Brassica napus (2n = 4x = 38, AACC) is an important allopolyploid crop derived from interspecific crosses between Brassica rapa (2n = 2x = 20, AA) and Brassica oleracea (2n = 2x = 18, CC). However, no truly wild B. napus populations are known; its origin and improvement processes remain unclear. Here, we resequence 588 B. napus accessions. We uncover that the A subgenome may evolve from the ancestor of European turnip and the C subgenome may evolve from the common ancestor of kohlrabi, cauliflower, broccoli, and Chinese kale. Additionally, winter oilseed may be the original form of B. napus. Subgenome-specific selection of defense-response genes has contributed to environmental adaptation after formation of the species, whereas asymmetrical subgenomic selection has led to ecotype change. By integrating genome-wide association studies, selection signals, and transcriptome analyses, we identify genes associated with improved stress tolerance, oil content, seed quality, and ecotype improvement. They are candidates for further functional characterization and genetic improvement of B. napus.

Necroptosis is mediated by a signaling complex called necrosome, containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated oligomerization, but the signaling events based on this scaffold has not been fully addressed. By using inducible dimer systems we found that RIP1-RIP1 interaction is dispensable for necroptosis; RIP1-RIP3 interaction is required for necroptosis signaling, but there is no necroptosis if no additional RIP3 protein is recruited to the RIP1-RIP3 heterodimer, and the interaction with RIP1 promotes the RIP3 to recruit other RIP3; RIP3-RIP3 interaction is required for necroptosis and RIP3-RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer-induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo-interaction in the complex, rather than whether RIP3 has formed homo polymer, is important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule autophosphorylation, which is required for the recruitment of MLKL. Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to induce necroptosis. As RIP1-RIP3 heterodimer itself cannot induce necroptosis, the RIP1-RIP3 heterodimeric amyloid fibril is unlikely to directly propagate necroptosis. We propose that the signaling events after the RIP1-RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis. Cell Death and Differentiation (2014) 21, 1709-1720; doi:10.1038/cdd.2014.77; published online 6 June 2014Necroptosis is a type of programmed necrosis characterized by necrotic morphological changes, including cellular organelle swelling, cell membrane rupture, 1-3 and dependence of receptor-interacting protein (RIP)1 4 and RIP3. [5][6][7] Physiological function of necroptosis has been illustrated in host defense, [8][9][10][11] inflammation, 12-16 tissue injury, 10,17,18 and development. [19][20][21] Necroptosis can be induced by a number of different extracellular stimuli such as tumor necrosis factor (TNF). TNF stimulation leads to formation of TNF receptor 1 (TNFR1) signaling complex (named complex I), and complex II containing RIP1, TRADD, FAS-associated protein with a death domain (FADD), and caspase-8, of which the activation initiates apoptosis. If cells have high level of RIP3, RIP1 recruits RIP3 to form necrosome containing FADD, [22][23][24] caspase-8, RIP1, and RIP3, and the cells undergo necroptosis. 25,26 Caspase-8 and FADD negatively regulates necroptosis, 27-30 because RIP1, RIP3, and CYLD are potential substrates of caspase-8. [31][32][33][34] Necrosome also suppresses apoptosis but the underlying mechanism has not been described yet. Mixed-lineage kinase domain-like (ML...

Developing yellow-seeded Brassica napus (rapeseed) with improved qualities is a major breeding goal. The intermediate and final metabolites of the phenylpropanoid and flavonoid pathways affect not only oil quality but also seed coat colour of B. napus. Here, the accumulation of phenolic compounds was analysed in the seed coats of black-seeded (ZY821) and yellow-seeded (GH06) B. napus. Using toluidine blue O staining and liquid chromatography–mass spectrometry, histochemical and biochemical differences were identified in the accumulation of phenolic compounds between ZY821 and GH06. Two and 13 unique flavonol derivatives were detected in ZY821 and GH06, respectively. Quantitative real-time PCR analysis revealed significant differences between ZY821 and GH06 in the expression of common phenylpropanoid biosynthetic genes (BnPAL and BnC4H), common flavonoid biosynthetic genes (BnTT4 and BnTT6), anthocyanin- and proanthocyandin-specific genes (BnTT3 and BnTT18), proanthocyandin-specific genes (BnTT12, BnTT10, and BnUGT2) and three transcription factor genes (BnTTG1, BnTTG2, and BnTT8) that function in the flavonoid biosynthetic pathway. These data provide insight into pigment accumulation in B. napus, and serve as a useful resource for researchers analysing the formation of seed coat colour and the underlying regulatory mechanisms in B. napus.

