17 research outputs found

    To allow or not to allow tipping: tipping strategy choice for service platforms under competition

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    To provide consumers with a channel to interact directly with service retailers, some service platforms have allowed consumers to incentivize service retailers for better service via tipping. There are pros and cons of allowing and not allowing tipping in terms of service levels and costs, which can affect consumer utility and platform profitability. By developing a game-theoretic model, we analyze the tipping strategy choices of platforms under competition. We find that when the service ability of service retailers is high, platforms with service retailer pricing should allow tipping, whereas for at least one platform with platform pricing, they should allow it only when the commission rate is also high. Interestingly, if consumers are concerned about service levels in addition to service prices during tipping, for platforms with platform pricing, only one platform should allow tipping when the service ability is medium. However, when the service ability is low or when the sensitiveness of the service level to tips exceeds the threshold, neither platform should allow tipping, regardless of pricing models. Finally, an all-win outcome for service platforms, service retailers, and consumers may be achieved only when platforms adopt different pricing models.</p

    TIPE2-deficient deficient mice exhibit greater iNOS induction and NO production in response to LPS challenge compared to WT controls.

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    <p>WT and TIPE2<sup>−/−</sup> mice injected intraperitoneal with phosphate buffered saline (PBS) or with LPS (1.5 mg/kg body weight) and sacrificed 3 or 24 h later. Sera concentration of NO and urea were examined (A and B). Liver and lung tissues of these animals were collected to extract total RNA and protein. The mRNA levels of iNOS, arginase I and arginase II in livers (B, D and E, left panels) and lungs (B, D and E, right panels) were examined by quantitative PCR at 3 h post-PBS or LPS challenge. iNOS protein levels in the livers (C, left panel) and lungs (C, right panel) were examined by Western blot at 24 h post-LPS challenge. Data are shown as means ±SE (n = 4) of one representative experiment. *P<0.05; **P<0.01; ***P<0.001.</p

    Increased IκBα, JNK and p38 phosphorylation in TIPE2-deficient macrophages.

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    <p>Peritoneal macrophages from WT and <i>TIPE2<sup>−/−</sup></i> mice (n = 4) were incubated with or without LPS (100 ng/mL) for the indicated times. Total cell lysates were examined with antibodies to total or phosphorylated IκBα, JNK1/2, p38 and ERK1/2 by Western blot. β-actin was served as a protein loading control.</p

    Effect of TIPE2 Overexpression on LPS-induced iNOS expression.

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    <p>RAW264.7 cells were stably transfected with TIPE2 plasmid or vector control. TIPE2 expression levels were determined by quantitative RT-PCR (<b>A</b>) and Western blot (<b>B</b>), respectively. For quantitative PCR, the results were presented as folds expression of TIPE2 RNA to that of β-actin. TIPE2 overexpression RAW264.7 cells or control cells were treated with 100 ng/mL LPS for 24 h, and iNOS mRNA (<b>C</b>) and protein (<b>D</b>) levels were detected by quantitative PCR and Western blot, respectively. Data are shown as mean ±SE of one representative experiment. **<i>P</i><0.01; ***<i>P</i><0.001.</p

    Table_4_An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats.xls

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    Sarcopenia is a senile disease with high morbidity, serious complications and limited clinical treatments. Menopause increases the risk of sarcopenia in females, while the exact pathogenesis remains unclear. To systematically investigate the development of hormone-related sarcopenia, we established a model of sarcopenia by ovariectomy and recorded successive characteristic changes. Furthermore, we performed the transcriptome RNA sequencing and bioinformatics analysis on this model to explore the underlying mechanism. In our study, we identified an integrated model combining obesity, osteoporosis and sarcopenia. Functional enrichment analyses showed that most of the significantly enriched pathways were down-regulated and closely correlated with endocrine and metabolism, muscle dysfunction, cognitive impairment and multiple important signaling pathways. We finally selected eight candidate genes to verify their expression levels. These findings confirmed the importance of estrogen in the maintenance of skeletal muscle function and homeostasis, and provided potential targets for further study on hormone-related sarcopenia.</p

    TIPE2 deficiency increases NO production but decreases urea production in macropahges.

