Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 is a pattern recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular anti-microbial activity, including phagocytosis and production of reactive oxygen species1, 2. In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 are excluded (Supplementary Figure 1). The “phagocytic synapse” now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular anti-microbial responses only when they are required.

Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epidermal growth factor receptor (HER). Systemic delivery of this proteincorrole complex results in tumor accumulation, which can be visualized in vivo owing to intensely red corrole fluorescence. Targeted delivery in vivo leads to tumor cell death while normal tissue is spared. These findings contrast with the effects of doxorubicin, which can elicit cardiac damage during therapy and required direct intratumoral injection to yield similar levels of tumor shrinkage compared with the systemically delivered corrole. The targeted complex ablated tumors at >5 times a lower dose than untargeted systemic doxorubicin, and the corrole did not damage heart tissue. Complexes remained intact in serum and the carrier protein elicited no detectable immunogenicity. The sulfonated gallium(III) corrole functions both for tumor detection and intervention with safety and targeting advantages over standard chemotherapeutic agents.heregulin ͉ human epidermal growth factor receptor ͉ cancer ͉ in vivo imaging ͉ porphyrinoids

A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors. ResultsA total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age-and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation. ConclusionKidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.

Background: Dectin-1 is a phagocytic receptor important for host immune responses to fungal infections. Results: Dectin-1 signaling directs LC3 to phagosomes leading to increased MHC class II recruitment and increased presentation of fungal-derived antigens. Conclusion: Dectin-1 signaling enhances the efficiency of MHC class II presentation of fungal-derived antigens. Significance: Dectin-1 signaling can influence how phagosomal contents are handled.

AIM:To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province, China. METHODS:A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province, China. Questionnaires, designed by co-working of epidemiologists and hepatologists, included demographic characteristics, current medication use, medical history and health-relevant behaviors, i.e., alcohol consumption, smoking habits, dietary habits and physical activities. Anthropometric measurements, biochemical tests and abdominal ultrasonography were carried out. RESULTS:Among the 3543 subjects, 609 (17.2%) were diagnosed having FLD (18.0% males, 16.7% females, P > 0.05). Among them, the prevalence of confirmed alcoholic liver disease (ALD), suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%, 1.8%, and 15.0%, respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age, gender and residency, the standardized prevalence of FLD in adults was 14.5%. Among them, confirmed ALD, suspected ALD and NAFLD were 0.5%, 2.3%, and 11.7%, respectively, in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%, P < 0.001). However, the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%, P < 0.05). Multivariate and logistic regression analysis indicated that male gender, urban residency, low education, high blood pressure, body mass index, waist circumference, waist to hip ratio, serum triglyceride and glucose levels were the risk factors for FLD.CONCLUSION: FLD, especially NAFLD, is prevalent in South China. There are many risk factors for FLD.