Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models.

Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets.

Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging.

The prevalent use of light-emitting diodes (LEDs) has caused revolutionary changes in modern life, but the potential hazards to health of blue light are poorly understood. N6-methyladenosine (m6A) is the most prevalent posttranscriptional modification in eukaryotes and can modulate diverse physiological processes by regulating mRNA fate. Here, to understand the effects and molecular mechanisms of daily low-intensity blue light exposure (BLE) and ascertain whether m6A methylation plays a role in BLE-induced phenotypes, we constructed a series of Drosophila models under different durations of daily low-intensity BLE and obtained multiomics profiles. Our results revealed that BLE could induce transcriptomic, m6A epitranscriptomic, and metabolomic reprogramming in Drosophila along with aging process. Importantly, the m6A methylation sites enriched in the 5' untranslated regions (UTRs) of Drosophila transcripts showed strong age specificity and could be altered by BLE. We experimentally validated that aging-related gene Tor and circadian rhythm-related gene per were regulated by 5' UTR-enriched m6A methylation. Overall, our study provides a systematic assessment of m6A RNA methylome reprogramming by BLE and aging in Drosophila model.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Assessment and Implication of PAHs and Compound-Specific δ13C Compositions in a Dated Marine Sediment Core from Daya Bay, China.

PAHs in a sediment core covering ~120 years from Daya Bay in South China Sea were extracted using Soxhlet and high performance thin layer chromatography, and the compound-specific δ13C were analyzed using gas chromatography-combustion-isotopic ratio mass spectrometry. The concentrations of PAHs ranged from 99.3 to 676 ng g-1, with high molecular weight PAHs as a key component. PAHs' compound-specific δ13C ranged from -35.02‱ to -16.14‱. The patterns of 16 PAHs, molecular ratios, and compound specific δ13C compositions indicate important pyrolytic and petrogenic sources: PAHs derived predominantly from pyrogenic sources (including coal and wood incomplete combustion) before the 1960s, while after the 1960s, they derived predominantly from mixed pyrogenic and petrogenic sources (including automotive exhaust emissions, oil spills, and coal and wood incomplete combustion). Our results can provide important insights into organic pollution emissions influenced by human activities and the urbanization of Daya Bay.

Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches.

The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 µM), ethyl paraben (20 ∼ 100 µM), propyl paraben (5 ∼ 20 µM), and butyl paraben (BuP, 2 ∼ 10 µM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic-pituitary-thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. The findings confirmed the developmental toxicity of the test parabens and their thyroid endocrine disruption effects, providing substantial evidence on the safety control of paraben-based preservatives.

Modeling the response of ecological service value to land use change through deep learning simulation in Lanzhou, China.

Land use (LU) changes caused by urbanization, climate, and anthropogenic activities alter the supply of ecosystem services (ES), which affects the ecological service value (ESV) of a given region. Existing LU simulation models extract neighborhood effects with only one data time slice, which ignores long-term dependence in neighborhood interactions. Previous studies on the dynamic relationship between LU change and ES in semi-arid areas is rare than that in humid coastal areas. Here, we selected a semi-arid city, Lanzhou, in Northwest China as the study area, to simulate LU changes in 2030 under natural growth (NG), ecological protection (EP), economic development (EP), and ecological protection-economic development (EPD) scenarios, using a novel deep learning method, named CL-CA. Convolutional neural network and long short term memory (CNN-LSTM) with cellular automata (CA) were utilized to extract the spatiotemporal neighborhood features. The overall simulation performance of the proposed model was larger than 0.92, which is surpassed that of LSTM-CA, artificial neural network (ANN)-CA, and recursive neural network (RNN)-CA. Ultimately, we utilized LU and ES to quantitatively evaluate the ESV changes. The results indicated that: (1) The variable trend of ESV in arid area is different from that in coastal humid areas. (2) Forest land and water were the main factors that affect the ESV change. (3) The EPD scenario was more suitable for sustainable urban development.

Development trajectory for the temporal and spatial evolution of the resilience of regional tourism environmental systems in 14 cities of Gansu Province, China.

