We study the formation of pro-environmental behaviors (PEBs) by integrating both the promoting (moral obligation) and inhibiting (moral disengagement) PEB mechanisms. Results of a sample of 285 tourists at a National Nature Reserve in China affirm that moral obligation positively affects PEB intention, while moral disengagement has significant negative impact. There is little difference in the relative importance of moral obligation and moral disengagement in affecting PEB intention. Social influence plays an important role in regulating the impacts of moral variables on PEB intentions. This study also broadens knowledge of the structure of PEB, by unveiling low-effort PEB intention as a precursor to high-effort PEB intention, and a mediator between moral obligation / moral disengagement and high-effort PEB intention. This study provides insights and implications for tourism practitioners and policy makers, and opens up future research exploration of the paradox of the promoting and inhibiting PEB mechanisms.

Background: Neuronal death is a major hallmark of Alzheimer's disease (AD). Necroptosis, as a programmed necrotic process, is activated in AD. However, what signals and factors initiate necroptosis in AD is largely unknown. Methods: We examined the expression levels of critical molecules in necroptotic signaling pathway by immunohistochemistry (IHC) staining and immunoblotting using brain tissues from AD patients and AD mouse models of APP/PS1 and 5×FAD. We performed brain stereotaxic injection with recombinant TNF-α, anti-TNFR1 neutralizing antibody or AAV-mediated gene expression and knockdown in APP/PS1 mice. For in vitro studies, we used TNF-α combined with zVAD-fmk and Smac mimetic to establish neuronal necroptosis models and utilized pharmacological or molecular biological approaches to study the signaling pathways. Results: We find that activated neuronal necroptosis is dependent on upstream TNF-α/TNFR1 signaling in both neuronal cell cultures and AD mouse models. Upon TNF-α stimulation, accumulated p62 recruits RIPK1 and induces its self-oligomerization, and activates downstream RIPK1/RIPK3/MLKL cascade, leading to neuronal necroptosis. Ectopic accumulation of p62 is caused by impaired autophagy flux, which is mediated by UVRAG downregulation during the TNF-α-promoted necroptosis. Notably, UVRAG overexpression inhibits neuronal necroptosis in cell and mouse models of AD. Conclusions: We identify a finely controlled regulation of neuronal necroptosis in AD by coordinated TNF-α signaling, RIPK1/3 activity and autophagy machinery. Strategies that could fine-tune necroptosis and autophagy may bring in promising therapeutics for AD.

Epigenetic modifications to histones dictate the differentiation of naïve CD4 + T cells into different subsets of effector T helper (T H) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T H 1, T H 2 and regulatory T (T reg) cells. However, whether and how EZH2 regulates follicular helper T (T FH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific T FH cells compared to those in T H 1 cells. Ablation of EZH2 in LCMV-specific CD4 + T cells leads to a selective impairment of early T FH cell fate commitment, but not late T FH differentiation or memory T FH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for T FH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs T FH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early T FH differentiation during acute viral infection.

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Encouraging individuals' environmentally responsible behaviours (ERBs) is becoming increasingly important for tourism destination management. This study was designed to investigate the formation of the ERBs of tourists from a broken windows theory perspective. Results from a sample of 307 tourists highlighted the antecedent role of tourists' perceived environment quality among the relationships between the variables of theory of planned behaviour (TPB), moral obligation, and the intention to engage in ERBs. The results of multiple mediation analysis revealed that the TPB variables and moral obligation act as full mediators in the effect of perceived environment quality on ERBs intention. The relative importance of the TPB variables and moral obligation in predicting the intention to engage in ERBs were also compared in this study.