Vacancies tailoring lattice anharmonicity of Zintl-type thermoelectrics.

While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.

Mangiferin for the Management of Liver Diseases: A Review.

The liver is a digestive and metabolic organ, and several factors can induce liver damage, which is a severe threat to human health. As a natural polyphenolic compound, mangiferin belongs to xanthone glucoside and mainly exists in many plants, such as mango. It is notorious that mangiferin has remarkable pharmacological activities such as anti-inflammatory, anti-tumor, antioxidative stress, antiviral and so on. Emerging evidence indicates the therapeutic benefits of mangiferin against liver disease, including liver injury, nonalcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, and hepatocellular carcinoma. This review aims to summarize the possible underlying signaling mediated by mangiferin in liver disease treatment and the available findings of mangiferin, which can be used to treat different liver diseases and may contribute to mangiferin as a therapeutic agent for liver disease in humans.

Mangiferin Protects DNase 2 Abundance via Nrf2 Activation to Prevent Cytosolic mtDNA Accumulation during Liver Injury.

SCOPE: Mitochondrial DNA (mtDNA) released into the cytosol serves as a member of damage-associated molecular patterns to initiate inflammatory responses. Mangiferin is a xanthonoid derivative, usually isolated from plants including mangoes and iris unguicularis. This study aims to investigate whether mangiferin prevents mtDNA accumulation in the cytosol with a focus on deoxyribonuclease 2 (DNase 2) protection from oxidative damage. METHODS AND RESULTS: Mangiferin administration effectively protects against hepatotoxicity in mice subjected to CCl4 challenge or bile duct ligation (BDL) surgery. Moreover, mangiferin activates nuclear factor erythroid 2-related factor (Nrf2)-antioxidant signaling, reduces cytosolic mtDNA accumulation, and suppresses Toll-like receptor 9 (TLR-9)/myeloid differentiation factor 88 (MyD88)-dependent inflammation in the liver. The study prepares hepatic mtDNA to stimulate hepatocytes, and finds that mangiferin protects DNase 2 protein abundance. mtDNA induces reactive oxygen species (ROS) production to promote DNase 2 protein degradation through oxidative modification, but mangiferin protects DNase 2 protein stability in a Nrf2-dependent manner. In hepatic Nrf2 deficiency mice, the study further confirms that Nrf2 induction is required for mangiferin to clear cytosolic mtDNA and block mtDNA-mediated TLR9/MyD88/nuclear factor kappa-B (NF-κB) inflammatory signaling cascades. CONCLUSION: These findings provide new insights into the role of mangiferin as a liver protecting agent, and suggest protection of DNase 2 as a novel therapeutic strategy for pharmacological intervention to prevent liver damage.

Semisynthetic aurones A14 protects against T-cell acute lymphoblastic leukemia via suppressing proliferation and inducing cell cycle arrest with apoptosis.

BACKGROUND: Acute lymphoblastic leukemia is an aggressive neoplasm and seriously threatens human health. A14 is one kind of semisynthetic aurone that exhibits the capability to inhibit prostate cancer, but little is known about the role of A14 on T-cell acute lymphoblastic leukemia. METHODS: Firstly, the effects of A14 on the ability of leukemia cells to proliferate were measured by Vi-cell counter. Then, we detected the cell cycle and apoptosis by flow cytometry and characterized the related protein expression using immunoblotting. In addition, we constructed stable luciferase expressing cell lines for use in a cell derived xenograft mouse model to measure the effect of A14 on T-cell acute lymphoblastic leukemia. RESULTS: Results exhibited that A14 markedly suppressed cell proliferation and induced G2/M phase arrest along with cell cycles regulating proteins changes. A14 led to apoptosis in leukemia cells, at least partly, through the cytochrome c signaling pathway. Experiments in cell derived xenograft mouse model also showed that A14 markedly ameliorated the survival rate. CONCLUSIONS: The present study revealed that semisynthetic aurones A14 can effectively protect against T-cell acute lymphoblastic leukemia progression both in vitro and in vivo, indicating the capability of A14 as a promising drug for the treatment of T-cell acute lymphoblastic leukemia.

Screening of high-efficiency and low-toxicity antitumor active components in Macleaya cordata seeds based on the competitive effect of drugs on double targets by a new laminar flow chip.

It is urgent to obtain targeted drugs that selectively bind to pathological targets rather than physiological targets in the early stage of drug screening. G-Quadruplex has become one of the important targets in the development of anti-tumor drugs. However, drugs that target quadruplexes may also bind to dsDNA, which may lead to adverse reactions. In this study, a new three-phase laminar flow chip was constructed to enable the multi-components of a traditional Chinese medicine extract to dynamically and competitively bind with G-quadruplex DNA (on target) and double-stranded DNA (off target), so as to select high-efficiency and low-toxicity anti-tumor drugs. The results showed that there were five compounds in the extracts of Macleaya cordata seeds that exhibited obvious differences in binding to the two targets. Furthermore, the binding constants and modes of four identified alkaloids as they bound to two DNA targets were verified by fluorescence spectra and molecular docking methods. The toxicity to HepG2 and LO2 cells from the four alkaloids was also compared. The results showed that sanguinarine and chelerythrine could be used as candidate drugs with stronger binding to HT24 than DNA26. The chip can also be used for other types of double-target screening of other traditional Chinese medicine extracts or compound libraries.

Mangiferin protects against alcoholic liver injury via suppression of inflammation-induced adipose hyperlipolysis.

Adipose dysfunction is closely associated with alcoholic liver disease. The impact of mangiferin on ethanol-induced liver injury and the probable underlying molecular mechanism has not been sufficiently addressed. In the present study, mice were subjected to a chronic plus a single binge ethanol feeding to induce liver injury. In addition, the differentiated adipocytes from primary mouse adipocytes were isolated and used for the mechanism studies. Our study demonstrated that mangiferin protects against ethanol induced adipose hyperlipolysis by restoring PDE3B stability, which is associated with activating the AMPK/TBK1 signaling and suppressing the noncanonical NF-κB activation, leading to the reduction of free fatty acid release and the amelioration of ethanol-induced liver injury. Our findings identify that mangiferin ameliorates alcoholic liver injury via suppression of inflammation-induced adipose hyperlipolysis, suggesting that mangiferin might be a potential effective agent for the management of alcoholic liver injury.