Blood lead and cadmium levels are negatively associated with bone mineral density in young female adults.

BACKGROUND: The organ toxicities of lead and cadmium have been extensively studied; however, studies of their toxic effects on bone remain limited, especially in young adults. The objective of this study was to examine the associations of blood lead levels (BLL) and blood cadmium levels (BCL) with bone mineral density (BMD) among young adults. METHODS: We performed a cross-sectional study using the National Health and Nutrition Examination Survey 2011-2018 database. Because of the skewed distribution, BLL and BCL were Ln-transformed for analysis. Weighted multivariate regressions were performed to evaluate the associations between LnBLL and LnBCL and lumbar BMD. Subgroup analyses were further performed. RESULTS: A total of 3234 participants aged 20-35 years were included in this study. No significant association between LnBLL and lumbar BMD was found (ß = - 5.6, 95%CI: - 13.5-2.3). However, in the subgroup analysis stratified by sex, this association became negative in women (ß = - 18.2, 95%CI: - 29.9- - 6.4). Moreover, this negative association was more prominent in female blacks (ß = - 35.5, 95%CI: - 63.4- - 7.6). On the other hand, a negative association between LnBCL and lumbar BMD was found (ß = - 7.4, 95%CI: - 14.0- - 0.8). In the subgroup analysis stratified by sex, this negative association only existed in women (ß = - 18.7, 95%CI: - 28.0- - 9.5). Moreover, this negative association was more prominent in female whites (ß = - 31.1, 95%CI: - 46.2- - 16.1). CONCLUSIONS: Our finding showed that both BLL and BCL were independently and negatively associated with lumbar BMD among young females, but not among young males.

Association between plasma total homocysteine level within normal range and bone mineral density in adults.

BACKGROUND: Growing evidence indicates that homocysteine is a noteworthy marker for general health status. However, research regarding plasma total homocysteine (tHcy) levels and bone mineral density (BMD) is sparse and controversial. Hence, we aimed to investigate the association between plasma tHcy level within normal range and lumbar BMD in adults. METHODS: In this cross-sectional study, using the National Health and Nutrition Examination Survey database, data on 10748 adults aged between 30 and 85 years were analyzed. The weighted multiple logistic regression analyses were conducted to evaluate the association between plasma tHcy level and lumbar BMD. The fitted smoothing curves were performed to explore potential non-linear relationships. When non-linearity was detected, we further calculated the inflection point using a recursive algorithm and constructed a weighted two-piecewise linear regression model. RESULTS: After adjusting for all the covariates, the association between plasma tHcy and lumbar BMD was different in various age groups (adults aged 30-49 years: ß = -0.0004, 95% CI -0.0025, 0.0018; adults aged 50-69 years: ß = 0.0001, 95% CI -0.0025, 0.0026; adults aged 70-85 years: ß = 0.0050, 95% CI 0.0008, 0.0092). In the subgroup analysis stratified by gender, this association also differed based on gender. There was a negative trend in females (aged 30-49 years: ß = -0.0022, 95% CI -0.0054, 0.0011; aged 50-69 years: ß = -0.0028, 95% CI -0.0062, 0.0007), and a positive trend in males (aged 30-49 years: ß = 0.0018, 95% CI -0.0012, 0.0048; aged 50-69 years: ß = 0.0027, 95% CI -0.0009, 0.0063) in both 30-49 years group and 50-69 years group. In the 70-85 years group, this association was significantly positive in males (ß = 0.0136, 95% CI 0.0068, 0.0204), but was not significantly different in females (ß = 0.0007, 95% CI -0.0046, 0.0060). CONCLUSION: The correlation between plasma tHcy level within the normal range and lumbar BMD differs by age and gender.

Discovery of novel pyruvate dehydrogenase kinases inhibitors by screening of an in-house small molecule library for anti-lung cancer therapeutics.

Pyruvate dehydrogenase kinases (PDKs) are widely over-expressed in various human solid cancers, making them attractive therapeutic targets for cancer treatment. Herein, we report the identification of structurally novel PDKs inhibitors by screening of an in-house small molecule library. Biochemical assay indicated that the identified compounds 1-4 inhibited PDK1 activity with EC50 values of 0.50, 1.99, 4.64, and 0.42 µM, respectively. The ITC analysis suggested that the identified compounds 1-4 were pan-isoform PDK inhibitors, which bound to and inhibited the four PDK isoforms. Moreover, 1-4 dose-dependently reduced pyruvate dehydrogenase complex phosphorylation in NCI-H1975 cell. Molecular docking suggested that the most potent compound 4 docked well in the ATP binding pocket of the four PDK isoforms, forming direct hydrogen bond interactions with the conserved amino acids Thr and Asp in ATP binding pocket of PDKs. The cell viability assay demonstrated that 4 potently blocked NCI-H1975 cell proliferation (IC50 = 3.32 µM), but had little effect on human normal lung cell MRC-5 even with the tested concentration up to 40 µM. All the data demonstrated that 4 was a promising lead for the development of structurally novel PDKs inhibitor for the cancer treatment.

[Studies on the photo-stability of poly p-(phenylene vinylene)].

The photo-stability of both MDMO-PPV film and MEH-PPV film, as irradiated under different conditions, and in the presence and absence of oxygen and visible light luminance, were studied by UV-Vis spectra and fluorescence spectra respectively. The maximum absorbance of them was at 500 nm, while the maximum fluorescence intensity of them were at 580 and 589 nm, respectively. In the presence of both oxygen and light irradiation, the fluorescence intensity was decreased and the films were damaged. Photocatalysis oxidation technology using solid-state nanocrystalline TiO2-PVC film was introduced to increase the photo-stability and some meaningful clues were observed.