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Carbon materials have become a focal point in supercapacitors (SCs) due to their perfect charge–discharge behavior, relatively low cost, and excellent electrochemical stability, but the limited electrochemical activity restricts their further development. MXenes (Ti3C2Tx) combine high electrical conductivity, hydrophilicity, and abundance surface functional groups, which contribute to high energy density when compounded with carbon materials. In this work, carbon material derived from mineral water bottles is modified with cetyltrimethylammonium bromide (CTAB) that spontaneously forms into porous heterogeneous structures with Ti3C2Tx under electrostatic interactions. The carbon material hinders the reaggregation of Ti3C2Tx, while Ti3C2Tx increases the electrochemical activity on the surface of the carbon material. A hierarchical porous carbon with a large specific surface area of 1754.3 m2 g−1, promoting the electrolyte migration kinetics and high specific capacitance in 6 m KOH electrolyte (404.1 F g−1 at 1 A g−1). The symmetric SC made as‐prepared carbon electrode shows an extended voltage window (1.8 V), an optimal energy density (31.19 Wh kg−1 at a power density of 450 W kg−1) and a low capacitance decay (1% after 15 000 cycles) in 1.5 m Na2SO4. The preparation of electrode material with a unique structure provides a practical and innovative strategy for the value‐added utilization of waste plastics. [ABSTRACT FROM AUTHOR]

Paramichelia baillonii is a rare and fast-growing tree species in subtropical China. The acidic red soil in southern China severely limits its growth as it lacks sufficient available phosphorus (P), resulting in declining soil fertility and nutrient availability. The effect of P deficiency on P. Baillonii growth, root attributes, and physiological response has not yet been reported. Understanding the adaptability of P. baillonii to low-P conditions can improve afforestation and soil management in southern China. Therefore, we conducted a pot experiment on 2-year-old saplings and treated them with different P levels. Results showed that P deficiency (0-5 mg L-1) decreased growth attributes, root morphological traits, and nutrient uptake of P. baillonii saplings compared to control (CK). Similarly, reduction in chlorophyll a, b, total chlorophyll, net photosynthetic rate (Pn), transpiration rate (Tr), and Gs were seen in low P treatment saplings compared to CK. Whereas superoxide dismutase, peroxidase, malondialdehyde, acid phosphatase activity, and soluble protein content increased with increasing P-deficiency up to 5 mg L-1, and soluble sugar showed oppsite trend. Moreover, the proteomics analysis identified 2721 proteins, 196 showing differential expression, with 90 up- and 106 down-regulated. Importantly, the metabolic activities increased in the pentose phosphate pathway, starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and phenylpropanoid biosynthesis pathways to sustain regular plant growth under P deficiency. This study delves into the dynamic morphophysiological and proteomic changes in response to P deficiency. Overall, growth and nutrient uptake were reduced, countered by adaptive biochemical and proteomic shifts, including heightened antioxidant activities and modifications in metabolic pathways, highlighting the resilient strategies of P. baillonii saplings under P deficiency. [ABSTRACT FROM AUTHOR]

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a). [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is a Gram‐negative, spiral‐shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa‐associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric‐related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. Methods: PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms—H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. Results: Most of the candidate antigens used as H. pylori vaccines in these literatures are whole‐cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. Conclusions: This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers. [ABSTRACT FROM AUTHOR]

As a vital chemical, ammonia (NH3) plays an irreplaceable role in many fields such as chemical synthesis and energy storage. Green renewable biomass can be converted into biofuels, but its nitrogen resources are underused throughout. Laser-driven pyrolysis is envisaged to debuts as a bridge to connect them to realize the direct conversion from nitrogen-rich biomass into ammonia. The pulsed laser-induced local-transient thermal effect recognized the biological nitrogen resources conversion, such as cheap and plentiful yeasts, to small gaseous molecules and achieved spectacular ammonia production rate up to 260.4 mg/h, an order of magnitude higher performance than thermochemical ammonia synthesis. Simultaneously, the tiny hot point generated by a low-energy laser (20W)guarantees the whole ammonia synthesis reaction systemis in amild environment of low temperature and normal pressure. Additionally, the remaining solid residue after laser-driven pyrolysis also can be further exploited as a highly active catalyst for electrocatalytic nitrate reduction reaction (NIRR). [ABSTRACT FROM AUTHOR]

