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ObjectiveThe correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites.DesignDifferential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics. Biliary molecules able to induce mast cell (MC) degranulation were revealed by in vitro and in vivo experiments, including liquid chromatography-mass spectrometry (MS)/MS and bioluminescence resonance energy transfer assays. Histamine (HA) receptor expression in CCA was mapped using a single-cell mRNA sequence. HA receptor functions were elucidated by patient-derived xenografts (PDX) in humanised mice and orthotopic models in MC-deficient mice. Genes involved in HA-induced proliferation were screened by CRISPR/Cas9.ResultsBile HA was elevated in CCA and indicated poorer prognoses. Cancer-associated fibroblasts (CAFs)-derived stem cell factor (SCF) recruited MCs, and bile N,N-dimethyl-1,4-phenylenediamine (DMPD) stimulated MCs to release HA through G protein-coupled receptor subtype 2 (MRGPRX2)-Gαq signalling. Bile-induced MCs released platelet-derived growth factor subunit B (PDGF-B) and angiopoietin 1/2 (ANGPT1/2), which enhanced CCA angiogenesis and lymphangiogenesis. Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively. HA promoted CCA cell proliferation by activating HRH1-Gαq signalling and hastened CAFs to secrete hepatocyte growth factor by stimulating HRH2-Gαs signalling. Solute carrier family 22 member 3 (SLC22A3) inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and SLC22A3deletion resulted in HA accumulation.ConclusionBile HA is released from MCs through DMPD stimulation and degraded via SLC22A3 import. Different HA receptors exhibit a distinct expression profile in CCA and produce different oncogenic effects. MCs promote CCA progression in a CCA-bile interplay pattern.

China is the world's largest furniture producer and exporter, but its furniture industry has always been at the bottom of the global value chain. Wooden furniture is the most important component of China's furniture industry. Its capacity and scale have been expanding; however, the industry's income and profit growth rate have declined. China's wooden furniture industry is in a period of transition, and industry regulators, participants, and even investors need to understand the future development trends of the industry. This study collected time series data for annual sales as well as the value of output, exports, and imports of the wooden furniture industry in China and used the autoregressive integrated moving average (ARIMA) model to predict future market supply and demand. The study found that each figure will continue to grow over the next 5 years. However, the industry as a whole will face the challenge of oversupply. In addition, the domestic market share on behalf of industrial competitiveness will decline year by year. Through a comprehensive and systematic analysis of the changing trend of China's wooden furniture production and its domestic and foreign markets, this study is the first to predict the supply and demand of research, filling the gap in the research field of wooden furniture, and its research ideas have some innovation. It can provide a reference for industry regulators, enterprise decision makers, and domestic and foreign investors., China is the world's largest furniture producer and exporter. The furniture industry in China has played an important role in the development of the national economy. The growth rate of [...]

The online-to-offline (020) business mode, designed to attract online shoppers to participate in in-person retail consumption, is rapidly emerging in popularity in China, and having a significant impact on traditional manufacturing. Taking the wooden furniture industry as a case study, this research surveyed consumers' attitudes toward using the 020 mode for wooden furniture shopping. Respondents were asked to rate their online and in-store experiences and attitudes about wooden furniture shopping via the 020 mode. On the basis of data processing of questionnaires, this study established hypotheses and conducted hypothesis testing by one-way analysis of variance and regression analysis. Results of this research indicated that Chinese consumers' attitudes about using the 020 mode for wooden furniture shopping were significantly affected by the region/city tiers in which the respondents resided. Consumers' attitudes in all regions were affected by subjective perceptions, the reputation and security of the Internet platform, and the quality of enterprise services. Specifically, those who live in tier 1 cities (most economically developed cities, e.g., Beijing, Tianjin) are more concerned about their shopping environment, whereas those who live in tier 3 cities (less economically developed cities) are more concerned about the Internet platform's service and promotions. Tier 2 cities (large cities that may be provincial capitals) are more concerned about convenience of online shopping and environment of the offline store. The results of this study could help enable business managers to develop appropriate marketing strategies for 020 wooden furniture shopping and provide reference for the transformation of business mode of wooden furniture manufacturing enterprises., China is the world's largest furniture manufacturer, producing over one third of the global total in 2016. The growth of the industry has been dramatic: the value of production nearly [...]