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Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1

Aberrant hepatic lipid metabolism is the major cause of non-alcoholic fatty liver disease (NAFLD) and is associated with insulin resistance and type 2 diabetes. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) is highly expressed in the liver, however its functional role in regulating NAFLD and associated metabolic disorders are not known. Male wildtype (WT) and hepatocyte Serpina3N knockout (HKO) mice were fed a control diet (CD), methionine and choline deficient (MCD) diet or high fat high sucrose (HFHS) diet to induce NAFLD and markers of lipid metabolism and glucose homeostasis were assessed. SerpinA3N protein was markedly induced in mice with fatty livers. Hepatic deletion of SerpinA3N attenuated steatosis which correlated with altered lipid metabolism genes, increased fatty acid oxidation activity and enhanced insulin signaling in mice with NAFLD. Additionally, SerpinA3N HKO mice had reduced epididymal white adipose tissue (eWAT) mass, leptin and insulin levels, improved glucose tolerance and enhanced insulin sensitivity which was associated with elevated insulin-like growth factor binding protein-1 (IGFBP1) and activation of the leptin receptor (LEPR)-STAT3 signaling pathway. Our findings provide a novel insight for the functional role for SerpinA3N in regulating NAFLD and glucose homeostasis.

Background: The risk of cardiovascular disease in type 1 diabetes remains extremely high, despite marked advances in blood glucose control and even the widespread use of cholesterol synthesis inhibitors. Thus, a deeper understanding of insulin regulation of cholesterol metabolism, and its disruption in type 1 diabetes, could reveal better treatment strategies. Methods: To define the mechanisms by which insulin controls plasma cholesterol levels, we knocked down the insulin receptor, FoxO1, and the key bile acid synthesis enzyme, CYP8B1. We measured bile acid composition, cholesterol absorption, and plasma cholesterol. In parallel, we measured markers of cholesterol absorption and synthesis in humans with type 1 diabetes treated with ezetimibe and simvastatin in a double-blind crossover study. Results: Mice with hepatic deletion of the insulin receptor showed marked increases in 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol. This phenotype was entirely reversed by hepatic deletion of FoxO1 . FoxO1 is inhibited by insulin and required for the production of 12α-hydroxylated bile acids, which promote intestinal cholesterol absorption and suppress hepatic cholesterol synthesis. Knockdown of Cyp8b1 normalized 12α-hydroxylated bile acid levels and completely prevented hypercholesterolemia in mice with hepatic deletion of the insulin receptor (n=5–30), as well as mouse models of type 1 diabetes (n=5–22). In parallel, the cholesterol absorption inhibitor, ezetimibe, normalized cholesterol absorption and low-density lipoprotein cholesterol in patients with type 1 diabetes as well as, or better than, the cholesterol synthesis inhibitor, simvastatin (n=20). Conclusions: Insulin, by inhibiting FoxO1 in the liver, reduces 12α-hydroxylated bile acids, cholesterol absorption, and plasma cholesterol levels. Thus, type 1 diabetes leads to a unique set of derangements in cholesterol metabolism, with increased absorption rather than synthesis. These derangements are reversed by ezetimibe, but not statins, which are currently the first line of lipid-lowering treatment in type 1 diabetes. Taken together, these data suggest that a personalized approach to lipid lowering in type 1 diabetes may be more effective and highlight the need for further studies specifically in this group of patients.

An environmentally friendly hydrometallurgical process was developed to recover vanadium and cesium selectively from spent sulfuric acid catalysts, and it has high recovery efficiency and economic advantages.

The behavior and mechanism of Li leaching from lithium aluminum silicate glass-ceramics which can be used as a secondary source of Li using aqueous NaOH solution was investigated. The Li leaching efficiency is increased with increasing concentration of NaOH, specific surface area, and reaction temperature. When leached under optimum conditions, 2 mol/L NaOH, 53 μm particle undersize, 1:10 solid/liquid ratio, 250 r/min stirring speed, 100°C reaction temperature, 12 hr, the Li leaching efficiency was approximately 70%. However, when the leaching experiment was performed for 48 hr, the concentration of Li+ ions contained in the leach liquor decreased from 1160 to 236 mg/L. To investigate the origin of this phenomenon, the obtained leach residue was analyzed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. These analyses show that zeolite was formed around the lithium aluminum silicate glass-ceramics, which affected the leaching of by adsorbing Li+ ions. In addition, using the shrinking-core model and the Arrhenius equation, the leaching reaction with NaOH was found to depends on the chemical reaction of the two reactants, with a higher than 41.84 kJ/mol of the activation energy.

