Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes

Background/AimsOverlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone.MethodsThis retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes.ResultsThe AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups.ConclusionsThe AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients

Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors

SummaryThe screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are blood-feeding, intestinal nematode parasites that infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a “proof-of-concept” for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analog that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity

Моделирование формирования структуры металломатричных композитов в процессе синтеза с оценкой эффективных свойств

Работа посвящена моделированию процесса кристаллизации композита с металлической матрицей и твердыми включениями с учетом условий синтеза (давление, скорость охлаждения), моделированию процесса формирования переходной зоны между частицами и матрицей и расчету эффективных свойств получаемых композитов.The work is devoted to modeling the crystallization process of metal matrix composite with solid inclusions, taking into account the synthesis conditions (pressure, cooling rate), to modeling the formation of the transition zone between particles and matrix, and calculating the effective properties of the resulting composites

A Study on the Underwater Energy Harvester with Two PVDFs Installed on the FTEH and CTEH at the End of the Support

In this study, two thin rectangular PVDFs were installed in the form of a cantilever on a FTEH (funnel-type energy harvester), and a CTEH (cymbal-type energy harvester) was fabricated in a form coupled to the upper part of the support. As a result of measuring the energy harvesting sensitivity according to the installation direction of the CTEH, a high voltage was measured in the structure installed on top of the support across all flow velocity conditions. A composite structure PVDF energy harvester combining CTEH and FTEH was fabricated and the amount of power generated was measured. As a result of measuring the open-circuit voltage of the PVDF energy harvester device with a composite structure to which the optimum resistance of CTEH of 241 kΩ and the optimum resistance of FTEH of 1474 kΩ were applied at a flow rate of 0.25 m/s, the output voltage compared to the RMS average value was 7 to 8.5 times higher for FTEH than for CTEH. When the flow rate was 0.5 m/s, the electrical energy charged for 500 s was measured as 2.0 μWs to 2.5 μWs, and when the flow speed was 0.75 m/s, it reached 2.5 μWs when charged for 300 s, generating the same amount when the flow rate increased by 50%. The time to do it was reduced by 66.7%

Energy-filtered acceleration of charge-carrier transport in organic thermoelectric nanocomposites

Nanocomposite systems have notably improved the thermoelectric (TE) figure-of-merit ZT of organic materials; however, further studies are required to reveal the underlying TE charge transport in the heterogeneous organic system. Here, the relationship between the TE properties and the energy structure of the organic TE nanocomposite is investigated by developing different internal potential steps in poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) with carbon quantum dots (CQDs) of tunable electronic bands. The charge transport across the insulating PSS layer was facilitated by embedded CQDs, which accelerated the high-energy hole transport and increased both the Seebeck coefficient and the electrical conductivity. With a carefully tuned internal potential step, PEDOT:PSS/CQD nanocomposite showed a power factor of 584 μW m-1 K-2, which was 3 times larger than that of pristine PEDOT:PSS and yields a high ZT = 0.32. This work provides a fresh perspective on the energy-filtering effect for the design of high-performance organic TE nanocomposites.11Nsciescopu

Impedance Coupled Voltage Boosting Circuit for Polyvinylidene Fluoride Based Energy Harvester

Polyvinylidene fluoride (PVDF) is an emerging method for energy harvesting by fluid motion with superior flexibility. However, the PVDF energy harvester, which has a high internal impedance and generates a low voltage, has a large power transmission loss. To overcome this problem, we propose an impedance-coupled voltage-boosting circuit (IC-VBC) that reduces the impedance of the PVDF energy harvester and boosts the voltage. SPICE simulation results show that IC-VBC reduces the impedance of the PVDF energy harvester from 4.3 MΩ to 320 kΩ and increases the output voltage by 2.52 times. We successfully charged lithium-ion batteries using the PVDF energy harvester and IC-VBC with low-speed wind power generation

A Funnel Type PVDF Underwater Energy Harvester with Spiral Structure Mounted on the Harvester Support

For the purpose of stably supplying electric power to the underwater wireless sensor, the energy harvesting technology in which a voltage is obtained by generating displacement in a piezoelectric material using flow-induced vibration is one of the most attractive research fields. The funnel type energy harvester (FTEH) with PVDF proposed in this study is an energy harvester in which the inlet has a larger cross-sectional area than the outlet and a spiral structure is inserted to generate a vortex flow at the inlet. Based on numerical analysis, when PVDF with L = 100 mm and t = 1 mm was used, the electric power of 39 μW was generated at flow velocity of 0.25 m/s. In experiment the average RMS voltage of FTEH increased by 0.0209 V when the flow velocity increased by 1 m/s. When measured at 0.25 m/s flow velocity for 25 s, it was shown that voltage doubler rectifier (VDR) generated a voltage of 133.4 mV, 2.25 times larger than that of full bridge rectifier (FBR), and the energy charged in the capacitor was 44.3 nJ, 14% higher in VDR than that of the FBR. In addition, the VDR can deliver power of 17.75 μW for 1 kΩ load. It is shown that if the voltage generated by the FTEH using the flow velocity is stored using the VDR electric circuit, it will greatly contribute to the stable power supply of the underwater wireless sensor

New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle

Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α1-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca2+-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α1-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC