Fucoxanthin ameliorated myocardial fibrosis in STZ-induced diabetic rats and cell hypertrophy in HG-induced H9c2 cells by alleviating oxidative stress and restoring mitophagy.

Diabetic cardiomyopathy (DCM) is one of the leading causes of death in diabetic patients, and is accompanied by increased oxidative stress and mitochondrial dysfunction. Fucoxanthin (FX), as a marine carotenoid, possesses strong antioxidant activity. The main purpose of our study was to explore whether FX could attenuate experimental cardiac hypertrophy by affecting mitophagy and oxidative stress. We found that FX improved lipid metabolism, myocardial damage, myocardial fibrosis and hypertrophy in the myocardial tissue of STZ-induced diabetic rats. Additionally, FX upregulated Nrf2 signaling to reduce the level of reactive oxygen species (ROS). FX also promoted Bnip3/Nix signaling to improve mitochondrial function and reduced the levels of mitochondrial and intracellular ROS, thereby reversing HG-induced H9c2 cell hypertrophy. However, treatment with the autophagy inhibitor CQ abolished the anti-hypertrophic effect of FX, accompanied by impaired mitochondrial function and increased ROS levels. In conclusion, we found that FX reduced the accumulation of TGF-ß1, FN and α-SMA to relieve myocardial fibrosis in STZ-induced diabetic rats, and FX up-regulated Bnip3/Nix to promote mitophagy and enhanced Nrf2 signaling to alleviate oxidative stress, thereby inhibiting hypertrophy in HG-induced H9c2 cells. These results imply that FX may be developed as a functional food for DCM.

Fucoxanthin regulates Nrf2 signaling to decrease oxidative stress and improves renal fibrosis depending on Sirt1 in HG-induced GMCs and STZ-induced diabetic rats.

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial cellular defense factor to cope with oxidative stress. Silent information regulator T1 (Sirt1) is a deacetylase with antioxidative stress activity. Fucoxanthin is a marine-derived carotenoid. This study was conducted to investigate whether fucoxanthin could alleviate oxidative stress by activating Sirt1/Nrf2 signaling to alleviate DN. In streptozotocin-induced diabetic rats, fucoxanthin treatment effectively improved renal function, alleviated glomerulosclerosis. Fucoxanthin reversed the decreased protein levels of Sirt1 and Nrf2 in the kidney of diabetic rats and glomerular mesangial cells cultured in high glucose. Conversely, EX527, a Sirt1 inhibitor, counteracted the effect of fucoxanthin on the expression of Nrf2. Furthermore, in vivo and vitro results showed that fucoxanthin treatment reversed the low expression and activity of superoxide dismutase and heme oxygenase 1, depending on Sirt1 activation. Our results suggest that fucoxanthin improves diabetic kidney function and renal fibrosis by activating Sirt1/Nrf2 signaling to reduce oxidative stress.

Controlling Ultra-Large Optical Asymmetry in Amorphous Molecular Aggregations.

Although ultra-large optical asymmetry appears in crystalline materials, distractions from the mesoscopic ordering often causes inauthenticity in chiropticity. In amorphous materials, however, it remains challenging and elusive to achieve large chiropticity. Herein, we report the quantitative control of chiral amplification, on amorphous supramolecular structures of cholesteryl-linked bis(dipyrrinato)zinc(II), to an exceptionally high level. A proper chiral packing of the building block at several molecular scale considerably contributes to the absorptive dissymmetry factor gabs , although the system is overall disordered. The intense and tunable aggregation strength renders a variable gabs value up to +0.10 and +0.31 in the solution and in film state. On this basis, a superior ON-OFF switching of chiropticity is realized under external stimuli. This work establishes a general design principle to control over ultra-large optical asymmetry on a wider scope of chiral materials.

Rational Design of 2-Chloroadenine Derivatives as Highly Selective Phosphodiesterase 8A Inhibitors.

