Honokiol Acts as a Potent Anti-Fibrotic Agent in the Liver through Inhibition of TGF-β1/SMAD Signaling and Autophagy in Hepatic Stellate Cells

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl₄). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-β (TGF-β1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl₄-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-β1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-β1/SMAD signaling and autophagy in HSCs.     

Web crippling strength of a steel sandwich panel with V-shaped webs

Steel sandwich panels with V-shaped web flutes (V-core panels) serve the structural functions of a proposed energy-efficient roof system for residential construction. Due to its intended use as a flexural member spanning between a ridge beam and a structural wall, and required slender webs for weight considerations, web crippling under end one-flange loading is a critical strength limit state for the V-core panels. Although the 2001 North American Specification for the Design of Cold-Formed Steel Structural Members provides a design procedure to address web crippling, those design rules were developed for members whose cross sections are different from that of V-core panels. Consequently, nine specimens were tested to collect data on V-core panels subjected to end one-flange loading. Test observations suggested that V-core panels behave very similarly to multi-web decks that are strapped and unfastened to the supports. Experimental data reported in the literature was used to modify the web crippling strength equation in the Specification to reflect these particular conditions. The modified equation was found to adequately predict the measured web crippling strength of V-core panels.     

Experimental investigation of link-to-column connections in eccentrically braced frames

The design of link-to-column connections in seismic-resistant eccentrically braced frames remains a largely unresolved problem. In order to address this problem, twenty-four large-scale specimens were tested under cyclic loading. The test parameters included the connection detail, link length, link section, and cyclic loading protocol. The test results suggest that link-to-column connections are susceptible to fracture at the link flange welds, regardless of the link length. A large number of specimens failed prematurely, before meeting the plastic link rotation requirement in US code provisions. However, two promising link-to-column connection details were developed as an outcome of this research. The new connection details include a detail using all-around fillet welds between the link and the column flange, and a reinforced connection detail that welds a pair of stiffeners in the first link web panel next to the column, parallel to the link web. Test specimens using either of these two details were able to exceed the plastic link rotation requirement.     

Identification of intestinal wall abnormalities and ischemia by modeling spatial uncertainty in computed tomography imaging findings

Intestinal abnormalities and ischemia are medical conditions in which inflammation and injury of the intestine are caused by inadequate blood supply. Acute ischemia of the small bowel can be life-threatening. Computed tomography (CT) is currently a gold standard for the diagnosis of acute intestinal ischemia in the emergency department. However, the assessment of the diagnostic performance of CT findings in the detection of intestinal abnormalities and ischemia has been a difficult task for both radiologists and surgeons. Little effort has been found in developing computerized systems for the automated identification of these types of complex gastrointestinal disorders. In this paper, a geostatistical mapping of spatial uncertainty in CT scans is introduced for medical image feature extraction, which can be effectively applied for diagnostic detection of intestinal abnormalities and ischemia from control patterns. Experimental results obtained from the analysis of clinical data suggest the usefulness of the proposed uncertainty mapping model.     

T-shape filtered arc deposition system with built-in electrostatic macro-particle trap for DLC film preparation

A T-shape filtered arc deposition system (T-FAD) is a powerful tool to prepare high-quality diamond-like carbon (DLC) films. Most macro-particles (droplets) emitted from the graphite cathode are caught at the extension duct of the droplet catcher or collector facing the cathode, and then the clean plasma bent 90° is transported toward the substrate. However, further droplet reduction is still required in order to realize a higher quality film without droplet incorporation. In the present study, T-FAD employed an electrostatic droplet trap (ES-trap). A cylindrical ES-trap was placed in the extension duct part of the T-shape duct of an electromagnetic plasma transportation and droplet filter. The ion current at the exit of the T-filter duct and the current flowing to the ES-trap were measured as a function of the ES-trap bias voltage for various ES-trap positions. The deposition rate and number of droplets were also measured. As a result, it was found that the optimum voltage of the ES-trap was + 35 V and that it was better to place the ES-trap closer to the plasma beam in order to obtain fewer droplets on the film without an excessive decrease in the deposition rate. In the optimum condition, the number of droplets on the DLC film prepared with ES-trap was reduced to 1/3 of that without the ES-trap.     

Structural Fluctuations of the Human Proteasome α7 Homo-Tetradecamer Double Ring Imply the Proteasomal α-Ring Assembly Mechanism

The 20S proteasome, which is composed of layered α and β heptameric rings, is the core complex of the eukaryotic proteasome involved in proteolysis. The α7 subunit is a component of the α ring, and it self-assembles into a homo-tetradecamer consisting of two layers of α7 heptameric rings. However, the structure of the α7 double ring in solution has not been fully elucidated. We applied cryo-electron microscopy to delineate the structure of the α7 double ring in solution, revealing a structure different from the previously reported crystallographic model. The D7-symmetrical double ring was stacked with a 15° clockwise twist and a separation of 3 Å between the two rings. Two more conformations, dislocated and fully open, were also identified. Our observations suggest that the α7 double-ring structure fluctuates considerably in solution, allowing for the insertion of homologous α subunits, finally converting to the hetero-heptameric α rings in the 20S proteasome.     

Development of self-conducting current bypass circuit for series-connected diodes in high power semiconductor light source

This paper proposes a self-conducting current bypass circuit for series-connected diodes in high power semiconductor light source. This circuit enables the main circuit current flow continuously, even if several of the diodes connected in series are open because of breakdowns. Herein, the composition, operation, and circuit design method of the proposed circuit are described. Moreover, the development of a simulation model of the fuse, which is an element of the circuit, is described. Furthermore, the simulation result of the proposed circuit using the fuse model is presented, and the method of determining the circuit constant based on the simulation result is demonstrated. Finally, by connecting a prototype circuit based on this study in parallel with series-connected diodes, we show that the main circuit current of 60 A flow continuously even when one of the diodes is open.     

Annular resonator with a Cassegrain configuration

An advanced annular resonator is studied both theoretically and experimentally. This resonator has a Cassegrain mirror configuration and is designed to extract circular and high-quality beams from annular gain media. We carried out beam propagation in this resonator, calculating the intensity distributions of the laser beam. We also proved the performance experimentally by applying the resonator to a CO2 laser. The operation of the new resonator is demonstrated successfully. The quality of the output beam is in good agreement with theoretical calculations of laser output power of 20 W.