Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

Extensive research on resource-constrained innovation has been conducted by scholars and practitioners in recent years. An interesting research avenue is how firms explore the process of the new product development (NPD) and the ideas generation to foster resource-constrained innovation. However, despite the importance of product development and creative ideas under the resource-constraints contexts, innovation methods for applying to the resource-constrained innovation and designers have received comparatively less attention. As a remedy, this paper proposes a resource-constrained innovation method (RCIM) to generate ideas for the NPD. The RCIM is mainly divided into four sections: Developing the resource-constrained innovation approaches, developing the resource-constrained innovation dimensions, generating the creative ideas and evaluating the creative ideas. First, the resource-constrained innovation algorithms are developed based on success factors, characteristics, and attributes of resource-constrained innovation and the TRIZ (Teopия Peшeния Изoбpeтaтeльcкиx Зaдaч in Russian; Theory of Inventive Problem Solving in English) inventive principles via the systematic literature review (SLR). Second, the innovation dimensions are categorized to structure a target technology by means of the morphological analysis (MA) and the Derwent manual codes (DMCs) mapping based on collected patents. Third, the creative ideas are generated for the NPD by combining the innovation dimensions with the resource-constrained innovation approaches. Finally, the creative ideas are evaluated by the frugal criteria. The RCIM will stimulate designers’ creativity for achieving sustainability and innovation within constraint-based scenarios, MA and TRIZ.

We developed a two-period duopoly model to show how consumers’ variety-seeking behavior affects the pricing and service level decisions of a traditional product and a sharing product. Our analysis revealed that, without considering the consumers’ variety-seeking behavior, the traditional product attracted consumers with a high level of service and high price, while the sharing product attracted consumers with a low level of service and low price. When we only considered variety-seeking behavior and did not adjust the service level, the product with the low level of service benefited from the consumers’ variety-seeking behavior, while the product with the high level of service lost profits. When we considered the variety-seeking behavior and adjusted the service level as well as the price, the sharing product was attractive to variety-seeking consumers and it gained a greater competitive advantage over the traditional product. For two periods, the number of variety-seeking consumers who switched from buying traditional products to buying sharing products was greater than those who switched from buying sharing products to buying traditional products. Furthermore, we found that when the consumers’ variety-seeking behavior was not obvious, the number of consumers shifting from the traditional product increased monotonically. In contrast, when the variety-seeking behavior was obvious, the number of consumers shifting from the traditional product decreased monotonically.

By linking green investments to corporate environmental performance from the perspective of efficiency, this paper quantifies and evaluates firm-level green investment efficiency, with SBM-DEA approach and hand-collected emission data of Chinese listed companies in polluting industries. We find that corporate green investment efficiency is overall low, primarily due to excessive green investments, suggesting that managers only invest extensively in environmental dimensions without considering the efficient allocation and value-creating use of limited resources. Further, we conduct the Tobit regression and demonstrate that local environmental enforcement has an inverted U-shaped effect on green investment efficiency of polluting firms. Notably, this effect is only statistically significant in Non-SOEs and small-scale enterprises. Moreover, we document a U-shaped relationship between local environmental enforcement and excessive green investments, and this relationship is also only pronounced in Non-SOEs and small-scale firms. Our findings indicate that local governments should optimize corporate green investment efficiency through differentiated environmental regulation. KEYWORDS Corporate green investment efficiency; green investments; environmental performance; local environmental enforcement; SBM-DEA CONTACT Yutao Chen

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The emergence of the sharing economy has affected consumers and traditional manufacturers. We focus on product sharing and analyze its impacts on the manufacturer that offers sequential innovation products. We develop a two-period model in which a monopoly manufacturer sells an old product and introduces a new product in each period; in the same period, an owner who bought a product for self-use from the manufacturer in the previous period may rent the product out because of the low self-use value in this period. Our analysis reveals that the sharing market increases or decreases the manufacturer’s profit, and this is mainly determined by the moral hazard cost and the salvage value of sharing products. Furthermore, the sharing market has an insignificant effect on the upgrading of products, but there is a bumping-down effect on old products’ sales. Finally, the effect of the sharing market on the revenue of the owner and the sharing platform mostly depends on the risk of moral hazard, and it also affects the manufacturer’s product rollover strategy.

Immunogenic cell death (ICD) of tumor cells occurs via various pathways that activate immune cell systems against cancer. Previous studies have demonstrated that shikonin (SK), a plant secondary metabolite, can confer strong pharmacological activities that activate ICD and strong immunogenicity of tumor cells. However, the exact hierarchical regulatory mechanisms including the molecular targets of SK-activated immunogenicity are still unknown. Here, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was revealed to serve as a specific protein target for SK. This binding plays a key role in SK-stimulated ICD activity and the suppression of post-transcriptional mRNA processing, including nuclear export activity of newly synthesized mRNAs in mammary carcinoma cells in vitro. Moreover, it also mechanistically mediates the anti-metastatic effect of a tumor cell lysate (TCL) vaccine, which can be readily generated from SK-treated 4T1 tumor cells (SK-TCL), and the derived tumor-immunogenicity of SK-TCL-treated dendritic cells in vivo. Together, the identification of hnRNPA1 as the intracellular molecular target provides compelling pharmacology-based knowledge for the potential clinical use of SK-induced immunogenicity. In addition, SK may also serve as a potent suppressor that interferes with specific post-transcriptional activities, a mechanism which may be useful for exploitation in cancer therapeutics.

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