In this paper, we present the detection of ore‐forming elements migrated from soil and rock to vegetation leaves using hyperspectral data. The rock, soil (C, B, and A layer), and vegetation (root, stem, and leaf) samples with the measurements of spectra and element concentrations in the vertical section of the abandoned pits were collected. The wavelet approach is applied to analyze the correlations between spectral features and element concentrations. The results show that the significant correlations are found at a lower order mother wavelets such as Haar. Moreover, the significant correlations are negative between Cu and Mo elements and the wavelet energy vector of the soil and rock to vegetation leaves spectrum. The results also show that ore‐forming elements migrated from rock and soil to vegetation leaves can be detected using hyperspectral data in the study area. Key Points: Detecting element transport law based on remote sensing technology [ABSTRACT FROM AUTHOR]

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA‐binding proteins in the insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2‐binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2‐ and serum response factor (SRF)‐treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3‐E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD. [ABSTRACT FROM AUTHOR]

The development of ethanol electrooxidation catalysts with high activity and robust stability is essential for the commercialization of direct ethanol fuel cells. However, because of their low C1 selectivity, the electrocatalytic efficiency of catalysts for complete ethanol oxidation is still far from satisfying. Herein, a novel 2D Pd--Au heterogeneous catalyst for enhancing C1 selectivity to achieve highly efficient ethanol oxidation through phase and interphase engineering is designed. It is found that owing to the plentiful amorphous/crystalline interphases, the selectivity of C1 pathway on Pd--Au heterocatalyst can be improved up to 33.2% at a low potential, 10.4 times higher than commercial Pd/C (3.2%). Furthermore, 89.1% of initial mass activity of Pd--Au HNS can be retained after the accelerated degradation test of 2000 potential cycles, much higher than those of Pd NS (39.3%), commercial Pd/C (34.4%), and Pt/C (11.4%). The CO stripping and in situ Fourier transform infrared experiments reveal that 2D Pd--Au heterocatalyst, with intricate design of the amorphous Pd domain and the crystalline Au cluster interface, has better antipoisoning properties and stronger C--C bond cleavage ability than pure Pd nanosheets. Density functional theory calculations further demonstrate that the introduction of Au clusters switches on the electroactivity of amorphous Pd as the electron pump to accomplish the complete oxidation of ethanol, in which the selectivity for C1 pathway is significantly boosted whereas the typical C2 pathway is substantially blocked. [ABSTRACT FROM AUTHOR]

A template-agent can affect defect formation as well as influence interface properties, due to the rapid growth of perovskite film from the solution. Herein, diethylammonium iodide (DAI) is used as an effective template-agent to control the perovskite crystallization during preparation. It is found that a very small amount of DAI in chlorobenzene (CB) can slow down the perovskite growth of the CH3NH3PbI3 (MAPbI3) film with more large grain size and compacted crystal-grains resulting in the lesser grain boundaries (GBs) in favor of carrier transport in perovskite solar cells (PSCs). Moreover, some redundant PbI2 can be digested to form DA2PbI4. One part of DA2PbI4 can form the sub-grains with the composition of (DA2PbI4)0.2(PbI2)0.8 to passivate the GB defects, and other part can cover the surface to passivate the surface defects in large MAPbI3 grains. Using an optimized DAI concentration of 0.5mg mL-1 in CB solution, the corrsponding MAPbI3 PSC achieves an increased power conversion efficiency of 20.31% with suppressed current--voltage hysteresis. This DAI passivation strategy provides a simple approach to effectively assist the grain-growth for improved device performance. [ABSTRACT FROM AUTHOR]

Yupingfeng granules (YPFG) were isolated from a traditional Chinese medicine (TCM) formulation composed of three herbs (Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Saposhnikoviae Radix). This formulation is used inTCM to tonify qi, and it can help strengthen exterior and reduce sweating. Nevertheless, the active components of YPFG remain unclear. In this study, the chemical constituents of YPFG were systematically characterized by ultra-performance liquid chromatography coupled with electrospray ionization/ quadrupole time-of-flight mass spectrometry (UPLC-ESIQ- TOF-MS). Fifty-eight compounds, namely, 20 flavonoids, 19 saponins, nine organic acids, four volatile coumarins, three lactones, one alkaloid, and two other components, were identified. In addition, the constituents of YPFG with the potential for in vivo bioactivities following oral administration were investigated in Sprague--Dawley rats. Thirteen compounds, namely, 11 flavonoid-related and 2 saponin-related components, were detected in rat plasma. After enriching flavonoids and saponins in YPFG by extraction, the extracts and YPFG were administrated to immunosuppressed rats, respectively. Plasma samples were analyzed by UPLC-ESI-Q-TOF-MS, and principal component analysis (PCA) confirmed that the extracts had similar effects toYPFG. This method could discover active ingredients inYPFG quickly and provide a scientific basis for quality control and mechanism research. [ABSTRACT FROM AUTHOR]

