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Cancer remains a highly lethal disease globally. The approach centered on REDOX-targeted mitochondrial therapy for cancer has displayed notable benefits. Plant polyphenols exhibit strong REDOX and anticancer properties, particularly by affecting mitochondrial function, yet their structural instability and low bioavailability hinder their utility. To overcome this challenge, researchers have utilized the inherent physical and chemical characteristics of polyphenols and their derivatives to develop innovative nanomedicines for targeting mitochondria. This review examines the construction strategies and anticancer properties of various types of polyphenol-based biological nanomedicine for regulating mitochondria in recent years, such as polyphenol self-assembly, metal–phenol network, polyphenol–protein, polyphenol–hydrogel, polyphenol–chitosan, and polyphenol–liposome. These polyphenolic nanomedicines incorporate enhanced features such as improved solubility, efficient photothermal conversion capability, regulation of mitochondrial homeostasis, and ion adsorption through diverse construction strategies. The focus is on how these polyphenol nanomedicines promote ROS production and their mechanism of targeting mitochondria to inhibit cancer. Furthermore, it delves into the benefits and applications of polyphenolic nanomedicine in cancer treatments, as well as the challenges for future research.

The present study investigated the influence of epigallocatechin-3-gallate (EGCG) and its autoxidation products on insulin sensitivity in db/db mice. Compared to EGCG, autoxidation products of EGCG alleviated diabetic symptoms by suppressing the deleterious renal axis of the renin-angiotensin system (RAS), activating the beneficial hepatic axis of RAS, and downregulating hepatic and renal SELENOP and TXNIP. A molecular weight fraction study demonstrated that polymeric oxidation products were of essential importance. The mechanism of action involved coating polymeric oxidation products on the cell surface to protect against cholesterol loading, which induces abnormal RAS. Moreover, polymeric oxidation products could regulate RAS and SELENOP at doses that were far below cytotoxicity. The proof-of-principal demonstrations of EGCG-derived polymeric oxidation products open a new avenue for discovering highly active polymeric oxidation products based on the oxidation of naturally occurring polyphenols to manage diabetes and other diseases involving abnormal RAS.

Refill friction stir spot welding (RFSSW) was applied to join the 2A12-T4 aluminum alloy successfully, and effects of the tool rotational speed on weld formation, microstructure evolution and mechanical properties of the RFSSW joint were investigated in detail. There existed macrostructure characteristics of bonding ligament and hook associated to the plasticized metal flow in the joint. The microstructure of the joint exhibited variations in the grain size, precipitates distribution and substructure in the width direction. A softened region existed in all the RFSSW joints and its formation could be attributed to the coarsening and dissolution of the S precipitates. Liquation cracks associated to the localized melting of S were observed in the stir zone of the joint produced at the highest rotational speed. The tensile-shear properties of the RFSSW joints were dependent on the hook geometry, distribution of the bonding ligament and hardness of the stir zone. With increasing the rotational speed from 900 to 1300 mm, the hook height increased, the bonding ligament at the weld periphery got more dispersed and the hardness of the stir zone decreased. The optimized RFSSW joint was obtained when the rotational speed was 1300 rpm, and the corresponding tensile-shear failure load was 10,030 N. Two different fracture modes, i.e. the shear fracture mode and shear-plug fracture mode, were identified in the tensile-shear tests. Keywords: Refill friction stir spot welding, Aluminum alloy, Precipitates evolution, Liquation cracks, Mechanical properties

Neurotransmitter catecholamines (dopamine, epinephrine, and norepinephrine) are liable to undergo oxidation, which copper is deeply involved in. Catecholamine oxidation-derived neurotoxicity is recognized as a pivotal pathological mechanism in neurodegenerative diseases. Glutamate, as an excitatory neurotransmitter, is enriched in the brain at extremely high concentrations. However, the chemical biology relationship of these two classes of neurotransmitters remains largely unknown. In the present study, we assessed the influences of glutamate on the autoxidation of catecholamines, the copper- and copper-containing ceruloplasmin-mediated oxidation of catecholamines, the catecholamine-induced formation of quinoprotein, catecholamine/copper-induced hydroxyl radicals, and DNA damage in vitro. The results demonstrate that glutamate, at a physiologically achievable molar ratio of glutamate/catecholamines, has a pronounced inhibitory effect on catecholamine oxidation, catecholamine oxidation-evoked hydroxyl radicals, quinoprotein, and DNA damage. The protective mechanism of glutamate against catecholamine oxidation could be attributed to its restriction of the redox activity of copper via chelation. This previously unrecognized link between glutamate, catecholamines, and copper suggests that neurodegenerative disorders may occur and develop once the built-in equilibrium is disrupted and brings new insight into developing more effective prevention and treatment strategies for neurodegenerative diseases.