The rapid development of the urban economy in China and the accompanying income growth experienced by urban residents have increased demand for tourism and leisure, which has brought pressure on the urban tourism environment system (UTES), making the contradiction between tourism economic development and the ecological environment increasingly acute. While seeking to rationalize the economic, social, and ecological benefits of tourism, reducing the fragility of the UTES and improving its anti-interference and recovery capabilities have become attracted significant attention from scholars in China and elsewhere. This paper establishes a definition of resilience for an UTES and constructs an evaluation index system for it in terms of the social, economic, and ecological environments. It also establishes an entropy weight-TOPSIS resilience evaluation model to measure resilience in regional systems, using ArcGIS to analyze the standard deviation ellipse and center of the gravity track of the resilience. System dynamics was used to construct diagrams of causal relationships and stock flow for the constituent elements of UTES to show the mechanisms that promote its resilience. This paper investigates 14 cities of Gansu Province in particular to simulate the resilience model of a regional system.

Sex differences in 10-year ischemic cardiovascular disease risk prediction in Chinese patients with prediabetes and type 2 diabetes.

BACKGROUND: Cardiovascular disease has become a serious public health problem in recent years in China. The aim of the study was to examine sex differences in cardiovascular risk factors and 10-year ischemic cardiovascular disease (ICVD) risk in Chinese patients with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). METHODS: This was a multi-site retrospective case-control study conducted from April-November 2016 using an electronic medical record database, involving 217 PreDM and 900 T2DM patients admitted to endocrinology units in four hospitals in China. CVD risk was estimated using the Chinese 10-year ICVD risk model. The differences in 10-year absolute ICVD risk according to PreDM, T2DM < 1 year, T2DM 1-5 years or T2DM ≥5 years and sex were analyzed using ANOVA. RESULTS: When compared to PreDM females, males with PreDM had significantly higher 10-year ICVD risk In contrast, the opposite pattern of 10-year ICVD risk was observed in T2DM; males had significantly lower 10-year ICVD risk. Moreover, compared to T2DM females, males with T2DM had a lower proportion s with moderate or greater ICVD risk (p < 0.001). When compared to PreDM males, males with T2DM < 1 year, and with T2DM 1-5 years had no difference in 10-year ICVD risk, but had higher ICVD risk with T2DM ≥5 years (p < 0.05). Compared to PreDM females, females with T2DM in all subgroups had higher ICVD risk (p < 0.05). Among those with T2DM, hypertension rates of awareness, treatment and control were 78.60%, 65.38% and 31.10%, respectively; hyperlipidemia rates of awareness, treatment and control were lower (29.15%, 8.30% and 3.47%, respectively). Females with T2DM had higher prevalence, awareness and treatment of hypertension and hyperlipidemia than males with T2DM (p < 0.001). CONCLUSIONS: There is a greater need for cardiovascular risk reduction programs for females with T2DM at diagnosis. Given the low numbers for awareness, treatment and control of hypertension and hyperlipidemia in both males and females, significant resources focused on them must be expended, specifically improving regular assessment of blood pressure and blood lipids. Strengthening the management of chronic diseases through adherence to evidence-based guidelines to enhance clinical treatment may reduce 10-year ICVD in patients with T2DM in China.

Comparison of the accuracy of classification models to estimate healthcare use and costs associated with COPD exacerbations in Saskatchewan, Canada: A retrospective cohort study.

OBJECTIVE: COPD is a high-cost disease and results in frequent contacts with the healthcare system. The study objective was to compare the accuracy of classification models with different covariates for classifying COPD patients into cost groups. METHODS: Linked health administrative databases from Saskatchewan, Canada, were used to identify a cohort of newly diagnosed COPD patients (April 1, 2007 to March 31, 2011) and their episodes of healthcare encounters for disease exacerbations. Total costs of the first and follow-up episodes were computed and patients were categorized as persistently high cost, occasionally high cost, and persistently low cost based on cumulative cost distribution ranking using the 75th percentile cutoff for high-cost status. Classification accuracy was compared for seven multinomial logistic regression models containing socio-demographic characteristics (i.e., base model), and socio-demographic and prior healthcare use characteristics (i.e., comparator models). RESULTS: Of the 1182 patients identified, 8.5% were classified as persistently high cost, 26.1% as occasionally high cost, and the remainder as persistently low cost. The persistently high-cost and occasionally high-cost patients incurred 10 times ($12 449 vs $1263) and seven times ($9334 vs $1263) more costs in their first exacerbation episode than persistently low-cost patients, respectively. Classification accuracy was 0.67 for the base model, whereas the comparator model containing socio-demographic and number of prior hospital admissions had the highest accuracy (0.72). CONCLUSIONS: Costs associated with COPD exacerbation episodes are substantial. Adding prior hospitalization to socio-demographic characteristics produced the highest improvements in classification accuracy. Accurate classification models are important for identifying potential healthcare cost management strategies.

