BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder.

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Resolving and Predicting Neighborhood Vulnerability to Urban Heat and Air Pollution: Insights From a Pilot Project of Community Science.

Urban heat and air pollution, two environmental threats to urban residents, are studied via a community science project in Los Angeles, CA, USA. The data collected, for the first time, by community members, reveal the significance of both the large spatiotemporal variations of and the covariations between 2 m air temperature (2mT) and ozone (O3) concentration within the (4 km) neighborhood scale. This neighborhood variation was not exhibited in either daily satellite observations or operational model predictions, which makes the assessment of community health risks a challenge. Overall, the 2mT is much better predicted than O3 by the weather and research forecast model with atmospheric chemistry (WRF-Chem). For O3, diurnal variation is better predicted by WRF-Chem than spatial variation (i.e., underestimated by 50%). However, both WRF-chem and the surface observation show the overall consistency in describing statistically significant covariations between O3 and 2mT. In contrast, satellite-based land surface temperature at 1 km resolution is insufficient to capture air temperature variations at the neighborhood scale. Community engagement is augmented with interactive maps and apps that show the predictions in near real time and reveals the potential of green canopy to reduce air temperature and ozone; but different tree types and sizes may lead to different impacts on air temperature, which is not resolved by the WRF-Chem. These findings highlight the need for community science engagement to reveal otherwise impossible insights for models, observations, and real-time dissemination to understand, predict, and ultimately mitigate, urban neighborhood vulnerability to heat and air pollution.

Improving surface PM2.5 forecasts in the United States using an ensemble of chemical transport model outputs: 2. bias correction with satellite data for rural areas.

This work serves as the second of a two-part study to improve surface PM2.5 forecasts in the continental U.S. through the integrated use of multi-satellite aerosol optical depth (AOD) products (MODIS Terra/Aqua and VIIRS DT/DB), multi chemical transport model (CTM) (GEOS-Chem, WRF-Chem and CMAQ) outputs and ground observations. In part I of the study, a multi-model ensemble Kalman filter (KF) technique using three CTM outputs and ground observations was developed to correct forecast bias and generate a single best forecast of PM2.5 for next day over non-rural areas that have surface PM2.5 measurements in the proximity of 125 km. Here, with AOD data, we extended the bias correction into rural areas where the closest air quality monitoring station is at least 125 - 300 km away. First, we ensembled all of satellite AOD products to yield the single best AOD. Second, we corrected daily PM2.5 in rural areas from multiple models through the AOD spatial pattern between these areas and non-rural areas, referred to as "extended ground truth" or EGT, for today. Lastly, we applied the KF technique to update the bias in the forecast for next day using the EGT. Our results find that the ensemble of bias-corrected daily PM2.5 from three models for both today and next day show the best performance. Together, the two-part study develops a multi-model and multi-AOD bias correction technique that has the potential to improve PM2.5 forecasts in both rural and non-rural areas in near real time, and be readily implemented at state levels.

Tubgcp3 is a mitotic regulator of planarian epidermal differentiation.

Tubgcp3/GCP3 (The centrosomal protein γ-tubulin complex protein 3) is a component of the γ-tubulin small complexes (γ-TuSCs) and γ-tubulin ring complexes (γ-TuRCs), which play critical roles in mitotic spindle formation during mitosis. However, its function in stem cell development has not been thoroughly elucidated. The planarian flatworm, which contains a large number of adult somatic stem cells (neoblasts), is a unique model to study stem cell lineage development in vivo. Here, we identified a homolog of Tubgcp3 in planarian Dugesia japonica, and found that Tubgcp3 is required for the maintenance of epidermal lineage. RNAi targeting Tubgcp3 resulted in tissue homeostasis and regeneration defect. Knockdown of Tubgcp3 reduced cell divisions and led to a loss of the mature epidermal cells. Our findings indicate that Tubgcp3 is a mitotic regulator and plays a crucial role in planarian epidermal differentiation.

