Silicon-based high-resolution and low-power-consumption two-dimensional beam scanner integrated with hybrid wavelength-tunable laser diode.

Optical phased array (OPA) is a useful device for achieving the solid-state beam scanner required in compact light detection and ranging. However, conventional OPAs actively control the phase difference between arrays. Therefore, power consumption is extremely high in a high-resolution OPA. Herein, we fabricated a passive OPA with a 128-channel silicon arrayed waveguide and Si-dot grating antennas with large apertures. Moreover, we integrated a hybrid wavelength-tunable laser diode with a passive OPA. The field of view was 43.9° × 10.4°, and the FWHM of the beam width was 0.233° × 0.0495°. The power consumption per antenna was 0.397 mW.

The structural changes of a bovine casein micelle during temperature change; in situ observation over a wide spatial scale from nano to micrometer.

Bovine milk is the complex colloidal system containing nano to micrometer scale components. Earlier, our research group reported the structural changes in bovine casein micelles in the temperature range of 10-40 °C by in situ small-angle X-ray scattering (SAXS) [H. Takagi, T. Nakano, T. Aoki and M. Tanimoto, Food Chem., 2022, 393, 133389]. In this study, we extend our previous research by investigating the temperature-associated structural alterations in casein micelles over a wide spatial scale using in situ SAXS and ultra-SAXS (USAXS). Furthermore, the temperature dependences of various physical properties of the casein micelles were investigated by analyzing the SAXS intensities. The USAXS results showed that micelles formed 1-dimensional aggregates and that these aggregate structures did not change in the temperature range of 10-40 °C. Changes in electron densities calculated from SAXS intensities showed that the voluminosity reduced and the weight fraction of protein inside the micelles increased during the heating process. The number of water domains in a micelle decreased when the temperature increased from 10 to 40 °C, but did not substantially change in the cooling run at a rate of 1 °C min-1. The number of colloidal calcium phosphate (NCCP) in a micelle can also be calculated from the SAXS intensities; NCCP increases upon heating. This study on the behavior of casein micelles with respect to temperature change in milk over a wide spatial scale showed that the casein micelle structure was sensitive to temperature and can change dramatically with temperature variations.

A SAXS and USAXS study of the influence of pH on the casein micelle structure.

Changes in milk pH significantly influence the behavior and physical properties of casein micelles; however, the effects of these changes on casein micelle structures are still unclear. The aim of this study was to elucidate the effect of changes in pH range from 5.9 to 7.1 on the structure of casein micelles in milk using small-angle X-ray scattering (SAXS) and ultra small-angle X-ray scattering (USAXS). The casein micelles formed one-dimensional aggregates. The micelle radius decreased with decreasing pH, whereas the size of the water domain increased. The distance between colloidal calcium phosphates (CCP) remained unchanged, whereas the CCP radius decreased with decreasing pH. Voluminosity, which was calculated from scattering intensities, increased at increased pH. In conclusion, the micelle structure changed significantly in response to changes in pH. Our findings help to understand the changes in the physical properties of milk at various pH levels in terms of the microscopic structure.

Radical Nitrososulfonation of Propargyl Alcohols: Thiazolidine-2,4-dione-Assisted Synthesis of 5-Alykyl-4-sulfonylisoxazoles.

In this study, we discover a good NO/HNO precursor, N-hydroxypyridinesulfonamide, and the regioselective radical nitrososulfonylation reaction of propargyl alcohols. Direct and unique isoxazole synthesis afforded a good-to-high yield of 5-alkyl-3-aryl-4-pyridinesulfonylisoxazoles. Copper-catalyzed aerobic oxidation could efficiently proceed in the presence of thiazolidine-2,4-dione. This work provides a powerful method for the synthesis and functionalization of alkyl-substituted isoxazoles and explores a new investigation route for drug-drug discovery.

Lactiplantibacillus plantarum 06CC2 upregulates intestinal ZO-1 protein and bile acid metabolism in Balb/c mice fed high-fat diet.

