Advances in bi-directional relationships for EZH2 and oxidative stress.

Over the past two decades, polycomb repressive complex 2(PRC2) has emerged as a vital repressive complex in overall cell fate determination. In mammals, enhancer of zeste homolog 2 (EHZ2), which is the core component of PRC2, has also been recognized as an important regulator of inflammatory, redox, tumorigenesis and damage repair signalling networks. To exert these effects, EZH2 must regulate target genes epigenetically or interact directly with other gene expression-regulating factors, such as LncRNAs and microRNAs. Our review provides a comprehensive summary of research advances, discoveries and trends regarding the regulatory mechanisms between EZH2 and reactive oxygen species (ROS). First, we outline novel findings about how EZH2 regulates the generation of ROS at the molecular level. Then, we summarize how oxidative stress controls EHZ2 alteration (upregulation, downregulation, or phosphorylation) via various molecules and signalling pathways. Finally, we address why EZH2 and oxidative stress have an undefined relationship and provide potential future research ideas.

Numerical Simulation of Fire in Underground Commercial Street.

In this study, while aiming at the prevention of fire accidents in underground commercial streets, an underground commercial street is selected as a research object, and the building fire is numerically simulated using the PyroSim software. Fire simulation scenarios are divided according to different fire zones by analyzing the temperature, carbon monoxide (CO) concentration, and visibility in the smoke layer inside a building. The available safe evacuation time is calculated according to the critical fire hazard judgment conditions. We found that the time when the flue gas temperature and CO concentration reached the critical value in the fire site was longer than the time when the visibility reached the critical value reducing or even avoiding the spread of smoke from the fire area to the evacuation stairs can provide effective help for crowd evacuation. Finally, the safety of the building is evaluated, and fire prevention countermeasures are defined based on the actual situation and fire numerical simulation results to reduce fire incidence, casualties, and economic losses.

Layperson's performance on an unconversant type of AED device: A prospective crossover simulation experimental study.

BACKGROUND: Diverse models of automated external defibrillators (AEDs) possess distinctive features. This study aimed to investigate whether laypersons trained with one type of AED could intelligently use another initial contact type of AED with varying features. METHODS: This was a prospective crossover simulation experimental study conducted among college students. Subjects were randomly trained with either AED1 (AED1 group) or AED2 (AED2 group), and the AED operation performance was evaluated individually (Phase I test). At the 6-month follow-up AED performance test (Phase II test), half of the subjects were randomly switched to use another type of AED, which formed two switches (Switch A: AED1-1 group vs. AED2-1 group; Switch B: AED2-2 group vs. AED1-2 group). RESULTS: A total of 224 college students participated in the study. In the phase I test, a significantly higher proportion of successful defibrillation and shorter shock delivery time to achieve successful defibrillation was observed in the AED2 group than in the AED1 group. In the phase II test, no statistical differences were observed in the proportion of successful defibrillation in Switch A (51.4% vs. 36.6%, P=0.19) and Switch B (78.0% vs. 53.7%, P=0.08). The median shock delivery time within participants achieving successful defibrillation was significantly longer in the switched group than that of the initial group in both Switch A (89 [81-107] s vs. 124 [95-135] s, P=0.006) and Switch B (68 [61.5-81.5] s vs. 95.5 [55-131] s, P<0.001). CONCLUSION: College students were able to effectively use AEDs different from those used in the initial training after six months, although the time to shock delivery was prolonged.

A magnetic nanofiber-based zwitterionic hydrophilic material for the selective capture and identification of glycopeptides.

