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A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular...
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A recently developed human PSC-derived skin organoid model has opened up new avenues for studying skin development, diseases, and regeneration. The current model has limitations since the generated organoids are enclosed, circular aggregates with an inside-out morphology with unintended off-target development of cartilage. Here, we first demonstrated that Wnt signaling activation resulted in larger organoids without off-target cartilage. We optimized further using an air-liquid interface (ALI) culture method to recapitulate structural features?representative of human skin tissue. Finally, we used the ALI-skin organoid platform to model atopic dermatitis byStaphylococcus aureus(SA) colonization and infection. SA infection led to a disrupted skin barrier and increased production?of epidermal- and dermal-derived inflammatory cytokines. Additionally, we found that pre-treatment withCutibacterium acneshad a protective effect?on SA-infected organoids. Thus, this ALI-skin organoid platform may be a useful tool for modeling human skin diseases and evaluating the efficacy of novel therapeutics.
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Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation...
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Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced MCC complex formation and subsequent mitochondrial Ca2+ accumulation and dysfunction. Finally, ectopic induction of MAM formation reverses the protective effect of PDK4 deficiency in alcohol-induced liver injury. Together, our study defines a mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD. Ca2+ overload-induced mitochondrial dysfunction is considered a contributing factor alcohol-associated liver disease pathogenesis. Here the authors report that PDK4 promotes Ca2?+?-channelling complex formation at the endoplasmic reticulum-mitochondria contact sites, which contributes to the pathogenesis of alcohol-associated liver disease in studies with male mouse and hepatocyte models.
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The stem bark of Toxicodendron vernicifluum (TVSB) has been widely used as a traditional herbal medicine and food ingredients in Korea. However, its application has been restricted due to its potential to cause allergies. Moreover...
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The stem bark of Toxicodendron vernicifluum (TVSB) has been widely used as a traditional herbal medicine and food ingredients in Korea. However, its application has been restricted due to its potential to cause allergies. Moreover, there is limited data available on the qualitative and quantitative changes in the composition of its phytochemicals during fermentation. Although the Formitella fraxinea-mediated fermentation method has been reported as an effective detoxification tool, changes to its bioactive components and the antioxidant activity that takes place during its fermentation process have not yet been fully elucidated. This study aimed to investigate the dynamic changes of urushiols, bioactive compounds, and antioxidant properties during the fermentation of TVSB by mushroom F. fraxinea. The contents of urushiols, total polyphenols, and individual flavonoids (fisetin, fustin, sulfuretin, and butein) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) significantly decreased during the first 10 days of fermentation, with only a slight decrease thereafter until 22 days. Free radical scavenging activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6- sulfonic acid) (ABTS), and ferric reducing/antioxidant power (FRAP) as an antioxidant function also decreased significantly during the first six to nine days of fermentation followed by a gentle decrease up until 22 days. These findings can be helpful in optimizing the F. fraxinea–mediated fermentation process of TVSB and developing functional foods with reduced allergy using fermented TVSB.
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Previous research has shown that both heat-treated green tea extract (HTGT) and enzymatically modified isoquercitrin (EMIQ) have anti-obesity effects. Given the absence of in vivo evidence demonstrating their synergistic effects, ...
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Previous research has shown that both heat-treated green tea extract (HTGT) and enzymatically modified isoquercitrin (EMIQ) have anti-obesity effects. Given the absence of in vivo evidence demonstrating their synergistic effects, our study aimed to elucidate the combined obesity prevention potential of HTGT and EMIQ in mice. Mice were treated with these compounds for 8 weeks, while being fed a high-fat diet, to investigate their preventive anti-obesity effects. We demonstrated that the co-treatment of HTGT and EMIQ results in a synergistic anti-obesity effect, as determined by a Kruskal-Wallis test. Furthermore, the combined treatment of HTGT and EMIQ was more effective than orlistat in reducing body weight gain and adipocyte hypertrophy induced by high-fat diet. The co-treatment also significantly reduced total body fat mass and abdominal fat volume. Additionally, the group receiving the co-treatment exhibited increased energy expenditure and higher glucose intolerance. We observed a dose-dependent upregulation of genes associated with mitochondrial oxidative metabolism and PKA signaling, which is linked to lipolysis, in response to the co-treatment. The co-treatment group displayed elevated cAMP levels and AMPK activation in adipose tissue and increased excretion of fecal lipids. The results indicate that the co-treatment of HTGT and EMIQ holds the potential to be a promising combination therapy for combating obesity. To further validate the anti-obesity effect of the combined treatment of HTGT and EMIQ in human subjects, additional clinical studies are warranted.
