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Psychological therapies are important for comprehensive chronic orofacial pain (COFP) treatment. This study is to validate the effects of psychological factors on oral health-related quality of life (OHRQoL) among COFP patients in China. Pain catastrophizing, which is a subjective cognitive emotion used to manage the psychological aspects of pain among COFP patients, was examined in relation to COFP severity and OHRQoL. All 479 participants were recruited in Changsha, Hunan Province, China. Cronbach’s alpha coefficients (0.868–0.960), composite reliability scores (0.924–0.969), and average variance extracted from each construct (0.555–0.753) all indicated a good model fit. Pearson’s correlation analysis showed that age and education status have a positive correlation with COFP severity, pain catastrophizing, and anxiety. COFP severity was related to anxiety, depression, and COFP-OHRQoL. Pain catastrophizing was related to employment status. Anxiety and depression symptoms indirectly mediated the correlation between COFP severity and COFP-OHRQoL. As a second-stage moderator, pain catastrophizing moderated the mediating effects of anxiety symptoms and depression symptoms. Our findings suggest that anxiety, depression, and pain catastrophizing should be evaluated jointly to improve COFP-OHRQoL among COFP patients. This evidence will help therapists to comprehensively treat patients for the best treatment effect.

Tourism is a lucrative business, and Swiss hotels rely heavily on international clientele to book their rooms. The Coronavirus pandemic has halted travel and hotel stays from March to June 2020. Based on Situational Crisis Communication Theory (SCCT), this paper investigates the messages Swiss hotels have posted on their official websites and Facebook pages to reassure guests that it is safe to book rooms in Switzerland again. The findings from 73 independent 4 and 5-star hotels show that most hotels did not publish messages regarding the Coronavirus or the measures they have taken; instead, the hotels posted positive messages about reopening their rooms and services. Official hotel websites emphasized deals and offers while the Facebook pages concentrated on enthusiastic ‘welcome back’ messages. The findings presented here contribute to the literature by offering the first results of a larger project on communication during the de-confinement stage of a pandemic.

This research investigates destination imagery of Switzerland as a travel destination. This research first conducted survey and content analysis to identify 23 unique statements reflecting travel in Switzerland. Through an online survey, this research collected 399 responses from French and Italian respondents. Based on the comparisons of association strength and association valence of every statement to the aggregated association strength and association valence, this research developed the Destination Imagery Diagnosis model. The results show that, overall, French and Italian respondents have strong and positive associations to statements related to Switzerland’s nature and opportunities for outdoor activities. Furthermore, respondents rated “Healthy lifestyle” and “Welcoming and friendly” positively but the associations to Switzerland were weaker. This research also identified marketing opportunities specifically for French and Italian respondents. The Destination Imagery Diagnosis Model serves as a new tool to compare destination imageries between markets or keep track of changes of destination imagery.

(1) Background: Using neuroscience to understand and influence consumer behavior often leads to ethical controversy. Thus, it is necessary to demystify the use of neuroscience for marketing purposes; the present paper, by accessing the worldwide academic performance in this domain, fulfills this objective. (2) Methods: All extant literature on neuromarketing indexed to the Scopus database—318 articles—was subjected to a bibliometric analysis through a mixed-method approach. (3) Results: The results show that Spain leads the ranks of the most productive countries, while Italian researchers clearly dominate in terms of collaboration. Regarding the most prominent topics, the connection between “Neuroscience” and “Advertising” is highlighted. The findings provide a better understanding of the state-of-the-art in neuromarketing studies, research gaps, and emerging research topics, and additionally provide a new methodological contribution by including SciVal topic prominence in the bibliometric analysis. (4) Conclusions: As practical implications, this study provides useful insights for neuromarketing researchers seeking funding opportunities, which are normally associated with topics within the top prominence percentile or emerging topics. In terms of originality, this study is the first to apply SciVal topic prominence to a bibliometric analysis of neuromarketing, and provides a new bibliometric indicator for neuromarketing research.

BackgroundMAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response.MethodsSix metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.ResultsCompared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment.ConclusionsMAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.