The effects of Lactiplantibacillus plantarum 06CC2 (LP06CC2), which was isolated from a Mongolian dairy product, on lipid metabolism and intestinal tight junction-related proteins in Balb/c mice fed a high-fat diet (HFD) were evaluated. The mice were fed the HFD for eight weeks, and the plasma and hepatic lipid parameters, as well as the intestinal tight junction-related factors, were evaluated. LP06CC2 slightly reduced the adipose tissue mass. Further, it dose-dependently decreased plasma total cholesterol (TC). The HFD tended to increase the plasma level of endotoxin and suppressed intestinal ZO-1 expression, whereas a low LP06CC2 dose increased ZO-1 expression and tended to reduce the plasma lipopolysaccharide level. Furthermore, a low LP06CC2 dose facilitated a moderate accumulation of Lactobacillales, a significant decrease in Clostridium cluster IV, and an increase in Clostridium cluster XVIII. The results obtained from analyzing the bile acids (BAs) in feces and cecum contents exhibited a decreasing trend for secondary and conjugated BAs in the low LP06CC2-dose group. Moreover, a high LP06CC2 dose caused excess accumulation of Lactobacillales and failed to increase intestinal ZO-1 and occludin expression, while the fecal butyrate level increased dose dependently in the LP06CC2-fed mice. Finally, an appropriate LP06CC2 dose protected the intestinal barrier function from the HFD and modulated BA metabolism.

Lactiplantibacillus plantarum 06CC2 Enhanced the Expression of Intestinal Uric Acid Excretion Transporter in Mice.

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is responsible for the excretion of foreign substances, such as uric acid (UA) and indoxyl sulfate (IS), from the body. Given the importance of increased ABCG2 expression in UA excretion, we investigated the enhancement of intestinal ABCG2 expression using Lactiplantibacillus plantarum 06CC2 (LP06CC2). Mice were reared on a potassium oxonate-induced high-purine model at doses of 0.02% or 0.1% LP06CC2 for three weeks. Results showed that LP06CC2 feeding resulted in increased ABCG2 expression in the small intestine. The expression level of large intestinal ABCG2 also showed a tendency to increase, suggesting upregulation of the intestinal excretion transporter ABCG2 by LP06CC2. Overall, LP06CC2 treatment increased fecal UA excretion and showed a trend towards increased fecal excretion of IS, suggesting that LP06CC2 treatment enhanced the expression of intestinal ABCG2, thereby promoting the excretion of UA and other substances from the intestinal tract.

Resistance exercise in early-stage ALS patients, ALSFRS-R, Sickness Impact Profile ALS-19, and muscle transcriptome: a pilot study.

Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed to evaluate the effect of a home-based exercise program on muscle strength, ALS scores, and transcriptome in ALS patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted in seven individuals with early-stage ALS. Participants were given 3 months of home-based resistance exercise focusing on the quadriceps muscles. The strength of exercised muscle was evaluated using bilateral quadriceps strength with manual muscle testing, handheld dynamometers, five times sit-to-stand, and Timed-Up-and-Go before and after the exercise program. In addition, changes in the Sickness Impact Profile ALS-19 (SIP/ALS-19) as the functional outcome measure and the transcriptome of exercised muscles were compared before and after the exercise. The primary outcome of muscle strength did not change significantly by the exercise program. The exercise program maintained the SIP/ALS-19 and the ALS Functional Rating Scale-Revised (ALSFRS-R). Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including parvalbumin. Three months of moderately intense strength and conditioning exercise maintained muscle strength of the exercised muscle and ALSFRS-R scores and had a positive effect on patients' muscle transcriptome.

Temperature dependence of the casein micelle structure in the range of 10-40 °C: An in-situ SAXS study.

Milk is used and processed under various environmental temperature, and its physicochemical properties are also strongly affected by temperature. Therefore, it is important to reveal the structure of milk at variable temperatures. In this study, the temperature dependence of the inner structure of bovine casein micelles in the temperature range of 10-40 °C was investigated by in-situ small-angle X-ray scattering (SAXS) method. The micelle size calculated from the SAXS profiles using a micelle model including water domains was almost independent of temperature. The water domain expanded and the distance between the colloidal calcium phosphates (CCP) decreased with increasing temperature. The number of CCPs in a micelle increased, because CCPs were newly formed by the transfer of calcium and inorganic phosphate from serum into the micelle. These structural changes occurred during the cooling process. Therefore, in the temperature range of 10-40 °C, the structure of the casein micelle varied sensitively with the temperature, and these structural changes were thermoreversible in nature.

Lactobacillus plantarum 06CC2 reduces hepatic cholesterol levels and modulates bile acid deconjugation in Balb/c mice fed a high-cholesterol diet.