High-performance affinity materials are highly required in the sample preparation process in mass spectrometry-based glycoproteomics studies. In this research, a novel magnetic nanofiber-based zwitterionic hydrophilic material is prepared for glycopeptide enrichment and identification. The one-dimensional hydroxyapatite nanofiber (HN) acted as the supporting substance for immobilizing both Fe3O4 nanoparticles and Au nanoparticles, following the surface modification with a zwitterionic tripeptide l-glutathione (GSH) via the affinity interactions between the thiol group in GSH and both Au and Fe3O4 to form the magHN/Au-GSH nanofiber. Owing to the unique structural features, excellent hydrophilicity, abundant zwitterionic molecules, and strong magnetic responsiveness, the as-prepared magHN/Au-GSH nanofiber possesses satisfactory specificity for glycopeptide enrichment. As a result, the magHN/Au-GSH nanofiber demonstrated great detection sensitivity (2 fmol), satisfying enrichment recovery (89.65%), large binding capacity (100 mg g-1), and high enrichment selectivity (1 : 100) toward glycopeptides. Furthermore, 246 N-glycosylated peptides corresponding to 104 N-glycosylated proteins were identified from only 1 µL human serum, revealing the great potential of this affinity nanofiber for glycopeptide enrichment and glycoproteomics research.

A new approach for Alzheimer's disease treatment through P-gp regulation via ibuprofen.

This study was aimed to investigate whether ibuprofen could alter the P-glycoprotein expression and function under Alzheimer's Disease condition and whether this alteration was induced by the inhibition of inflammatory reaction. APP/PS1 mice were used as AD model mice and ibuprofen-treated AD mice were given ibuprofen for 5 months. Then, Abcb1a/1b mRNA levels and P-gp expression were evaluated by qRT-PCR and western blot. Abcb1 mRNA levels were significantly reduced in AD mice compared to control mice, and it could be restored by ibuprofen treatment. Meanwhile, P-gp expression result showed a similar trend. Aß plaques in cerebral cortices and hippocampus were investigated via immunohistochemical, and the results revealed that Aß plaques were reduced in ibuprofen-treated AD mice compared with the AD mice, indicated that P-gp function may be recovered by ibuprofen treatment. qRT-PCR and ELISA were used to determined TNF-α, IL-1ß, IL-6 and NF-κB levels. The results demonstrated that TNF-α, IL-1ß mRNA levels and NF-κB expression were all significantly upregulated in AD mice in comparison with the control mice, and ibuprofen treatment could suppress the increase of inflammatory factors. In conclusion, the P-gp expression and function were suppressed in AD condition by activating inflammatory reaction, and then causing the Aß efflux decreased. However, upregulating P-gp could increase the Aß efflux in further to treat AD via inhibiting the inflammatory factors expression.

Tuning the upconversion photoluminescence lifetimes of NaYF4:Yb3+, Er3+ through lanthanide Gd3+ doping.

The multiplexing capacity of conventional fluorescence materials are significantly limited by spectral overlap and background interference, mainly due to their short-lived fluorescence lifetimes. Here, we adopt a novel Gd3+ doping strategy in NaYF4 host materials, realized tuning of upconversion photoluminescence (UCPL) lifetimes at selective emissions. Time-correlated single-photon counting (TCSPC), was applied to measure the photoluminescence lifetimes accurately. We demonstrated the large dynamic range of lifetimes of upconversion nanoparticles with good upconversion quantum yields, mainly owing to the dominance of high efficient energy transfer upconversion mechanism. The exceptional tunable properties of upconversion materials allow great potential for them to be utilized in biotechnology and life sciences.

Analytical link bandwidth model based square array reception for non-line-of-sight ultraviolet communication.

An analytical model is presented firstly in this paper to formulate the link bandwidth of non-line-of-sight (NLOS) ultraviolet (UV) channel. The link bandwidth is characterized by three geometrical parameters including transmitter (Tx) elevation angle, receiver (Rx) field of view (FOV), and transceiver separation distance, and further expressed as a closed-form through software-aided numerical fitting. Comparison with the link bandwidth obtained via a Monte Carlo model is done to verify the feasibility of this model. Based on this model, we investigate the diversity reception on the NLOS UV communication from a new perspective. A spatially squared distributed Rx array is customized for the NLOS UV channel. Lower temporal broadening is enabled, leading to a higher link bandwidth. Numerical results suggest that over 100% improvement of the link bandwidth is predicted by the square array reception and the ratio grows rapidly with the narrowing of Tx beam divergence. Therefore, this paper provides a guide for link analysis and receiver design for NLOS UV communication.