Swiss tourism relies heavily on international clientele to book rooms and purchase goods and services. However, from March to June 2020, due to the COVID-19 pandemic, travel and subsequent bookings slowed and, in some cases, stopped altogether. Based predominantly on Situational Crisis Communication Theory (SCCT), this paper investigates Swiss hotels’ messages on their official Facebook pages and the SCCT strategies they employed during this crisis. The findings from 48 independent four- and five-star hotels show that the Victimage strategy was the most often employed when communicating about the COVID-19 pandemic in general. Further, most hotels published positive messages during this period (68%) and strongly emphasized their roles as victims at this time. Only 5% of the messages posted were negative messages. Hotels ‘blamed’ the government and the sanitary measures for their closing or reduced services. The findings presented here contribute to the literature by offering a pattern of crisis responses from Swiss hotels in the early period of the pandemic. These results are currently being updated with the messages communicated in the 12 months since the beginning of this study. The findings of this crisis communication during an early stage of the pandemic will be used to make concrete recommendations for the strategies that should be implemented in the future if the COVID-19 crisis continues or when faced with other crises.

Shipyard hoisting process is a project type manufacturing process which entails more sophisticated elements and relationships than other kinds of processes, this feature brings particular challenges when constructing a structured description of the process, called enterprise model, to introduce various Computer Integrated Manufacturing (CIM) technologies. However, most of the modelling methods devised so far do not consider the individual demand of project type manufacturing process. Therefore, we envisage the necessity to expand, extend, and refactor current methodologies in order to exploit this remaining dimension. In this line, we present a dedicated method aiming at appropriately modelling the project type manufacturing process, it employs seven collaborative views and task-centric idea to emphasize work flow abstraction without sticking to the material flow abstraction as current methods do, which is the key factor to successfully achieve horizontal functions/organizations integration and vertical management hierarchies integration for this special process. The proposed method adopts semi-formal meta model to interpret its framework, building blocks and constraints graphically and rigorously. All these works are performed taking shipyard hoisting process as example. According to the modelling method, a two-stage Computer Aided Process Planning (CAPP) method is also initiated to demonstrate how the process model can serve as the bridge to converge manufacturing technology and information technology. Furthermore, a CAPP prototype is developed to carry out case study with an actual shipyard hoisting process. The study reveals promising contributions to not only enhancing the industrial competitiveness but also enriching the enterprise modelling research on project type manufacturing process.

AIM: To investigate the regulation of autophagy on high glucose-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells.METHODS: In order to investigate the changes of EMT and autophagy induced by high glucose, HLE-B3 cells were divided into two groups. In NC group, cells were cultured in DMEM with 5.5mmol/L glucose, and in HG group, cells were treated with DMEM in addition with 30mmol/L glucose for 12h, 24h, and 48h. Western blot was used to detect the expression of EMT-marker proteins(E-cadherin and α-SMA)and autophagy-marker proteins(LC3, Beclin 1 and SQSTM1/p62). Wound healing assay was conducted to observe the migration ability. To investigate the regulation of autophagy on EMT, we employed rapamycin, an agonist of autophagy. HLE-B3 cells were divided into 4 groups. Two of them were mentioned as above, and the other two groups were treated with high glucose combined with DMSO(DMSO)and high glucose combined with 200nmol/L rapamycin(RAPA), respectively. Migration ability of cells was evaluated by Transwell assay. Expressions of proteins, such as EMT marker proteins, molecules in TGF-β signaling pathway(TGF-β2, Smad2/3, p-Smad2/3, Snail), and autophagy markers were detected by Western blot. The intracellular co-localization of SQSTM1/p62 and Smad2/3 was observed by immunofluorescence staining, and their interaction was confirmed by co-immunoprecipitation assay. RESULTS: The expression of E-cadherin, LC3 Ⅱ/Ⅰ, and Beclin 1 in HLE-B3 cells of HG group gradually decreased(F=67.52, 163, 206; all PF=53.37, 302.1; all PPPP>0.05)in RAPA group compared with HG group and DMSO group, cell migration was also suppressed(all PCONCLUSION: High glucose stimulates the process of EMT and suppresses the autophagy in HLE-B3 cells. Autophagy regulates EMT by interacting with Smad2/3 via SQSTM1/p62, altering the amount of Smad2/3 which works in the TGF-β signaling pathway.

