The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1ß, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-ß1 and p-ERK in a concentration-dependent manner, as well as TGF-ß1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC.

Fossil and Nonfossil Sources of Winter Organic Aerosols in the Regional Background Atmosphere of China.

Carbonaceous aerosols (CA) from anthropogenic emissions have been significantly reduced in urban China in recent years. However, the relative contributions of fossil and nonfossil sources to CA in rural and background regions of China remain unclear. In this study, the sources of different carbonaceous fractions in fine aerosols (PM2.5) from five background sites of the China Meteorological Administration Atmosphere Watch Network during the winter of 2019 and 2020 were quantified using radiocarbon (14C) and organic markers. The results showed that nonfossil sources contributed 44-69% to total carbon at these five background sites. Fossil fuel combustion was the predominant source of elemental carbon at all sites (73 ± 12%). Nonfossil sources dominated organic carbon (OC) in these background regions (61 ± 13%), with biomass burning or biogenic-derived secondary organic carbon (SOC) as the most important contributors. However, the relative fossil fuel source to OC in China (39 ± 13%) still exceeds those at other regional/background sites in Asia, Europe, and the USA. SOC dominated the fossil fuel-derived OC, highlighting the impact of regional transport from anthropogenic sources on background aerosol levels. It is therefore imperative to develop and implement aerosol reduction policies and technologies tailored to both the anthropogenic and biogenic emissions to mitigate the environmental and health risks of aerosol pollution across China.

Efficient degradation of imidacloprid by surface discharge cold plasma: Mechanism of interaction between ROS and molecular structure and evaluation of residual toxicity.

Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.

[Composition Characteristics and Sources of Non-polar Organic Compounds in PM2.5 in the Background Atmosphere of Yangtze River Delta].

In order to explore the composition and source characteristics of non-polar organic compounds (NPOCs) in atmospheric fine particulate matter in the Yangtze River Delta region, 129 PM2.5 samples were collected at the Regional Atmospheric background station in Lin'an from December 2019 to November 2020. Including polycyclic aromatic hydrocarbons (PAHs), n-alkanes, and hopanes, the main sources of organic aerosols were investigated using molecular tracers, eigen ratios, and orthogonal matrix factorization models. The results showed that the average annual mass concentration of PM2.5 in Lin'an was approximately (32.36±20.44) µg·m-3, and the average annual mass concentration of NPOCs was approximately (59.05±40.39) ng·m-3, showing the seasonal characteristics of being high in winter and low in summer. n-alkanes mainly came from fossil fuels and biomass (grass, wood, etc.) burning, followed by cuticle wax emission from higher plants. PAHs mainly came from the mixed contribution of non-fossil sources such as coal burning motor vehicle emissions and biomass combustion. Hopanes were mainly derived from motor vehicle emissions, which were also affected by coal burning in winter. Backward trajectory cluster analysis and potential source analysis showed that Lin'an was mainly affected by external air mass transport. Combined with the orthogonal matrix-factor decomposition model, NPOCs observed during the sampling period were analyzed, and non-fossil sources such as coal burning sources, transportation emission sources, and biomass combustion were obtained. In winter, transportation sources were the main source, accounting for 59%. In spring and summer, coal burning was the main source, accounting for 58% and 57%, respectively. In autumn, biomass combustion and other non-fossil sources dominated, accounting for 64%.

Sociodemographic Factors Associated with Dietary Intake of Thiamine, Riboflavin, and Niacin among Chinese Adults in 2015.

OBJECTIVE: To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China. METHODS: We derived our data from the China Health and Nutrition Survey (CHNS) among 12,241 individuals aged 18-64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins. RESULTS: Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city. CONCLUSION: We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Well-tailored strategies and policies are needed to improve nutritional status in China.

Secular trends in sedentary behaviors and associations with weight indicators among Chinese reproductive-age women from 2004 to 2015: findings from the China Health and Nutrition Survey.

