Trade-in strategies in closed-loop supply chain when considering manufacturer entrustment behavior and wholesale price contract

Many enterprises are implementing trade-in programs through multiple methods, but some lack experience or insufficient conditions to carry out the trade-in program. The previous literature did not consider the impacts of the manufacturer authorizing the third-party information platform (3IP) to implement the trade-in strategy for each member of the closed-loop supply chain. To address this gap, we established three models based on consumer choice behavior: (1) the benchmark model without trade-in strategy; (2) the trade-in model with manufacturer entrustment behavior; (3) the extension model with wholesale price contract. We obtained and compared the equilibrium solutions of the three models. Our results indicate that, compared to the case where there is no entrustment, the manufacturer’s profit is higher if they entrust the 3IP to implement the trade-in program under certain conditions (which is related to the proportion of primary and replacement consumers in the market). Under reasonable circumstances, we find that introducing a wholesale price contract can benefit the manufacturer and increase the profit of the 3IP, stimulate the 3IP to carry out trade-in better, and achieve a win-win situation. Some numerical examples are provided to explain these findings further.</p

Enhanced FGFR signaling in the epithelium of <i>Msx1^d/dMsx2^d/d</i> uteri.

<p>A. The level of p-FRS2 was examined in the uterine sections of <i>Msx1^f/fMsx2^f/f</i> (upper panel) and <i>Msx1^d/dMsx2^d/d</i> (lower panel) mice on day 4 of pregnancy by immunohistochemistry. Magnification: a and d: 10×, b and e: 20×, c and f: 40×. B. The level of p-ERK was examined in the uterine sections of <i>Msx1^f/fMsx2^f/f</i> (upper panel) and <i>Msx1^d/dMsx2^d/d</i> (lower panel) mice on day 4 of pregnancy by immunohistochemistry. Magnification: a and d: 10×, b and e: 20×, c and f: 40×. L, G and S indicate luminal epithelium, glandular epithelium, and stroma respectively. C. FGFR-specific inhibitor PD173074 was applied to one uterine horn of <i>Msx1^d/dMsx2^d/d</i> (n = 3) mice on day 3 of pregnancy. The other horn served as vehicle-treated control. Uterine horns were collected on day 4 morning and sections were subjected to immunohistochemistry to detect p-FRS2, Ki67, and Muc-1.</p

Expression of <i>Msx</i>1 and <i>Msx</i>2 in the uterus during early pregnancy.

<p>Real-time PCR was performed to monitor the expression of mRNAs corresponding to <i>Msx1</i> and <i>Msx2</i> in uterus on days 1 to 5 of gestation. The relative levels of gene expression on different days of pregnancy were determined by setting the expression level of <i>Msx1</i> mRNA (A, Left panel) and <i>Msx2</i> mRNA (B, Left panel) on day 1 of pregnancy at 1.0. <i>Rplp0</i>, encoding a ribosomal protein, was used to normalize the level of RNA. Uterine sections from day 1 to day 5 (a–e) of pregnancy were subjected to immunohistochemical analysis using anti-MSX1 (A, Right panel) and anti-MSX2 (B, Right panel) antibodies. Panel f shows uterine sections from day 3 pregnant mice treated with non-immune IgG. L, G and S indicate luminal epithelium, glandular epithelium and stroma, respectively.</p

Ablation of uterine <i>Msx</i>1 and <i>Msx</i>2 leads to female infertility.

<p>The results of a six-month breeding study are shown.</p

Enhanced ESR1 activity in the luminal epithelium of <i>Msx1^d/dMsx2^d/d</i> uteri.

<p>A. Uterine sections obtained from <i>Msx</i>1<i>^f/f Msx</i>2<i>^f/f</i> (left panel) and <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> (right panel) mice on day 4 of pregnancy were subjected to IHC using antibodies against PGR (top panel, a and b), ESR1 (middle panel, c and d) and phospho-ESR1 (lower panel, e and f). B. Real-time PCR was performed to analyze the expression of E-regulated genes, lactotransferrin (<i>Ltf</i>), Clca3, lipocalin2 and Muc-1 in uteri of <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> and <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> mice on day 4 of pregnancy. The level of <i>Ck18</i> was used as internal control to normalize gene expression. The data are represented as the mean fold induction ± SEM, *p<0.05. C. Real-time PCR was performed to analyze the expression of P-regulated genes, Ihh, COUP-TF II, Hand2 and Hoxa10, in uteri of <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice on day 4 of pregnancy. The level of <i>Rplp0</i> or <i>Ck18</i> was used as internal control to normalize gene expression.</p

Mechanism of Msx1 and Msx2 action in mouse uterus.

<p>In normal pregnancy, MSX1 and MSX2 act to repress WNT and β-catenin signaling and inhibit FGF synthesis in the uterine stroma, thereby suppressing stromal-epithelial cross-talk. In the absence of MSX1 and MSX2, FGFs are induced, activating the epithelial FGFR-ERK1/2 pathway, and promoting epithelial proliferation. Activated ERK1/2 then phosphorylates epithelial ESR1. This triggers transcriptional activation of ESR1 and expression of its target genes, such as <i>Muc-1</i>, which prevent the functional transformation of the luminal epithelium to receptive state, blocking embryo implantation.</p

Enhanced proliferation in the uterine epithelium and lack of receptivity in <i>Msx1^d/dMsx2^d/d</i> mice.