A single oxidative leaching process was developed for simultaneous enhancement of dissolution of nickel and precipitation of lanthanum by using Na2S2O8 in sulfuric acid solution from a heat-treated mixture of batteries containing 50 wt.% alkaline batteries, 25 wt.% Ni-MH batteries, and 25 wt.% Ni-Cd batteries. The effect of leaching parameters was investigated, including the concentrations of sulfuric acid, Na2S2O8, and H2O2, the temperature, and the leaching time. The results show that almost all metals such as zinc, manganese, and cadmium are dissolved by 2 M sulfuric acid, but the leaching efficiency of nickel is 86.8%. However, in a leaching process using Na2S2O8, the leaching efficiency of Ni is enhanced while lanthanum is selectively precipitated in the form of NaLa(SO4)2·H2O at the same time, and this result is supported by XRD, ICP, and SEM analysis. Under the optimum conditions of 2 M H2SO4, 10 vol.% H2O2, 10 vol.% 1 M Na2S2O8, and 95 ℃, 97.8% of the nickel is leached while 98.8% of the lanthanum is selectively precipitated. This study shows that the separation and purification stages can be simplified to recover La and valuable metals.

Liver regeneration requires intrahepatic and extrahepatic metabolic reprogramming to meet the high hepatic bioenergy demand for liver cell repopulation. This study aims to elucidate how pyruvate dehydrogenase kinase 4 (PDK4), a critical regulator of glucose and lipid metabolism, coordinates metabolic regulation with efficient liver growth. We found that hepatic Pdk4 expression was elevated after two‐thirds partial hepatectomy (PHx). In Pdk4 −/− PHx mice, the liver/body weight ratio was more rapidly restored, accompanied by more aggressive hepatic DNA replication; however, Pdk4 −/− mice developed more severe hypoglycemia. In Pdk4 −/− PHx livers, the pro‐regenerative insulin signaling was potentiated, as demonstrated by early peaking of the phosphorylation of insulin receptor, more remarkable induction of the insulin receptor substrate proteins, IRS1 and IRS2, and more striking activation of Akt. The hepatic up‐regulation of CD36 contributed to the enhanced transient regeneration‐associated steatosis in Pdk4 −/− PHx mice. Notably, CD36 overexpression in mice promoted the recovery of liver/body weight ratio and elevated intrahepatic adenosine triphosphate after PHx. CD36 expression was transcriptionally suppressed by FOXO1 (forkhead box protein O1), which was stabilized and translocated to the nucleus following AMPK (adenosine monophosphate–activated protein kinase) activation. PHx remarkably induced AMPK activation, which became incompetent to respond in Pdk4 −/− livers. Moreover, we defined that PDK4‐regulated AMPK activation directly depended on intracellular adenosine monophosphate in vitro and in regenerative livers. Conclusion: PDK4 inhibition reprograms glucose and lipid metabolism to promote liver regeneration by enhancing hepatic insulin/Akt signaling and activating an AMPK/FOXO1/CD36 regulatory axis of lipid. These findings may lead to potential therapeutic strategies to prevent hepatic insufficiency and liver failure., In this study, we tested our hypothesis that PDK4‐mediated metabolic reprogramming energizes efficient liver growth. We elucidated the role of PDK4 in liver regeneration using the PHx model, defined PDK4 regulation of hepatic insulin signaling in regenerative livers and unraveled PDK4 as a critical mediator of hepatic lipid metabolism through regulating a novel AMPK/FOXO1/CD36 axis to promote LR efficiency.