Pyropheophorbide‐a (Pyro) is a promising multifunctional molecule for multimodal tumour imaging and photodynamic therapy, but its clinical applications are seriously restricted by the limited tumour accumulation capability. Here, we designed and synthesized a small‐molecule probe that achieved specific dual‐modal tumour imaging based on Pyro. Briefly, a novel molecule combining Pyro, an RGD dimer peptide (3PRGD2) and 64Cu, was designed and synthesized, and the obtained molecule, 64Cu‐Pyro‐3PRGD2, exhibited high tumour specificity in both positron emission tomography and optical imaging in vivo. c (RGDfk) peptide blocking significantly reduced the efficacy of the probe, which confirmed the integrin αVβ3 targeting of this molecular probe. 64Cu‐Pyro‐3PRGD2 had very low accumulation in normal organs and could be rapidly cleared through kidney metabolism, which prevented the potential damage to adjacent normal tissues. Overall, combining tumour targeting, dual‐modal imaging, and biosafety, 64Cu‐Pyro‐3PRGD2 has the potential for clinical use as a molecular imaging probe for tumour diagnosis. [ABSTRACT FROM AUTHOR]

Crystal phase engineering is a powerful strategy for regulating the performance of electrocatalysts towards many electrocatalytic reactions, while its impact on the nitrogen electroreduction has been largely unexplored. Herein, we demonstrate that structurally ordered body‐centered cubic (BCC) PdCu nanoparticles can be adopted as active, selective, and stable electrocatalysts for ammonia synthesis. Specifically, the BCC PdCu exhibits excellent activity with a high NH3 yield of 35.7 μg h−1 mg−1cat, Faradaic efficiency of 11.5 %, and high selectivity (no N2H4 is detected) at −0.1 V versus reversible hydrogen electrode, outperforming its counterpart, face‐centered cubic (FCC) PdCu, and most reported nitrogen reduction reaction (NRR) electrocatalysts. It also exhibits durable stability for consecutive electrolysis for five cycles. Density functional theory calculation reveals that strong orbital interactions between Pd and neighboring Cu sites in BCC PdCu obtained by structure engineering induces an evident correlation effect for boosting up the Pd 4d electronic activities for efficient NRR catalysis. Our findings open up a new avenue for designing active and stable electrocatalysts towards NRR. [ABSTRACT FROM AUTHOR]

The design and development of non‐noble metal alternatives with superior performance and promising long‐term stability that is comparable or even better than those of noble‐metal‐based catalysts is a significant challenge. Here, we report the thermal‐induced phase engineering of non‐noble‐metal‐based nanowires with superior electrochemical activity and stability for the methanol oxidation reaction (MOR) under alkaline conditions. The optimized Cu–Ni nanowires deliver an unprecedented mass activity of 425 mA mg−1, which is 4.3 times higher than that of the untreated one. Detailed catalytic investigations show that the enhanced performance is due to the large active area, the increased number of active sites (NiOOH), and fast methanol electrooxidation kinetics. In addition, the generated hollow feature in the nanowires provides a unique void space to release the volume expansion, where the activity can be maintained for 5 h without a distinct activity decay. The present work emphasizes the importance of precisely phase modulating of nanomaterials for the design of non‐noble metal electrocatalysts towards the MOR, which opens up a new pathway for the design of cost‐effective electrocatalysts with promising activity and long‐term stability. [ABSTRACT FROM AUTHOR]

To study the cost of epilepsy in China, and, therefore, provide essential information on the burden of the disease to individuals and society. A cost-of-illness study was performed on a retrospective cohort of medically treated patients. Data on clinical characteristics, utilization of sources, and costs were collected from 289 patients in a standardized format. Direct medical care costs was Chinese yuan, renminbi (RMB) 2,529 (USD 372) per year per patient, of which antiepileptic drugs (RMB 1,651 or USD 243) accounted for the major cost component. Nonmedical direct costs were much less than direct health care costs, averaging approximately RMB 756 (USD 111). Costs due to loss of productivity averaged approximately RMB 1,968 (USD 289) per patient per year. Taken together, the overall mean annual cost for epilepsy per patient in our series was approximately RMB 5,253 (USD 773), and these costs accounted for more than half of the mean annual income. Total cost was significantly associated with disease severity and different responses to drug treatment. In addition, new antiepileptic drugs and the number of drugs taken were closely related with the drug cost. The results indicate that the economic burden of epilepsy to both Chinese patients and the nation is heavy, and the composition proportions of the costs in China have many similar features and some noteworthy differences with that of other countries. [ABSTRACT FROM AUTHOR]

