Search

One of the key issues in sustainable tourism research is the gap between tourists’ expressed friendly attitudes towards sustainable behaviors and their actual behaviors. Although many “low-carbon” themed restaurants have emerged during the low-carbon transformation of the Chinese tourism industry, low-carbon food services have not been significantly improved. This study takes food as the entry point to explore tourists’ behavior and attitudes towards low-carbon tourism in relation to food. We conducted two interviews. The first interview was a semi-structured contextual interview with 120 tourists who had experiences in food streets, aiming to identify the core user group: low-carbon attitude-friendly tourists with high-carbon food behaviors. The second interviews was an in-depth interview based on grounded theory with 29 core users, analyzing the four main reasons for their high-carbon food behaviors and their requirements for low-carbon food services in tourism. Based on this, we extracted four design elements for low-carbon tourism food services: low-carbon information show service, low-carbon service product attractiveness improvement, low-carbon food environment atmosphere creation, and service providers’ low-carbon behaviors. Through these four service elements, we constructed a low-carbon tourism food service design framework based on the core users’ needs, discussed the mechanism of service elements, and provided service design suggestions accordingly. The research results can be helpful for tourism providers, low-carbon tourism researchers, and designers.

One of the key issues in sustainable tourism research is the gap between tourists' expressed friendly attitudes towards sustainable behaviors and their actual behaviors. Although many "low-carbon" themed restaurants have emerged during the low-carbon transformation of the Chinese tourism industry, low-carbon food services have not been significantly improved. This study takes food as the entry point to explore tourists' behavior and attitudes towards low-carbon tourism in relation to food. We conducted two interviews. The first interview was a semi-structured contextual interview with 120 tourists who had experiences in food streets, aim-ing to identify the core user group: low-carbon attitude-friendly tourists with high-carbon food behaviors. The second interviews was an in-depth interview based on grounded theory with 29 core users, analyzing the four main reasons for their high-carbon food behaviors and their re-quirements for low-carbon food services in tourism. Based on this, we extracted four design ele-ments for low-carbon tourism food services: low-carbon information show service, low-carbon service product attractiveness improvement, low-carbon food environment atmosphere creation, and service providers' low-carbon behaviors. Through these four service elements, we constructed a low-carbon tourism food service design framework based on the core users' needs, discussed the mechanism of service elements, and provided service design suggestions accordingly. The re-search results serve tourism providers, low-carbon tourism researchers, and designers.

The water gas shift reaction (WGS) process on the NiM(111) bimetallic surfaces (M = Fe, Co, Cu, Zn) are studied by density functional theory method and experimental studies. The NiCo and NiCu exhibit the optimum catalytic activity and CO2 selectivity.

With the introduction of “carbon neutrality”, promoting carbon peaking and carbon neutrality has become contingent upon the vigorous development of pure electric vehicles. The development of electric minivans is receiving substantial backing from the government as China’s logistics vehicle market undergoes a transformation. The drivers of electric minivans in China’s Shanxi Province are the objects of this research, whose purpose was to establish a service model based on the four elements of service design and grounded theory to clarify the key factors of user guarantee for electric minivans. We conducted a pilot study using questionnaires, user patterns, user interviews, and a user journey map to determine the user needs for electric minivan user service guarantees. NVivo was used to analyze and code the user interview data qualitatively. The research findings can serve as a resource for entrepreneurs, service providers, managers, and designers of electric minivans.

Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.

We observed unexpected thiazole 1B formation when 2,6-dichlorobenzothioamide 1 and ethyl bromopyruvate were reacted under basic conditions at elevated temperatures in ethanol. Thiazole 1B, regio-isomeric to that expected under conventional Hantzsch conditions, was extensively characterized and later confirmed by single crystal X-ray structure. We carried out this transformation with several substituted benzothioamides and found that the formation of the unexpected thiazole regio-isomer was highly dependent on the steric as well as the electronic characteristics of the ortho-substituents on the phenyl ring. A mechanism to account for this novel transformation was proposed.

A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors, revealed pyridine 1 as a promising starting point for lead identification. Initial expansion of 3 separate regions of the molecule led to eventual identification of cyclopropyl amide 46, a potent lead analog with good kinase selectivity, physicochemical properties, and pharmacokinetic profile. Analysis of the binding modes of the series in TYK2 and JAK2 crystal structures revealed key interactions leading to good TYK2 potency and design options for future optimization of selectivity.

Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1 and JAK2 selectivity relative to 3. Further optimization eventually led to compound 37 that showed good TYK2 enzyme and interleukin-12 (IL-12) cell potency, as well as acceptable cellular JAK1 and JAK2 selectivity and excellent oral exposure in mice. When tested in a mouse IL-12 PK/PD model, compound 37 showed statistically significant knockdown of cytokine interferon-γ (IFNγ), suggesting that selective inhibition of TYK2 kinase activity might be sufficient to block the IL-12 pathway in vivo.

We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models.

We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models.

TYK2 is a JAK family protein tyrosine kinase activated in response to multiple cytokines, including type I IFNs, IL-6, IL-10, IL-12, and IL-23. Extensive studies of mice that lack TYK2 expression indicate that the IFN-α, IL-12, and IL-23 pathways, but not the IL-6 or IL-10 pathways, are compromised. In contrast, there have been few studies of the role of TYK2 in primary human cells. A genetic mutation at the tyk2 locus that results in a lack of TYK2 protein in a single human patient has been linked to defects in the IFN-α, IL-6, IL-10, IL-12, and IL-23 pathways, suggesting a broad role for TYK2 protein in human cytokine responses. In this article, we have used a panel of novel potent TYK2 small-molecule inhibitors with varying degrees of selectivity against other JAK kinases to address the requirement for TYK2 catalytic activity in cytokine pathways in primary human cells. Our results indicate that the biological processes that require TYK2 catalytic function in humans are restricted to the IL-12 and IL-23 pathways, and suggest that inhibition of TYK2 catalytic activity may be an efficacious approach for the treatment of select autoimmune diseases without broad immunosuppression.

We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models.

SAR about the piperidine core in a series of MC4R agonists is described. A number of alkyl substituents that furnish compounds with good affinity and functional potency are reported.