Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle–liver–adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.     

MOFBOTS: Metal–Organic‐Framework‐Based Biomedical Microrobots

Motile metal?organic frameworks (MOFs) are potential candidates to serve as small‐scale robotic platforms for applications in environmental remediation, targeted drug delivery, or nanosurgery. Here, magnetic helical microstructures coated with a kind of zinc‐based MOF, zeolitic imidazole framework‐8 (ZIF‐8), with biocompatibility characteristics and pH‐responsive features, are successfully fabricated. Moreover, it is shown that this highly integrated multifunctional device can swim along predesigned tracks under the control of weak rotational magnetic fields. The proposed systems can achieve single‐cell targeting in a cell culture media and a controlled delivery of cargo payloads inside a complex microfluidic channel network. This new approach toward the fabrication of integrated multifunctional systems will open new avenues in soft microrobotics beyond current applications.     

Morphological changes of calcium hexaboride powder synthesized from condensed boric acid-polyol product

We previously reported a novel low-temperature synthesis method for calcium hexaboride (CaB₆) powder via the transient formation of boron carbide (B₄C) using a condensed boric acid (H₃BO₃)-polyol product. In this study, the effect of the type of polyol on the morphology of the CaB₆ powder was investigated. Three types of polyol, glycerin, mannitol, and poly(vinyl alcohol) (PVA), were used for the preparation of condensed H₃BO₃-polyol products since the B₄C particles prepared from these polyols exhibit different morphologies. CaB₆ powder was successfully synthesized at a low temperature of 1400?°C regardless of the polyol used. The size of the obtained CaB₆ particles varied with the polyol used, which reflected the size of the B₄C particles prepared using the corresponding polyol. These results indicate that the morphology of the obtained CaB₆ powder is derived from that of the transiently formed B₄C particles.     

Combination of AFM with an objective-type total internal reflection fluorescence microscope (TIRFM) for nanomanipulation of single cells

A new instrument was constructed by combining an objective-type total internal reflection fluorescence microscope with an atomic force microscope (AFM). Our purpose of constructing such an instrument is to detect and confirm the result of cellular level manipulations made with the AFM part through the detection system of the highly sensitive fluorescence microscope part. In this combination, manipulations are now possible from the nanometer to the micrometer scales and the fluorescence detection system is sensitive enough even for localizing single molecules. In this paper, we applied the system as a precise intracellular injector (nanoplanter). Fluorescent beads were first chemically immobilized onto a ZnO whisker that was glued to an AFM tip and were injected into a living BALB/3T3 cell together with the whisker. It was demonstrated that the system could clearly show the result of injection, that is, the presence of a small number of fluorescent beads in the cell.     

Effects of aging and HIF-1alpha deficiency on permeability of hippocampal vessels

We examined age-related changes in the blood-brain barrier (BBB) of neural cell-specific hypoxia inducible factor-1alpha (HIF-1alpha) deficient mice, which showed hydrocephalus with neuronal cell loss, to investigate an effect of neural cell-specific HIF-1alpha deficiency or hydrocephalus on vascular function. Vascular permeability of horseradish peroxidase (HRP) and binding of cationized ferritin (CF) particles to the endothelial cell luminal surface, as a marker of glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was significantly decreased in the cortex in mutant mice compared with that of control mice, although it was not paralleled by increased vascular permeability. In addition, strong staining for HRP was seen around vessels located along the hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP appeared in an increasing number of the endothelial cell abluminal vesicles and within the thickened basal lamina of arterioles in the hippocampus, showing increased vascular permeability. There were no leaky vessels in 10-week-old mutant mice or 10-week-old and 24-month-old control mice. These findings suggest the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF-1alpha deficient mice.     

PRECISION CUTTING OF MOLDING DIE USING SQUARE END MILL

The precision cutting of a molding die is realized using a square end mill on a 5-axis control machine. In this study, first the tool setting errors are analyzed and the compensation method of the errors is proposed. The effectiveness of compensation in precision cutting is confirmed. Next, the form accuracy of the spiral tool pass is compared with contour one in precision cutting of a spherical surface. Finally, the molding die with spherical surface is manufactured using a square end mill made out of single-crystal diamond based on the results of the compensation of the errors and the comparison of the two tool passes, and the form accuracy and surface roughness of the molding die are measured.     

Large array of sub-10-nm single-grain Au nanodots for use in nanotechnology

A uniform array of single-grain Au nanodots, as small as 5-8 nm, can be formed on silicon using e-beam lithography. The as-fabricated nanodots are amorphous, and thermal annealing converts them to pure Au single crystals covered with a thin SiO(2) layer. These findings are based on physical measurements, such as atomic force microscopy (AFM), atomic-resolution scanning transmission electron microscopy, and chemical techniques using energy dispersive X-ray spectroscopy. A self-assembled organic monolayer is grafted on the nanodots and characterized chemically with nanometric lateral resolution. The extended uniform array of nanodots is used as a new test-bed for molecular electronic devices.     

Low‐Temperature Synthesis of Calcium Hexaboride Powder via Transient Boron Carbide Formation

Calcium hexaboride (CaB₆) powder was synthesized by carbothermal reduction using a low‐temperature synthesis method for boron carbide (B₄C) powder. A B₄C precursor consisting of boron oxide (B₂O₃) and carbon components was prepared from a condensed boric acid (H₃BO₃)‐poly(vinyl alcohol) (PVA) product by thermal decomposition in air, which was then mixed with calcium carbonate (CaCO₃) powder. CaB₆ was formed via the transient formation of calcium borate (Ca₃B₂O₆) and B₄C, which were in close contact owing to the finely dispersed B₂O₃/carbon structure of the B₄C precursor. CaB₆ powder with fine particles was synthesized by heat treatment at 1400°C for 10 h in an Ar flow.     

A novel polysaccharide involved in the pellicle formation of Acetobacter aceti

Acetobacter aceti IFO 3284 has been shown to have two types of strains: one forms a smooth-surfaced colony (S strain) and the other forms a rough-surfaced colony (R strain) (Matsushita et al., 1992). In this study, both S and R strains were isolated and characterized. The S strain grew well in submerged culture but very poorly in static culture. In contrast, the R strain grew well in static culture by floating on the surface of the culture medium, as well as in shaking submerged culture. Scanning electron microscopy revealed that the R strain was covered by some amorphous materials that were not seen in the S strain. The R strain produced 5-fold higher levels of sugars related to polysaccharides responsible for pellicle formation than the S strain did. Unlike cellulose of Acetobacter xylinum, the polysaccharides of the R strain were cellulase-resistant and alkaline-sensitive. The polysaccharides were not secreted into the culture medium, and more than 90% of them were retained in the membrane fraction when the cells were disrupted under mild conditions by lysozyme treatment. Furthermore, the polysaccharides were shown to be mainly attached to the outer membrane when separated. After solubilization with beta-octylglucoside, the membrane-attached polysaccharides were purified by several steps including enzyme treatment, column chromatography and alcohol precipitation. The purified polysaccharide was estimated to have an apparent molecular mass of 700-kDa based on Sephacryl S-500 column chromatography, and to be composed of two monosaccharides, glucose and rhamnose, at an approximately equimolar ratio. Thus, in this study, we clarified that the A. aceti R strain produced a polysaccharide associated with the flotation of the cells on the medium surface, like A. xylinum, and that the polysaccharide was a novel one consisting of glucose and rhamnose.     

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.