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Digitalization is now playing an empowering role in the process of servitization, which changes the approach to product and service delivery for service-oriented manufacturers (SM) and sales service integrators (SSI). However, few studies concentrate on the pricing and coordination of the product service supply chain (PSSC) under digital transformation. The purpose of the study is to explore how digitalization supports servitization and enables value co-creation among stakeholders in the supply chain by influencing pricing decisions. We take the automobile manufacturing industry as an example, and construct a two-stage Stackelberg game model of PSSC considering the product network externality and service digitalization level. The optimal pricing strategies under centralized and decentralized decisions are given, and the coordination contract of PSSC is designed. The results show that the optimal values of variables in the digital environment are higher in general than in the non-digital environment. The emphasis of SM on digitalization is positively related to the product network externality, the service delivery advantage, the digitalization level, and the profit of advanced services. We also find that basic and advanced services of SSI are gradually losing the potential to create value, whereas the advanced service of SM continues to generate higher profits. Service delivery advantages of SM and SSI can enhance the profitability of advanced services. The dual revenue-sharing contract can realize the coordination of PSSC. The results contribute to related studies on digitalization, servitization, as well as pricing and coordination in the product service supply chain.

Immunotherapy has led to a paradigm shift in the treatment of cancer. Current cancer immunotherapies are mostly antibody-based, thus possessing advantages in regard to pharmacodynamics (e.g., specificity and efficacy). However, they have limitations in terms of pharmacokinetics including long half-lives, poor tissue/tumor penetration, and little/no oral bioavailability. In addition, therapeutic antibodies are immunogenic, thus may cause unwanted adverse effects. Therefore, researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy, as small molecules may overcome the above disadvantages associated with antibodies. Further, small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment, and may be combined to elicit synergistic effects. Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy. In this review, we describe the current progress in small molecule-based immunomodulators (inhibitors/agonists/degraders) for cancer therapy, including those targeting PD-1/PD-L1, chemokine receptors, stimulator of interferon genes (STING), Toll-like receptor (TLR), etc. The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.

This study aims to resolve the difficult problem of manufacturers’ service outsourcing strategy decision-making, with services divided into two types: hygienic and motivational. We build a value creation model for the manufacturer, service contractor, and customer under different outsourcing strategies, and we examine optimal outsourcing decision-making in various scenarios and its effect on the value creation of related entities. The results indicate that motivational services have a lower bound characterized by service utility. When the manufacturer derives services higher than this lower bound, it should operate its own motivational service and outsource the hygienic service to create greater value. When the manufacturer is limited by resources or capabilities and is required to outsource the motivational service, it can maintain value creation by setting an appropriate contract coefficient. The service contractor should undertake motivational services within the contract boundary negotiated by the manufacturer and conduct hygienic services outside the boundary. Theoretically, outsourcing both service types can maximize customer value, but this may not achieve the manufacturers’ optimal value creation.

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour in the central nervous system (CNS). As the ideal targets for GBM treatment, Src family kinases (SFKs) have attracted much attention. Herein, a new series of imidazo[4,5-c]pyridin-2-one derivatives were designed and synthesised as SFK inhibitors. Compounds 1d, 1e, 1q, 1s exhibited potential Src and Fyn kinase inhibition in the submicromolar range, of which were next tested for their antiproliferative potency on four GBM cell lines. Compound 1s showed effective activity against U87, U251, T98G, and U87-EGFRvIII GBM cell lines, comparable to that of lead compound PP2. Molecular dynamics (MDs) simulation revealed the possible binding patterns of the most active compound 1s in ATP binding site of SFKs. ADME prediction suggested that 1s accord with the criteria of CNS drugs. These results led us to identify a novel SFK inhibitor as candidate for GBM treatment.