Improving Surface PM2.5 Forecasts in the United States Using an Ensemble of Chemical Transport Model Outputs: 1. Bias Correction With Surface Observations in Nonrural Areas.

This work is the first of a two-part study that aims to develop a computationally efficient bias correction framework to improve surface PM2.5 forecasts in the United States. Here, an ensemble-based Kalman filter (KF) technique is developed primarily for nonrural areas with approximately 500 surface observation sites for PM2.5 and applied to three (GEOS-Chem, WRF-Chem, and WRF-CMAQ) chemical transport model (CTM) hindcast outputs for June 2012. While all CTMs underestimate daily surface PM2.5 mass concentration by 20-50%, KF correction is effective for improving each CTM forecast. Subsequently, two ensemble methods are formulated: (1) the arithmetic mean ensemble (AME) that equally weights each model and (2) the optimized ensemble (OPE) that calculates the individual model weights by minimizing the least-square errors. While the OPE shows superior performance than the AME, the combination of either the AME or the OPE with a KF performs better than the OPE alone, indicating the effectiveness of the KF technique. Overall, the combination of a KF with the OPE shows the best results. Lastly, the Successive Correction Method (SCM) was applied to spread the bias correction from model grids with surface PM2.5 observations to the grids lacking ground observations by using a radius of influence of 125 km derived from surface observations, which further improves the forecast of surface PM2.5 at the national scale. Our findings provide the foundation for the second part of this study that uses satellite-based aerosol optical depth (AOD) products to further improve the forecast of surface PM2.5 in rural areas by performing statistical analysis of model output.

A molecular perspective for global modeling of upper atmospheric NH3 from freezing clouds.

Ammonia plays a key role in the neutralization of atmospheric acids such as sulfate and nitrates. A few in situ observations have supported the theory that gas-phase NH3 concentrations should decrease sharply with altitude and be extremely low in the upper troposphere and lower stratosphere (UTLS). This theory, however, seems inconsistent with recent satellite measurements and is also not supported by the aircraft data showing highly or fully neutralized sulfate aerosol particles by ammonium in the UTLS in many parts of the world. Here we reveal the contributions of deep convective clouds to NH3 in the UTLS by using integrated cross-scale modeling, which includes molecular dynamic simulations, a global chemistry transport model, and satellite and aircraft measurements. We show that the NH3 dissolved in liquid cloud droplets is prone to being released into the UTLS upon freezing during deep convection. Because NH3 emission is not regulated in most countries and its future increase is likely persistent from agricultural growth and the warmer climate, the effect of NH3 on composition and phase of aerosol particles in the UTLS can be significant, which in turn can affect cirrus cloud formation, radiation, and the budgets of NOx and O3.

Comparison of the life-history parameters and competition outcome with Moina macrocopa between two morphs of Brachionus forficula.

In rotifers, the costs of morphological defenses, especially the development of long spines, have been investigated for several decades. However, the obtained results were inconsistent and the underlying reasons were complicated. Investigations on more species might be helpful to find out the reasons. In the present study, Brachionus forficula was selected as the model organism. The differences in developmental durations, life-table demography, starvation resistant time and the competitive ability with Moina macrocopa were compared between B. forficula with long (LPS) and short (SPS) posterior spines. The results showed that LPS showed relatively longer durations of juvenile stage at 1.0 × 106, 2.0 × 106 and 4.0 × 106 cells/ml Scenedesmus obliquus, and longer embryo stage at 2.0 × 106 cells/ml S. obliquus than SPS. The intrinsic rate of population increase and net reproduction rate were lower in LPS than SPS, suggesting the energy input to reproduction decreased. The starvation resistant time was also reduced in LPS, in comparison to SPS, further supporting that LPS consumed more energy, which might be directed to the development of long spines. All these results revealed that LPS spent more energy for individual growth than SPS, which might be used to develop long spines. Moreover, the maximum population density and population growth rate of LPS were always lower than those of SPS, suggesting that LPS might have a weaker competition ability with M. macrocope than SPS.

Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia / 中国医学科学院学报

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.

