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As the e-commerce landscape diversifies, suppliers are faced with the critical decision of how to effectively launch their products through e-commerce channels with varying business models. This study aims to explore the strategic considerations for a supplier launching products through two distinct e-commerce channels: one based on a direct sale model and the other on a reselling model. It builds a theoretical model to examine the supplier’s decision-making across three strategic options: a simultaneous launch through both channels, a sequential launch starting with the direct sale model followed by the reselling model, and vice versa. The equilibria of those options are derived through game analysis and further compared. The results reveal that for suppliers under a non-alliance pricing contract, a simultaneous product launch across both channels is the most advantageous approach. Conversely, in scenarios where an alliance pricing contract is in place, the optimal strategy shifts towards a sequential launch. The decision of which channel to ally with—whether the direct sale or the reselling model—hinges critically on the difference in service efficiency and the intensity of competition between the channels. This nuanced analysis highlights the importance of strategic flexibility and alignment with channel dynamics in maximizing product launch success in the evolving e-commerce environment.

Fish parvalbumin is a major allergen known to cause allergy and has been a serious concern of food safety all over the world. Recombinant allergen has been broadly applied in allergy diagnosis and immunotherapy in recent years, but different immune activities of several recombinant allergens compared with their natural forms were found. To further characterize and explain the difference between natural and recombinant allergens, in this study, the difference of structure, Ca2+ binding, IgE/IgG binding activity, degranulation ability and digestion stability between natural and recombinant turbot parvalbumins were compared. Both recombinant and natural parvalbumins bind to specific immunoglobulin E from fish allergic patients and rabbit IgG antibody, whereas recombinant parvalbumin showed lower IgG binding activity in inhibition assays. Moreover, recombinant parvalbumin showed comparable ability with natural parvalbumin in Ku812 cells degranulation assay. Besides, intestinal digestion stability of recombinant parvalbumin was similar with natural form while gastric digestion stability was reduced. In addition, similar secondary structure change as well as different tertiary structure change between recombinant and natural parvalbumins due to heating, Ca2+ depletion and heating after Ca2+ depletion was characterized by spectra analysis. Different Ca2+ binding of two forms of parvalbumins was also found according to their different structural changes after Ca2+ depletion. These results revealed that recombinant turbot parvalbumin preserved fundamental immunological properties of its natural form while improper folding of tertiary led to its different Ca2+ binding, lower IgG binding activity and digestion stability.

The axis orthogonal importance sampling method proves to be one version of efficient importance sampling methods since the quasi-Monte Carlo simulation is its basic ingredient, in which it is now a common practice to transform low-discrepancy sequences from the uniform distribution to the normal distribution by the well-known inverse transformation. As a valid transformation method for low-discrepancy sequences, the Box-Muller transformation is introduced into the axis orthogonal importance sampling method and compared with the inverse transformation in this paper for structural reliability sensitivity analysis. Three representative quasi-random sequences with low discrepancy are presented to generate samples following the target distribution and explore the interaction with the transformation method, which is used as a sample plan along the tangent plane at the most probable failure point in the axial orthogonal importance sampling for structural reliability analysis and reliability sensitivity analysis. The numerical experiments show that the reliability sensitivity analysis method by means of the Box-Muller transformation is a good alternative to the inverse transformation to generate samples from low-discrepancy sequences to the normal distribution. In particular, the scheme of the Box-Muller transformation combined with the Sobol sequence needs fewer samples with more accuracy and is more applicable for solving reliability sensitivity analysis in various nonlinear problems.

Fish as an important food source, with the increase of consumption rate, the resulting allergic phenomenon increased year by year. Food allergen in aquatic products was an important allergy-inducing factor, which had a great impact on the body’s tissue, inflammatory factors, immunoglobulin and intestinal flora. The research objective of this study was to evaluate the allergenic risk of turbot parvalbumin (PV) and provided effective biological reference markers for the safety assessment of aquatic products. Results showed PV has high purity, high binding capacity with IgE and IgG, influenced release of inflammatory factors in DCs (IL-6/10/12p70), induced allergic response in mice. PV increased the levels of PV-specific IgE, total IgE, IgG1, monocyte chemotactic protein 1(MCP-1), histamine, tryptase significantly. PV obviously mutagenic effect on spleen, intestinal tissue. Sequencing of microbial diversity showed that microorganism Ruminiclostridium and Alistipes in PV group changed significantly, which proved that the structure of intestinal microorganism has changed. In summary, Turbot parvalbumin triggered fish allergic responses by induced imbalance of inflammatory factors and microbial composition of IL-6/10/12p70, IgE/IgG and Ruminiclostridium, Alistipes. These results indicated that PV had high-risk allergy inducing ability, and the changes of the above indicators provided biological reference markers for risk assessment of the safety of aquatic products intake.Graphic abstract