Hepatic steatosis is an initial manifestation of alcoholic liver disease. An imbalance of hepatic lipid processes including fatty acid uptake, esterification, oxidation, and triglyceride secretion leads to alcoholic fatty liver (AFL). However, the precise molecular mechanisms underlying the pathogenesis of AFL remain elusive. Here, we show that mice deficient in microRNAs (miRs)-141 and -200c display resistance to the development of AFL. We found that miR-200c directly targets HNF1 homeobox B (Hnf1b), a transcriptional activator for microsomal triglyceride transfer protein (Mttp), as well as apolipoprotein O (ApoO), an integral component of the mitochondrial contact site and cristae organizing system complex. We show that expression of these miRs is significantly induced by chronic ethanol exposure, which is accompanied by reduced HNF1B and APOO levels. Furthermore, miR-141/200c deficiency normalizes ethanol-mediated impairment of triglyceride secretion, which can be attributed to the restored levels of HNF1B and MTTP, as well as phosphatidylcholine abundance. Moreover, we demonstrate that miR-141/200c deficiency restores ethanol-mediated inhibition of APOO expression and mitochondrial dysfunction, improving mitochondrial antioxidant defense capacity and fatty acid oxidation. Taken together, these results suggest that miR-200c contributes to the modulation of lipid homeostasis in AFL disease by cooperatively regulating Hnf1b and ApoO functions.

본 연구에서는 카지노 방문객과의 직접적인 접촉에 의한 카지노 종사자의 감정노동이 직무스트레스, 감정소진, 이직의도에 미치는 영향 관계를 규명하고자 하였다. 강원랜드 카지노 종사자들을 대상으로 설문을 진행하였으며, 최종 243부의 설문자료를 활용하여 연구가설을 검정하였고, 결과는 다음과 같다. 첫째, 감정노동으로서 표면행위는 직무스트레스에 정(+)의 영향을 미치는 것으로, 내면행위는 직무스트레스에 정(+)의 영향을 미치지 않는 것으로 확인되었다. 둘째, 감정노동으로서 표면행위는 감정소진에 정(+)의 영향을 미치는 것으로, 내면행위는 감정소진에 정(+)의 영향을 미치지 않는 것으로 확인되었다. 셋째, 직무스트레스는 감정소진과 이직의도에 정(+)의 영향을 미치며, 감정소진은 이직의도에 정(+)의 영향을 미치는 것으로 확인되었다. 연구결과는 효율적인 인적자원의 관리를 위해 카지노 종사자의 표면행위와 직무스트레스에 주목해야 할 필요가 있음을 제시하고 있다. 이러한 결과에 대한 분석을 토대로, 본 연구는 카지노 운영의 효율성을 증대시키기 위해 인적자원의 운영방안에 대한 기초 자료를 제시하였다. 향후 효율적이고 경쟁력 있는 인적자원관리를 위해 카지노 종사자들의 감정노동을 업무 및 개인적 특성에 따라 관리할 필요가 있다.

The mechanism of Li leaching from lithium aluminum silicate glass-ceramics was investigated to facilitate the recovery of Li. The experimental process was divided into the phase transition of the crystal structure through heat treatment and the Li leaching process using NaOH. Phase transition of the crystal structure based on the reaction temperature and heat treatment time was examined through X-ray diffraction analysis. The effects of the NaOH concentration, particle size, stirring speed, reaction temperature, solid/liquid ratio, and reaction time on Li leaching from heat-treated LAS was investigated. The results show that the crystal structure of lithium aluminum silicate glass-ceramics transitioned from hexagonal to tetragonal, and the efficiency of Li leaching from lithium aluminum silicate glass-ceramics before and after heat treatment was 68% and 99.6%, respectively. Accordingly, heat treatment increased the Li leaching efficiency by approximately 1.5-fold. To investigate the cause of the improvement of leaching efficiency, we calculated the lattice constant by using the interplanar spacing and Miller indices obtained from the X-ray diffraction analysis results for the respective powder samples. The results show that the crystal structure expanded approximately four-fold, and the reactivity with NaOH increased.