<p>A. Immunohsitochemical localization of Ki67 in the uterine sections of <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> (left panel, a and c) and <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> (right panel, b and d) mice on day 4 of pregnancy. Panels a and b indicate lower magnification (20×) and c and d indicate higher magnification (40×). L and G indicate luminal epithelium and glandular epithelium respectively. B. Real-time PCR was performed to analyze the expression of glandular factors, <i>Lif</i>, <i>Foxa2</i> and <i>Spink3</i> in uteri of <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> and <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> mice on day 4 of pregnancy. The level of <i>Ck18</i> was used as internal control to normalize gene expression. The data are represented as the mean fold induction ± SEM, ***p<0.0001. C. Transmission electron microscopy of uterine sections obtained from <i>Msx1^f/f Msx2^f/f</i> (left panel, a and b) and <i>Msx1^d/dMsx2^d/d</i> (right panel, c and d) mice on day 4 of pregnancy. Panels a and c indicate lower magnification (5Kx) and b and d indicate higher magnification (30Kx). D. Immunohistochemical analysis of Muc-1 expression in the uterine sections of <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> (upper panel) and <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> (lower panel) mice on day 1 (a and d), day 4 (b and e) and day 5 (c and f) of pregnancy. L indicates luminal epithelium.</p

Lack of uterine <i>Msx</i>1 and <i>Msx</i>2 causes implantation failure.

<p>A. Embryo implantation sites were examined in <i>Msx1^f/fMsx2^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice by the vascular permeability assay, which can be scored as distinct blue bands (red arrows) following an injection of Chicago blue dye on day 5 of pregnancy (D5, n = 6) or direct eye-visualization of implanted embryo on day 6 (D6, n = 4) and on day 7 (D7, n = 4) of pregnancy. The graph represents the quantification of implantation sites in <i>Msx1^f/fMsx2^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice on day 5 of pregnancy. B. Failure of embryo attachment in <i>Msx1^d/dMsx2^d/d</i> uteri. Histological analysis of uterine sections obtained from <i>Msx1^f/fMsx2^f/f</i> (a) and <i>Msx1^d/dMsx2^d/d</i> (b) mice on day 5 (n = 3) of pregnancy by Hematoxylin and Eosin staining. Note the intimate contact between embryo and luminal epithelium in <i>Msx</i>1<i>^f/fMsx</i>2<i>^f/f</i> mice and the free floating embryo in the uterine lumen of <i>Msx</i>1<i>^d/dMsx</i>2<i>^d/d</i> mice. L and E indicate luminal epithelium and embryo respectively.</p

Wnt/β-catenin signaling controls FGF synthesis in uterine stromal cells.

<p>A. Real-time PCR was performed to analyze the expression of Wnt ligands in uterine epithelial cells of <i>Msx1^f/fMsx2^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice on day 4 of pregnancy. The level of <i>Ck18</i> was used as internal control to normalize gene expression. The data are represented as the mean fold induction ± SEM, *p<0.01, ***p<0.0001. B. Real-time PCR was performed to analyze the expression of Wnt ligands in uterine stromal cells of <i>Msx1^f/fMsx2^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice on day 4 of pregnancy. C. Real-time PCR was performed to analyze the expression of Fgf family members in uterine stromal cells of <i>Msx1^f/fMsx2^f/f</i> and <i>Msx1^d/dMsx2^d/d</i> mice on day 4 of pregnancy. The level of <i>Rplp0</i> was used as internal control to normalize gene expression. The data are represented as the mean fold induction ± SEM, *p<0.01, **p<0.001, ***p<0.0001. D. The level of active β-catenin in uterine sections of <i>Msx1^f/fMsx2^f/f</i> (left panel) and <i>Msx1^d/dMsx2^d/d</i> (right panel) mice on day 4 of pregnancy was analyzed by IHC. (Magnification: a and c: 10×, b and d: 40×) E. Primary stromal cells were isolated from uteri of <i>Msx1^d/dMsx2^d/d</i> mice on day 3 of pregnancy and transfected with siRNA targeted to the β-catenin mRNA. Total RNA was isolated 24 h after transfection to analyze the expression of Fgf family members by Real-time PCR. The level of <i>Rplp0</i> was used as an internal control to normalize gene expression. The data are represented as the mean fold induction ± SEM, *p<0.01, **p<0.001, ***p<0.0001.</p

Additional file 1 of Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies

Supplementary Material 1: Supplementary Figure S1. The association between PPS of patients with colon cancer and common DEGs. Supplementary Figure S2. The association between RFS of patients with colon cancer and common DEGs. Supplementary Figure S3. The expression profiles of common DEGs between cancerous and normal groups. Supplementary Figure S4. The expression of SERPINA3 in the colon cancer tissues with different clinical stages. Supplementary Figure S5. The expression of SERPINA3 in various immune cells by CIERSORT (GEPIA2021). Supplementary Figure S6. Prediction for targets between SERPINA3 3’UTR and miR-137-3p/miR-296-5. (A) MiR-137-3p-targeted sequence of SERPINA3 3’UTR. (B) MiR-296-5p-targeted sequence of SERPINA3 3’UT