Comprehensive analysis of microglia gene and subpathway signatures for glioma prognosis and drug screening: linking microglia to glioma.

Glioma is the most common malignant tumors in the brain. Previous studies have revealed that, as the innate immune cells in nervous system, microglia cells were involved in glioma pathology. And, the resident microglia displayed its specific biological roles which distinguished with peripheral macrophages. In this study, an integrated analysis was performed based on public resource database to explore specific biological of microglia within glioma. Through comprehensive analysis, the biological characterization underlying two conditions, glioma microglia compared to glioma macrophage (MicT/MacT) as well as glioma microglia compared to normal microglia (MicT/MicN), were revealed. Notably, nine core MicT/MicN genes displayed closely associations with glioma recurrence and prognosis, such as P2RY2, which was analyzed in more than 2800 glioma samples from 25 studies. Furthermore, we applied a random walk based strategy to identify microglia specific subpathways and developed SubP28 signature for glioma prognostic analysis. Multiple validation data sets confirmed the predictive performance of SubP28 and involvement in molecular subtypes. The associations between SuP28 score and microglia M1/M2 polarization were also explored for both GBM and LGG types. Finally, a comprehensive drug-subpathway network was established for screening candidate medicable molecules (drugs) and identifying therapeutic subpathway targets. In conclusions, the comprehensive analysis of microglia related gene and functional signatures in glioma pathobiologic events by large-scale data sets displayed a framework to dissect inner connection between microglia and glioma, and identify robust signature for glioma clinical implications.

Endothelial dysfunction and transcriptome aberration in mouse aortas induced by black phosphorus quantum dots and nanosheets.

Black phosphorus (BP) nanomaterials have shown great potential in versatile applications including biomedicine and potentially interact with vessel walls following intravenous injection in biomedical usage or environmental exposure. However, it remains unknown whether the exposure to BP nanomaterials induces alterations of the endothelium and further vascular injury. Herein, the endothelial function of human umbilical vein endothelial cells (HUVECs) and the structure and transcriptome of C57BL/6 mouse aortas are evaluated after the exposure to BP quantum dots (BPQDs) and nanosheets (BPNSs). BPNSs with irregular shapes and larger lateral size are more prone to inhibit in vitro angiogenesis at non-cytotoxic concentrations and markedly trigger platelet adhesion to HUVECs compared to BPQDs. Decreased nitric oxide (NO) production resulting from endothelial NO synthase (eNOS) dysregulation is involved in the BP-induced endothelial dysfunction. Both BPQDs and BPNSs at 0.8 and 6.4 µg mL-1 inhibit eNOS enzymatic activity through dephosphorylation of eNOS-Ser1177 and phosphorylation of eNOS-Thr495, but unlike BPQDs, BPNSs also downregulate eNOS expression. Despite no pathological damage in the structure of mouse aortas, BPQDs and BPNSs trigger aberration of aortic transcriptome involved in vasoconstriction abnormality, metabolic disturbance, and immune perturbation. This study demonstrates the adverse effect of BP nanomaterials on vasculature, and suggests that the morphological attribute of BP plays a crucial role in the vascular risks.

Identification of the Core Pollen-Specific Regulation in the Rice OsSUT3 Promoter.

The regulatory mechanisms of pollen development have potential value for applications in agriculture, such as better understanding plant reproductive regularity. Pollen-specific promoters are of vital importance for the ectopic expression of functional genes associated with pollen development in plants. However, there is a limited number of successful applications using pollen-specific promoters in genetic engineering for crop breeding and hybrid generation. Our previous work led to the identification and isolation of the OsSUT3 promoter from rice. In this study, to analyze the effects of different putative regulatory motifs in the OsSUT3 promoter, a series of promoter deletions were fused to a GUS reporter gene and then stably introduced into rice and Arabidopsis. Histochemical GUS analysis of transgenic plants revealed that p385 (from -385 to -1) specifically mediated maximal GUS expression in pollen tissues. The S region (from -385 to -203) was the key region for controlling the pollen-specific expression of a downstream gene. The E1 (-967 to -606), E2 (-202 to -120), and E3 (-119 to -1) regions enhanced ectopic promoter activity to different degrees. Moreover, the p385 promoter could alter the expression pattern of the 35S promoter and improve its activity when they were fused together. In summary, the p385 promoter, a short and high-activity promoter, can function to drive pollen-specific expression of transgenes in monocotyledon and dicotyledon transformation experiments.