Acetaminophen (APAP) is a commonly used pain and fever reliever but is also the most frequent cause of drug-induced liver injury. The mechanism pertaining acetaminophen toxicity has been well documented, whereas mechanisms of hepatotoxicity are not well established. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N), a serine protease inhibitor, is synthesized in the liver but the role of SerpinA3N in relation to APAP-induced liver injury is not known. Wild-type and hepatocyte-specific SerpinA3N knockout (HKO) mice were injected intraperitoneally with a single dose of PBS or APAP (400 mg/kg) for 12 hours, and markers of liver injury, cell death, and inflammation were assessed. SerpinA3N expression was highly induced in mice with APAP overdose. SerpinA3N HKO mice had diminished liver injury and necrosis as shown by lower alanine aminotransferase and interleukin-6 levels, accompanied by suppressed inflammatory cytokines and reduced neutrophil infiltration. The reduced oxidative stress was associated with enhanced antioxidant enzyme capabilities. Taken together, hepatocyte SerpinA3N deficiency reduced APAP-induced liver injury by ameliorating inflammation and modulating the 5' AMP-activated protein kinase-unc-51-like autophagy activating kinase 1 signaling pathway. Our study provides novel insights into a potential role for SerpinA3N in APAP-induced liver injury. SIGNIFICANCE STATEMENT: Our studies indicate that serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) may have a pathophysiological role in modulating acetaminophen (APAP)-induced liver injury. More specifically, mice with hepatic deletion of SerpinA3N suppressed inflammation and liver injury to reduce APAP-induced hepatotoxicity. Controlling the inflammatory response offers possible approaches for novel therapeutics; therefore, understanding the pathophysiological role of SerpinA3N in inducing liver injury may add to the development of more efficacious treatments.

To manufacture TiO2, a high-purity synthetic rutile, the recovery of Ti was investigated using a hydro-metallurgical process. Using a feed solution containing 32050 mg/L Ti, 110 mg/L Si, 88 mg/L Nb, 2614 mg/L Fe, and 130 mg/L Zr, solvent-extraction experiments were conducted with alkyl phosphine oxide in conjunction with diluents such as kerosene and xylene. The results showed that the extraction mechanism of both diluents was very similar to slope analysis, which had a value of 1.9, however, the extraction equilibrium constant value of organic&ndash, metallic species in xylene as a diluent was lower than in kerosene as a diluent. This result affected the stripping efficiency of Ti in particular, therefore, xylene was selected as a diluent. To recover Ti ion from a leaching solution, a series of experiments was conducted, such as the McCabe&ndash, Thiele method and countercurrent simulation test for extraction and stripping of Ti. As a result, Ti and impurities such as Fe and Zr were extracted to 99.9% from Si and Nb under optimal conditions using countercurrent four-stage extraction, with 1 M Cyanex 923 at a ratio of organic phase/ aqueous phase=3. In the stripping test, Ti was selectively stripped to 90.1% from Fe and Zr in the organic phase by 1 M HCl. The obtained powder, which was hydrolyzed from an impurity-free solution, was analyzed to a purity of 99.9% by inductively coupled plasma. The TiO2, which has a spherical shape and a diameter of approximately 2 &micro, m according to SEM, was evident by XRD.

This study concerns ultrasonic thermoforming of Thermoplastic polyurethane (TPU) film for the fabrication of a television speaker diaphragm. The speaker diaphragm has a convex-protruded feature with a rounded-rectangular shape on which a number of micro-corrugations are formed for sound quality improvement. This diaphragm has generally been manufactured out of thin TPU film using a thermoforming process, which required cycle time as long as several minutes for proper heating and cooling of the polymer film and mold. In this study, an ultrasonic thermoforming process was introduced to reduce the cycle time to fabricate the diaphragm by taking advantage of the rapid and localized heating capability of ultrasonic vibration energy. To improve the forming quality of a large diaphragm for a television speaker, infrared heating was added to the process to preheat the TPU film before the forming stage. Various processing parameters including ultrasonic thermoforming and infrared heating conditions were investigated in relation to the forming quality. As a consequence, the diaphragm could be fabricated with acceptable forming ratios (> 95 % in the band region and > 70 % in the micro-corrugations) and short cycle time (12 s). This means that the proposed process is superior to conventional thermoforming processes that require long cycle time (> 200 s).

Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step towards understanding development, regeneration and cancer. The transcriptional regulator Yes-associated protein 1 (YAP) is a key regulator of liver size, development and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it. The effects of YAP are mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α). YAP inhibits the ability of PGC1α to bind to and activate transcription from the promoters of its gluconeogenic targets and the effects of YAP are blunted upon knockdown of PGC1α. In vivo, constitutively active YAP lowers plasma glucose levels and increases liver size. YAP therefore appears to reprogram cellular metabolism, diverting substrates away from the energy consuming process of gluconeogenesis, and towards the anabolic process of growth.