To validate the hypothesis that Tyr748 is a crucial residue to aid the discovery of highly selective phosphodiesterase 8A (PDE8A) inhibitors, we identified a series of 2-chloroadenine derivatives based on the hit clofarabine. Structure-based design targeting Tyr748 in PDE8 resulted in the lead compound 3a (IC50 = 0.010 µM) with high selectivity with a reasonable druglike profile. In the X-ray crystal structure, 3a bound to PDE8A with a different mode from 3-isobutyl-1-methylxanthine (a pan-PDE inhibitor) and gave a H-bond of 2.7 Å with Tyr748, which possibly interprets the 220-fold selectivity of 3a against PDE2A. Additionally, oral administration of compound 3a achieved remarkable therapeutic effects against vascular dementia (VaD), indicating that PDE8 inhibitors could serve as potential anti-VaD agents.

Tilapia Skin Peptides Ameliorate Diabetic Nephropathy in STZ-Induced Diabetic Rats and HG-Induced GMCs by Improving Mitochondrial Dysfunction.

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes, and mitochondrial dysfunction has been observed in the kidneys of diabetic patients. Tilapia skin peptides (TSPs) are mixtures of small-molecular-weight peptides derived from tilapia skin. Rising evidence suggests that bioactive peptides from marine sources are beneficial for DN. This study aimed to investigate whether TSPs can alleviate the pathological progress in experimental DN by improving mitochondrial dysfunction through the activation of Bnip3/Nix signaling. In the current study, TSPs treatment alleviated the metabolic parameters and renal morphology in streptozotocin-induced diabetic rats. Additionally, TSPs treatment significantly activated Bnip3/Nix signaling and improved the mitochondrial morphology, reversed the over-production of mitochondrial superoxide and cellular reactive oxygen species and the decreased mitochondrial membrane potential, thereby inhibiting the expressions of fibronectin, collagen IV and intercellular cell adhesion molecule-1 in glomerular mesangial cells induced by high glucose. Collectively, our results suggest that TSPs show the renoprotective effect on DN by improving mitochondrial dysfunction, and they can be a potential therapeutic strategy for DN.

Chirality Transfer in Carbon Dot-Composited Sol-Gel Systems for Excitation-Dependent Circularly Polarized Luminescence.

In situ control of a circularly polarized luminescent (CPL) signal is desirable but rarely addressed. Even to compare with traditional chemical regulations, controlling the CPL signal at the material level using simple physical manipulation (such as photoexcitation) can be more convenient and preferable. In this work, we have constructed carbon dot-based composite luminescent materials with CPL activity. The materials can exist in the sol-gel state in a mixture solvent by chiral co-assembly, and chirality transfer occurred in the supramolecular assemblies and induced the CPL activity. Owing to the unique luminescent properties of the carbon dot component, the obtained CPL signal of the composite system is therefore excitation-dependent. The control ability of the CPL signal may allow the composite materials to find potential usage in advanced chirality-related fields.

An excitation-dependent ratiometric dual-emission strategy for the large-scale enhancement of fluorescent tint control.

An alternative and convenient strategy for preparing carbon dots (CDs) with multicolor and dual-emission fluorescence is described. For this dual-emission characteristic, the short-wavelength emission reveals unique excitation-dependent fluorescence behavior, during which the long-wavelength emission remains unshifted regardless of the excitation. Consequently, such excitation-dependent ratiometric dual emission can be applied into a fluorescent tint control of this material between the cold and warm white-light regions. This unique property allows the CDs to be further translated into film sheets for visual detection of the irradiation source, and to also be conjugated with calf thymus DNA for multichannel bioimaging. These results offer new insights for the development of easy-to-handle techniques for material luminescent color tuning.

Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs.

As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN.

Crystal Multi-Conformational Control Through Deformable Carbon-Sulfur Bond for Singlet-Triplet Emissive Tuning.

