Concomitant NAFLD Facilitates Liver Metastases and PD-1-Refractory by Recruiting MDSCs via CXCL5/CXCR2 in Colorectal Cancer.

BACKGROUND & AIMS: Both nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effects of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated. METHODS: We observed the effect of concomitant NAFLD on CRLM in the mouse model and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment and then tested the therapeutic application based on the mechanisms. Finally we validated our findings in the clinical samples. RESULTS: Here we prove that in different mouse models, NAFLD induces F4/80+ Kupffer cells to secret chemokine CXCL5 and then recruits CXCR2+ MDSCs to promote the growth of CRLM. CRLM with NAFLD background is refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2+ MDSCs, as well as the hazard of liver metastases in CRC patients. CONCLUSIONS: Collectively, our findings highlight the significance of selective CXCR2+/CD11b+/Gr-1+ subset myeloid cells in favoring the development of CRLM with NAFLD background and identify a pharmaceutical medicine that is already available for the clinical trials and potential treatment.

Using machine learning to estimate the incidence rate of intimate partner violence.

It is difficult to accurately estimate the incidence rate of intimate partner violence (IPV) using traditional social survey methods because IPV victims are often reluctant to disclose their experiences, leading to an underestimation of the incidence rate. To address this issue, we applied machine learning algorithms to predict the incidence rate of IPV in China based on data from the Third Wave Survey on the Social Status of Women in China (TWSSSCW 2010). Specifically, we examined five unbalanced sample-processing methods and six machine learning algorithms, choosing the random under-sampling ensemble method and the random forest algorithm to impute the missing data. Analysis of the complete data showed that the incidence rates of physical violence, verbal violence, and cold violence were 7.10%, 13.74%, and 21.35%, respectively, which were higher than the incidence rates in the original dataset (4.05%, 11.21%, and 17.95%, respectively). The robustness of our findings was further confirmed by analysis using different training sets. Overall, this study demonstrates that better tools need to be developed to accurately estimate the incidence rates of IPV. It also serves as a useful guide for future research that imputes missing data using machine learning.

Effects of Sulfamethoxazole and Florfenicol on Growth, Antioxidant Capacity, Immune Responses and Intestinal Microbiota in Pacific White Shrimp Litopenaeus vannamei at Low Salinity.

Antibiotic residue may pose a serious risk to aquaculture, and the culture of Litopenaeus vannamei in a low-salinity environment is a growing trend over the world. Here, we aimed to understand the combined effect of low salinity and sulfamethoxazole (SMZ) and florfenicol (FLO) antibiotics on L. vannamei. The growth performance, immune functions, antioxidant capacity and intestinal microbiota were investigated. Compared with the control group, the weight gain and survival rate significantly decreased (p < 0.05) in shrimp after they were exposed to low-salinity (salinity 3) water and the mixture of antibiotics and low-salt conditions for 28 days. The antioxidant activities of SOD and T-AOC, shown at low salinity and in the higher concentration of the SMZ treatment group (SMZH), were significantly decreased, while the GST activity was significantly increased in each treatment group in comparison with the control group. The expression of immune-related genes, including TOLL, LvIMD, PPO and HSP, in the low concentration of the SMZ treatment group (SMZL) was higher than that in the other groups. The diversity of intestine microbiota was disturbed with a lower Shannon index in the low-salinity and SMZH groups, and a higher Simpson index in the SMZH group. Proteobacteria, Actinobacteria and Bacteroidetes were the dominant phyla in the gut of L. vannamei. At the genus level, Microbacterium, Shewanella, Aeromonas, Acinetobacter, Gemmobacter, Paracoccus and Lysobacter were significantly decreased in the low-salinity group. However, the abundance of opportunistic pathogens belonging to the genus Aeromonas in the FLO group was increased. The predicted microbe-mediated functions showed that the pathway for "amino acid metabolism" and "replication and repair" was significantly inhibited in both the low-salinity and antibiotic-exposed groups. All the findings in this study indicate that the combined effect of antibiotics and low salinity on L. vannamei negatively impacted the physiological and intestinal microbiota functions.

Aberrant ROS Served as an Acquired Vulnerability of Cisplatin-Resistant Lung Cancer.

