No abstract

Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8 + T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.

This study attempts to investigate the perceived authenticity of consumers in Chinese traditional branded restaurants, as well as to investigate the specific factors that contribute to consumers' perceived authenticity. It constructs a systematic model addressing whether, and how, consumers' perceived authenticity, can influence their behavioural intentions through perceived quality of food, service, and dining environment, as well as perceived values in traditional branded restaurants. Results were derived from a mixed-method approach where 68 consumers were initially interviewed, followed by interviewer-administered questionnaire survey with additional 418 consumers. Qualitative analysis, along with exploratory factor analysis and confirmatory factor analysis confirmed five factors that influencing consumers' authenticity perceptions: historical and cultural value, brand value, nostalgia, environment authenticity, and food authenticity. Structural equation modelling analysis revealed positive impacts of consumers' perceived authenticity and perceived service quality on their perceived value of dining experience, which in turn predict consumers' behavior intentions.

Background:Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures.Methods:A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining.Results:There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68–0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20–0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15–1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29–12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size ⩽ 2 cm.Conclusions:For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.

Daily particulate matter with particles less than 2.5 μm in aerodynamic diameter (PM2.5) and total suspended particulates (TSP) were analyzed for chemical composition and daily PM10, SO2, and NO2 were monitored by automatic monitoring systems on the seven sites over China along the pathway of the long‐range transport of the dust from 20 March to 19 April 2007. The highest recorded dust and daily Air Pollution Index topped 500 for the first time since 2002, when the routine continuous monitoring of PM10 was initiated in Shanghai. The daily 24 h average PM10 concentration of 648 μg m−3 was observed on 2 April 2007. The ratios of SO2/PM10, NO2/PM10, and PM2.5/PM10 were 0.066, 0.077, and 15.5% on 2 April 2007, which were significantly different from the nondust day and could be used as the index to judge the occurrence of dust in Shanghai. On the peak dusty day, the ratios of crustal matter rose to 70% and 64% of the total mass of PM2.5 and TSP, respectively, while the ratios were 13% and 37% on nondust days. The ratio of Ca/Al in the dust aerosol in Shanghai was much closer to that in Duolun and Yulin near Mongolia Gobi rather than that in Tazhong of Taklimakan desert, indicating that the dust was transported from Mongolia Gobi instead of Taklimakan desert in Xinjiang province. The compositions of sea salt aerosol in PM2.5 and TSP, combined with back trajectories, indicated that the dust passed through the East China Seas before reaching Shanghai, which is one of the typical dust pathways that lead to heavily polluted days in Shanghai due to dust transport. The anthropogenic sources along the pathway also partially contributed to the PM pollution in Shanghai during this dust event.