LncRNA-LINC00152 down-regulated by miR-376c-3p restricts viability and promotes apoptosis of colorectal cancer cells.

Recent studies have demonstrated that the crucial regulatory roles of long noncoding RNAs (lncRNAs) in tumorigenesis. Expression levels of several lncRNAs are abnormally up-regulated or down-regulated and play a primary role in colorectal cancer (CRC) cell tumorigenesis. However, the potential role and regulatory mechanisms of the novel human lncRNA, LINC00152, in CRC cells are poorly understood. Here, we found that LINC00152 expression was significantly decreased in CRC tissues and CRC cell lines, and this change was more frequent in patients with advanced stage (tumor-node-metastasisi (TNM) III and IV). Overexpression of LINC00152 (LINC000152over) resulted in decreased cell viability and increased apoptosis in CSC cell lines (HT-29 and SW480). Furthermore, decreased Ki-67 and B-cell lymphoma-2 (Bcl-2), and increased Fas, were observed in CSC cells. However, a change in Bax expression was undetected. Interestingly, microRNA (miR)-376c-3p down-regulated the expression of LINC00152 in CSC cells. Overexpression of miR-376c-3p (miR-376c-3pover) enhanced viability and limited apoptosis of CSC cells. In addition, miR-376c-3pover suppressed the effect of LINC00152over on the viability and apoptosis of CSC cells. Taken together, these data indicate that LINC00152 in CSC cells negatively regulated by miR-376c-3p, restricts cell viability and stimulates cell apoptosis, possibly by modulating the expression of Ki-67, Bcl-2, and Fas. MiR-376c-3p/LINC00152 plays an important role in the pathogenesis of CRC and may serve as a potential target for its diagnosis and treatment.

Inhibition of Nonsmall Cell Lung Cancer Cell Migration by Protein Arginine Methyltransferase 1-small Hairpin RNA Through Inhibiting Epithelial-mesenchymal Transition, Extracellular Matrix Degradation, and Src Phosphorylation In Vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Protein arginine methyltransferases 1 (PRMT1) is over-expressed in a variety of cancers, including lung cancer, and is correlated with a poor prognosis of tumor development. This study aimed to investigate the role of PRMT1 in nonsmall cell lung cancer (NSCLC) migration in vitro.</p><p><b>METHODS</b>In this study, PRMT1 expression in the NSCLC cell line A549 was silenced using lentiviral vector-mediated short hairpin RNAs. Cell migration was measured using both scratch wound healing and transwell cell migration assays. The mRNA expression levels of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1, 2 (TIMP1, 2) were measured using quantitative real-time reverse transcription-polymerase chain reaction. The expression levels of protein markers for epithelial-mesenchymal transition (EMT) (E-cadherin, N-cadherin), focal adhesion kinase (FAK), Src, AKT, and their corresponding phosphorylated states were detected by Western blot.</p><p><b>RESULTS</b>Cell migration was significantly inhibited in the PRMT1 silenced group compared to the control group. The mRNA expression of MMP-2 decreased while TIMP1 and TIMP2 increased significantly. E-cadherin mRNA expression also increased while N-cadherin decreased. Only phosphorylated Src levels decreased in the silenced group while FAK or AKT remained unchanged.</p><p><b>CONCLUSIONS</b>PRMT1-small hairpin RNA inhibits the migration abilities of NSCLC A549 cells by inhibiting EMT, extracellular matrix degradation, and Src phosphorylation in vitro.</p>