Enhancement of the upconversion photoluminescence of hexagonal phase NaYF4:Yb3+,Er3+ nanoparticles by mesoporous gold films.

Efficient enhancement of photoluminescence in rare-earth activated upconversion materials is of great significance for their practical applications in various fields. In this work, three-dimensional mesoporous gold films were fabricated by a low-cost and facile dealloying approach to improve the upconversion photoluminescence efficiency. The mesoporous Au films exhibit good chemical stability, large-area uniformity and abundant distribution of porous nanospaces. Varying the time of the dealloying process leads to modification of the pore size distribution, surface roughness and residual Ag content, resulting in effective tuning of the wavelength of the broadband localized surface plasmon resonance (LSPR). Enhancement factors were identified to be a function of the dealloying time. With the optimized upconversion photoluminescence enhancement, a 41-fold increase was achieved with the mesoporous gold substrate which had been dealloyed for 8 days. These results pave the way to overcome the limitation of poor upconversion efficiency for widespread practical applications in life science and energy fields.

Received response based heuristic LDPC code for short-range non-line-of-sight ultraviolet communication.

Through slight modification on typical photon multiplier tube (PMT) receiver output statistics, a generalized received response model considering both scattered propagation and random detection is presented to investigate the impact of inter-symbol interference (ISI) on link data rate of short-range non-line-of-sight (NLOS) ultraviolet communication. Good agreement with the experimental results by numerical simulation is shown. Based on the received response characteristics, a heuristic check matrix construction algorithm of low-density-parity-check (LDPC) code is further proposed to approach the data rate bound derived in a delayed sampling (DS) binary pulse position modulation (PPM) system. Compared to conventional LDPC coding methods, better bit error ratio (BER) below 1E-05 is achieved for short-range NLOS UVC systems operating at data rate of 2Mbps.

Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.

Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis. Here we found that, in addition to StAR, MBP/DBP increased the steroidogenesis by a cytoskeletal protein, vimentin. Briefly, in murine adrenocortical tumor (Y1) and the mouse Leydig tumor (MLTC-1) cells, vimentin regulated the secretion of progesterone. When these two cells were exposure to MBP, the DNA demethylation in the vimentin promoter was observed. In addition, MBP also induced the activation of nuclear factor kappa B (NF-κB, a transcriptional regulator of vimentin). These two processes improved the transcriptional elevation of vimentin. Knockdown of NF-κB/vimentin signaling blocked the DBP/MBP-induced steroidogenesis. These in vitro results were also confirmed via an in vivo model. By identifying a mechanism whereby DBP/MBP regulates vimentin, our results expand the understanding of the endocrine disrupting potential of phthalate esters.

miRNA-200c mediates mono-butyl phthalate-disrupted steroidogenesis by targeting vimentin in Leydig tumor cells and murine adrenocortical tumor cells.

The reproductive toxicity of plasticizer di-n-butyl phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) has been demonstrated in rodents. The objective of this study was to explore roles of vimentin and miRNA-200c in steroidogenesis interfered by MBP. Mouse Leydig tumor cells (MLTC-1) and murine adrenocortical tumor cells (Y1) were employed and exposed to various levels of MBP (10(-7), 10(-6), 10(-5) and 10(-4)M). Steroid hormone production was increased significantly when MLTC-1 and Y1 cells were exposed to MBP at 10(-7)M. Additionally, vimentin and steroidogenic acute regulatory protein (StAR) expressions were upregulated at the same dose. It was found that MBP increased the steroidogenesis by facilitating the cholesterol transfer process by vimentin. In contrast, miRNA-200c expression was depressed at doses of MBP (10(-7)M) in both cells. Moreover, vimentin expression and progesterone production were increased in both MLTC-1 and Y1 cells after miRNA-200c expression was artificially inhibited. These results strongly suggested that MBP raised steroid hormone synthesis via upregulated vimentin by miRNA-200c.

