescence rhythm was then measured using an in vivo imaging system. AIN-93M, the control mouse diet with a protein:fat:carbohydrate (PFC) ratio of 14.7:9.5:75.8, caused a significant phase advance (7.3 h) in the liver clock compared with that in 24 h fasted mice, whereas human diets caused significant but smaller phase advances (4.7-6.2 h). Compared with healthy and high fat/sucrose-induced DB mice, adenine-induced CKD mice showed attenuation of a phase-advance with a normal diet. There were no significant differences in phase-advance values between human diets (normal, DB, and CKD). In addition, a normal-carbohydrate diet (PFC ratio of 20.3:23.3:56.4) and a low-carbohydrate diet (PFC ratio of 36.4:42.9:20.7) caused similar phase advances in peripheral clocks. The present results strongly suggest that scheduled feeding with human diets can cause phase advances in the peripheral clocks of not only healthy, but also DB and CKD mice. This discovery provides support to the food-induced entrainment of peripheral clocks in human clinical trials.

Social jetlag and menstrual symptoms among female university students.

Menstrual symptoms may have a significant impact on women's lives. Many women experience menses-related health problems, such as menstrual pain, heavy menstrual bleeding, and premenstrual syndrome, during their reproductively fertile years. Circadian misalignment in shift workers has been reported to contribute to menstrual cycle irregularity and/or painful menstruation. However, the relationship between social jetlag (SJL) and menstrual symptoms/menstrual cycle has not been elucidated. In this study, we aimed to elucidate this relationship among female university students. One-hundred and fifty female university students (mean [SD]: 18.8 [0.71]-years old) completed self-reported questionnaires consisting of menstrual symptoms and menstrual cycle, sleep quality and sleep habits, quality of life, and demographic variables. The average menstrual cycle was 32.0 [5.4] days. The percentage of students who showed menstrual cycle irregularity, having less than 25 days or more than 39 days of menstrual cycle during the previous four menstrual cycles, was 60.6%. SJL, the difference between mid-sleep time on free days and mid-sleep time on school days, was categorized into small (absolute SJL < 1 h) or large (≥1 h). Overall, 78.0% of participants had SJL ≥ 1 h. Among the menstrual symptoms, pain, behavioral change, and water retention subscale scores were significantly higher in the SJL ≥ 1 h group than in the SJL < 1 h group. However, no significant differences were found in concentration, autonomic reaction, or negative affect subscale scores between the two groups. The menstrual cycle was 31.2 [5.5] days in the SJL < 1 h group and 32.2 [5.4] days in the SJL ≥ 1 h group, without significant difference. Logistic regression analysis showed that more than 1 h of SJL was a significant associated factor with severe menstrual symptom, independently of sleep duration and late chronotype. This study indicated that SJL was a significant factor associated with severe menstrual symptoms, suggesting the possibilities of association between circadian system and reproductive function among humans.

Anxiolytic effects of γ-oryzanol in chronically- stressed mice are related to monoamine levels in the brain.

AIMS: The present study was aimed to investigate the anxiolytic effect of γ-oryzanol (GORZ) during chronic restraint stress treatment (CRST), which is a well-documented model of stress-related disorders, like anxiety, and its potential molecular mechanisms. MATERIALS AND METHODS: In this experiment, 5-week-old male ICR mice were used and the concentration of GORZ was fixed at 0.5% in the mouse standard diet (14% casein, AIN 93 M). Mice were immobilized daily for 3 h from ZT 2.5 to 5.5 (ZT0 was designated as light-on time) for 20 consecutive days, followed by behavioral testing, including the open field test (OFT) and elevated plus maze (EPM) test. The concentration of serum corticosterone (CORT) was measured. In addition, the expression of central monoamine neurotransmitters with their metabolites in the hippocampus, cerebral cortex, and amygdala of the brain were examined. KEY FINDINGS: 0.5% GORZ partially blocked stress-induced reduction of body weight gain while stressed mice had significantly lower body weights during the entire experimental period. Further, 0.5% GORZ treatment could significantly improve the main behavioral parameters even in CRST situations. The significant increase in serum CORT levels indicated CRST-induced stress, which was almost unaffected by 0.5% GORZ treatment. Moreover, 0.5% GORZ also supported the anxiolytic mechanism with enhancement of 5-HIAA and NE levels in the amygdala of brain after CRST. SIGNIFICANCE: Taken together, our studies suggested that 0.5% GORZ is a potential therapeutic drug candidate against anxiety under chronic stress conditions.

γ-oryzanol ameliorates the acute stress induced by behavioral anxiety testing in mice.

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.

α-Arylation of alkylamines with sulfonylarenes through a radical chain mechanism.

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.

Glucagon and/or IGF-1 Production Regulates Resetting of the Liver Circadian Clock in Response to a Protein or Amino Acid-only Diet.

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.

Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue.

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.

mRNA expression of platelet activating factor receptor (PAFR) in peripheral blood mononuclear cells is associated with albuminuria and vascular dysfunction in patients with type 2 diabetes.

AIMS: Renal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM). METHODS: We recruited 95 patients with T2DM. After matching for gender, age, BMI and HbA1c levels, the patient cohort included 42 with normoalbuminuria, 28 with microalbuminuria, and 25 with macroalbuminuria. All patients in the three groups were assessed for urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), flow-mediated dilatation (FMD), and mRNA expression in PBMCs. RESULTS: The mRNA expression of platelet activating factor receptor (PAFR) differed most markedly between the three groups and was significantly higher in the macroalbuminuric group (p < 0.001 vs. normoalbuminuric group; p < 0.05 vs. microalbuminuric group). PAFR mRNA expression significantly correlated with log transformed ACR (ρ = 0.424, p < 0.001) but not eGFR. PAFR mRNA expression also had a significant negative correlation with FMD (ρ = -0.379, p < 0.001). Furthermore, the prevalence of macrovascular complications, particularly stroke, was significantly higher in patients with elevated PAFR mRNA expression in PBMCs. CONCLUSIONS: PAFR overexpression in PBMCs may link diabetic nephropathy to macroangiopathy through impairment of endothelial function in patients with T2DM.

Dominant formation of disulfidic linkages in the sulfur cross-linking reaction of isoprene rubber by using zinc stearate as an activator.

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.

Necessity of two-dimensional visualization of validity in the nanomechanical mapping of atomic force microscopy for sulphur cross-linked rubber.

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.