Lung cancer has become a global health issue in recent decades. Approximately 80-85% of cases are non-small-cell lung cancer (NSCLC). Despite the high rate of resistance, cisplatin-base chemotherapy is still the main treatment for NSCLC patients. Thus, overcoming cisplatin resistance is urgently needed in NSCLC therapy. In this study, we identify NADPH metabolism and reactive oxygen species (ROS) levels as the main causes accounting for cisplatin resistance. Based on a small panel consisting of common chemotherapy drugs or compounds, APR-246 is proved to be an effective compound targeting cisplatin-resistant NSCLC cells. APR-246 specially inhibits proliferation and colony formation of cisplatin-resistant cells. In details, APR-246 can significantly cause G0/G1 accumulation and S phase arrest of cisplatin resistant cells and gives rise to severe mitochondria dysfunction as well as elevated apoptosis. Further study proves that it is the aberrant ROS levels as well as NRF2/SLC7A11/GSH axis dysfunction accounting for the specific antitumor effects of APR-246. Scavenging ROS with N-acetylcysteine (NAC) disrupts the inhibitory effect of APR-246 on cisplatin-resistant cells. Mechanistically, NRF2 is specifically degraded by the proteasome following its own ubiquitylation in APR-246-treated cisplatin-resistant cells, which in turn decreases NRF2/SLC7A11/GSH axis activity. Our study provides new insights into the biology driving cisplatin resistance of lung cancer and highlights APR-246 as a potential therapeutic reagent for overcoming cisplatin resistance.

Exploring the Longitudinal Relationship Between Lockdown Policy Stringency and Public Negative Emotions Among 120 Countries During the COVID-19 Pandemic: Mediating Role of Population Mobility.

Background: To limit the spread of COVID-19, governments worldwide have implemented a series of lockdown policies to restrict the social activities of people. Although scholars suggest that such policies may produce negative effects on public emotions, the existing research is limited because it only provides a cross-sectional snapshot of the effect of lockdown policies in small and local samples. Using large-scale longitudinal cross-country data, the current study aims to gain a better understanding of the dynamic effect of lockdown policies on public emotions and their underlying mechanisms. Methods: Drawing on a large-scale longitudinal data from multiple sources, the study employs fixed-effects models to analyze the association between lagged lockdown policy stringency and public negative emotions among 120 countries from February to July 2020 (N = 9,141 country-day observations). The bootstrapping mediation test is used to examine the mediation effects of increased population mobility in residential areas. Results: The results show a statistically significant and positive association between lagged lockdown policy stringency and general public negative emotion (standardized coefficient = 0.32, CI = 0.30-0.35, p < 0.001). This pattern remains similar to other specific negative emotions, such as depression, anxiety, hopelessness, and helplessness. Moreover, the negative health effects of lockdown policy stringency are significantly mediated by increased mobility in residential areas (51-74% points, p < 0.001). Conclusion: The findings confirm that stringent lockdown policies have a negative effect on public emotions via confining population mobility residential areas. To tackle the COVID-19, future public health policies should pay more attention to the unintended negative consequences of lockdown measures on public emotions.

The greener, the happier? The effects of greenspace on residents' happiness in contemporary urban China.

In recent years, research has begun to touch upon the associations between the natural environment and individuals' subjective wellbeing; however, whether such associations would vary among different groups of people remains under-studied. Using four waves (2010-2013) of data from the Chinese General Social Survey, we investigate the group-specific correlation between environment-specifically, greenspace exposure-and individuals' happiness in contemporary urban China. For this study, the normalized difference vegetation index at the county level is a proxy for greenspace exposure. The results from the ordered logit model indicate that county-level green vegetation is associated with individuals' happiness level, but such effects vary with a household's relative deprivation. While greenspace exposure is positively associated with happiness among individuals from less deprived families, it is negatively associated with happiness among those from deprived households. These findings contribute to the body of knowledge of the heterogeneous effect of greenspace on residents' subjective well-being.

PM2.5 exposure and anxiety in China: evidence from the prefectures.