PRDM14 promotes the migration of human non-small cell lung cancer through extracellular matrix degradation in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As a novel molecular markerof non-small cell lung cancer (NSCLC), PRDI-BF1 and RIZ homology domain containing protein 14 (PRDM14) is over-expressed in NSCLC tumor tissues. Extracellular matrix degradation mediated by the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) is one of the most important mechanism in lung cancer metastasis. This study aimed to determine if PRDM14 promoted the migration of NSCLC cells through extracellular matrix degradation mediated by change of MMP/TIMP expression.</p><p><b>METHODS</b>The expression of PRDM14 was down-regulated in human cell line A 549 after transfection with lentiviral vector-mediated short-hairpin ribonucleic acids (shRNAs) which targeted the PRDM14 promoter. Cellular migration of shRNA-infected cells was detected by a scratch wound healing assay and transwell cell migration assay. Expression levels of MMP1, MMP2, TIMP1, and TIMP2 were measured by quantitative real-time polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Migration of PRDM14-shRNA-infected cells was significantly inhibited relative to control cells as measured by the scratch wound healing (P < 0.05) and transwell cell migration assays (P < 0.01). The expression of MMP1 in A549 cells infected by PRDM14-shRNA was down-regulated significantly (P < 0.01), whereas the expression of TIMP1 and TIMP2 was up-regulated significantly (P < 0.01).</p><p><b>CONCLUSIONS</b>PRDM14 accelerates A549 cells migration in vitro through extracellular matrix degradation. PRDM14 is considered as a potential therapeutic target in metastatic NSCLC.</p>

[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.

Roles of trichorhinophalangeal syndrome-1 gene in normal breast development and breast cancer / 中国医学科学院学报

GATA transcription factor family members have been found to involve in the growth and differentiation of mammary gland. Among them GATA-3 is regarded as the most critical regulator involving the tumorigenesis of breast cancer (BC). Recently, trichorhinophalangeal syndrome-1 gene (TRPS-1), a new GATA family member, has been identified to be highly prevalent in breast cancer. Compared with ER-negative breast cancer, the expression of TRPS-1 is higher in ER-positive breast cancer and was significantly correlates with estrogen receptor, progesterone receptor, and GATA-3, indicating it may serve as a ductal epithelial cell-specific regulator in the differentiation of breast ductal epithelial cells. Studies have shown that miR221/222 is able to downregulate the expression of an epithelial cell marker E-cadherin by targeting TRPS-1, resulting in mammary epithelial cells transition to mesenchymal cell (EMT). In addition, it has been well accepted that, and the Science and Technology Bureau of Jiaxing (2012AY1071-2)TRPS-1 plays a role in the differentiation of several other cell types including kidney nephric mesenchymal cells, columnar chondrocytes, and osteoclasts, indicating that TRPS-1 involves in mesenchymal-to-epithelial cell transition (MET). In this article, we summarize the roles of GATA transcription factor TRPS-1 in ductal epithelial cells and the roles of its gene and protein expressions in predicting the prognosis of breast cancer.

Vibrio vulnificus induces acute necrosis of dendritic cells via toll-like receptor 2 and 4 pathways / 中华传染病杂志

Objective To explore how Vibrio vulnificus (Vv) invades dendritic cells (DC) and induces acute necrosis of DC via toll-like receptor (TLR) 2 and 4 pathways.Methods Vv 1.1758 strain and DC 2.4 mixed culture model was established,observed the infection rates of DC with optical microscope,the location of Vv and structural changes of DC by transmission electron microscope.The expression levels of TLR2 and TLR4 mRNA were determined by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and tumor necrosis factor-α (TNFα) protein titers were measured by enzyme-linked immunosorbent assay (ELISA).DNA ladder qualitative test was used to detect cell apoptosis,while flow cytometry was used to quantify cell apoptosis and necrosis rates.Statistical analysis was done by chi-square test and one-way ANOVE.Results The infection rates of DC after 0.5,1,2,4 and 6 h of mixed culture were (7.8±0.8) ％,(13.9± 1.1) ％,(34.6±4.9) ％,(77.8± 10.2)％ and (95.8 ± 13.1)％,respectively.Vv was generally located in the internal cell membrane of DC 2.4.After 2 h co-culture,nuclear chromatins of DC became active and intranuclear apoptosis bodies appeared.After 4 h,cytoplasmic vacuoles appeared,chromatin gathered,and cell membranes were seriously damaged.After 6 h,mitochondria was highly swelled and distorted,and cell apoptosis and necrosis occurred.TLR2 and TLR4 mRNA levels reached peak values after co-culture for 0.5 h; TNF-α level began to increase at 1 h (P＜0.05) and reached peak values at 2 h.DNA Ladder electrophoresis presented scouring necrosis after 2 h culture and apoptotic bands appeared between 720 bp and 900 bp after 4 to 5 h culture.Early apoptosis rates of DC after 2,4 and 6 h culture were (3.1±3.8)％,(7.8±4.7)％ and (12.7±8.2)％,and necrosis rates of DC were (16.7±12.5)％,(41.6±25.9)％ and (75.5±33.6)％,higher than that of control group (all P＜0.05).Conclusions Vv infects DC and induce DNA degradation through up-regulated expression of TLR2 and TLR4 and increasing of TNF-α inflammatory mediators.During cell degradation,apoptosis and necrosis coexist,while necrosis is predominant.