Psychometric properties of the Chinese version of the Menopause-Specific Quality-of-Life questionnaire.

OBJECTIVE: The Menopause-Specific Quality-of-Life (MENQOL) questionnaire was developed as a specific tool to measure the health-related quality-of-life of postmenopausal women. Thus far, the Chinese version questionnaire has not been subjected to psychometric assessment with a large sample. This study aims to evaluate the validity and reliability of the Chinese version of the MENQOL specific to postmenopausal women in China. METHODS: A total of 1,137 menopausal symptomatic and 491 menopausal asymptomatic women from eight cities in China were recruited using a convenience sampling method. Psychometric properties were evaluated by descriptive statistics, validity, and reliability. Reliability was assessed for each subscale of the MENQOL through internal consistency reliability with Cronbach's α and intersubscale correlations. Item-domain correlations, principal components analysis (PCA), and confirmatory factor analysis were performed to determine construct validity. t tests were used to compare the differences between the menopausal symptomatic and asymptomatic women and to evaluate the discriminate validity. Pearson correlation coefficients were calculated between MENQOL scores and the Kupperman index to assess criterion-related validity. RESULTS: The most common symptoms in Chinese menopausal symptomatic women were "experiencing poor memory" (94.4%), "feeling tired or worn out" (93.8%), "aching in muscle and joints" (89.4%), "low backache" (86.9%), "decrease in physical strength" (86.6%), "aches in back of neck or head" (86.2%), "difficulty sleeping" (83.6%), "accomplishing less than I used to" (83.4%), "feeling a lack of energy" (83.3%), "change in your sexual desire" (81%), and "hot flash" (80.7%) among others. The symptoms of "increased facial hair" were rarely seen (9.9%). The vasomotor domain, as well as psychosocial, physical, and sexual domains showed high reliability (Cronbach's α 0.84, 0.87, 0.89, and 0.86, respectively). Item-domain correlation analysis showed that all items correlated more strongly with their own domains than with other domains. In the PCA, after deleting the "increased facial hair" item, items in the vasomotor, sexual, and psychosocial subscales loaded on their respective domains by and large, and items in the physical subscale divided into two factors. The PCA revealed a latent structure of the Chinese version of MENQOL nearly identical to the original MENQOL domains. The confirmatory factor analysis demonstrated that the questionnaire fits well with a four-domain model. The MENQOL can discriminate between menopausal symptomatic women with asymptomatic women as it showed good discriminate validity. Criterion-related validity was confirmed by a significant correlation between MENQOL scores and the Kupperman index. CONCLUSIONS: This study showed that Chinese version of MENQOL has good psychometric properties and would be suitable to measure the health-related quality-of-life of Chinese menopausal women except for item 21 (increased facial hair).

Identifying Distinct Healthcare Pathways During Episodes of Chronic Obstructive Pulmonary Disease Exacerbations.

Healthcare pathways are important to measure because they are expected to affect outcomes. However, they are challenging to define because patients exhibit heterogeneity in their use of healthcare services. The objective of this study was to identify and describe healthcare pathways during episodes of chronic obstructive pulmonary disease (COPD) exacerbations. Linked administrative databases from Saskatchewan, Canada were used to identify a cohort of newly diagnosed COPD patients and their episodes of healthcare use for disease exacerbations. Latent class analysis (LCA) was used to classify the cohort into homogeneous pathways using indicators of respiratory-related hospitalizations, emergency department (ED) visits, general and specialist physician visits, and outpatient prescription drug dispensations. Multinomial logistic regression models tested patients' demographic and disease characteristics associated with pathway group membership. The most frequent healthcare contact sequences in each pathway were described. Tests of mean costs across groups were conducted using a model-based approach with χ² statistics. LCA identified 3 distinct pathways for patients with hospital- (n = 963) and ED-initiated (n = 364) episodes. For the former, pathway group 1 members followed complex pathways in which multiple healthcare services were repeatedly used and incurred substantially higher costs than patients in the other pathway groups. For patients with an ED-initiated episode, pathway group 1 members also had higher costs than other groups. Pathway groups differed with respect to patient demographic and disease characteristics. A minority of patients were discharged from ED or hospital, but did not have any follow-up care during the remainder of their episode.Patients who followed complex pathways could benefit from case management interventions to streamline their journeys through the healthcare system. The minority of patients whose pathways were not consistent with recommended follow-up care should be further investigated to fully align COPD treatment in the province with recommended care practices.

An economic method to build a puffing instrument for drug application in vitro.