BACKGROUND: Anxiety disorders are among the most common mental health concerns today. While numerous factors are known to affect anxiety disorders, the ways in which environmental factors aggravate or mitigate anxiety are not fully understood. METHODS: Baidu is the most widely used search engine in China, and a large amount of data on internet behavior indicates that anxiety is a growing concern. We reviewed the annual Baidu Indices of anxiety-related keywords for cities in China from 2013 to 2018 and constructed anxiety indices. We then employed a two-way fixed effect (FE) model to analyze the relationship between PM2.5 exposure and anxiety at the prefectural level. RESULTS: The results indicated that there was a significant positive association between PM2.5 and anxiety index. The anxiety index increased by 0.1565258 for every unit increase in the PM2.5 level (P < 0.05), which suggested that current PM2.5 levels in China pose a considerable risk to mental health. CONCLUSION: The enormous impact of PM2.5 exposure indicates that the macroscopic environment can shape individual mentality and social behavior, and that it can be extremely destructive in terms of societal mindset.

The Association Between PM2.5 and Depression in China.

While China has been experiencing unprecedented economic growth, depression is becoming one of the most striking social and mental health problems in recent years. Such a paradox to progress may partially be due to the notoriously poor air quality of the country. To verify this argument, we constructed an index of the prevalence of depression (IPD) using internet search query volumes in Baidu to proxy the potential depression and examined how IPD is associated with PM2.5, the major air pollutant in China. Our results from 2-way fixed effects models reveal that a 100 µg·m-3 increase in previous week's PM2.5 in a city is significantly associated with 0.279 increase in its IPD, comparable to 7.34 hours decrease in weekly daylight, and such relationship is particularly pronounced in the spring and summer and in East and South areas. Our findings of large-scale pattern suggest that PM2.5 at current levels in China poses serious mental health risks.

Starvation-induced suppression of DAZAP1 by miR-10b integrates splicing control into TSC2-regulated oncogenic autophagy in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of all incident esophageal cancers, with a 5-year survival rate of < 20%. Autophagy is of particular importance in cancers; however, the detailed regulatory mechanisms of oncogenic autophagy in ESCC have not been fully elucidated. In the present study, we address how splicing control of TSC2 is involved in mTOR-regulated oncogenic autophagy. Methods: Alternative splicing events controlled by DAZAP1 in ESCC cells were identified via RNAseq. Differential phosphorylation of short or long TSC2 splicing variants by AKT and their impacts on mTOR signaling were also examined. Results: We found that starvation-induced miR-10b could enhance autophagy via silencing DAZAP1, a key regulator of pre-mRNA alternative splicing. Intriguingly, we observed a large number of significantly changed alternative splicing events, especially exon skipping, upon RNAi of DAZAP1. TSC2 was verified as one of the crucial target genes of DAZAP1. Silencing of DAZAP1 led to the exclusion of TSC2 exon 26 (from Leu947 to Arg988), producing a short TSC2 isoform. The short TSC2 isoform cannot be phosphorylated at Ser981 by AKT, which resulted in continuous activation of TSC2 in ESCC. The active TSC2 inhibited mTOR via RHEB, leading to continually stimulated oncogenic autophagy of ESCC cells. Conclusions: Our data revealed an important physiological function of tumor suppressor DAZAP1 in autophagy regulation and highlighted the potential of controlling mRNA alternative splicing as an effective therapeutic application for cancers.

Migration status, emotional engagement, and social exclusion in Chinese schools.

INTRODUCTION: Since migration has become one of the pressing issues of our time, the school engagement of migrant children in the destination cities has drawn increasing scholarly attention. While most existing studies have focused on the cognitive and behavioral dimensions of school engagement of migrant children compared to local children, the emotional dimension has received less scholarly attention. Using a large-scale, national representative, school-level longitudinal survey data conducted in 2014 in China, this study examined the effect of migration status on children's emotional engagement in school. METHODS: This study was conducted with 15,872 Chinese junior high school students (mean age = 13.52, SD = 1.24) using ordered logistic regression. KHB mediation analysis was employed to explain migration-emotional engagement linkage. RESULTS: Compared with urban local children, both rural and urban migrant children are less likely to feel closely connected to their peers in school and are more likely to feel bored and to express escapism. The KHB mediation analysis further suggests that compared with the number of friends and proportions of the same-school friends, the percentages of local friends at the same school mediate most of the effect of migration status on all three measures of emotional engagement, particularly for rural migrant children. CONCLUSIONS: These findings revealed that although both social exclusion and the absence of friendship play statistically significant mediation roles, social exclusion is of vital importance in understanding the differences between migrant and local children in emotional engagement.

