GITRL impairs hepatocyte repopulation by liver progenitor cells to aggravate inflammation and fibrosis by GITR+CD8+ T lymphocytes in CDE Mice.

As an alternative pathway for liver regeneration, liver progenitor cells and their derived ductular reaction cells increase during the progression of many chronic liver diseases. However, the mechanism underlying their hepatocyte repopulation after liver injury remains unknown. Here, we conducted progenitor cell lineage tracing in mice and found that fewer than 2% of hepatocytes were derived from liver progenitor cells after 9 weeks of injury with a choline-deficient diet supplemented with ethionine (CDE), and this percentage increased approximately three-fold after 3 weeks of recovery. We also found that the proportion of liver progenitor cells double positive for the ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL, also called Tnfsf18) and SRY-related HMG box transcription 9 (Sox9) among nonparenchymal cells increased time-dependently upon CDE injury and reduced after recovery. When GITRL was conditionally knocked out from hepatic progenitor cells, its expression in nonparenchymal cells was downregulated by approximately fifty percent, and hepatocyte repopulation increased by approximately three folds. Simultaneously, conditional knockout of GITRL reduced the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumour necrosis factor receptor (GITR)-positive CD8+ T lymphocytes. Mechanistically, GITRL stimulated cell proliferation but suppressed the differentiation of liver progenitor organoids into hepatocytes, and CD8+ T cells further reduced their hepatocyte differentiation by downregulating the Wnt/ß-catenin pathway. Therefore, GITRL expressed by liver progenitor cells impairs hepatocyte differentiation, thus hindering progenitor cell-mediated liver regeneration.

Diethyldithiocarbamate inhibits the activation of hepatic stellate cells via PPARα/FABP1 in mice with non-alcoholic steatohepatitis.

Activation of hepatic stellate cells (HSCs) is the main course of liver fibrosis which is positively correlated with adverse clinical outcomes in non-alcoholic steatohepatitis (NASH). Diethyldithiocarbamate (DDC) attenuates NASH related liver fibrosis in mice, but its underlying mechanisms remains unclear. In this study, the data showed that DDC inhibited the activation of HSCs in high fat choline-deficient, L-amino acid-defined (CDAA) diet induced NASH. Double Immunofluorescence analysis showed that the baseline expression of peroxisome proliferator-activated receptor α (PPARα) is high in HSCs in normal mouse liver and notably decreases in the NASH liver, indicating that PPARα might be associated with the activation of HSCs. While, DDC upregulated PPARα in HSCs in the NASH liver. Mixture of free fatty acid was used to induce steatosis of hepatocytes. Human HSCs (LX-2 cells) were activated after co-cultured with steatotic hepatocytes, and DDC inhibited the activation of LX-2 cells. Meanwhile, DDC upregulated PPARα and FABP1, and promoted the accumulation of LDs in LX-2 cells. PPARα small interfering RNA blocked these effect of DDC. These findings suggest that PPARα is associated with the activation of HSCs in the context of NASH. DDC improves NASH related fibrosis through inhibiting the activation of HSCs via PPARα/FABP1.

Association between Green Space Structure and the Prevalence of Asthma: A Case Study of Toronto.

Asthma is a chronic inflammatory disease that can be caused by various factors, such as asthma-related genes, lifestyle, and air pollution, and it can result in adverse impacts on asthmatics' mental health and quality of life. Hence, asthma issues have been widely studied, mainly from demographic, socioeconomic, and genetic perspectives. Although it is becoming increasingly clear that asthma is likely influenced by green spaces, the underlying mechanisms are still unclear and inconsistent. Moreover, green space influences the prevalence of asthma concurrently in multiple ways, but most existing studies have explored only one pathway or a partial pathway, rather than the multi-pathways. Compared to greenness (measured by Normalized Difference Vegetation Index, tree density, etc.), green space structure-which has the potential to impact the concentration of air pollution and microbial diversity-is still less investigated in studies on the influence of green space on asthma. Given this research gap, this research took Toronto, Canada, as a case study to explore the two pathways between green space structure and the prevalence of asthma based on controlling the related covariates. Using regression analysis, it was found that green space structure can protect those aged 0-19 years from a high risk of developing asthma, and this direct protective effect can be enhanced by high tree diversity. For adults, green space structure does not influence the prevalence of asthma unless moderated by tree diversity (a measurement of the richness and diversity of trees). However, this impact was not found in adult females. Moreover, the hypothesis that green space structure influences the prevalence of asthma by reducing air pollution was not confirmed in this study, which can be attributed to a variety of causes.

Does the Connectivity of Urban Public Green Space Promote Its Use? An Empirical Study of Wuhan.