    No full text
    <p>Peritoneal macrophages from WT and <i>TIPE2<sup>−/−</sup></i> mice were treated with 100 ng/mL LPS for 0 h, 3 h, and 24 h. iNOS mRNA (<b>A</b>) and protein (<b>B</b>) levels were determined by quantitative PCR and Western blot, respectively. Expression levels of arginase I and arginase II mRNA were examined by quantitative RT-PCR (<b>D</b> and <b>C</b>). Cells were stimulated with 100 ng/mL LPS for 24 h, and culture supernatants were harvested for measurement of NO and urea (<b>E</b> and <b>F</b>). Data are shown as means ±SE (n = 4) of one representative experiment. *<i>P</i><0.05.</p

    Table_1_An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats.xls

    No full text
    Sarcopenia is a senile disease with high morbidity, serious complications and limited clinical treatments. Menopause increases the risk of sarcopenia in females, while the exact pathogenesis remains unclear. To systematically investigate the development of hormone-related sarcopenia, we established a model of sarcopenia by ovariectomy and recorded successive characteristic changes. Furthermore, we performed the transcriptome RNA sequencing and bioinformatics analysis on this model to explore the underlying mechanism. In our study, we identified an integrated model combining obesity, osteoporosis and sarcopenia. Functional enrichment analyses showed that most of the significantly enriched pathways were down-regulated and closely correlated with endocrine and metabolism, muscle dysfunction, cognitive impairment and multiple important signaling pathways. We finally selected eight candidate genes to verify their expression levels. These findings confirmed the importance of estrogen in the maintenance of skeletal muscle function and homeostasis, and provided potential targets for further study on hormone-related sarcopenia.</p

    Discovery of Effective Dual PROTAC Degraders for Neurodegenerative Disease-Associated Aggregates

    No full text
    The aggregation of specific proteins is a histopathological hallmark in various neurodegenerative diseases (NDs), among which Alpha-synuclein (α-Syn) and tau have received increased attention. The targeted protein degradation (TPD) strategy has been studied in the treatment of NDs, but multitarget bifunctional molecules have been ignored. Herein, a series of effective dual PROTAC degraders were developed, which could degrade α-Syn aggregates and total tau simultaneously. The degradation effects were evaluated in vitro, and the results showed that T3 could significantly knockdown α-Syn aggregates and total tau in the degradation efficiency with DC50 of 1.57 ± 0.55 and 4.09 ± 0.90 μM, respectively. Further mechanistic exploration showed that the degradation effect was mediated by the ubiquitin–proteasome system (UPS). Additionally, the therapeutic efficacy of T3 was confirmed in an MPTP-induced PD mouse model. Our results suggest that these dual PROTACs may provide a potential therapeutic strategy for NDs

    Discovery of Effective Dual PROTAC Degraders for Neurodegenerative Disease-Associated Aggregates

    No full text
    The aggregation of specific proteins is a histopathological hallmark in various neurodegenerative diseases (NDs), among which Alpha-synuclein (α-Syn) and tau have received increased attention. The targeted protein degradation (TPD) strategy has been studied in the treatment of NDs, but multitarget bifunctional molecules have been ignored. Herein, a series of effective dual PROTAC degraders were developed, which could degrade α-Syn aggregates and total tau simultaneously. The degradation effects were evaluated in vitro, and the results showed that T3 could significantly knockdown α-Syn aggregates and total tau in the degradation efficiency with DC50 of 1.57 ± 0.55 and 4.09 ± 0.90 μM, respectively. Further mechanistic exploration showed that the degradation effect was mediated by the ubiquitin–proteasome system (UPS). Additionally, the therapeutic efficacy of T3 was confirmed in an MPTP-induced PD mouse model. Our results suggest that these dual PROTACs may provide a potential therapeutic strategy for NDs

    Discovery of Effective Dual PROTAC Degraders for Neurodegenerative Disease-Associated Aggregates

    No full text
    The aggregation of specific proteins is a histopathological hallmark in various neurodegenerative diseases (NDs), among which Alpha-synuclein (α-Syn) and tau have received increased attention. The targeted protein degradation (TPD) strategy has been studied in the treatment of NDs, but multitarget bifunctional molecules have been ignored. Herein, a series of effective dual PROTAC degraders were developed, which could degrade α-Syn aggregates and total tau simultaneously. The degradation effects were evaluated in vitro, and the results showed that T3 could significantly knockdown α-Syn aggregates and total tau in the degradation efficiency with DC50 of 1.57 ± 0.55 and 4.09 ± 0.90 μM, respectively. Further mechanistic exploration showed that the degradation effect was mediated by the ubiquitin–proteasome system (UPS). Additionally, the therapeutic efficacy of T3 was confirmed in an MPTP-induced PD mouse model. Our results suggest that these dual PROTACs may provide a potential therapeutic strategy for NDs
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