BACKGROUND: Overweight and obesity are rising among Chinese reproductive-age women, while some studies have focused on the relationship between sedentary behavior and obesity in certain populations, none has focused on Chinese reproductive-age women specifically. This study examined secular trends in leisure time sedentary behaviors (watching television time, computer time and reading time, and the total sedentary time) among Chinese reproductive-age women and the association of those behaviors with five weight indicators-body mass index (BMI), waist circumference (WC) and overweight, obesity, and abdominal obesity status. METHODS: A prospective cohort study was conducted with Chinese reproductive-age women aged 15-49 who had participated in two or more rounds of the China Health and Nutrition Survey (CHNS), and completed the questionnaire and anthropometric measurements. The exposure variables were the average weekly time spent on three leisure time sedentary behaviors (watching television, using computer, and reading) and the total sedentary time (the sum of the above three sedentary time and video game time). Mixed-effect linear models were produced to explore the secular trends of the mean hours of these sedentary behaviors and the total sedentary time after adjusting covariates. Models were also produced to study the effects of these types of sedentary behavior levels on BMI and WC. Mixed-effect logistic regression models were produced to study the effects of the sedentary behavior levels on overweight, obesity, and abdominal obesity status. RESULTS: The total sedentary time among the reproductive-age women increased over time across most of age, region, educational levels, and income groups from 2004 to 2015. Television hours fluctuated, it increased and then declined over time across most of age, region, and income groups. Computer hours continually increased over time across all age, region, educational level, and income groups. Reading hours gradually decreased over time across most of age, region, educational level, and income groups. Those with a moderate level of television time (14 to <35 h/week) had 1.08 cm larger WCs and were 1.31 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Those with a high level of television time (≥35 h/week) had 1.74 cm larger WCs, 0.66 kg/m2 larger BMIs, were 1.50 times more likely to be overweight and were 1.47 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Greater computer, reading time, and total sedentary time were not associated with WC, BMI, overweight, obesity, or abdominal obesity. CONCLUSIONS: These findings showed that among Chinese reproductive-age women ages 15-49, secular trends of computer time increased rapidly, reading time decreased gradually and television time fluctuated but showed not much difference from 2004 to 2015. The sharp increase in computer time far outweighed the decline in reading time. As a result, the overall sedentary behavior time of Chinese reproductive-age women gradually increased. These findings provided strong evidence that greater television time was significantly associated with higher BMI, WC, and higher risks of overweight, abdominal obesity among Chinese reproductive-age women. Computer, reading, and the total sedentary time were not associated with those weight indicators.

Antithermal Quenching of Luminescence in Zero-Dimensional Hybrid Metal Halide Solids.

Zero-dimensional (0D) hybrid metal halides have emerged as a new generation of luminescent phosphors owing to their high radiative recombination rates, which, akin to their three-dimensional cousins, commonly demonstrate thermal quenching of luminescence. Here, we report on the finding of antithermal quenching of luminescence in 0D hybrid metal halides. Using (C9NH20)2SnBr4 single crystals as an example system, we show that 0D metal halides can demonstrate antithermal quenching of luminescence. A combination of experimental characterizations and first-principles calculations suggests that antithermal quenching of luminescence is associated with trap states introduced by structural defects in (C9NH20)2SnBr4. Importantly, we find that antithermal quenching of luminescence is not only limited to (C9NH20)2SnBr4 but also exists in other 0D metal halides. Our work highlights the important role of defects in impacting photophysical properties of hybrid metal halides and may stimulate new efforts to explore metal halides exhibiting antithermal quenching of luminescence at higher temperatures.

Association of Red Meat Usual Intake with Serum Ferritin and the Risk of Metabolic Syndrome in Chinese Adults: A Longitudinal Study from the China Health and Nutrition Survey.