Nuclear receptors (NRs) are ligand-dependent transcription factors that are involved in various biological processes including metabolism, reproduction, and development. Upon activation by their ligands, NRs bind to their specific DNA elements, exerting their biological functions by regulating their target gene expression. Bile acids are detergent-like molecules that are synthesized in the liver. They not only function as a facilitator for the digestion of lipids and fat-soluble vitamins but also serve as signaling molecules for several nuclear receptors to regulate diverse biological processes including lipid, glucose, and energy metabolism, detoxification and drug metabolism, liver regeneration, and cancer. The nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), vitamin D receptor (VDR), and small heterodimer partner (SHP) constitute an integral part of the bile acid signaling. This chapter reviews the role of the NRs in bile acid homeostasis, highlighting the regulatory functions of the NRs in lipid and glucose metabolism in addition to bile acid metabolism.

Nuclear receptors (NRs) are ligand-dependent transcription factors that are involved in various biological processes including metabolism, reproduction, and development. Upon activation by their ligands, NRs bind to their specific DNA elements, exerting their biological functions by regulating their target gene expression. Bile acids are detergent-like molecules that are synthesized in the liver. They not only function as a facilitator for the digestion of lipids and fat-soluble vitamins but also serve as signaling molecules for several nuclear receptors to regulate diverse biological processes including lipid, glucose, and energy metabolism, detoxification and drug metabolism, liver regeneration, and cancer. The nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), vitamin D receptor (VDR), and small heterodimer partner (SHP) constitute an integral part of the bile acid signaling. This chapter reviews the role of the NRs in bile acid homeostasis, highlighting the regulatory functions of the NRs in lipid and glucose metabolism in addition to bile acid metabolism.

Forkhead box O (FOXO) proteins comprise a superfamily of transcription factors that play important roles in controlling various biological processes. Transcriptional control constitutes a crucial component in regulating complex biological processes. The identification of cis-regulatory elements is essential to understand the regulatory mechanism of gene expression. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is widely used to identify the cis-regulatory elements of transcription factors and other DNA-binding proteins on a genome-wide level. It is a powerful tool to analyze the regulatory networks underlying the biological processes. Here, we describe a detailed protocol for preparing ChIP-seq samples that are used for sequencing and subsequent data analyses.

Forkhead box O (FOXO) proteins comprise a superfamily of transcription factors that play important roles in controlling various biological processes. Transcriptional control constitutes a crucial component in regulating complex biological processes. The identification of cis-regulatory elements is essential to understand the regulatory mechanism of gene expression. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is widely used to identify the cis-regulatory elements of transcription factors and other DNA-binding proteins on a genome-wide level. It is a powerful tool to analyze the regulatory networks underlying the biological processes. Here, we describe a detailed protocol for preparing ChIP-seq samples that are used for sequencing and subsequent data analyses.

We investigate the separation of manganese by an antagonistic effect from a leaching solution of ternary cathodic material of spent lithium-ion batteries that contain 11,400 mg L −1 Co, 11,700 mg L −1 Mn, 12,200 mg L −1 Ni, and 5300 mg L −1 Li using a mixture of alkyl monocarboxylic acid and di-(2-ethylhexyl)phosphoric acid extractants. pH isotherm, distribution coefficient, separation factor, McCabe–Thiele diagram, selective scrubbing, and countercurrent extraction tests are carried out to prove an antagonistic effect and to recover manganese using alkyl monocarboxylic in the mixed extractant. Slope analysis is used to determine the extraction mechanism between a mixture of extractants and valuable metals. An increasing concentration of alkyl monocarboxylic acid in the mixture of extractants results in a decrease in distribution coefficient of cobalt and manganese, however, the separation factor value (β (Mn/Co) ) increases at pH 4.5. This is caused by slope analysis where alkyl monocarboxylic acid disrupts the extraction mechanism between di-(2-ethylhexyl)phosphoric acid and cobalt. Finally, continuous countercurrent extraction in a mini-plant test demonstrate the feasibility of manganese recovery from cobalt, nickel, and lithium.