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Homologous recombination (HR) is critical for error-free repair of DNA double-strand breaks. Chromatin loading of RAD51, a key protein that mediates the recombination, is a crucial step in the execution of the HR repair. Here, we ...
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Homologous recombination (HR) is critical for error-free repair of DNA double-strand breaks. Chromatin loading of RAD51, a key protein that mediates the recombination, is a crucial step in the execution of the HR repair. Here, we present evidence that SUMOylation of RAD51 is crucial for the RAD51 recruitment to chromatin and HR repair. We found that topoisomerase 1-binding arginine/serine-rich protein (TOPORS) induces the SUMOylation of RAD51 at lysine residues 57 and 70 in response to DNA damaging agents. The SUMOylation was facilitated by an ATM-induced phosphorylation of TOPORS at threonine 515 upon DNA damage. Knockdown of TOPORS or expression of SUMOylation-deficient RAD51 mutants caused reduction in supporting normal RAD51 functions during the HR repair, suggesting the physiological importance of the modification. We found that the SUMOylation-deficient RAD51 reduces the association with its crucial binding partner BRCA2, explaining its deficiency in supporting the HR repair. These findings altogether demonstrate a crucial role for TOPORS-mediated RAD51 SUMOylation in promoting HR repair and genomic maintenance.
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Objectives:This research aimed to confirm the efficacy of oriental medicine in sixth cranial nerve palsy and to evaluate the quality of the studies. Methods:Using the medical subject heading (MeSH) keywords “abducens nerve palsy”...
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Objectives:This research aimed to confirm the efficacy of oriental medicine in sixth cranial nerve palsy and to evaluate the quality of the studies. Methods:Using the medical subject heading (MeSH) keywords “abducens nerve palsy”, “abducens nerve paralysis”, “sixth nerve palsy”, “herbal medicine”, “Chinese medicine”, “oriental medicine” and “acupuncture”, we collected the research papers through an electronic database search in Oriental Medicine Advanced Searching Integrated System (OASIS), National Discovery for Science Leaders (NDSL), PubMed, Cochran Library, and China National Knowledge Infrastructure (CNKI). Results:A total of 136 papers were searched from the databases. Among these, 15 case reports and 8 randomized controlled trials (RCTs) met our criteria. 17 articles were found on the use of acupuncture as the main intervention, 11 on the use of herbal medicine as the main intervention, and 9 on the use of electroacupuncture as the main intervention. The frequently used acupoints were LI4, EX-HN5, GB1, BL2, TE23, LR3, BL1, ST2, GB20, and ST36. All 23 studies confirmed the efficacy of Korean medicine. According to the assessment using the risk of bias, the overall quality of the RCTs was low. Conclusions:Twenty-three papers suggested that Korean medicine treatment for abducens nerve palsy was effective in many cases. Analyzing the potential bias was difficult.
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We present climate responses of Representative Concentration Pathways (RCPs) using the coupled climate model HadGEM2 AO for the Coupled Model Intercomparison Project phase 5 (CMIP5). The RCPs are selected as standard scenarios for...
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We present climate responses of Representative Concentration Pathways (RCPs) using the coupled climate model HadGEM2 AO for the Coupled Model Intercomparison Project phase 5 (CMIP5). The RCPs are selected as standard scenarios for the IPCC Fifth Assessment Report and these scenarios include time paths for emissions and concentrations of greenhouse gas and aerosols and land-use/land cover. The global average warming and precipitation increases for the last 20 years of the 21st century relative to the period 1986-2005 are +1.1℃/+2.1% for RCP2.6, +2.4℃/+4.0% for RCP4.5, +2.5℃/+3.3% for RCP6.0 and +4.1℃/+4.6% for RCP8.5, respectively. The climate response on RCP 2.6 scenario meets the UN Copenhagen Accord to limit global warming within two degrees at the end of 21st century, the mitigation effect is about 3℃ between RCP2.6 and RCP8.5. The projected precipitation changes over the 21st century are expected to increase in tropical regions and at high latitudes, and decrease in subtropical regions associated with projected poleward expansions of the Hadley cell. Total soil moisture change is projected to decrease in northern hemisphere high latitudes and increase in central Africa and Asia whereas near-surface soil moisture tends to decrease in most areas according to the warming and evaporation increase. The trend and magnitude of future climate extremes are also projected to increase in proportion to radiative forcing of RCPs. For RCP 8.5, at the end of the summer season the Arctic is projected to be free of sea ice.