The association between PM2.5 exposure and suicidal ideation: a prefectural panel study.

BACKGROUND: Suicidal ideation is subject to serious underestimation among existing public health studies. While numerous factors have been recognized in affecting suicidal thoughts and behaviors (STB), the associated environmental risks have been poorly understood. Foremost among the various environment risks were air pollution, in particular, the PM2.5. The present study attempted to examine the relationship between PM2.5 level and local weekly index of suicidal ideation (ISI). METHODS: Using Internet search query volumes in Baidu (2017), the largest internet search engine in China, we constructed a prefectural panel data (278 prefectures, 52 weeks) and employed dynamic panel GMM system estimation to analyze the relationship between weekly concentration of PM2.5 (Mean = 87 µg·m- 3) and the index of suicidal ideation (Mean = 49.9). RESULTS: The results indicate that in the spring and winter, a 10 µg·m- 3 increase in the prior week's PM2.5 in a Chinese city is significantly associated with 0.020 increase in ISI in spring and a 0.007 increase in ISI in winter, after taking account other co-pollutants and meteorological conditions. CONCLUSION: We innovatively proposed the measure of suicidal ideation and provided suggestive evidence of a positive association between suicidal ideation and PM2.5 level.

Mapping Public Concerns of Electronic Cigarettes in China.

E-cigarettes have gained growing visibility in recent years. However, there lacks a panoramic image of e-cigarette concerns, particularly in low-income countries, such as China. Studying the public concern at a macro level may help reveal the development of the e-cigarette market, and potential health burden of a province as a whole, which is crucial for the policy regulation of the e-cigarette market, and for the allocation of medical resources in the future. In this research, we attempt to provide the first representative portrait of e-cigarette concerns by using the index of e-cigarette search (ICS), which is constructed by online query of e-cigarette-related words/phrases of 31 provinces spanning from 2011 to 2014 in Baidu, the most popular search engine in China. E-cigarette concerns in all Chinese provinces increased over the time span. Our results from fixed-effects models further show that ICS is positively associated with the number of beds in medical institutions and road density of the province, but negatively associated with the proportion of urban population. In sum, provincial health care, infrastructure and urbanization are pivotal in shaping e-cigarette concerns at the provincial level in China.

The Health Consequences of Social Mobility in Contemporary China.

Although numerous studies have shown the importance of an individual's socioeconomic status on his or her self-rated health status, less well-known is whether self-perceived class mobility, a measure highly correlated with an individual's de facto social class and past mobility experiences, affects self-rated health. In this paper, we attempt to fill the gap by examining how perception of class mobility is associated with self-rated health. Using eight waves of Chinese General Social Survey data spanning the years 2005 to 2015, we conducted an analysis at the micro (individual) level and the macro (provincial) level. Analyses at both levels yielded consistent results. At the individual level, we employed ordered logistic regression and found that the perception of experiencing downward mobility was associated with significantly lower self-rated health in both rural and urban areas compared with those who consider themselves to be upwardly mobile or immobile. At the provincial level, the findings from static panel analysis further revealed that there is a positive relationship between the self-perceived class mobility and self-rated health level.

International visibility as determinants of foreign direct investment: An empirical study of Chinese Provinces.

While previous studies use economic and institutional variables to explain transnational investment operations, we argue that regionally-specific international visibility can significantly influence the investment decisions of foreign firms with spatial and temporal dynamics. Empirically, we extract the usage frequency of the names of all of the Chinese provinces in millions of English-language books from Google Books N-gram corpus to construct the index of international visibility as a proxy measurement of international prominence. Results from dynamic panel data analysis (1994-2004) using the Generalized Method of Moments demonstrate that the level of international visibility of a province has a positive effect on the inflows of foreign direct investments, controlling for a set of economic and institutional factors. Further analyses show that this visibility effect varies with different state images of China formed in various historical periods and is stronger with regard to inland provinces compared to coastal provinces. Our results are robust across alternative corpora and different model specifications.

Using the Baidu Search Index to Predict the Incidence of HIV/AIDS in China.