We have demonstrated previously that melatonin attenuates hepatotoxicity triggered by high doses of (−)-epigallocatechin-3-gallate (EGCG) in mice. The current work investigated the influence of melatonin on the oncostatic activity of EGCG in two cancer cell lines, wherein melatonin induced an opposite response of p21. In human tongue cancer TCA8113 cells, melatonin-induced p21 and EGCG-mediated formation of quinoproteins were positively associated with the oncostatic effects of melatonin and EGCG. Melatonin-stimulated an increase in p21 which was correlated with a pronounced nuclear translocation of thioredoxin 1 and thioredoxin reductase 1, both of which are known to induce p21 via promoting p53 trans-activation. Melatonin did not influence the EGCG-mediated increase of quinoprotein formation nor did EGCG impair melatonin-induced p21 up-regulation. Co-treatment with both agents enhanced the cell-killing effect as well as the inhibitory activities against cell migration and colony formation. It is known that p21 also plays a powerful anti-apoptotic role in some cancer cells and confers these cells with a survival advantage, making it a target for therapeutic suppression. In human hepatocellular carcinoma HepG2 cells, melatonin suppressed p21 along with the induction of pro-survival proteins, PI3K and COX-2. However, EGCG prevented against melatonin-induced PI3K and COX-2, and melatonin probably sensitized HepG2 cells to EGCG cytotoxicity via down-regulating p21, Moreover, COX-2 and HO-1 were significantly reduced only by the co-treatment, and melatonin aided EGCG to achieve an increased inhibition on Bcl2 and NFκB. These events occurring in the co-treatment collectively resulted in an enhanced cytotoxicity. In addition, the co-treatment also enhanced the inhibitory activities against cell migration and colony formation. Overall, the results gathered from these two cancer cell lines with a divergent p21 response to melatonin show that the various oncostatic activities of melatonin and EGCG together are more robust than each agent alone, suggesting that they may be useful partners in fighting cancer.

The method of Generalized Maximum Entropy (GME), proposed in Golan, Judge and Miller (1996), is an information-theoretic approach that is robust to multicolinearity problem. It uses an objective function that is the sum of the entropies for coefficient distributions and disturbance distributions. This method can be generalized to the weighted GME (W-GME), where different weights are assigned to the two entropies in the objective function. We propose a data-driven method to select the weights in the entropy objective function. We use the least squares cross validation to derive the optimal weights. MonteCarlo simulations demonstrate that the proposedW-GME estimator is comparable to and often outperforms the conventional GME estimator, which places equal weights on the entropies of coefficient and disturbance distributions.

Privacy amplification means that the communication parties extract a shorter but highly confidential string [S] by negotiating on the public channel while sharing a partially confidential string S. Enemy only knows part of the information of the string S and the information that it knows about [S] is almost negligible. Recently, people use the generative adversarial networks (GANs) to realize the secure communication with the present of the adversary. This paper proposes to use the generative adversarial network to achieve a privacy amplification scheme when the adversary ability is limited. First, this paper proposes a privacy amplification implementation scenario. The two parties use the conversation information to generate identical keys, and the adversary listens to the conversation information. Then, with reference to the neural network structure in the basic encrypted communication model of Abadi et al., a privacy amplified communication model is built. The experiment tests the privacy amplified communication when the enemy knows part of the information or the opponent's computing power is weak. By modifying the activation function, increasing the complexity of the model and modifying the filter of convolutional neural network, the final results show that when the adversary gets 70% of the communication information, or when the communicator is more complex than the adversary model, both parties can negotiate a secure key to complete the function of security enhancement.