Quercetin Suppresses Cyclooxygenase-2 Expression and Angiogenesis through Inactivation of P300 Signaling

Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers

Copula-Based Joint Probability Analysis of Compound Floods from Rainstorm and Typhoon Surge: A Case Study of Jiangsu Coastal Areas, China

Coastal areas are vulnerable to floods caused by rainstorms and typhoons. It is necessary to ascertain the risk of floods caused by both of these extreme weather events. A conceptual risk model is proposed to evaluate the rainstorm risk, typhoon surge risk, and the compound risk in the coastal areas of Jiangsu Province during the period of 1960–2012. The results of the model show that the typhoon surge risk in the study region is greater than the rainstorm risk. Three Archimedean copulas were used to fit the joint probability distributions of the compound events. The Frank copula and the Gumbel copula proved to be the best-fitting joint distribution function for the Huaibei plain district and the Lixiahe district, respectively. The probability of the extreme compound events not happening is less than 90% in the study region. This means that the flood risk is mainly subject to the encounter of a low-level rainstorm and a low-level typhoon surge. The study shows that the northern region of Jiangsu Province is more vulnerable to the compound risk, and that we should pay more attention to the floods caused by the compound events of rainstorm and typhoon surge

Digital nanophotonics: the highway to the integration of subwavelength-scale photonics

Nanophotonic devices with high densities are extremely attractive because they can potentially merge photonics and electronics at the nanoscale. However, traditional integrated photonic circuits are designed primarily by manually selecting parameters or employing semi-analytical models. Limited by the small parameter search space, the designed nanophotonic devices generally have a single function, and the footprints reach hundreds of microns. Recently, novel ultra-compact nanophotonic devices with digital structures were proposed. By applying inverse design algorithms, which can search the full parameter space, the proposed devices show extremely compact footprints of a few microns. The results from many groups imply that digital nanophotonics can achieve not only ultra-compact single-function devices but also miniaturized multi-function devices and complex functions such as artificial intelligence operations at the nanoscale. Furthermore, to balance the performance and fabrication tolerances of such devices, researchers have developed various solutions, such as adding regularization constraints to digital structures. We believe that with the rapid development of inverse design algorithms and continuous improvements to the nanofabrication process, digital nanophotonics will play a key role in promoting the performance of nanophotonic integration. In this review, we uncover the exciting developments and challenges in this field, analyse and explore potential solutions to these challenges and provide comments on future directions in this field

Temporal variation of plankton and zoobenthos communities in a freshwater reservoir: Structure feature, construction mechanism, associated symbiosis and environmental response

Phytoplankton, zooplankton and zoobenthos, due to their tiny size and high reproductive efficiency, usually hold an essential position in freshwater reservoir biomes. Understanding their community traits and symbiosis mechanism is crucial for determining the nature of water ecological environment and the water ecosystem’s evolution. However, the dynamics of interspecific and environmental interactions, as well as community-building processes, are currently unclear. Here, the structure feature, construction mechanism, associated symbiosis and environmental response of plankton and zoobenthos communities were studied in a freshwater reservoir. The features of phytoplankton, zooplankton, and zoobenthos communities varied significantly by season. Dispersal limitation played an important role in the construction of phytoplankton, zooplankton and zoobenthos communities, and the influence degree decreased in order. Phytoplankton communities showed a stronger distance-decay of similarity than zooplankton communities, while zoobenthos communities did not exhibit any discernible distance-decay of similarity. Co-existence network displayed primarily positive interactions between phytoplankton, zooplankton and zoobenthos all year round (92.23% positive in summer, 86.36% positive in autumn, 100% positive in winter and 67.35% positive in spring). Variation partitioning analyses showed that geographical variables had a stronger influence on community distribution than environmental factors. Mantel test revealed that the communities diversity was significantly associated with temperature, dissolved oxygen, nutrients N and nutrients P. Temperature exhibited the highest explanation rate for seasonal variation in phytoplankton (11.48%, p < 0.001) and zooplankton (16.22%, p < 0.001), according to redundancy analysis. These findings provide a thorough comprehension of the biological communities' dynamic equilibrium in a freshwater reservoir aquatic systems

Additional file 2: of Expanded base editing in rice and wheat using a Cas9-adenosine deaminase fusion

Figure S1. The sequences of the sgRNA expression vectors for rice and wheat. Figure S2. Product purity of plant ABE for rice genomic sites. Figure S3. Product purity of plant ABE for wheat genomic sites. Figure S4. The effect of spacer length of esgRNA on indel efficiency. Figure S5. Identification and analysis of the rice plantlets with targeted A to G conversions by pH-PABE-7-esgRNA. Figure S6. Identification and analysis of the wheat plantlets with targeted A to G conversions by PABE-7. Figure S7. Constructs used for base editing of TaDEP1 and TaGW2 and detection of transgene integration in the resultant T0 mutants. Table S1. Description of sgRNA target sites and sequences. Table S2. Potential off-target sites analyzed for OsACC-T1 endogenous genomic loci. Table S3. PCR primers used in this study. (DOC 6095 kb

Additional file 1: of Expanded base editing in rice and wheat using a Cas9-adenosine deaminase fusion

Sequences Complete coding sequences of the PABE-1 to PABE-7 fusion cistrons optimized in this study. (DOCX 4108 kb

Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS. METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545. FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed. INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment. FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section