Previous study suggested that dietary intake of Lactobacillus plantarum 06CC2 (LP06CC2) isolated from Mongolian dairy products showed various health beneficial effects. Here, the effect of LP06CC2 on the cholesterol metabolism in mice fed a cholesterol-loaded diet was evaluated. Cholesterol and LP06CC2 were incorporated into the AIN93G-based diet to evaluate the effect on cholesterol metabolism in Balb/c mice. Serum and liver cholesterol levels were significantly increased in mice fed a cholesterol-loaded diet whereas the LP06CC2 ingestion suppressed the increase of liver cholesterol. LP06CC2 suppressed the increase of the hepatic damage indices. The increase of the cecal content and fecal butyrate were observed in mice fed LP06CC2. The analysis of bile acids clearly showed that LP06CC2 increased their deconjugation indicating the decrease of bile acid absorption. The protein expression of hepatic Cyp7A1 was also suppressed by LP06CC2 in mice fed cholesterol. Finally, in vitro studies showed that LP06CC2 had the most potent ability to deconjugate bile acids using glycocholate among the tested probiotic lactic acid bacteria isolated from Mongolian dairy products. Taken together, LP06CC2 is a promising microorganism for the reduction of the cholesterol pool via modulation of bile acid deconjugation.

Enhanced in-cell folding of reversibly cationized transcription factor using amphipathic peptide.

The intracellular delivery of functionally active transcription factor proteins is emerging as a promising technique for artificial regulation of cellular functions. However, in addition to the cell membrane, which acts as a barrier to macromolecules, the aggregation-favored properties of structurally flexible transcription factor proteins limit the application of this method. In-cell folding technique can be used to overcome these issues. This technique solubilizes denatured protein by reversible alkyl-disulfide cationization (S-cationization), and simultaneously endows efficient intracellular delivery and folding to the biologically active conformation in the reducing environment of the cytosol. Because cationized protein is internalized into cells by adsorption-mediated endocytosis, endosomal escape is crucial for this technique. In this study, we utilized a sensitive luciferase reporter gene assay to quantitatively evaluate in-cell folding of the artificial transcription factor GAL4-VP16. Although the cationic moiety of S-cationized protein was slightly affected, co-transduction of amphipathic peptide Endo-PORTER dramatically improved in-cell folding efficiency. Live cell imaging of fluorescent-labeled GAL4-VP16 revealed that some of the proteins diffused into the cytosol and nucleus through co-transduction with Endo-PORTER. Real-time monitoring of light output of luciferase revealed the kinetics of in-cell folding, supporting that endosomal-release assisted by Endo-PORTER was stimulated by endosome acidification. Because this method can transduce proteins uniformly and repeatedly into living cells, S-cationized transcription factor proteins are widely applicable for the artificial regulation of cellular functions.

High serum high-sensitivity C-reactive protein concentrations are associated with relative cardiac sympathetic overactivity during the early morning period in type 2 diabetic patients with metabolic syndrome.

Sympathetic activation is associated with metabolic syndrome (MS) and increased risk of cardiovascular disease. The aim of this study was to investigate whether cardiac autonomic activity or sympathovagal balance, as estimated by a 24-hour power spectral analysis of heart rate variation, is associated with serum concentrations of high-sensitivity C-reactive protein (hs-CRP), a sensitive predictor for cardiovascular events, in type 2 diabetic patients with and without MS. We studied 104 type 2 diabetic patients (50 female and 54 male). The diagnosis of MS was based on the National Cholesterol Education Program Adult Treatment Panel III criteria. Based on the serum hs-CRP, diabetic patients were also divided into 3 groups: low risk (CRP < 1.0 mg/L), moderate risk (1.0 < or = CRP < or = 3.0), and high risk (CRP > 3.0). Heart rate variation was determined automatically every 5 minutes over 24 hours using an ambulatory Holter electrocardiographic recording. Power spectral analysis of the R-R intervals was performed by fast Fourier transformation. Low frequency (LF, both sympathetic and parasympathetic activities), high frequency (HF, pure parasympathetic activity), and the ratio of LF to HF, an index of sympathovagal balance, were used as indices of cardiac autonomic activity. Blood concentrations of hs-CRP, interleukin 6, and plasminogen activator inhibitor 1 were higher in diabetic patients with than in those without MS (P < .0001, P = .0056, and P < .0001, respectively). Both the 24-hour mean LF and the LF-to-HF ratio were also significantly higher in diabetic patients with than in those without MS (P = .0397 and P = .0483, respectively). The LF-to-HF ratio at 6:00 am was significantly higher in diabetic patients with a high CRP concentration than in those with a low or moderate CRP concentration (P < .001 and P < .01, respectively). Only urinary albumin and hs-CRP were independent factors predicting the LF-to-HF ratio at 6:00 am in diabetic patients. In conclusion, type 2 diabetic patients with MS have elevated markers of inflammation and evidence of cardiac sympathetic predominance. High serum concentrations of hs-CRP are associated with relative cardiac sympathetic overactivity during the early morning in type 2 diabetic patients.

Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus.

Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = -0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes.

Anemia is associated with an elevated serum level of high-molecular-weight adiponectin in patients with type 2 diabetes independently of renal dysfunction.

Low serum adiponectin is associated with a high incidence of type 2 diabetes or coronary artery disease in the general population. Paradoxically, serum adiponectin is elevated in patients with chronic kidney disease (CKD), such as overt diabetic nephropathy. The current study aimed to investigate whether anemia was independently associated with the serum level of high-molecular-weight (HMW) adiponectin in patients with type 2 diabetes. We studied 207 type 2 diabetic patients (92 women and 115 men). Anemia was defined as a hemoglobin (Hb) <13.0g/dL in men and <12.0g/dL in women according to the guidelines of the World Health Organization (WHO). Overt nephropathy (CKD) was defined as clinical proteinuria and /or estimated glomerular filtration rate (eGFR) lower than 60mL/min for more than 3 months. The diabetic patients were divided into 4 groups according to the presence or absence of anemia and/or CKD. Serum HMW adiponectin levels were measured by a sandwich enzyme-linked immunosorbent assay. In all 207 patients with type 2 diabetes, serum total and HMW adiponectin levels were correlated positively with age, the duration of diabetes, high-density lipoprotein (HDL) cholesterol, urinary albumin, and serum erythropoietin, whereas negative correlations were found with body mass index, triglyceride, eGFR, Hb, hematocrit, and high sensitivity C-reactive protein. A stepwise regression analysis demonstrated that among several significant variables, Hb had the strongest independent influence on HMW adiponectin (beta =-0.487, P < 0.001). Diabetic patients of both sexes with anemia and CKD had the highest serum levels of HMW adiponectin among the 4 groups. In conclusion, anemia is associated with marked elevation of serum HMW adiponectin levels in diabetic patients who have CKD, and this elevation is independent of renal function.

Low-dose pioglitazone increases serum high molecular weight adiponectin and improves glycemic control in Japanese patients with poorly controlled type 2 diabetes.

We investigated the effects of low-dose pioglitazone (7.5mg/day) on serum high molecular weight (HMW) adiponectin and fluid retention (estimated from hematocrit) in 14 male and 16 female patients with type 2 diabetes. All of them were being treated with sulfonylureas and had poor glycemic control. Patients were given 7.5 mg/day of pioglitazone and were followed for 12 weeks at monthly intervals. In all 30 patients, HbA1c was significantly decreased after 12 weeks of treatment with pioglitazone (8.2+/-0.7% vs. 7.4+/-0.8%, P<0.0001). Serum HMW adiponectin increased markedly from 5.2 (2.4, 8.6) microg/ml at baseline to 9.8 (4.1, 12.6) microg/ml at the end of pioglitazone treatment (P<0.0001). When the changes were evaluated separately for each sex, diabetic men showed no increase of body weight or BMI after treatment, while HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In diabetic women, neither body weight nor BMI increased after treatment with pioglitazone, as was the case for the men. HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In conclusion, low-dose pioglitazone therapy could significantly improved glycemic control and markedly increased serum HMW adiponectin in both male and female Japanese patients with type 2 diabetes.

Effects of losartan on serum total and high-molecular weight adiponectin concentrations in hypertensive patients with metabolic syndrome.