A high greenness level can enhance green space use and outdoor physical activity. However, rapid urbanization and high-density development have led to the loss or fragmentation of green space, especially urban public green space (PGS). With the aim of increasing the health benefits from PGS, some planners and researchers suggest connecting existing PGSs to encourage urban residents to use the PGS, and thus, to improve public health. Does this suggestion stand with robustness? By taking 42 sub-districts in the inner area of Wuhan as the study objects, this paper examines the correlation between the connectivity of PGS and its use. We also explore how the characteristics of PGS and the facilities/functions in the neighboring areas influence this relationship by using Location Based Service data (WeChat-Yichuxing data), point of interest (POI) data, and remote-sensing image, etc. Using Regression Analysis, we found that there is no high correlation between PGS use and its connectivity. The possible causes might be attributed to the fact that PGS use is profoundly influenced by multifaceted competing impact factors, and no one can stand dominantly. It is interesting to see that the density of companies is positively, but slightly, related to PGS use.

Super-efficient in Vivo Two-Photon Photodynamic Therapy with a Gold Nanocluster as a Type I Photosensitizer.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions via generating excess cytotoxic reactive oxygen species. However, due to the limited penetration depth of visible excitation light and the intrinsic hypoxia microenvironment of solid tumors, the efficacy of PDT in the treatment of cancer, especially deep-seated or large tumors, is unsatisfactory. Herein, we developed an efficient in vivo PDT system based on a nanomaterial, dihydrolipoic acid coated gold nanocluster (AuNC@DHLA), that combined the advantages of large penetration depth in tissue, extremely high two-photon (TP) absorption cross section (σ2 ∼ 106 GM), efficient ROS generation, a type I photochemical mechanism, and negligible in vivo toxicity. With AuNC@DHLA as the photosensitizer, highly efficient in vivo TP-PDT has been achieved.

CO2 emissions patterns of 26 cities in the Yangtze River Delta in 2015: Evidence and implications.

As a country with the highest CO2 emissions and at the turning point of socio-economic transition, China's effort to reduce CO2 emissions will be crucial for climate change mitigation. Yet, due to geospatial variations of CO2 emissions in different cities, it is important to develop city-specific policies and tools to help control and reduce CO2 emissions. The key question is how to identify and quantify these variations so as to provide reference for the formulation of the corresponding mitigation policies. This paper attempts to answer this question through a case study of 26 cities in the Yangtze River Delta. The CO2 emissions pattern of each city is measured by two statistics: Gini coefficient to describe its quantitative pattern and Global Moran's I index to capture its spatial pattern. It is found that Gini coefficients in all these cities are all greater than 0.94, implying a highly polarized pattern in terms of quantity; and the maximum value for Global Moran's I index is 0.071 with a standard deviation of 0.021, indicating a weak spatial clustering trend but strong difference among these cities. So, it would be more efficient for these cities at current stage to reduce CO2 emissions by focusing on the large emission sources at certain small localities, particularly the very built-up areas rather than covering all the emission sources on every plot of the urban prefectures. And by a combination of these two metrics, the 26 cities are regrouped into nine types with most of them are subject to type HL and ML. These reclassification results then can serve as reference for customizing mitigation policies accordingly and positioning these policies in a more accurate way in each city.

Intracellular Temperature Sensing: An Ultra-bright Luminescent Nanothermometer with Non-sensitivity to pH and Ionic Strength.

Luminescence thermometry usually suffer from cellular complexity of the biochemical environment (such as pH and ionic strength), and thus the accuracy and reliability of the determined intracellular temperature are directly affected. Herein, a photoluminescent nanothermometer composed of polymer encapsulated quantum dots (P-QD) has been developed. And the prepared nanothermometer exhibits some advantages: such as non-sensitivity to pH and ionic strength, as well as high detection sensitivity and ultrahigh reversibility. The intracellular temperature was accurately determined under physiological conditions with different pH and ionic strength, and direct measurement of thermogenesis in individual cells has been achieved.

Extremely high brightness from polymer-encapsulated quantum dots for two-photon cellular and deep-tissue imaging.

Materials possessing high two photon absorption (TPA) are highly desirable for a range of fields, such as three-dimensional data storage, TP microscopy (TPM) and photodynamic therapy (PDT). Specifically, for TPM, high TP excitation (TPE) brightness (σ × Ï•, where σ is TPA cross-sections and ϕ is fluorescence quantum yield), excellent photostability and minimal cytotoxicity are highly desirable. However, when TPA materials are transferred to aqueous media through molecule engineering or nanoparticle formulation, they usually suffer from the severely decrease of quantum yield (QY). Here, we report a convenient and efficient method for preparing polymer-encapsulated quantum dots (P-QD). Interestingly, the QY was considerably enhanced from original 0.33 (QDs in THF) to 0.84 (P-QD in water). This dramatic enhancement in QY is mainly from the efficiently blocking nonradiative decay pathway from the surface trap states, according to the fluorescence decay lifetimes analysis. The P-QD exhibits extremely high brightness (σ × Ï• up to 6.2 × 10(6) GM), high photostability, excellent colloidal stability and minimal cytotoxicity. High quality cellular TP imaging with high signal-to-background ratio (> 100) and tissue imaging with a penetration depth of 2200 µm have been achieved with P-QD as probe.