Oxidative stress is a major pathogenic mechanism in Parkinson’s disease (PD). As an important cellular antioxidant, glutathione (GSH) balances the production and incorporation of free radicals to protect neurons from oxidative damage. GSH level is decreased in the brains of PD patients. Hence, clarifying the molecular mechanism of GSH deficiency may help deepen our knowledge of PD pathogenesis. Here we report that the astrocytic dopamine D2 receptor (DRD2) regulates GSH synthesis via PKM2-mediated Nrf2 transactivation. In addition we find that pyridoxine can dimerize PKM2 to promote GSH biosynthesis. Further experiments show that pyridoxine supplementation increases the resistance of nigral dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in wild-type mice as well as in astrocytic Drd2 conditional knockout mice. We conclude that dimerizing PKM2 may be a potential target for PD treatment., Dopamine agonists increase brain glutathione levels. Here the authors identify noncanonical signalling by Nrf2 as a potential mechanism for the neuroprotective effects of dopamine D2 receptor activation.

For the first time, a convenient, online couplable, sensitive and environmentally friendly sample pretreatment method, namely, magnetism-reinforced in-tube solid phase microextraction (MR/IT-SPME) was proposed to effectively enrich heavy metal ions (HMIs). Monolithic capillary microextraction column embedded modified Fe3O4 magnetic nanoparticles (MCEN) was conveniently synthesized and employed as the microextraction column of MR/IT-SPME. Subsequently, the MCEN was put into a magnetic coil which was utilized to exert variable magnetic field during extraction procedure. Three HMIs, including Cu(II), Co(II) and Hg(II), were selected as studied ions and reacted with chelating agent sodium diethyldithiocarbamatetrihydrate to form metallic coordination compounds. The complexes were infused to the MCEN to perform the MR/IT-SPME extraction and then online determined by high-performance liquid chromatography equipped with diode array detection (HPLC-DAD). A series of key parameters affecting the extraction performance were investigated in detail. Results revealed that the exertion of magnetic field in adsorption and desorption steps favored the adsorption and release of the coordination compounds, with the extraction efficiencies enhanced from 47-65% to 67-89%. Finally, the developed online MR/IT-SPME-HPLC-DAD approach was successfully applied to determine studied HMIs in environmental water and seafood samples. The confirmatory experiments further evidenced the reliability and feasibility of the introduced approach for the analysis of trace HMIs in complex samples.

In recent years in China’s booming market economy, along with the transformation of the market economy on the reform of the state-owned economic system also came into being, in order to increase the source of profit channels of state-owned enterprises, do a good job of the value-added work of state-owned enterprise assets, many state-owned enterprises choose to diversify development, and this trend is now very obvious. The development of enterprises has also produced a number of problems that have had a significant impact on the quality and returns of investments, causing unnecessary losses and increasing unnecessary risks for many state-owned enterprises. The article will be based on the current situation of investment projects and management of state-owned enterprises, analyze the problems that exist in them, put forward effective improvement measures and targeted countermeasure suggestions for the investment management of state-owned enterprises, and promote the high-quality development of state-owned enterprises.

The resource utilization of sewage sludge can solve its disposal issue essentially. Meanwhile the removal of diclofenac (DCF) in wastewater is an emerging environmental problem. In this study, a novel strategy of sludge utilizing via hydrothermal - peroxydisulfate (PDS) dewatering coupled pyrolysis process was proposed. The obtained sludge-derived biochar (HSC) could be as candidate to activate PDS to degrade DCF. Results indicated that exceed 90% of DCF was eliminated within 30 min in HSC-PDS/DCF ternary system under the optimized condition (0.6 mmol/L PDS and 0.5 mg/L HSC, without temperature and pH pre-adjusting). The inner mechanism of HSC-PDS/DCF system was revealed as follows: (1) Major: CO in quinones and ketone structure in HSC accelerated the degradation of DCF via non-radical pathway (electron transfer and

Background MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Methods Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Results Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. Conclusions MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.