The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo.

This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.

CuI-catalyzed C1-alkynylation of tetrahydroisoquinolines (THIQs) by A3 reaction with tunable iminium ions.

A CuI-catalyzed A(3) (amines, aldehydes and alkynes) reaction of tetrahydroisoquinolines (THIQs), aldehydes, and alkynes to give C1-alkynylated THIQ products (endo-yne-THIQs) was developed. This redox neutral C1-alkynylation of THIQs, which was conducted under mild conditions, has a broad scope for the used aldehydes and alkynes. It was proposed that the A(3) reaction first generates in situ exo-iminium ions, which then isomerize to endo-iminium ions and react with copper acetylides to give the endo alkynylated THIQs (endo-yne-THIQs).

Mild-condition synthesis of allenes from alkynes and aldehydes mediated by tetrahydroisoquinoline (THIQ).

A practical 1,2,3,4-tetrahydroisoquinoline (THIQ)-mediated synthesis of 1,3-disubstituted allenes from terminal alkynes and aldehydes under mild conditions in the presence of CuBr first and then ZnI2 was reported. This telescoped allene synthesis reaction includes three consecutive steps and two reactions: first, a room-temperature CuBr-catalyzed synthesis of propargylamines, exo-yne-THIQs, from terminal alkynes, aldehydes, and THIQ, then filtration of the CuBr catalyst, and finally the ZnI2-mediated allene synthesis from the generated exo-yne-THIQs under mild conditions (either at room temperature or heating at 50 or 75 °C). A wide range of aliphatic or aromatic aldehydes and terminal alkynes are tolerated, affording the allene products in up to 92% yield. Especially, temperature-sensitive aldehydes can be used in the reaction system. Preliminary exploration of the asymmetric allene synthesis has also been conducted, and a moderate enantioselectivity has been achieved. Finally, the relative reactivities of several secondary amines were compared with THIQ, showing that THIQ is the best of these amines in the synthesis of allenes under mild reaction conditions.

[Effects of di-butyl phthalate on the reproductive system of adolescent male rats].

OBJECTIVE: To explore the effects of di-butyl phthalate (DBP) on the reproductive system of adolescent male rats. METHODS: Sprague-Dawley (SD) rats aged 5 weeks were assigned to receive corn oil (vehicle control) or DBP orally at 10, 100 and 500 mg/(kg x d) for 30 days. After the exposure, the testis, epididymis, liver and pituitary of the rats were weighted and their ratios to the body weight obtained. Histopathological changes of the testis and epididymis were examined by Hematoxylin-eosin staining, the levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum were measured by radioimmunoassay, and the relative mRNA expressions of the steroidogenesis acute regulatory protein (StAR), proliferating cell nuclear antigen (PCNA), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and scavenger receptor (SR) were detected by real-time quantitative RT-PCR. RESULTS: DBP induced significant histopathological changes in the testicular tissue at 100 and 500 mg/(kg x d), and decreased the testicular and epididymal weights, inhibited the mRNA expressions of StAR and PCNA, reduced the levels of T and LH, and elevated the level of FSH at 500 mg/(kg x d). At the dose of 10 mg/(kg x d), DBP increased serum LH and FSH and the mRNA expression of P450scc. While the SR mRNA expression showed no significant changes in all the groups. CONCLUSION: High level of DBP has apparent toxic effect on reproductive system of male rats. Low - dose DBP can increase the level of serum gonadotropin LH and affect the mRNA expression of P450scc in the testis.