Localization of Vibrio vulnificus infection in dendritic cells and its effects on the cytoskeleton / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vibrio vulnificus (Vv) is an estuarine bacterium that can cause primary septicemia as well as serious wound infections. However, little is known about the mechanisms by which Vv infects dendritic cells (DCs) and its effects on cytoskeleton. In this study, we aimed to investigate the invasion, internalization, and the organelles damage of the cultured dendritic cells (a DC 2.4 strain) during Vv infection.</p><p><b>METHODS</b>The study model was the cultured DCs infected by a Vv 1.758 strain. Electron microscopy was used to observe the localization of bacteria at the different time points of infection, cell morphology, and the process of organelles changes. The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined under a fluorescence microscope.</p><p><b>RESULTS</b>The Vv were pinocytosised into the DC cells through double-sides, and localized at 1 - 2 mm of the inner side membrane. It took 1.3, 1.9, and 3.4 hours to reach the infection ratio of 25%, 50%, and 75%, respectively. Using electron microscopy, the DCs had been observed to have developed chromatin aggregation within 4.0 hours, and significant cytoskeleton structure disruption was noted within 6.0 hours.</p><p><b>CONCLUSION</b>The high lethality of Vv infection may be associated with the direct disruption of the DCs cytoskeleton structure.</p>

Simulated seasonal variations in wet acid depositions over East Asia.

The air quality modeling system Regional Atmospheric Modeling System-Community Multi-scale Air Quality (RAMS-CMAQ) was applied to analyze temporospatial variations in wet acid deposition over East Asia in 2005, and model results obtained on a monthly basis were evaluated against extensive observations, including precipitation amounts at 704 stations and SO4(2-), NO3-, and NH4+ concentrations in the atmosphere and rainwater at 18 EANET (the Acid Deposition Monitoring Network in East Asia) stations. The comparison shows that the modeling system can reasonably reproduce seasonal precipitation patterns, especially the extensive area of dry conditions in northeast China and north China and the major precipitation zones. For ambient concentrations and wet depositions, the simulated results are in reasonable agreement (within a factor of 2) with observations in most cases, and the major observed features are mostly well reproduced. The analysis of modeled wet deposition distributions indicates that East Asia experiences noticeable variations in its wet deposition patterns throughout the year. In winter, southern China and the coastal areas of the Japan Sea report higher S04(2-) and NO3- wet depositions. In spring, elevated SO4(2-) and NO3-wet depositions are found in northeastern China, southern China, and around the Yangtze River. In summer, a remarkable rise in precipitation in northeastern China, the valleys of the Huaihe and Yangtze rivers, Korea, and Japan leads to a noticeable increase in SO4(2-) and NO3- wet depositions, whereas in autumn, higher SO4(2-) and NO3-wet depositions are found around Sichuan Province. Meanwhile, due to the high emission of SO2, high wet depositions of SO4(2-) are found throughout the entire year in the area surrounding Sichuan Province. There is a tendency toward decreasing NO3- concentrations in rainwater from China through Korea to Japan in both observed and simulated results, which is a consequence of the influence of the continental outflow from Eurasia. The same tendency is not found for SO4(2-).

[Changes of brain oxidative stress induced by nano-alumina in ICR mice].