Crystal-state luminophores have been of great interest in optoelectronics for years, whereas the excited state regulation at the crystal level is still restricted by the lack of control ways. We report that the singlet-triplet emissive property can be profoundly regulated by crystal conformational distortions. Employing fluoro-substituted tetrakis(arylthio)benzene luminophores as prototype, we found that couples of molecular conformations formed during different crystallizations. The deformable carbon-sulphur bond essentially drove the distortion of the molecular conformation and varied the stacking mode, together with diverse non-covalent interactions, leading to the proportional adjustment of the fluorescence and phosphorescence bands. This intrinsic strategy was further applied for solid-state multicolor emissive conversion and mechanoluminescence, probably offering new insights for design of smart crystal luminescent materials.

Astaxanthin ameliorates experimental diabetes-induced renal oxidative stress and fibronectin by upregulating connexin43 in glomerular mesangial cells and diabetic mice.

Oxidative stress is the major cause of renal fibrosis in the progression of DN. Connexin43 (Cx43) exerts an anti-fibrosis effect on diabetic kidneys. The current study aimed to investigate whether astaxanthin (AST) could ameliorate the pathological progression of DN by upregulating Cx43 and activating the Nrf2/ARE signaling, which is a pivotal anti-oxidative stress system, to strengthen the cellular anti-oxidative capacity and diminish fibronectin (FN) accumulation in HG-induced glomerular mesangial cells (GMCs). Our hypothesis was verified in GMCs and the kidneys from db/db mice by western blot, immunofluorescence, immunohistochemistry, immunoprecipitation, dual luciferase reporter assay and reactive oxygen related detection kits. Results showed that AST simultaneously upregulated the Cx43 protein level and promoted the Nrf2/ARE signaling activity in the kidney of db/db mice and HG-treated GMCs. However, Cx43 depletion abrogated the Nrf2/ARE signaling activation induced by AST. AST reduced the interaction between c-Src and Nrf2 in the nuclei of GMCs cultured with HG, thereby enhancing the Nrf2 accumulation in the nuclei of GMCs. Our data suggested that AST promoted the Nrf2/ARE signaling by upregulating the Cx43 protein level to prevent renal fibrosis triggered by HG in GMCs and db/db mice. c-Src acted as a mediator in these processes.

[Freezing resistance and injury indices for different cultivars of winter-spring wheat in Huang-Huai-Hai Plain. I . Comparison of freezing resistance for different cultivars of winter-spring wheat during mid-winter period].

The relationships between mortality rate and low temperature for different cultivars of winter-spring wheat during mid-winter period were identified through two-year outdoor potting experiments and indoor manually controlled freezing experiments. We defined the lethally critical temperature and the density of antifreeze capability when the mortality rate reached 10%, 20% and 50% for different cultivars of winter-spring wheat during mid-winter period. The strong-winterness wheat (Yanda 1817 and Jing 411) showed the best freezing resistance and the 50%-lethal temperatures (LT50) of these two cultivars were -21.5 °C and -21.2 °C, respectively. The freezing resistance of winterness wheat and weak-winternes wheat were worse than that of strong-winterness wheat. The LT50 of winterness wheat cultivars Nongda 211 and Nongda 5363 were -21.1 °C and -20.3 °C, while that of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 were -18.5 °C and -18.4 °C , respectively. Springness wheat (Zheng 9023 and Yanzhan 4110) showed the worst freezing resistance, and the LT50 were -15.4 °C and -14.7 °C, respectively. When temperature declined to freezing injury occurred, mortality rate increment for weak-winterness wheat was the highest for each 1 °C decrease. The mortality rates of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 increased by 16.8% and 25.8%, and that of winterness wheat cultivars Nongda 211 and Nongda 5363 increased by 14.7% and 18.9%. The mortality rate of strong-winterness wheat cultivars Yanda 1817 and Jing 411 increased by 15.4% and 13.1%, and that of springiness wheat cultivas Zheng 9023 and Yanzhan 4110 increased by 13.8% and 15.1%. Comparatively, if temperature decreased continuously after the occurrence of freezing injury, the weak-winterness wheat would suffer greater risk.