The extraction of nickel from a leach liquor containing cobalt, manganese and lithium of Li-ion batteries cathode material using a mixture of Versatic 10 acid and LIX84-I was investigated. The leach liquor of LiB cathode material obtained with H2SO4/H2O2 as the lixiviant was purified by precipitating the leached aluminum, iron and copper as hydroxides by adjusting the pH to ~ 5. To extract nickel, the effect of Versatic 10 acid concentration was the experimental variable in the mixture of extractants. The pH-isotherms revealed the synergistic effect on nickel caused by the increasing concentration of Versatic 10 acid which decreased the pH50 for nickel extraction and pH 5 was chosen as the most suitable pH for solvent extraction. A loading isotherm at pH 5 was constructed by changing the O/A ratio. The McCabe Thiele diagram predicted the possibility of using three stages to extract over 98% nickel, which was confirmed experimentally. The stripping test was carried out from loaded organic of Versatic 10 acid alone, LIX 84-I alone and the combination of Versatic 10 acid and LIX 84-I. Slow stripping of nickel from LIX 84-I indicated that LIX 84-I and Versatic 10 acid acted as the extractant and synergist, respectively.

A study on selective separation of Zn from a leaching solution by disposal batteries including various type batteries was carried out to understand the recovery behaviour of Zn in leaching solution. Selective recovery of Zn in leaching solution including Mn, Cd, Cu ion was difficult due to its similar physicochemical behaviour. Experiment results by present leaching solution with 279 µm undersize indicated that the best condition for leaching is 1 M H

Insulin coordinates the complex response to feeding, affecting numerous metabolic and hormonal pathways. Forkhead box protein O1 (FoxO1) is one of several signaling molecules downstream of insulin; FoxO1 drives gluconeogenesis and is suppressed by insulin. To determine the role of FoxO1 in mediating other actions of insulin, we studied mice with hepatic deletion of the insulin receptor, FoxO1, or both. We found that mice with deletion of the insulin receptor alone showed not only hyperglycemia but also a 70% decrease in plasma insulin-like growth factor 1 and delayed growth during the first 2 months of life, a 24-fold increase in the soluble leptin receptor and a 19-fold increase in plasma leptin levels. Deletion of the insulin receptor also produced derangements in fatty acid metabolism, with a decrease in the expression of the lipogenic enzymes, hepatic diglycerides, and plasma triglycerides; in parallel, it increased expression of the fatty acid oxidation enzymes. Mice with deletion of both insulin receptor and FoxO1 showed a much more modest phenotype, with normal or near-normal glucose levels, growth, leptin levels, hepatic diglycerides, and fatty acid oxidation gene expression; however, lipogenic gene expression remained low. Taken together, these data reveal the pervasive role of FoxO1 in mediating the effects of insulin on not only glucose metabolism but also other hormonal signaling pathways and even some aspects of lipid metabolism.

Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c-/- mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c-/- MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression. Inflammation was attenuated and F4/80 macrophage activation was suppressed in miR-141/200c-/- mice, as evidenced by decreased serum aminotransferases and IL-6 and reduced hepatic proinflammatory, neutrophil, and profibrotic genes. Treatment with LPS in BM-derived macrophages isolated from miR-200c/141-/- mice polarized macrophages toward the M2 antiinflammatory state by increasing Arg1 and IL-10 levels while decreasing the M1 marker iNOS. In addition, elevated phosphorylated AMPK (p-AMPK), p-AKT, and p-GSK3β and diminished TLR4 and p-mTOR/p-4EBP1 proteins were observed. Lipidomics and metabolomics revealed alterations of TG and phosphatidylcholine (PC) lipid species by miR-141/200c deficiency. In summary, miR-141/200c deficiency diminished NASH-associated hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways.

Clavicle medial end fracture is rare, and it has not been studied extensively. Although there is debate regarding its treatment methods, because of the complications of conservative treatment, surgical treatment has been considered more than conservative treatment. This study describes a surgical method using double-plate fixation for treatment of clavicle medial end fractures in which plates were used on each anterior and superior border according to the anatomical structure of the clavicle. In addition, we report operative results of three patients treated by double-plate fixation.