[Pathologic bacterial distribution and antibiotic resistance in induced sputum of infants aged from 1 to 3 months with lower respiratory tract infection].

OBJECTIVE: To investigate the pathologic bacterial distribution and their antibiotic resistance in infants aged from 1 to 3 months with lower respiratory tract infection, so as to provide instructions for clinical application of antibiotics. METHODS: Induced sputum was extracted from 622 cases of hospitalized infants aged from 1 to 3 months with lower respiratory tract infection between January 2013 and December 2013, and microbial sensitivity test was performed with agar diffusion sensitivity test. RESULTS: A total of 379 (60.9%) strains of bacteria were isolated from induced sputum in the 622 infants. The Gram-negative strains were detected in 325 strains (85.8%), and the Gram-positive strains were found in 50 strains (13.2%) in the 379 strains. The others were Fungal strains (4 strains, 1.1%). The Gram-negative bacteria included Escherichia coli (31.1%) and Klebsiella pneumoniae (18.2%), with extended-spectrum ß-lactamases (ESBLs) production of 48.3% and 52.2% respectively. The average rate of antibiotic resistance for ESBLs-producing bacteria was 53%. ESBLs-producing bacteria were highly resistant (100%) to ampicillin and cefotaxime, but sensitive to carbapenems. Staphylococcus aureus (10.0%) was the dominant bacteria in Gram-positive bacteria. A lower proportion of methicillin-resistant Staphylococcus aureus (1.8%) was observed, however the resistance rate of methicillin-resistant Staphylococcus aureus to ß-lactam antibiotics were 100%. CONCLUSIONS: Escherichia coli and Klebsiella pneumoniae are the main pathogenic bacteria causing lower respiratory tract infection in infants aged from 1 to 3 months. ESBLs-producing bacteria accounted for over 48%, and the antibiotic resistance rate were more than 53% in these infants. These results provide a basis for the first empirical clinical use of antimicrobial in infants with lower respiratory tract infection.

Covert thermal barcodes based on phase change nanoparticles.

An unmet need is to develop covert barcodes that can be used to track-trace objects, and authenticate documents. This paper describes a new nanoparticle-based covert barcode system, in which a selected panel of solid-to-liquid phase change nanoparticles with discrete and sharp melting peaks is added in a variety of objects such as explosive derivative, drug, polymer, and ink. This method has high labeling capacity owing to the small sizes of nanoparticles, sharp melting peaks, and large scan range of thermal analysis. The thermal barcode can enhance forensic investigation by its technical readiness, structural covertness, and robustness.

Printed multilayer microtaggants with phase change nanoparticles for enhanced labeling security.

There is an urgent need to develop taggants that can be used to identify objects, prevent fraud, and deter counterfeiting with high reliability, high capacity, and minimal effort. This paper describes a new multilayer covert taggant based on phase change nanoparticles (metals and eutectic alloys). A panel of selected nanoparticles with different melting temperatures have been added in matrix materials together with fluorescent dye and printed on substrates to form micro-/macrofeatures that contain thermal, fluorescence signature, and structural components. The multilayer taggants can greatly enhance security level for many commercial and forensic applications by their extremely large labeling capacity, coding readiness, and covertness.

[Correlation of the stress reaction and temperament in children with bronchial asthma].

OBJECTIVE: To study the correlation between the temperament dimension and the stress reaction in children with bronchial asthma. METHODS: Between February 2008 and May 2010, two hundred and twenty children with bronchial asthma and aged from 3-7 years were enrolled (asthma group). Eighty children without asthma, respiratory tract infections, serious body diseases and mental disorders who were age- and gender-matched to the asthma group served as the control group. The Carry temperament rating scales were filled by the children's parents from the asthma and control groups. The serum levels of cortisol at 8am and 4pm and nerve growth factor (NGF) were measured by immunochemiluminescent assays. RESULTS: The scores of the rhythmicity and persistence in temperament dimensions in the asthma group were significantly lower than those in the control group; in contrast, the scores of phobotaxis, response intensity, emotion entity, adaptability and attention dispersion in the asthma group were significantly higher than those in the control group (P<0.05). The levels of serum cortisol at 8am and 4pm were lower, while the serum level of NGF was higher in the asthma group than those in the control group (P<0.05). The scores of response intensity, emotion entity and adaptability in temperament dimensions were positively correlated with serum NGF level (r=0.348,0.468,0.195, respectively; P<0.05), and inversely correlated with serum cortisol level at 8 am (r=-0.297, -0.462, -0.152, respectively; P<0.05) in the asthma group. CONCLUSIONS: The temperament dimension is associated with the stress reaction in children with bronchial asthma. This provides a basis for the treatment of bronchial asthma by neuropsychological adjustment.