Based on a panel of 30 provinces and a timeframe from January 2009 to December 2013, we estimate the association between monthly human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) incidence and the relevant Internet search query volumes in Baidu, the most widely used search engine among the Chinese. The pooled mean group (PMG) model show that the Baidu search index (BSI) positively predicts the increase in HIV/AIDS incidence, with a 1% increase in BSI associated with a 2.1% increase in HIV/AIDS incidence on average. This study proposes a promising method to estimate and forecast the incidence of HIV/AIDS, a type of infectious disease that is culturally sensitive and highly unevenly distributed in China; the method can be taken as a complement to a traditional HIV/AIDS surveillance system.

Laugh and grow fat: Happiness affects body mass index among Urban Chinese adults.

Previous studies have extensively examined the relationship between body mass index (BMI) and subjective well-being (SWB) but have mainly focused on the effects of BMI on SWB, leaving the question of whether BMI can be influenced by SWB largely neglected. In this study, we present the first empirical evidence on the effects of SWB on BMI among adults, using data combined from four waves of the Chinese General Social Survey (CGSS) (2010-2013). We find that, among urban Chinese adults, those who have a higher level of happiness tend to have higher BMI, after extensively controlling for a constellation of individual sociodemographic and health attributes. Further analyses using the instrumental variable method and propensity score matching provided similar results.

Subjective well-being in the new China: religion, social capital, and social status.

We present the first nationally representative evidence on the relationship between religion and subjective well-being for the case of China. Research on Western societies tends to find a positive association between being religious and level of well-being. China provides an interesting critical case as the religious population is growing rapidly and the religious and socioeconomic environments are profoundly different from Western societies, implying different mechanisms might be at work. We hypothesize to find a positive association between religion and well-being in China too, but argue social capital, for which strong evidence is often found in Western societies, is unlikely to be an important mechanism because religion in China is generally non-congregational. Instead, we argue that the private and subjective dimension of religion matters for well-being in China by helping adherents have an improved sense of social status relative to the non-religious in the context of rapid social change and growing inequality. Our results generally support these predictions.

Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014.

BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.

Economic performance and public concerns about social class in twentieth-century books.

What is the association between macroeconomic conditions and public perceptions of social class? Applying a novel approach based on the Google Books N-gram corpus, this study addresses the relationship between public concerns about social class and economic conditions throughout the twentieth century. The usage of class-related words/phrases, or "literary references to class," in American English-language books is related to US economic performance and income inequality. The findings of this study demonstrate that economic conditions play a significant role in literary references to class throughout the century, whereas income inequality does not. Similar results are obtained from further analyses using alternative measures of class concerns as well as different corpora of English Fiction and the New York Times. We add to the social class literature by showing that the long-term temporal dynamics of an economy can be exhibited by aggregate class concerns. The application of massive culture-wide content analysis using data of unprecedented size also represents a contribution to the literature.

Application of the yeast-surface-display system for orally administered salmon calcitonin and safety assessment.

High manufacturing costs and oral delivery are the constraints in clinical application of calcitonin. We selected surface-displayed Saccharomyces cerevisiae as a low-cost and safe carrier for oral delivery of salmon calcitonin (sCT). The sCT DNA fragment, optimized according to the codon preference of S. cerevisiae, was synthesized and cloned into the plasmid M-pYD1 to yield recombinant yAGA2-sCT, which was induced to express sCT by galactose for 0, 12, and 24 h. sCT expression was detected on the cell surface by indirect immunofluorescence and peaked at 12 h. About 65% recombinants expressed sCT on flow cytometry. The in vivo and in vitro activity of recombinant sCT was determined by detecting bioactivity of antiosteoclastic absorption on bone wafers and orally administering yAGA2-sCT to Wistar rats, respectively. For safety assessment of yAGA2-sCT, we observed abnormalities, morbidity, and mortality and determined body weight, serum chemistry parameters, hematological parameters, and organ weight. In vitro bioactivity of the recombinant sCT was similar to that of commercial sCT, Miacalcic; oral administration of 5 g/kg yAGA2-sCT induced a long-term hypocalcemic effect in Wistar rats and no adverse effects. This study demonstrates that yAGA2-sCT anchoring sCT protein on a S. cerevisiae surface has potential for low-cost and safe oral delivery of sCT.