This paper analyzes the intersection of individual lives and historical context by examining how cohort membership, historical conditions, and individual maturation influence subjective well-being in urban China. We use cross-classified multilevel models and repeated measures of happiness from seven waves of the Chinese General Social Survey (CGSS 2003–2013, N = 43,308). The results indicate that individuals born between 1956 and 1961 experienced setbacks at various pivotal moments throughout their life, including education, employment, economic stability, and social connections, and this cohort reports a lower overall sense of happiness when compared to other cohorts. The effect of aging on happiness comprises a U-shaped pattern; the middle-aged are the least happy. We observe an upward trend in happiness from 2003 to 2013. These results are confirmed by using subjective socioeconomic status (SES) as an alternative measure of well-being from CGSS 2003 and CGSS 2005 (N = 11,992). This paper contributes to studies of market transition by identifying the birth cohort as an important mechanism of inequality. It also augments the life-course paradigm by highlighting the significance of timing when individual lives intersect with historical context.

Background: Chinese and Korean Americans have lower colorectal cancer (CRC) screening rates than other racial/ ethnic groups, which may be explained by a low level of CRC knowledge and a high level of misconceptions. This study explores the role of knowledge in CRC screening among these groups. Methods: Chinese (N=59) and Korean (N=61) Americans older than 50 were recruited from the Washington D.C. Metropolitan area. They completed a detailed survey and participated in focus groups to discuss their knowledge on CRC and CRC screening. Seventeen physicians, community leaders, and patient navigators participated in key informant interviews. Using a mixed methods approach, data were analyzed quantitatively and qualitatively. Results: Participants lacked knowledge about CRC and CRC screening. More than half did not know that screening begins at age 50 and there are several types of tests available. More than 30% thought CRC screening was not necessary if there were no symptoms or there was nothing they could do to prevent CRC. Focus group findings suggested understanding about CRC was limited by an inadequate source of linguistically and culturally relevant health information. For example, many participants considered CRC a western condition mainly caused by unhealthy diet. This led to under-estimations about their susceptibility to CRC. Knowledge was positively associated with self-reported screening. Participants who had higher knowledge scores were more likely to report ever having had a colonoscopy and confidence in ability to have CRC screening. Conclusions: Mixed-methods analysis provides multi-faceted perspectives on CRC knowledge and its influence on screening. Study findings can help inform interventions to increase CRC screening among Chinese and Korean Americans.

A striking feature of pathogenic Candida species is morphological plasticity that facilitates environmental adaptation and host infection. Candida auris is an emerging multidrug-resistant fungal pathogen first described in Japan in 2009. In this study, we demonstrate that clinical isolates of C. auris have multiple colony and cellular morphologies including the yeast, filamentous, aggregated, and elongated forms. This phenotypic diversity has been observed in eight clinical isolates of C. auris representing four major genetic clades, suggesting that it could be a general characteristic. We further demonstrate that different cell types of C. auris exhibit distinct antifungal resistance and virulence properties in a Galleria mellonella infection model. Our findings imply that morphological diversity is an important biological feature of C. auris and could be a contributor to its emergence and rapid prevalence worldwide.

Lay summary

Candida auris is an emerging multidrug-resistant fungal pathogen. Morphological analyses indicate that filamentation is a general feature of clinical isolates of C. auris. This ability is associated with antifungal resistance and virulence.

The progression and malignancy of many tumors are associated with increased tissue stiffness. Conversely, the oncogenically transformed cells can be confined in soft stroma. Yet, the underlying mechanisms by which soft matrix confines tumorigenesis and metastasis remain elusive. Here, we show that pancreatic cancer cells are suppressed in the soft extracellular matrix, which is associated with YAP1 degradation through autophagic-lysosomal pathway rather than Hippo signal mediated proteasome pathway. In the soft stroma, PTEN is upregulated and activated, which consequently promotes lysosomal biogenesis, leading to the activation of cysteine-cathepsins for YAP1 degradation. In vitro, purified cathepsin L can directly digest YAP1 under acidic conditions. Lysosomal stress, either caused by chloroquine or overexpression of cystatin A/B, results in YAP1 accumulation and malignant transformation. Likewise, liver fibrosis induced stiffness can promote malignant potential in mice. Clinical data show that down-regulation of lysosomal biogenesis is associated with pancreatic fibrosis and stiffness, YAP1 accumulation, and poor prognosis in PDAC patients. Together, our findings suggest that soft stroma triggers lysosomal flux-mediated YAP1 degradation and induces cancer cell dormancy.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.