Thiamphenicol (TAP) is an amphenicol antibiotic, which has a broad-spectrum inhibitory effect on both gram-positive and gram-negative bacteria. Since it is widely used in animals and aquaculture, its residues in environment may bring potential risk for human health and ecosystems. While TAP can be removed through conventional physical or chemical methods, its bioremediation using microorganisms is less studied. Here, we report the removal of TAP by a bacterial strain, Aeromonas hydrophila HS01, which can remove more than 90.0% of TAP in a living cell-dependent manner. Our results indicated that its removal efficiency can be greatly affected by the growth condition. Proteomics studies revealed a number of differentially expressed proteins of HS01 in the presence of TAP, which may play critical roles in the transportation and degradation of TAP. All these results indicate bacterial strain A. hydrophila HS01 is a new microbial resource for efficiently removing TAP, and may shed new insights in developing bioremediation approaches for TAP pollution.

Characterizing protein–protein interactions (PPIs) is an effective method to help explore protein function. Here, through integrating a newly identified split human Rhinovirus 3 C (HRV 3 C) protease, super-folder GFP (sfGFP), and ClpXP-SsrA protein degradation machinery, we developed a fluorescence-assisted single-cell methodology (split protease-E. coli ClpXP (SPEC)) to explore protein–protein interactions for both eukaryotic and prokaryotic species in E. coli cells. We firstly identified a highly efficient split HRV 3 C protease with high re-assembly ability and then incorporated it into the SPEC method. The SPEC method could convert the cellular protein-protein interaction to quantitative fluorescence signals through a split HRV 3 C protease-mediated proteolytic reaction with high efficiency and broad temperature adaptability. Using SPEC method, we explored the interactions among effectors of representative type I-E and I-F CRISPR/Cas complexes, which combining with subsequent studies of Cas3 mutations conferred further understanding of the functions and structures of CRISPR/Cas complexes., Wang et al. developed a fluorescence-assisted single-cell methodology (split protease-E. coli ClpXP (SPEC)) to characterise protein-protein interactions for both eukaryotic and prokaryotic species in E. coli cells. Their method can quantify these interactions with high sensitivity, easy manipulation, and broad temperature adaptability

Microplastics (MPs), as emerging contaminant detected in dyeing sludge (DS), inevitably affected the subsequent treatment and disposal of DS. However, the effect of MPs on the predominant disposal path (incineration) of DS remains far from explicit. This study used thermogravimetry-mass spectrometry (TG-MS) method to explore the effect of representative MPs, polyethylene terephthalate (PET) and polyvinyl chloride (PVC), on combustion characteristics, gas evolution and kinetics on DS combustion. Results showed that PET inhibited the whole combustion of DS by physical barrier. Relatively, PVC delayed the combustion of light volatile but promoted heavy volatile and char reaction due to HCl catalyst. Generally, MPs deteriorated the combustibility, burnout performance and combustion stability of DS. MPs aggravated HCl and gaseous N emissions. Noticeably, the interactions between DS and PVC accelerated the emissions of gaseous pollutants, especially under high dose condition. DAEM and FWO models could well describe the combustion kinetic of DS containing MPs. MPs led to an increase in activation energy of DS, namely, it deteriorated the combustion efficiency of DS. The combustion mechanisms could be divided into two stages: (1) diffusion (D

DNA nanowalkers moving progressively along a prescribed DNA track are useful tools in biosensing, molecular theranostics and biosynthesis. However, stochastic DNA nanowalkers that can perform in living cells have been largely unexplored. We report the development of a novel stochastic bipedal DNA walker that, for the first time, realizes direct intracellular base excision repair (BER) fluorescence activation imaging. In our design, the bipedal walker DNA was generated by BER-related human apurinic/apyrimidinic endonuclease 1 (APE1)-mediated cleavage of DNA sequences at an abasic site in the intracellular environment, and it autonomously travelled on spherical nucleic acid (SNA) surfaces via catalyzed hairpin assembly (CHA). Our nanomachine outperforms the conventional single leg-based DNA walker with an improved sensitivity, kinetics and walking steps. Moreover, in contrast to the single leg-based DNA walker, the bipedal DNA walker is capable of monitoring the fluorescence signal of reduced APE1 activity, thus indicating amplified intracellular imaging. This bipedal DNA-propelled DNA walker presents a simple and modular amplification mechanism for intracellular biomarkers of interest, providing an invaluable platform for low-abundance biomarker discovery leading to the accurate identification and effective treatment of cancers., The developed DNA bipedal walker represents improved sensitivity, kinetics and walking steps for intracellular fluorescence imaging of base-excision repairing.