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Predicting student dropout from universities is an imperative but challenging task. Numerous data-driven approaches that utilize both student demographic information (e.g., gender, nationality, and high school graduation year) and...
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Predicting student dropout from universities is an imperative but challenging task. Numerous data-driven approaches that utilize both student demographic information (e.g., gender, nationality, and high school graduation year) and academic information (e.g., GPA, participation in activities, and course evaluations) have shown meaningful results. Recently, pretrained language models have achieved very successful results in understanding the tasks associated with structured data as well as textual data. In this paper, we propose a novel student dropout prediction framework based on demographic and academic information, using a pretrained language model to capture the relationship between different forms of information. To this end, we first formulate both types of information in natural language form. We then recast the student dropout prediction task as a natural language inference (NLI) task. Finally, we fine-tune the pretrained language models to predict student dropout. In particular, we further enhance the model using a continuous hypothesis. The experimental results demonstrate that the proposed model is effective for the freshmen dropout prediction task. The proposed method exhibits significant improvements of as much as 9.00% in terms of F1-score compared with state-of-the-art techniques.
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Political perspective detection in news media—identifying political bias in news articles—is an essential but challenging low-resource task. Prompt-based learning (i.e., discrete prompting and prompt tuning) achieves promising r...
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Political perspective detection in news media—identifying political bias in news articles—is an essential but challenging low-resource task. Prompt-based learning (i.e., discrete prompting and prompt tuning) achieves promising results in low-resource scenarios by adapting a pre-trained model to handle new tasks. However, these approaches suffer performance degradation when the target task involves a textual domain (e.g., a political domain) different from the pre-training task (e.g., masked language modeling on a general corpus). In this paper, we develop a novel multi-stage prompt tuning framework for political perspective detection. Our method involves two sequential stages: a domain- and task-specific prompt tuning stage. In the first stage, we tune the domain-specific prompts based on a masked political phrase prediction (MP3) task to adjust the language model to the political domain. In the second task-specific prompt tuning stage, we only tune task-specific prompts with a frozen language model and domain-specific prompts for downstream tasks. The experimental results demonstrate that our method significantly outperforms fine-tuning (i.e., model tuning) methods and state-of-the-art prompt tuning methods on the SemEval-2019 Task 4: Hyperpartisan News Detection and AllSides datasets.
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Due to its excellent material properties, silver-graphene oxide (Ag-GO) is being studied for diverse applications, such as antimicrobial agents, catalysts and absorbents. Such use of Ag-GO may lead to its release into terrestrial ...
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Due to its excellent material properties, silver-graphene oxide (Ag-GO) is being studied for diverse applications, such as antimicrobial agents, catalysts and absorbents. Such use of Ag-GO may lead to its release into terrestrial ecosystems, but little is known about the impact of Ag-GO on plants. In the present study, we determined the effects of Ag-GO on seed germination and early growth of crop species by analyzing the germination rate, growth of roots and shoots, hydrogen peroxide (H2O2) accumulation, and the uptake of Ag in alfalfa, radish and cucumber treated with 0.2–1.6 mg mL?1 of Ag-GO. Ag-GO treatment increased the shoot growth of radish at 0.2–1.6 mg mL?1 but decreased that of cucumber at 0.8 mg mL?1. In addition, Ag-GO enhanced the root elongation of radish at 0.2 mg mL?1 but inhibited that of alfalfa at 0.2, 0.8 and 1.6 mg mL?1. Ag-GO treatment induced H2O2 production in alfalfa, radish and cucumber in a concentration-dependent manner. Larger amounts of Ag accumulated in the seedlings as the concentration of Ag-GO increased, and such accumulation suggests that Ag may be transferred to higher trophic levels when plants are exposed to Ag-GO in ecosystems. Our study can, thus, serve as an important basis for setting guidelines for the release of nanomaterials into the environment.
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