OBJECTIVE: The present study aimed to investigate the association of red meat usual intake with metabolic syndrome (MetS), and explore the contribution of red meat usual intake to serum ferritin. METHODS: Based on the data from the longitudinal China Health and Nutrition Survey (CHNS), 2,797 healthy adults aged 18-75 years without hypertension, diabetes, and MetS were selected in 2009 as subjects and follow-up studies were carried out till 2015. We used the National Cancer Institute (NCI) method to estimate the usual intake of foods. Multivariable logistic regressions were performed to evaluate the association between red meat usual intake and the risk of MetS. Quantile regression analysis was used to study the relationship between red meat consumption and serum ferritin levels. RESULTS: After adjusting for potential confounders, red meat, and fresh red meat were positively associated with the risk of MetS ( RR = 1.41, 95% CI: 1.05-1.90 and RR = 1.37, 95% CI: 1.02-1.85, respectively). These relationships showed increasing trend ( P < 0.05). The level of serum ferritin increased significantly with the number of MetS components ( P < 0.05). The quantile regression analysis showed that red meat and fresh red meat usual intake had a significant positive association with serum ferritin levels across the entire conditional serum ferritin distribution ( P < 0.05). Processed red meat did not exhibit a similar association. CONCLUSION: Higher red meat usual intake was associated with an increased risk of MetS and elevated serum ferritin levels.

Defective [Bi2 O2 ]2+ Layers Exhibiting Ultrabroad Near-Infrared Luminescence.

Aurivillius phases have been routinely known as excellent ferroelectrics and have rarely been deemed as materials that luminesce in the near-infrared (NIR) region. Herein, it is shown that the Aurivillius phases can demonstrate broadband NIR luminescence that covers telecommunication and biological optical windows. Experimental characterization of the model system Bi2.14 Sr0.75 Ta2 O9-x , combined with theoretical calculations, help to establish that the NIR luminescence originates from defective [Bi2 O2 ]2+ layers. Importantly, the generality of this finding is validated based on observations of a rich bank of NIR luminescence characteristics in other Aurivillius phases. This work highlights that incorporating defects into infinitely repeating [Bi2 O2 ]2+ layers can be used as a powerful tool to space-selectively impart unusual luminescence emitters to Aurivillius-phase ferroelectrics, which not only offers an optical probe for the examination of defect states in ferroelectrics, but also provides possibilities for coupling of the ferroelectric property with NIR luminescence.

Population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV.

Lopinavir (LPV) is a protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infections. Current studies on LPV are mainly focused on Caucasians, and none have investigated the population pharmacokinetics (PPK) of LPV in Chinese population. The present study aimed to develop a PPK model for oral LPV in Chinese adults who are HIV-infected. A total of 460 LPV concentrations from 174 Chinese patients who received LPV/ritonavir (LPV/r) 400/100 mg orally every 12 hours (q12h) were analysed using the non-linear mixed-effects modelling approach. Simulations of the LPV concentration profile were performed with different dosing regimens. A one-compartment model with first-order absorption and elimination process described the data. The estimated apparent clearance (CL/F) and volume of distribution (V/F) (% relative standard error [RSE]) for oral LPV were 5.9 L/h (3%) and 117 L (8%), respectively. Body-weight was identified as a covariate on CL/F. In patients who weighed between 45 and 115 kg and received the standard 400/100 mg q12h regimen, the probability of achieving target trough concentration (Ctrough ) of 1 mg/L was >98% for PI-naïve patients and the probability of achieving target Ctrough of 4 mg/L was <80% for PI-pretreated patients. This is the first population pharmacokinetic study to characterise the PK of LPV in Chinese patients with HIV infection. There were no obvious ethnic differences in the PK of LPV between the Chinese population and Caucasian population. The simulations demonstrated that the standard dosing regimen of 400/100 mg q12h (LPV/r tablets) appears to be sufficient for PI-naïve patients but suboptimal for PI-pretreated patients. Therefore, the regimen of 800/200 mg q12h was recommended for PI-pretreated patients. Further investigation of dosage recommendation could be helpful in optimising LPV therapy for HIV infections.

Dietary Zinc Intake and Its Association with Metabolic Syndrome Indicators among Chinese Adults: An Analysis of the China Nutritional Transition Cohort Survey 2015.