High-molecular weight (HMW) adiponectin may have the most biologic activity among several isoforms. We investigated long-term effects of losartan on serum concentrations of total and HMW adiponectin in hypertensive patients with metabolic syndrome (MS) by serial measurements over 6 months. Forty hypertensive patients first received 50 mg of losartan. Upward titration of the losartan dose was implemented to reach a target blood pressure of less than 140/90 mm Hg. Serum total adiponectin and HMW adiponectin were measured at study entry (baseline), the 3-month treatment time point, and the end of the 6-month period. Non-HMW adiponectin (ie, medium- and low-molecular weight adiponectin) was calculated as total adiponectin--HMW adiponectin. Diagnosis of MS was done by current standard criteria. In hypertensive patients without MS (n = 21), the serum total adiponectin increased from 9.8 +/- 5.4 microg/mL at baseline to 11.1 +/- 6.2 microg/mL at 6 months (P < .01). Furthermore, the serum total adiponectin was significantly higher at 6 months than at 3 months (P < .01). Serum HMW adiponectin also increased from 5.7 +/- 3.9 microg/mL at baseline to 6.6 +/- 4.4 microg/mL at 6 months (P < .01). In hypertensive patients with MS, the serum total adiponectin increased from 6.0 +/- 2.7 mug/mL at baseline to 6.7 +/- 3.3 microg/mL at 3 months and to 7.0 +/- 3.1 microg/mL at 6 months (P < .01 for both). Furthermore, the serum HMW adiponectin concentration was significantly higher at 6 months than at 3 months (P < .001). However, the serum non-HMW adiponectin concentration did not change during treatment in either group. In conclusion, serum total and HMW adiponectin concentrations increase after 6 months of losartan treatment in hypertensive patients, irrespective of the presence or absence of MS.

Profound reduction in T-helper (Th) 1 lymphocytes in peripheral blood from patients with concurrent type 1 diabetes and Graves' disease.

Type 1 diabetes likely is mediated by T-helper (Th) 1 lymphocytes, while Graves' disease may involve Th2 predominance. We investigated the balance between Th1 and Th2 cells and between Th1- and Th2-associated chemokine receptor expression on peripheral lymphocytes in subjects including patients with coexisting type 1 diabetes and Graves' disease. Peripheral blood mononuclear cells of all subjects were examined by flow cytometry for intracellular cytokines (IFN-gamma for Th1; IL-4 for Th2) and expression of the chemokine receptors CXCR3 (Th1-associated) and CCR4 (Th2-associated). Plasma concentrations of interferon-inducible protein (IP)-10, a CXCR3 ligand, and thymus and activation-regulated chemokine (TARC), a CCR4 ligand, were measured by enzyme-linked immunosorbent assays. IFN-gamma producing-T lymphocytes were significantly fewer in patients with coexisting type 1 diabetes and Graves' disease (12.4 +/- 6.8%, n = 6) than in healthy control subjects (19.9 +/- 4.1%, n = 6; P < 0.01) or patients with type 2 diabetes (19.1 +/- 4.5%, n = 5; P < 0.05). We found no significant difference in IFN-gamma-producing T lymphocytes between healthy controls and patients with only type 1 diabetes (n = 8) or Graves' disease (n = 5). Plasma IP-10 concentrations were significantly higher in patients with coexisting type 1 diabetes and Graves' disease than in control subjects (106.3 +/- 30.48 vs. 66.7 +/- 25.3 pg/ml, P = 0.0343). Considering only patients with type 1 diabetes alone, duration of diabetes correlated positively with IFN-gamma-producing T lymphocytes (r = 0.773, P = 0.0242) and the ratio of CXCR3 to CCR4 receptor expression (r = 0.947, P = 0.0004). In conclusion, Th1-associated T lymphocytes were fewer in peripheral blood from patients having both type 1 diabetes and Graves' disease than in those with either disease alone. Numbers of peripheral Th1 lymphocytes increased with increasing time from onset of type 1 diabetes in patients with type 1 diabetes alone.

Phosphorylation of starch and dextrin by dry-heating in the presence of phosphate, and their calcium phosphate-solubilizing ability.

Starch and dextrin were phosphorylated by dry-heating in the presence of phosphate, and their properties were examined. The phosphorylation of starch was accelerated with decreasing moisture, rising incubation temperature and prolongation of the incubation period. However, a rise in incubation temperature, and lengthened incubation period caused increased browning and degradation. A decrease in the pH from 5.5 to 3.0 resulted in a modest increase of phosphorylation, but also marked browning and degradation. When potato starch was phosphorylated at 140 degrees C and pH 5.5 for 24 h, its phosphorus content was increased up to 3.47%, with fewer side reactions. Phosphorlylated starch and dextrin had calcium phosphate-solubilizing abitity. Phosphorylated dextrin with 2.42% phosphorus had about half the calcium phosphate-solubilizing ability of casein phosphopeptide (CPP). The possibility of substituting of phosphorylated starch and dextrin for CPP as a calcium phosphate-absorption enhancing material is discussed herein.