Background and aims: Obesity, especially abdominal obesity, has been considered a risk factor for diabetic complications. Many abdominal obesity indices have been established, including neck circumference (NC), waist-to-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI) and the Chinese visceral adiposity index (CVAI). However, studies investigating the associations between these indices and diabetic complications are limited. The objective of this study was to investigate the associations of the abdominal obesity indices with cardiovascular and cerebrovascular disease (CVD), diabetic kidney disease (DKD) and diabetic retinopathy (DR). Methods: A total of 4658 diabetic participants were enrolled from seven communities in Shanghai, China, in 2018. Participants completed questionnaires and underwent blood pressure, glucose, lipid profile, and urine albumin/creatinine ratio measurements; fundus photographs; and anthropometric parameters, including height, weight, waist circumference (WC), NC and hip circumference (HC). Results: In men, a one standard deviation (SD) increase in CVAI level was significantly associated with a greater prevalence of CVD (OR 1.35; 95% CI 1.13, 1.62) and DKD (OR 1.38; 95% CI 1.12, 1.70) (both P < 0.05). In women, a one SD increase in CVAI level was significantly associated with a greater prevalence of CVD (OR 1.32; 95% CI 1.04, 1.69) and DKD (OR 2.50; 95% CI 1.81, 3.47) (both P < 0.05). A one SD increase in NC was significantly associated with a greater prevalence of CCA plaque in both men (OR 1.26; 95% CI 1.10, 1.44) and women (OR 1.20; 95% CI 1.07, 1.35). These associations were all adjusted for potential confounding factors. Conclusions: CVAI was most strongly associated with the prevalence of CVD and DKD among the abdominal obesity indices, and NC was unique associated with the prevalence of CCA plaque in Chinese adults with diabetes.

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Plasmonic nanostructures are of potential in acting as a type of optical agents for cancer photothermal therapy. To effectively function as photothermal therapy agents, plasmonic nanostructures are strongly desired to have good biocompatibility and high photothermal conversion efficiencies. In this study, poly(diallyldimethylammonium chloride)-coated porous Pt nanoparticles are synthesized for photothermal therapy. The Pt nanoparticles possess broadband near-infrared light absorption in the range from 650 to 1200 nm, therefore allowing for selecting different laser wavelengths for photothermal therapy. The as-prepared Pt nanoparticles exhibit remarkable photothermal conversion efficiencies under 809 and 980 nm laser irradiation. In vitro studies indicate that the Pt nanoparticles display good biocompatibility and high cellular uptake efficiencies through an endocytosis pathway. Photothermal heating using 808 nm laser irradiation (>7.0 W cm , 3 min) leads to notable cytotoxic effect, and more than 70% of cells are photothermally ablated after 3 min irradiation at 8.4 W cm . Furthermore, simultaneous application of photothermal therapy synergistically enhances the cytotoxicity of an anti-cancer drug doxorubicin. Therefore, the porous Pt nanoparticles have great potential as an attractive photothermal agent for cancer therapy.

Objective. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and easily measurable laboratory index indicating systemic inflammation, while the application of many other inflammatory markers has been limited in daily clinical practice. However, large population studies about investigating the associations of the NLR level with diabetic complications including cardiovascular and cerebrovascular diseases (CVD), diabetic kidney disease (DKD), and diabetic retinopathy (DR) in the same population were limited. The aim of our study is to evaluate the associations between the NLR level and the prevalence of CVD, DKD, and DR in adults with diabetes simultaneously. Methods. A cross-sectional survey of 4,813 diabetic adults was conducted in seven communities in China. Persons underwent several medical examinations, including the measurement of anthropometric factors, blood pressure, routinely analyzed leukocyte characteristics, glucose, lipid profiles, urine albumin/creatinine ratio, and fundus photographs. Results. Compared with the first quartile of the NLR level, the odds of having CVD was significantly increased by 21% for participants in the highest quartile (OR 1.21; 95% CI 1.00, 1.47) (P for trend<0.05). Similarly, the prevalence of DKD among participants in the highest quartile of the NLR level was significantly increased by 150% (OR 2.50; 95% CI 1.95, 3.19) (P for trend<0.05). However, no association was found between the NLR level and the prevalence of DR (P for trend>0.05). These associations were all fully adjusted. Conclusions. A higher NLR level was associated with an increased prevalence of CVD and DKD, other than DR, in diabetic adults.

Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11–45 µg/kg/day) starting on the day 1 after first immunization. The arthritis scores (P<0.05) and the arthritis incidence (P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11∼45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05). Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS–RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS–RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-β-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the angiogenic activators and inhibiting the activation of mitogen-activated protein kinase downstream signal pathway.