Hepatocytes express adrenergic receptors (ARs) that modulate several functions, including liver regeneration, hepatocyte proliferation, glycogenolysis, gluconeogenesis, synthesis of urea and fatty acid metabolism. Adrenergic hepatic function in adults is mainly under the control of α1-ARs; however, the mechanism through which they influence diverse processes remains incompletely understood. This study describes a novel α1-AR-mediated transactivation of signal transducer and activator of transcription-3 (Stat3) in primary and transformed hepatocytes. Treatment of primary rat hepatocytes with the α1-AR agonist, phenylephrine (PE), induced a rapid phosphorylation of Stat3. PE also increased Stat3 phosphorylation, DNA binding and transcription activity in transformed human hepatocellular carcinoma cells (Hep3B). The PE-induced Stat3 phosphorylation, DNA binding and reporter activity were completely blocked by the selective α1-AR antagonist, prazosin. In addition, transfection of Hep3B cells with human α1B-AR expression vector also enhanced Stat3 phosphorylation and reporter activity. Moreover, overexpression of RGS2, a protein inhibitor of Gq/11 signaling, blocked PE-induced Stat3 phosphorylation and reporter activity. The observations that PE induced the formation of c-Src-Stat3 binding complex and phosphorylation of epidermal growth factor receptor (EGFR) and that inhibiting Src and EGFR prevented PE-induced Stat3 activation indicate the involvement of Src and EGFR. Taken together, these observations demonstrate a novel α1-AR-mediated Stat3 activation that involves Gq/11, Src, and EGFR in hepatic cells. J. Cell. Physiol. 216: 486–497, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We recently reported that intermittent hypoxia facilitated the proliferation of neural stem/progenitor cells (NPCs) in the subventricule zone and hippocampus in vivo. Here, we demonstrate that hypoxia promoted the proliferation of NPCs in vitro and that hypoxia-inducible factor (HIF)-1α, which is one of the key molecules in the response to hypoxia, was critical in this process. NPCs were isolated from the rat embryonic mesencephalon (E13.5), and exposed to different oxygen concentrations (20% O2, 10% O2, and 3% O2) for 3 days. The results showed that hypoxia, especially 10% O2, promoted the proliferation of NPCs as assayed by bromodeoxyuridine incorporation, neurosphere formation, and proliferation index. The level of HIF-1α mRNA and protein expression detected by RT-PCR and western blot significantly increased in NPCs subjected to 10% O2. To further elucidate the potential role of HIF-1α in the proliferation of NPCs induced by hypoxia, an adenovirus construct was used to overexpress HIF-1α, and the pSilencer 1.0-U6 plasmid as RNA interference vector targeting HIF-1α mRNA was used to knock down HIF-1α. We found that overexpression of HIF-1α caused the same proliferative effect on NPCs under 20% O2 as under 10% O2. In contrast, knockdown of HIF-1α inhibited NPC proliferation induced by 10% O2. These results demonstrated that moderate hypoxia was more beneficial to NPC proliferation and that HIF-1α was critical in this process. [ABSTRACT FROM AUTHOR]

The article describes a study examining the crystallization behavior of a series of poly(L-lactide)-poly(ethylene glycol) (PLLA-PEG) diblock copolymers for drug delivery applications in the form of microparticles, nanoparticles, micelles and hydrogels. The authors discuss the overall isothermal crystallization and subsequent melting behavior of diblock copolymers of ethylene oxide/lactide ratios, based on results obtained from differential scanning calorimetry. They use the Lauritzen-Hoffman theory to compare the morphology and melt crystallization behavior of the diblock copolymer with PLLA homopolymers.