The dietary zinc consumed in Chinese households has decreased over the past decade. However, the national dietary zinc intake in the last five years has seldom been investigated. Using data from 12,028 participants 18 to 64 years old (52.9% male) in the China Nutritional Transition Cohort Survey (CNTCS) 2015, we describe the intake of dietary zinc and the contributions of major foods and we examine the relationship between the level of dietary zinc intake and metabolic syndrome indicators, including blood pressure, fasting glucose, and triglycerides (TG), in Chinese adults. We assessed dietary zinc intake using 24 h recalls on three consecutive days. The mean daily dietary zinc intake for all participants was 10.2 milligrams per day (males 11.2 mg/day, females 9.4 mg/day, p < 0.001). The mean daily dietary zinc density for all participants was 5.2 mg/day per 1000 kilocalories. Among all participants, 31.0% were at risk of zinc deficiency, with dietary zinc intakes of less than the Estimated Average Requirement (EAR) (males 49.2%, females 14.8%, p < 0.050), and 49.9% had adequate dietary zinc intakes, equal to or greater than the recommended nutrient intake (RNI) (males 30.7%, females 67.0%, p < 0.050). We found substantial gender differences in dietary zinc intake and zinc deficiency, with nearly half of the men at risk of zinc deficiency. Males of younger age, with higher education and incomes, and who consumed higher levels of meat, had higher zinc intakes, higher zinc intake densities, and higher rates of meeting the EAR. Among all participants, grains, livestock meat, fresh vegetables, legumes, and seafood were the top five food sources of zinc, and their contributions to total dietary zinc intake were 39.5%, 17.3%, 8.9%, 6.4%, and 4.8%, respectively. The groups with relatively better dietary zinc intakes consumed lower proportions of grains and higher proportions of livestock meat. For males with adequate dietary zinc intake (≥RNI), TG levels increased by 0.219 millimoles per liter (mmol/L) compared with males with deficient dietary zinc intake (

Gender difference in the association between food away-from-home consumption and body weight outcomes among Chinese adults.

OBJECTIVE: The present study aimed to explore the associations between food away-from-home (FAFH) consumption and body weight outcomes among Chinese adults. DESIGN: FAFH was defined as food prepared at restaurants and the percentage of energy from FAFH was calculated. Measured BMI and waist circumference (WC) were used as body weight outcomes. Quantile regression models for BMI and WC were performed separately by gender. SETTING: Information on demographic, socio-economic, diet and health parameters at individual, household and community levels was collected in twelve provinces of China. SUBJECTS: A cross-sectional sample of 7738 non-pregnant individuals aged 18-60 years from the China Health and Nutrition Survey 2011 was analysed. RESULTS: For males, quantile regression models showed that percentage of energy from FAFH was associated with an increase in BMI of 0·01, 0·01, 0·01, 0·02, 0·02 and 0·03 kg/m2 at the 5th, 25th, 50th, 75th, 90th and 95th quantile, and an increase in WC of 0·04, 0·06, 0·06, 0·04, 0·06, 0·05 and 0·07 cm at the 5th, 10th, 25th, 50th, 75th, 90th and 95th quantile. For females, percentage of energy from FAFH was associated with 0·01, 0·01, 0·01 and 0·02 kg/m2 increase in BMI at the 10th, 25th, 90th and 95th quantile, and with 0·05, 0·04, 0·03 and 0·03 cm increase in WC at the 5th, 10th, 25th and 75th quantile. CONCLUSIONS: Our findings suggest that FAFH consumption is relatively more important for BMI and WC among males rather than females in China. Public health initiatives are needed to encourage Chinese adults to make healthy food choices when eating out.

Epidemics of overweight and obesity among growing childhood in China between 1997 and 2009: Impact of Family Income, Dietary Intake, and Physical Activity Dynamics.