OBJECTIVE: To investigate the brain oxidative stress injury induced by nano-alumina particles in ICR mice. METHODS: Sixty male ICR mice were randomly divided into 6 groups: control group, solvent control group, 100 mg/kg micro-alumina particles group, 3 groups exposed to nano-alumina particles at the doses of 50, 100 and 200 mg/kg. The mice were exposed by nasal drip for 30 days. Then levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in brain tissues of mice were detected. RESULTS: There was no difference of SOD activity in mouse brain between control group [(17.32 +/- 6.23)U/gHb] and 50 mg/kg nano-alumina particles group [(17.89 +/- 1.82) U/gHb]. The SOD activity [(4.93 +/- 2.30)U/gHb] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05). The MDA levels in 3 nano-alumina particles groups were (0.76 +/- 0.13), (1.00 +/- 0.30) and (1.16 +/- 0.39)nmol/ml, respectively, which were significantly higher than that [( 0.24 +/- 0.09)nmol/ml] in control group (P < 0.05). The GSH levels in 3 nano-alumina particles groups were (0.72 +/- 0.08), (0.55 +/- 0.19) and (0.61 +/- 0.20)mg/gpro, respectively, which were significantly lower than that [(1.55 +/- 0.34)mg/gpro]] in control group (P < 0.05). The CAT activity in 50 and 100 mg/kg nano-alumina particles groups were (10.40 +/- 3.84) and (10.40 +/- 2.00)U/mgpro, respectively, which were significantly higher than that [(5.79 +/- 0.96) U/mgpro] in control group (P < 0.05). The CAT activity [(3.25 +/- 1.04)U/mgpro] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05 ). CONCLUSION: Nano-alumina particles can induce the oxidative stress damage in brain tissues of mice.

Depressive symptoms and occupational stress among Chinese female nurses: the mediating effects of social support and rational coping.

The study reported here was designed to investigate the relationship between depressive symptoms and occupational stress in female nurses in China during the period June-July 2008. The hypothesis tested was that social support and rational coping would mediate the effects of occupational stress on depressive symptoms. Our structural equation modeling revealed that social support and rational coping were negatively correlated with depressive symptoms. Social support and rational coping mediated the effects of occupational stress on depressive symptoms. Role overload, role insufficiency, and role boundary were predictive of depressive symptoms. These results indicated that lessening occupational stress and strengthening social support and rational coping could decrease depressive symptoms among Chinese female nurses.

The Vibrio vulnificus localization in the dendritic cells and its effect on dendritic cells cytoskeleton structure during infection / 中华微生物学和免疫学杂志

Objective To investigate the invasion,internalization and the organelles damage of the cultured dendritic cells ( DC2.4 strain) during Vibrio vulnificus (Vv) infection.Methods The study model was the cultured DCs infected by Vv 1.1758 strain.Electron microscopy was used to observe the localization of bacteria in different time point of infection,cell morphology and the process of organelles changes.The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined by the fluorescence microscope.Results The Vv were pinocytosed into the DC cells through double-sides,and localized at 1-2 μm of the inner side membrane.It cost 1.27,1.87,3.43 hours reaching the infection ratio of 25％,50％,75％,respectively.Using electron microscopy,the DCs had been observed the phagosome formation within 1h,chromatin activation within 2 h,chromatin aggregation 4 h,and the significant cytoskeleton structure disruption within 6 h.Endoplasmic reticulum,mitochondria and lysosomes became swollen.In DCs,the protruding filaments gradually reduced,and their shape changed from the point-like to the linearlike aggregation at the inner side of the plasma membrane,extended microtubules disappeared,the microtubules at the outside nuclear membrane striking rearranged.Conclusion After DC was infected by Vv,the bacteria were pinocytosed into the inner side of DC membrane,and the microfilaments were observed to move from the cytoplasm to cell membrane.In addition,the microtubules moved from the synapse and the cell membrane to the nuclear membrane.The high lethality of Vv could provoke to the DCs cytoskeleton rearrangements.