Recent evidence indicates that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are involved in hepatocarcinogenesis. This study was designed to evaluate the possible interaction between the COX-2 and EGFR signaling pathways in human hepatocellular carcinoma (HCC) cells. Immunohistochemical analysis using serial sections of human HCC tissues revealed positive correlation between COX-2 and EGFR in HCC cells (P < 0.01). Overexpression of COX-2 in cultured HCC cells (Hep3B) or treatment with PGE2 or the selective EP1 receptor agonist, ONO-DI-004, increased EGFR phosphorylation and tumor cell invasion. The PGE2-induced EGFR phosphorylation and cell invasiveness were blocked by the EP1 receptor siRNA or antagonist ONO-8711 and by two EGFR tyrosine kinase inhibitors, AG1478 and PD153035. The EP1-induced EGFR transactivation and cell invasion involves c-Src, in light of the presence of native binding complex of EP1/Src/EGFR and the inhibition of PGE2-induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor, PP2. Further, overexpression of COX-2 or treatment with PGE2 also induced phosphorylation of c-Met, another receptor tyrosine kinase critical for HCC cell invasion. Moreover, activation of EGFR by EGF increased COX-2 promoter activity and protein expression in Hep3B and Huh-7 cells, whereas blocking PGE2 synthesis or EP1 attenuated EGFR phosphorylation induced by EGF, suggesting that the COX-2/PGE2/EP1 pathway also modulate the activation of EGFR by its cognate ligand. These findings disclose a cross-talk between the COX-2/PGE2/EP1 and EGFR/c-Met signaling pathways that coordinately regulate human HCC cell invasion. J. Cell. Physiol. 207: 261–270, 2006. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Summary Asymmetric localization of proteins is essential to many biological functions of bacteria. Shigella IcsA, an outer membrane protein, is localized to the old pole of the bacillus, where it mediates assembly of a polarized actin tail during infection of mammalian cells. Actin tail assembly provides the propulsive force for intracellular movement and intercellular dissemination. Localization of IcsA to the pole is independent of the amino-terminal signal peptide (Charles, M., Perez, M., Kobil, J.H., and Goldberg, M.B., 2001, Proc Natl Acad Sci USA 98: 9871–9876) suggesting that IcsA targeting occurs in the bacterial cytoplasm and that its secretion across the cytoplasmic membrane occurs only at the pole. Here, we characterize the mechanism by which IcsA is secreted across the cytoplasmic membrane. We present evidence that IcsA requires the SecA ATPase and the SecYEG membrane channel (translocon) for secretion. Our data suggest that YidC is not required for IcsA secretion. Furthermore, we show that polar localization of IcsA is independent of SecA. Finally, we demonstrate that while IcsA requires the SecYEG translocon for secretion, components of this apparatus are uniformly distributed within the membrane. Based on these data, we propose a model for coordinate polar targeting and secretion of IcsA at the bacterial pole. [ABSTRACT FROM AUTHOR]

Reactive oxygen species stimulate transformation of quiescent retinoid-containing hepatic stellate cells (qHSCs) into retinoid-deficient proliferating and fibrogenic activated phenotype (aHSCs). We observed that superoxide (SO) can also cause apoptosis of rat aHSCs. This study investigated mechanisms of the effects of SO on the two HSC phenotypes. Unstimulated qHSCs exhibited spontaneous caspase-3 activity, DNA damage and apoptosis, which were not affected by SO. In contrast, SO caused DNA damage and apoptosis in aHSCs. The basal glutathione (GSH) and activities of SOD, catalase and glutathione peroxidase (GPx) were significantly lower in aHSCs than qHSCs. SO treatment increased GSH content, and activities of SOD, catalase and GPx in qHSCs but not in aHSCs. Incubation of aHSCs with retinoic acid increased GSH content and GPx activity, but did not alter the activities of SOD and catalase. SO treatment of retinoic acid-treated aHSCs caused further increase in GSH content and GPx activity, and inhibited its death-inducing effects. Finally, oxidative stress induced by tertbutylhydroperoxide caused apoptosis of aHSCs in CCl4-induced cirrhotic rat but not of qHSCs in control rats: Thus absence of retinoids, and lower GSH and activities of antioxidant enzymes seem to render aHSCs susceptible to the damaging effects of SO, which may have important implications in liver pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Beta-catenin regulates expression of multiple regulators of oxidative stress in the liver and thus, may be involved in the pathogenesis of nonalcoholic steatohepatitis. Here, we examined the role of beta-catenin in steatohepatitis using the murine methionine-choline-deficient (MCD) diet model. Methods: Two-month-old liver-specific beta-catenin knockout mice and genetically matched control littermates were fed either the MCD diet or control diet for 2 weeks and then sacrificed for analysis. Results: On the control diet, beta-catenin knockout mice showed mild microvesicular steatohepatitis and two-fold higher transaminases, compared with normal histology and liver enzymes in the control animals. On the MCD diet, beta-catenin knockout animals exhibited severe macrovesicular steatosis (80-100%), grade 3-4 inflammation, and stage 1-2 fibrosis, compared with mild to moderate steatohepatitis and no fibrosis in the control animals. Both MCD-fed strains had five- to ten-fold higher transaminase levels, but only knockout mice had ten-fold higher total bilirubin level. Conclusions: Liver-specific loss of beta-catenin causes a striking increase in liver injury and fibrosis in mice fed the MCD diet, suggesting an important protective role of beta-catenin in the pathogenesis of liver injury in this model of steatohepatitis. [ABSTRACT FROM AUTHOR]