Levels and patterns of DDTs in maternal colostrum from an island population and exposure of neonates.

Dichlorodiphenyltrichloroethane (DDT) was heavily used in the past in many regions of the world. The occurrence of DDTs in island populations may be elevated if the island is adjacent to major DDT consumption estuaries, such as the Yangtze River Delta. In this study, colostrum samples were collected from maternal-neonate pairs (n = 106) from the Shengsi Island, located directly downstream from the Yangtze River outlet. DDT isomers and enantiomer compositions were analyzed by gas chromatography equipped with mass spectrometer (GC/MS) and GC/MS-MS. The average levels of p,p'-DDE, o,p'-DDD, p,p'-DDD, o,p'-DDT, p,p'-DDT and total DDTs were 1.32, 0.03, 0.09, 0.08, 0.48, and 1.93 µg g(-1) lipid weight, respectively. Maternal age and pregnancy body mass index (BMI) were positively associated with levels of DDTs (p < 0.05). High (DDE+DDD)/DDT and p,p'-DDE/p,p'-DDT ratios suggested that current DDT residues originated primarily from historical use of DDT products, but new sources may also contribute partially to some high o,p'-DDT/p,p'-DDT ratios. Enantiomeric enrichment was found for the (-)-enantiomer of o,p'-DDD and the (+)-enantiomer of o,p'-DDT, suggesting stereoselective attenuation. Based on breast milk consumption, the average daily intake of DDTs by neonates was 8.33 ± 7.34 µg kg(-1)bw per day, which exceeded the WHO's tolerable daily intake guideline of 0.01 mg kg(-1) bw per day by 25%, implying some neonates in the Yangtze River region are potentially at high risk from exposure to DDTs.

Sharp-Hook Acupuncture (Feng Gou Zhen) for Patients with Periarthritis of Shoulder: A Randomized Controlled Trial.

The Feng Gou Zhen (sharp-hook acupuncture) as a traditional form of ancient acupuncture is said to be particularly effective for managing periarthritis of shoulder. We conducted this randomized controlled trial to evaluate the effectiveness of Feng Gou Zhen as an add-on compared to conventional analgesics for patients with PAS. 132 patients were randomly assigned in a 1 : 1 ratio to either a acupuncture group receiving sharp-hook acupuncture plus acupoint injection with conventional analgesics or a control group. Patients from both groups were evaluated at week 0 (baseline), week 1, and week 4. The primary outcome measure was the change from baseline shoulder pain, measured by Visual Analogue Scale at 7 days after treatment. Secondary outcome measures include the (i) function of shoulder joint and (ii) McGill pain questionnaire. The results showed that patients in acupuncture group had better pain relief and function recovery compared with control group (P < 0.05) at 1 week after treatment. Moreover, there were statistical differences between two groups in VAS and shoulder joint function and McGill pain questionnaire at 4 weeks after treatment (P < 0.05). Therefore, the sharp-hook acupuncture helps to relieve the pain and restore the shoulder function for patients with periarthritis of shoulder.

MPINet: metabolite pathway identification via coupling of global metabolite network structure and metabolomic profile.

