Game Theoretic Analysis of Pricing and Cooperative Advertising in a Reverse Supply Chain for Unwanted Medications in Households

Improper disposal of household unwanted medications (UMs) is an emergency problem around the world that adversely affects the sustainability of the environment and human’s health. However, the current disposal practices, mainly based on advertising and collecting status, are unsatisfactory in most countries and regions. Thus, some scholars proposed an alternative disposal practice that is to provide incentives to customers. This study aims to compare a Single Model (advertising only) with a Joint Model (advertising with take-back pricing) in a two-echelon reverse supply chain (RSC) that is composed of one disposer and one collector. In each model, four games (non-cooperative, collector as the Stackelberg leader, disposer as the Stackelberg leader, and cooperative) were established in order to identify the optimal pricing and advertising strategies for both members. The results of the study indicate that there is a Pareto dominant range for Joint Model compared to Single Model, whereas Single Model has no Pareto improvement in any games. Furthermore, in non-cooperative games of Joint Model, it is better to implement the leader-follower structure rather than simultaneous movement structure. Additionally, it is verified that the cooperative game is feasible, which leads to the cooperation between the disposer and the collector, and the extra profit from the cooperation can be shared based on the Nash bargaining game. However, in Single Model, it is better for the disposer to act as a channel leader and the collector figures the follower

Alarm Calling in Plateau Pika (<i>Ochotona curzoniae</i>): Evidence from Field Observations and Simulated Predator and Playback Experiments

Acoustic communication plays a vital role in passing or sharing information between individuals. Identifying the biological meaning of vocal signals is crucial in understanding the survival strategies of animals. However, there are many challenges in identifying the true meaning of such signals. The plateau pika (Ochotona curzoniae) is a call-producing mammal endemic to the Qinghai–Tibet plateau (QTP) and considered a keystone species owing to its multiple benefits in alpine rangeland ecosystems. Previous studies have shown that plateau pikas emit alarm calls as part of their daily activities. However, only field observations have been used to identify these alarm calls of the plateau pika, with no attempts at using playback experiments. Here, we report the alarm calling of plateau pikas through field observations as well as simulated predator and playback experiments in the Eastern QTP from 2021 to 2022. We found that both female and male adults emitted alarm calls, the signals of which comprised only one syllable, with a duration of 0.1–0.3 s. There were no differences in the characteristics between the observed alarm calls and those made in response to the simulated predator. The duration of the alarm call response varied with altitude, with plateau pikas living at higher altitudes responding at shorter durations than those at lower altitudes

Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development

<div><p>The tree-like structure of the mammalian lung is generated from branching morphogenesis, a reiterative process that is precisely regulated by numerous factors. How the cell surface and extra cellular matrix (ECM) molecules regulate this process is still poorly understood. Herein, we show that epithelial deletion of Heparan Sulfate (HS) synthetase <i>Ext1</i> resulted in expanded branching tips and reduced branching number, associated with several mesenchymal developmental defects. We further demonstrate an expanded <i>Fgf10</i> expression and increased FGF signaling activity in <i>Ext1</i> mutant lungs, suggesting a cell non-autonomous mechanism. Consistent with this, we observed reduced levels of SHH signaling which is responsible for suppressing <i>Fgf10</i> expression. Moreover, reactivating SHH signaling in mutant lungs rescued the tip dilation phenotype and attenuated FGF signaling. Importantly, the reduced SHH signaling activity did not appear to be caused by decreased <i>Shh</i> expression or protein stability; instead, biologically active form of SHH proteins were reduced in both the <i>Ext1</i> mutant epithelium and surrounding wild type mesenchymal cells. Together, our study highlights the epithelial HS as a key player for dictating SHH signaling critical for lung morphogenesis.</p></div

Activation of SHH attenuates the increase of tip area and FGF signaling in <i>Ext1</i> mutants.

<p>(A-H) Representative images of explant cultures treated with DMSO or SAG for 48h. Treatment of <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs with SHH signaling agonist SAG rescued the tip dilation phenotype. The epithelium was outlined with grey line (E-H). (I -L) The corresponding enlarged view of the boxed area in (E-H). (M) Quantification of average tip area of the buds. Data were presented as mean ± SEM. *<i>p</i><0.05, n = 3 for each group.(N-Q) Representative images of ISH showing <i>Fgf10</i> expression of lung explant cultures treated with DMSO or SAG for 48h. Addition of SAG attenuated <i>Fgf10</i> expression in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs. (R-U) Representative images of pERK staining of lung explant cultures treated with DMSO or SAG for 48h, SAG treatment attenuated epithelial pERK staining in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs, the epithelium was highlighted by white dashed lines. Scale bars: A-H, 500μm; N-Q,500μm; R-U, 50μm.</p

<i>Ext1</i> mutant lungs exhibit a decrease in SHH-FGF10 signaling.

<p>(A) qPCR analysis of key components of FGF signaling pathway in lungs from E14.5. The expression of <i>Fgf10</i>, <i>Etv4</i>, <i>Spry2</i>, <i>Dusp6</i> and <i>Bmp4</i> were increased, while the expression of <i>Etv5</i> was decreased in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs compared to control lungs. Data were presented as mean ± SEM. *<i>p</i><0.05, n≥3. (B-E) Wholemount and section RNA ISH of <i>Fgf10</i> in E12.5 lungs. The <i>Fgf10</i> expression was increased in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> lungs, and its expression domain was expanded instead of the split expression pattern seen in control lungs (arrowheads in B and D). (F and G) Immunofluorescent staining for phosphorylated -ERK in E12.5 lungs. The expression domain was expanded and the intensity was much stronger in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs compared to control lungs, reflecting an increased FGF signaling activity. (H) qPCR analysis of key components of SHH signaling pathway in lungs from E14.5. The expression of <i>Shh</i> was not significantly changed while the SHH targets (<i>Gli1</i>, <i>Ptch1</i> and <i>Hhip1</i>) were all decreased. Data were presented as mean ± SEM. *<i>p</i><0.05, n≥3. (I-L) Wholemount and section RNA ISH of <i>Shh</i> in E12.5 lungs. The expression of <i>Shh</i> was not significantly altered in <i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i> mutant lungs. (M-P) Section RNA ISH of <i>Ptch1</i> and <i>Gli1</i> in E12.5 lungs. <i>Ptch1</i> and <i>Gli1</i> expression levels were significantly reduced. (Q-R) β-gal staining showing the expression of <i>Gli1</i>^<i>lacz</i> allele in control lungs (<i>Ext1</i>^<i>f/w</i><i>; Shh</i>^<i>cre</i><i>; Gli1</i>^{<i>lacz/+</i>}) and mutant lungs (<i>Ext1</i>^<i>f/f</i><i>; Shh</i>^<i>cre</i><i>; Gli1</i>^{<i>lacz/+</i>}). The staining intensity was decreased in mutant lungs, indicating a decreased <i>Gli1</i> expression. Scale bars: B, C, I and J, 500μm; D, E and K-R, 100μm; F and G, 50μm.</p

Loss of <i>Ext1</i> in the lung epithelium abrogates HS synthesis.

<p>(A-H) Immunofluorescent staining for HS (3G10) and HS (10E4) in lungs at E12.5. <i>Ext1</i> deletion abrogated the 3G10 signaling in the epithelium and basement membrane (A-D), and the 10E4 signaling in the epithelium (E-H). Scale bar: 50μm.</p