The growth of endometrial stromal cells (ESCs) at implantation sites may be a potential factor affecting the success rate of embryo implantation. Incremental proofs demonstrated that ncRNAs (e.g. miRNAs, lncRNAs and circRNAs) were involved in various biological procedures, including proliferation and apoptosis. In this study, the role of miR‐100‐5p on proliferation and apoptosis of goat ESCs in vitro and embryo implantation in vivo was determined. The mRNA expression of miR‐100‐5p was significantly inhibited in the receptive phase (RE) rather than in the pre‐receptive phase (PE). Overexpression of miR‐100‐5p suppressed ESCs proliferation and induced apoptosis. The molecular target of MiR‐100‐5p, HOXA1, was confirmed by 3′‐UTR assays. Meanwhile, the product of HOXA1 mRNA RT‐PCR increased in the RE more than that in the PE. The HOXA1‐siRNA exerted significant negative effects on growth arrest. Instead, incubation of ESCs with miR‐100‐5p inhibitor or overexpressed HOXA1 promoted the cell proliferation. In addition, Circ‐9110 which acted as a sponge for miR‐100‐5p reversed the relevant biological effects of miR‐100‐5p. The intrinsic apoptosis pathway was suppressed in ESCs, revealing a crosstalk between Circ‐9110/miR‐100‐5p/HOXA1 axis, PI3K/AKT/mTOR, and ERK1/2 pathways. To further evaluate the progress in study on embryo implantation regulating mechanism of miR‐100‐5p in vivo, the pinopodes of two phases were observed and analysed, suggesting that, as similar as in situ, miR‐100‐5p was involved in significantly regulating embryo implantation in vivo. Mechanistically, miR‐100‐5p performed its embryo implantation function through regulation of PI3K/AKT/mTOR and ERK1/2 pathways by targeting Circ‐9110/miR‐100‐5p/HOXA1 axis in vivo.

A response surface method for reliability analysis based on iteratively-reweighted-least-square extreme learning machines (IRLS-ELM) is explored in this paper, in which, highly nonlinear implicit performance functions of structures are approximated by the IRLS-ELM. Monte Carlo simulation is then carried out on the approximate IRLS-ELM for structural reliability analysis. Some numerical examples are given to illustrate the proposed method. The effects of parameters involved in the IRLS-ELM on accuracy in reliability analysis are respectively discussed. The results exhibit that a proper number of samples and neurons in hidden layer nodes, an appropriate regularization parameter, and the number of iterations for reweighting are of important assurance to obtain reasonable precision in estimating structural failure probability.

Intestinal microecology was closely related to immune regulation, but the related mechanism was still unclear. This study aimed to reveal how microorganisms improved immune response via casepase-3 and Bak of FAS/CD95 pathway. Bifidobacterium animalis F1-7 inhibited the melanoma B16-F10 cells in vitro effectively; had a potent anticancer effect of lung cancer mice; effectively improved the spleen immune index and CD3 + (75.8%) and CD8 + (19.8%) expression level; strengthened the phagocytosis of macrophages; inhibited the overexpression of inflammatory factors IL-6 (319.10 ± 2.46 pg/mL), IL-8 (383.05 ± 9.87 pg/mL), and TNF-α (2003.40 ± 11.42 pg/mL); and promoted the expression of anti-inflammatory factor IL-10 (406.00 ± 3.59 pg/mL). This process was achieved by promoting caspase-8/3 and BH3-interacting domain death agonist (Bid), Bak genes, and protein expression. This study confirmed the B. animalis F1-7 could act as an effective activator to regulate immune response by promoting the expression of caspase-8/3, Bid and Bak genes, and proteins and by activating the FAS/CD95 pathway. Our study provided a data support for the application of potentially beneficial microorganisms of B. animalis F1-7 as an effective activator to improve immunity. Graphical abstract

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are primary liver cancers with different therapeutic methods and prognoses. This study aims to investigate the ultrasonography and enhanced computed tomography (CT) features of these cancers and improve the early diagnosis rate. We retrospectively analyzed the clinical and imaging data of 319 patients diagnosed with HCC and 124 patients diagnosed with ICC, confirmed by pathology. A total of 443 patients were eligible in this study. From the perspective of clinical data, between HCC and ICC patients existed significant differences in age, gender, hepatic background, serum tumor markers of AFP and CA19.9, chronic hepatitis B/C and lymph node infiltration (p<0.05), but not in tumor size, microvascular invasion, serum tumor markers of CEA and CA125 (P>0.05). With respect to ultrasonography features, HCC patients had a higher proportion than ICC patients in splenomegaly (p=0.001), while ICC patients had a higher proportion than HCC patients in absence/not rich vascularity and intrahepatic bile duct dilatation (p<0.05). With respect to CT features, HCC patients were significantly different from ICC patients in the three-phase enhanced CT value mean, enhanced intensity and homogeneity of nodules (P<0.05). A multivariate logistic regression analysis was performed to further clarify the correlation of these indices. However, only age≤60 years (OR=1.861, P=0.045), male (OR=3.850, P<0.001), AFP>7ng/ml (OR=0.119, P<0.001), lymph node infiltration (OR=5.968, P<0.001), intrahepatic bile duct dilatation (OR=2.414, P=0.04), splenomegaly (OR=0.081, P<0.001), rim APHE (OR=3.109, P=0.002), and iso- or hyper enhancement (OR=0.188, P<0.001) were independent risk factors. While there are overlapping ultrasonography and CT features between HCC and ICC, the integration of tumor markers and specific imaging characteristics can be beneficial in distinguishing between the two.

Background Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. Methods Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs). DCs were loaded with a peptide pool of multiple HCC-related tumor antigens, and T cells were stimulated by these DCs. Results Thirteen patients with HCC received repeated MASCT after tumor resection during which their immune responses were examined. After three courses of MASCT, the frequency of regulatory T cells in the patients’ PBMCs significantly decreased ( p  < 0.001), while the antigen peptide pool-triggered T cell proliferation ( p  < 0.001) and IFNγ production ( p  = 0.001) were significantly enhanced. The specific T cell responses against each antigen in the pool were detected in 11 patients, but with individualized distinct patterns. The most immunogenic TAAs for HCC are survivin, CCND1, and RGS5. Moreover, the antigen-specific immune responses observed in tumor-free patients’ PBMCs were significantly stronger than that in the patients with recurrence ( p  = 0.037). Conclusions Our study demonstrates that MASCT is well-tolerated by patients with HCC and elicits strong and dynamic immune responses specifically against multiple tumor associated antigens, which may correlate with clinical outcomes.