High-throughput metabolomics technology, such as gas chromatography mass spectrometry, allows the analysis of hundreds of metabolites. Understanding that these metabolites dominate the study condition from biological pathway perspective is still a significant challenge. Pathway identification is an invaluable aid to address this issue and, thus, is urgently needed. In this study, we developed a network-based metabolite pathway identification method, MPINet, which considers the global importance of metabolites and the unique character of metabolomic profile. Through integrating the global metabolite functional network structure and the character of metabolomic profile, MPINet provides a more accurate metabolomic pathway analysis. This integrative strategy simultaneously captures the global nonequivalence of metabolites in a pathway and the bias from metabolomic experimental technology. We then applied MPINet to four different types of metabolite datasets. In the analysis of metastatic prostate cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of the two type 2 diabetes datasets, we show that MPINet has the potentiality for identifying novel pathways related with disease and is reliable for analyzing metabolomic data. Finally, we extensively applied MPINet to identify drug sensitivity related pathways. These results suggest MPINet's effectiveness and reliability for analyzing metabolomic data across multiple different application fields.

Potential estrogenic effects of phosphorus-containing flame retardants.

As the substitute of polybrominated diphenyl ethers (PBDEs), further assessments about the potential ecological safety and health risks of phosphorus-containing flame retardants (PFRs) are required because the worldwide demand for PFRs has been increasing every year. In this study, we examined the agonistic/antagonistic activity of a group of PFRs by three in vitro models (luciferase reporter gene assay, yeast two-hybrid assay, and E-screen assay). Molecule docking was used to further explain the interactions between ERα and PFRs. Data from luciferase reporter gene analysis showed three members of the nine tested PFRs significantly induced estrogenic effects, with the order of TPP > TCP > TDCPP, while TCEP and TEHP have remarkable antiestrogenic properties with calculated REC20 and RIC20 values of 10(-6) M or lower. Results from the luciferase reporter gene method are generally consistent with results obtained from the yeast two-hybrid assay and E-screen, except for the positive estrogenic activity of TBP in E-screen testing. Docking results showed that binding between ligands and ERα was stabilized by hydrophobic interactions. As a proposed alternative for brominated flame retardant, PFRs may have anti/estrogenic activity via ERα at the low dose typical of residue in environmental matrix or animals. PFRs with a short chain, halogen, and benzene ring in the substituent group tend to be estrogenic. Our research suggests that comprehensive evaluations, including health and ecological assessments, are required in determining whether PFRs are preferable as an emerging industrial substitute.

Bacterial energetics, stoichiometry, and kinetic modeling of 2,4-dinitrotoluene biodegradation in a batch respirometer.

A stoichiometric equation and kinetic model were developed and validated using experimental data from batch respirometer studies on the biodegradation of 2,4-dinitrotoluene (DNT). The stoichiometric equation integrates bacterial energetics and is revised from that in a previous study by including the mass balance of phosphorus (P) in the biomass. Stoichiometric results on O2 consumption, CO2 evolution, and nitrite evolution are in good agreement with respirometer data. However, the optimal P requirement is significantly higher than the stoichiometrically derived P, implying potentially limited bioavailability of P and the need for buffering capacity in the media to mitigate the adverse pH effect for optimal growth of DNT-degrading bacteria. An array of models was evaluated to fit the O2/CO2 data acquired experimentally and the DNT depletion data calculated from derived stoichiometric coefficients and cell yield. The deterministic, integrated Monod model provides the goodness of fit to the test data on DNT depletion, and the Monod model parameters (Ks, X0, mumax, and Y) were estimated by nonlinear regression. Further analyses with an equilibrium model (MINTEQ) indicate the interrelated nature of medium chemical compositions in controlling the rate and extent of DNT biodegradation. Results from the present batch respirometer study help to unravel some key factors in controlling DNT biodegradation in complex remediation systems, in particular the interactions between acidogenic DNT bacteria and various parameters, including pH and P, the latter of which could serve as a nutrient, a buffer, and a controlling factor on the bioavailable fractions of minerals (Ca, Fe, Zn, and Mo) in the medium.