BACKGROUND: Obesity has become a major health problem among children and adolescents worldwide. This study aimed to examine the trends of overweight and obesity among childhood in China and assess their associations with family income, dietary intake, and physical activity (PA) between 1997 and 2009. METHODS: Two waves of cross-sectional data of Chinese children and adolescents aged 7-17 years from the China Health and Nutrition Survey were used. Weight and height were measured following standardized procedures. Dietary intake was assessed by 3 consecutive 24-h recalls. Childhood overweight and obesity were defined using the International Obesity Task Force-recommended body mass index cut-offs. Multivariate linear regression analysis was used to examine the associations of family income with diet intakes and PA. Multivariate logistic regression analysis was conducted to assess the associations of overweight and obesity with family income, dietary intake, and PA. RESULTS: The prevalence of childhood overweight and obesity increased from 12.6% in 1997 to 22.1% in 2009, particularly in the medium- and high-family income groups, which increased by 102.7% and 90.3%, respectively. Higher fat intake (% energy), and moderate and vigorous PA were significantly associated with overweight and obesity in final model (odds ratio [OR] = 1.01, 95% confidence interval [CI]: 1.00-1.02, P = 0.004; and OR = 0.99, 95% CI: 0.98-1.00, P = 0.036, respectively). CONCLUSIONS: The prevalence of overweight and obesity among Chinese children and adolescents has increased between 1997 and 2009. Reducing fat intake and increasing PA may help obesity prevention.

[Proteomic analysis of peripheral blood mononuclear cells to identify potential markers of fibrosis in chronic hepatitis B].

OBJECTIVE: To identify non-invasive biomarkers for diagnosis and/or prognosis of liver fibrosis in chronic hepatitis B (CHB). METHODS: Peripheral blood samples were obtained from 48 patients with CHB, including 24 with mild fibrosis (stage 1, S1) and 24 with severe fibrosis (stage 4, S4), and subjected to Ficoll density gradient centrifugation in order to obtain enriched samples of peripheral blood mononuclear cells (PBMCs).The PBMC proteomes of the two groups were assessed by first separating the total proteins by two-dimensional gel electrophoresis (2DE) and then identifying the differentially expressed proteins by liquid chromatography combined with tandem mass spectrometry (LCMS/MS). RESULTS: The enriched PBMC samples from the S1 group and the S4 group had similar amounts of platelets [(19.268+/- 6.413) * 109/L and(19.480+/- 6.538) * 109/L, respectively); however, for both, the platelet amounts were 5 to 15-fold lower than that of the normal reference (100-300 *109/L). There was no significant difference found between the platelet amounts in the S1 patients and healthy controls (P=0.930). Twelve differentially expressed proteins were identified through 2DE-LC-MS/MS, including proteins such as moesin and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 that are involved in various biological processes like cell movement, cell adhesion, kinase signaling and transcription. CONCLUSION: s The 12 proteins with differential expression in S1 and S4 patients with CHB and liver fibrosis may represent markers related to development and/or progression of liver fibrosis.

[Proteomic study on effect of tangcao pill on microsome CYP450].

Tangcao pill is commonly applied in adjuvant and even alternative therapy for patients with AIDS. However, the herb contains complex ingredients, but with unknown effect against anti-HIV drug and unknown function. Because CYP450 emzyme is the main metabolic enzymes of the drug, it is of important significance to study the regulation of CYP450 enzymes before and after the combined administration of Tangcao pill and EFV. Proteomics, due to its high throughout and high sensitivity, has been widely applied in CYP450 enzyme study. In this paper, liver microsomes were separated through differential centrifugation. Their proteins were separated through SDS-PAGE. The three protein bands that CYP450 enzymes were located were cut and identified by liquid chromatography tandem mass spectrometry. Totally 16 CYP450 isoenzymes were identified. Furthermore, in order to make a quantitative analysis on the effect of tang herb on CYP450 emzyme, the multiple reaction monitoring (MRM) technology based on MS was adopted. The CYP2C11 was selected based on the results of the mass spectrum identification of proteins. The characteristic polypeptides were obtained through searching Expasy blast database. The m/z of the fragment ions was less than 800. In the paper, the m/z of ion pairs of CYP2C11 were 711.5/232.1, 711.5/319.2, 711.5/466.2 and 711.5/595.3, and the m/z of ESAT-6 (internal standard, IS) were 735.5/215.3, 735.5/389.3, 735.5/460.3 and 735.5/524.3. The relative peak (analyte/IS) area was adopted for the relative quantitative analysis. Compared with the EFV single administration group, the EFV and Tangcao pill combined administration group showed a 1.6-fold increase in CYP2C11. The results of the paper indicated that Tangcao pill may affect drug metabolism by regulating metabolic enzymes such as CYP2C11, but the specific mechanism still unknown.

Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B.

BACKGROUND AND AIM: Due to known limitations of liver biopsy, reliable non-invasive serum biomarkers for chronic liver diseases are needed. We performed serum peptidomics for such investigation in compensated chronic hepatitis B (CHB) patients. METHODS: Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed peptides in sera from 40 CHB patients (20 with S0G0-S1G1 and 20 with S3G3-S4G4). Ion pair quantification from differentially expressed peptides in a validation set of sera from 86 CHB patients was done with multiple reaction monitoring (MRM). RESULTS: 21 differentially represented peptide peaks were found through LC-MS/MS. Ion pairs generated from eleven of these peptides (m/z < 800) were quantified by MRM. Summed peak area ratios of 6 ion pairs from peptide m/z 520.3 (176.1, 353.7, 459.8, 503.3, 351.3, 593.1), which was identified as dihydroxyacetone kinase (DAK) fragment, decreased from mild to advanced stages of fibrosis or inflammation. Area Under Receiver Operating Characteristic Curves (AUROCs) of five ion models discriminating fibrosis degrees were 0.871 ~ 0.915 (S2-4 versus S0-1) and 0.804 ~ 0.924 (S3-4 versus S0-2). AUROCs discriminating inflammation grades were 0.840 ~ 0.902 (G2-4 versus G0-1) and 0.787 ~ 0.888 (G3-4 versus G0-2). The diagnostic power of these models provides improved sensitivity and specificity for predicting disease progression as compared to aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Forn's index and serum DAK protein. CONCLUSIONS: The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated CHB patients.

[Effects of maternal exposure to nano-alumina during pregnancy on neurodevelopment in offspring mice].

OBJECTIVE: To observe the effects of maternal exposure to nano-alumina during pregnancy on the neurodevelopment in offspring mice. METHODS: Female ICR mice began to be exposed to nano-alumina 10 d before mating, and the nano-alumina exposure lasted till offspring mice were born. All the female mice were randomly divided into 5 groups: solvent control group (saline), nano-carbon group (11.76 mg/ml), micro-alumina group (50 mg/ml), 50 nm alumina group (50 mg/ml), and 13 nm alumina group (50 mg/ml). All the mice were treated by nasal drip (10 µl/time) 3 times daily till offspring mice were born. Physiological indices, reflex and sensory function test, endurance test, Morris water maze test, positioning and navigation test, and open field test were used to evaluate the neurodevelopment of newborn mice. RESULTS: On day 28, the body weight of 13 nm alumina group (16.73±4.04 g) was significantly lower than that of solvent control group (20.45±2.50 g) (P<0.01); the 13 nm alumina group had significantly delayed time to ear opening compared with the solvent control group (4.91±0.78 d vs 4.45±0.50 d, P<0.01); compared with the solvent control group, the nano-carbon group, micro-alumina group, 50 nm alumina group, and 13 nm alumina group had significantly delayed time to eruption of teeth (10.05±0.23 d vs 10.32±0.48 d, 10.75±0.45 d, 10.32±0.47 d, and 10.79±0.49 d, P<0.05 or P<0.01). On days 4 and 7 after birth, compared with the solvent control group, other groups had significantly decreased proportions of mice which passed the cliff avoidance test (P < 0.05 or P < 0.01). On days 12 and 14 after birth, compared with the solvent control group, the nano-carbon group, 50 nm alumina group, and 13 nm alumina group had significantly reduced pre-suspension time in the endurance test (P < 0.05 or P < 0.01). The Morris water maze and positioning and navigation tests showed that the 13 nm alumina group had a significantly increased 5 d incubation period compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of platform crossings (P < 0.05 or P < 0.01). The open field test showed that the nano-carbon group and 13 nm alumina group had reduced numbers of rearings compared with the solvent control group (P < 0.05); compared with the solvent control group, other groups had significantly reduced numbers of modifications (P < 0.01). CONCLUSION: Maternal exposure to nano-alumina (13 nm) during pregnancy has inhibitory effects on the physical development and early behavioral development in newborn mice and can also inhibit the learning and memory abilities and adaptability to new environment in offspring mice. The neurodevelopmental toxicity of nano-alumina to newborn mice increases as the particle sizes of nano-alumina decrease, which has been demonstrated by the endurance test and number of rearings.

Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B.

BACKGROUND AND AIM: Because of the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are needed. The aim of this study was to identify such markers by the use of serum proteomics in chronic hepatitis B (CHB). METHODS: Two-dimensional gel electrophoresis (2-DE) was used to identify differentially expressed protein spots in sera from 40 CHB patients [20 with mild fibrosis (S0-S1) and 20 with severe fibrosis (S3-S4)]. Mass spectrometry (MS) based multiple reaction monitoring (MRM) was used to quantify peptide ions of differential protein spots in another set of sera from 86 CHB patients with different liver fibrosis (S0-S4). RESULTS: Seven differentially expressed protein spots were found by 2-DE. Fourteen peptide ions of seven target protein spots were quantified by MS-based MRM. Summed peak areas ratio (SPAR) values of peptide ions from protein spot 1, 4 and 8, identified as apo serum transferrin, complement component C3c and transferrin, were significantly different from non-fibrosis (S0) to fibrosis stage 4. AUROCs of models established by peptide ions (protein spot 1, 4, 8) and model consisting of a combination of all ions were 0.848∼0.966 (S2-S4 versus S0-S1) and 0.785∼0.875 (S3-S4 versus S0-S2). Only the peptide ions model of transferrin had better sensitivity and specificity for predicting fibrosis stages than did aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forn's index. CONCLUSIONS: Serum peptide ions of transferrin, detected by proteomic MRM, are new and promising biomarkers for staging liver fibrosis in CHB patients.

[Plasma proteome analysis of chronic hepatitis B patients with different stages of liver fibrosis].

OBJECTIVE: To identify plasma biomarkers with specific relation to the various liver fibrosis stages that can be used to assess hepatitis B virus (HBV)-infected patients for non-invasive liver fibrosis and to evaluate the prognosis of the liver fibrosis. METHODS: Plasma samples were collected from 80 HBV-positive patients at the Hepatitis Department of Shanghai Public Health Clinical Center between September 2008 and January 2011. The samples were grouped according to the patient's stage of hepatic fibrosis determined by liver biopsy: S0-1 (n = 40), S2-3 (n = 20), and S4 (n = 20). Each plasma sample was processed to remove the two most abundant proteins, albumin and immunoglobulin G (IgG), and then resolved by two-dimensional (2D) electrophoresis. ImageMaster 2D analysis software was used to identify differentially expressed proteins related to the liver fibrosis stages. After trypsin digestion, the differential proteins were identified by online reversed-phase nano-flow liquid chromatography coupled with electrospray ionization ion trap mass spectrometry (MS). RESULTS: The patients in the three groups were not significantly different in age (range: 30-50 years; P = 0.053) or sex (x² = 0.155, P = 0.926). Low-abundance proteins were efficiently enriched by the albumin/IgG depletion method. Fourteen differentially expressed proteins were detected among the S0-1, S2-3 and S4 groups, all of which were identified by tandem MS and included fibrinogen gamma chain, haptoglobin, complement C3, Ig kappa chain C region, and apolipoprotein A-I. CONCLUSION: Plasma proteomic analysis of chronic hepatitis B patients identified a panel of differentially expressed proteins related to different stages of liver fibrosis. These proteins may represent diagnostic and prognostic biomarkers of HBV-related hepatic fibrosis.

Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice.

The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 µmol/kg/day) or cis-permethrin (90 µmol/kg/day) alone or in combination (100 µmol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.