BACKGROUND: In in vitro electrophysiological studies, a quick application of picoliters of drug within milliseconds is required to avoid the desensitization of membrane receptors. However, conventional gravity-fed drug delivery devices sometime fail to achieve this. Moreover, the high financial cost of the advanced drug delivery system often limits the application of commercial instruments in academic research. NEW METHOD: Taking advantage of the availability of data acquisition system and software in almost every electrophysiology laboratory, a simple puffing device was designed and assembled using low-cost commercially off-the-shelf components to inject picoliter amounts of drugs. RESULTS: An optimal drug delivery with precise timing and volume was achieved using the custom made puffing device. The glutamate-evoked currents of cortical neurons recorded with patch-clamp technique were maintained for a prolonged period of time. Similarly, puffed inhibitory transmitters including GABA and glycine also produced satisfactory currents. COMPARISON WITH EXISTING METHOD(S): Our custom-made puffing system holds the advantage over conventional gravity-fed systems in operating within milliseconds of time. The channel number of the new device can easily be increased by simply adding more identical modules in parallel, and thus offering more flexibility than commercial puffing devices. CONCLUSIONS: This custom-made puffing device can be characterized as reliable, modular and inexpensive system for modern drug delivery research and application.

[Analysis of malaria situation in Quanzhou City, 1963-2012].

OBJECTIVE: To understand the situation of malaria in Quanzhou City for 50 years, so as to provide the evidence for eliminating malaria. METHODS: The data of epidemic situation of malaria and intermediary surveillance were collected and analyzed statistically from 1963 to 2012. RESULTS: The incidence of malaria has been periodically increased, but seasonal distribution was not obvious. The incidence in economically developed areas was significantly lower than that in the slow economic development areas. The patients were mainly young adults, and the careers were mainly the farmer, worker and migrant worker. The vivax malaria was the main type and the main vector was Anopheles minimus. The incidence of malaria has been less than 1/100,000 since 1997. From 2004, all of the patients were imported, mainly came from Africa and Southeast Asia. CONCLUSIONS: After more than 50 years' comprehensive prevention and treatment, the incidence of malaria has been maintained at a low level. We should strengthen the control and management of imported malaria, and consolidate the achievements in malaria prevention, so as to achieve the aim of malaria elimination.

Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis.

BACKGROUND: Cathepsin cysteine proteases play multiple roles in the life cycle of parasites such as food uptake, immune invasion and pathogenesis, making them valuable targets for diagnostic assays, vaccines and drugs. The purpose of this study was to identify a cathepsin B of Clonorchis sinensis (CsCB) and to investigate its diagnostic value for human helminthiases. RESULTS: The predicted amino acid sequence of the cathepsin B of C. sinensis shared 63%, 52%, 50% identity with that of Schistosoma japonicum, Homo sapiens and Fasciola hepatica, respectively. Sequence encoding proenzyme of CsCB was overexpressed in Escherichia coli. Reverse transcription PCR experiments revealed that CsCB transcribed in both adult worm and metacercaria of C. sinensis. CsCB was identified as a C. sinensis excretory/secretory product by immunoblot assay, which was consistent with immunohistochemical localization showing that CsCB was especially expressed in the intestine of C. sinensis adults. Both ELISA and western blotting analysis showed recombinant CsCB could react with human sera from clonorchiasis and other helminthiases. CONCLUSIONS: Our findings revealed that secreted CsCB may play an important role in the biology of C. sinensis and could be a diagnostic candidate for helminthiases.

[On clinical application and assessment of Menopause-Specific Quality of Life (Chinese Version)].

OBJECTIVE: To introduce Menopause-Specific Quality of Life (MENQOL) into China, and to evaluate the quality of its Chinese Version. METHODS: MENQOL was translated into Chinese language and the reverse translation was done by several specialists. After retest study on 30 cases, validity, reliability and responsiveness were implemented in 409 cases with menopause syndrome in the multicenter study. RESULTS: 7 components were extracted in factor analysis, and the total cumulative contribution was 59.476%. By correlation analysis, 7 components were divided into four domains: vasomotor, psychosocial, physical and sexual items, same as in the English Version. The test-retest reliability of four domains were 0.806, 0.804, 0.941, 0.940 respectively. Cronbach alpha of four domains were 0.7258, 0.8234, 0.8475, 0.8641 respectively. There had been significant changes after treatment noticed. CONCLUSION: The measurement properties of MENQOL-Chinese Version including effectueness, reliability were met with satisfaction and seemed to be adaptable to Chinese menopause women.