We calculate the rate of the rare decay 11Be into Be10+p+e−+ν¯e using Halo effective field theory, thereby describing the process of beta-delayed proton emission. We assume a shallow 1/2+ resonance in the 10Be−p system with an energy consistent with a recent experiment by Ayyad et al. and obtain bp=4.9−2.9+5.6(exp.)−0.8+4.0(theo.)×10−6 for the branching ratio of this decay, predicting a resonance width of ΓR=(9.0−3.3+4.8(exp.)−2.2+5.3(theo.)) keV. Our calculation shows that the experimental branching ratio and resonance parameters of Ayyad et al. are consistent with each other. Moreover, we analyze the general impact of a resonance on the branching ratio and demonstrate that a wide range of combinations of resonance energies and widths can reproduce branching ratios of the correct order. Thus, no exotic mechanism (such as beyond the standard model physics) is needed to explain the experimental decay rate.

Background/Aims: Bidens pilosa L. (Bp) is widely distributed in China and has been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of the extract of Bp on androgen deficiency dry eye and determine its possible mechanisms. Methods: Twenty-four rats were randomly divided into four groups: Group Con (control), Group Sal (physiological saline), Group Fin (oral finasteride), and Group Bp (oral finasteride and Bp). The dry eye model was established in group Fin and group Bp. Aqueous tear quantity was measured with phenol red-impregnated cotton threads with anesthesia. Tear film breakup time (BUT) and corneal epithelial damage were evaluated by fluorescein staining. Animals were sacrificed at 28 days, and ocular tissues (lacrimal gland and cornea) were evaluated with light microscopy; gene microarray analysis for inflammatory cytokines and Western blot were also performed. Results: Finasteride administration effectively induced dry eye in rats by 14 days after administration. Group Fin rats had significantly higher fluorescein staining scores and lower aqueous tear quantity and BUT than the group Con rats, and notable inflammatory cell infiltrates were observed in the lacrimal gland of group Fin rats. The fluorescein staining score, aqueous tear quantity and BUT significantly improved with Bp treatment in the group Bp rats, and the structures of the lacrimal gland were well maintained without significant lymphocyte infiltration. Cytokine antibody array data identified the cytokines B7-2/Cd86, IL-1β, IL-4, IL-6, IL-10, MMP-8, FasL, TNF-α and TIMP-1 as candidates for validation by Western blot. Expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in group Fin were upregulated compared with group Con. Levels of anti-inflammatory cytokines, such as IL-4 and IL-10, in group Fin were also upregulated compared with those in group Con. Compared with group Fin, IL-1β, FasL, and TNF-α were significantly decreased in group Bp. Conclusion: The extract of Bp appears to be effective for the treatment of androgen deficiency dry eye in rats by improving aqueous tear quantity, maintaining tear film stability, and inhibiting the inflammation of the lacrimal gland.

Greenhouse eggplant monocropping in China has contributed to the aggravation of soil-borne diseases, reductions in crop quality and yield, and the degradation of physical and chemical soil properties. Crop rotation is one effective way of alleviating the problems of continuous cropping worldwide; however, few studies have reported changes in soil bacterial community structures and physical and chemical soil properties after Brassica vegetables had been rotated with eggplant in greenhouses. In this experiment, mustard-eggplant (BFN) and oilseed rape-eggplant (BFC) rotations were studied to identify changes in the physicochemical properties and bacterial community structure in soil that was previously subject to monocropping. Samples were taken after two types of Brassica plants incorporated into soil for 15 days to compare with continually planted eggplant (control, CN) and chemical disinfection of soil (CF) in greenhouses. MiSeq pyrosequencing was used to analyze soil bacterial diversity and structure in the four different treatments. A total of 55,129 reads were identified, and rarefaction analysis showed that the soil treatments were equally sampled. The bacterial richness of the BFC treatment and the diversity of the BFN treatment were significantly higher than those of the other treatments. Further comparison showed that the bacterial community structures of BFC and BFN treatments were also different from CN and CF treatments. The relative abundance of several dominant bacterial genera in the BFC and BFN treatments (such as Flavobacteria, Stenotrophomonas, Massilia and Cellvibrio, which played different roles in improving soil fertility and advancing plant growth) was distinctly higher than the CN or CF treatments. Additionally, the total organic matter and Olsen-P content of the BFC and BFN treatments were significantly greater than the CN treatment. We conclude that Brassica vegetables-eggplant crop rotations could provide a more effective means of solving the problems of greenhouse eggplant monocultures.