Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. PURPOSE: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. METHODS: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. RESULTS: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. CONCLUSION: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.

Hierarchically Structured Nanocomposites via Mixed-Graft Block Copolymer Templating: Achieving Controlled Nanostructure and Functionality.

Integrating inorganic and polymerized organic functionalities to create composite materials presents an efficient strategy for the discovery and fabrication of multifunctional materials. The characteristics of these composites go beyond a simple sum of individual component properties; they are profoundly influenced by the spatial arrangement of these components and the resulting homo-/hetero-interactions. In this work, we develop a facile and highly adaptable approach for crafting nanostructured polymer-inorganic composites, leveraging hierarchically assembling mixed-graft block copolymers (mGBCPs) as templates. These mGBCPs, composed of diverse polymeric side chains that are covalently tethered with a defined sequence to a linear backbone polymer, self-assemble into ordered hierarchical structures with independently tuned nano- and mesoscale lattice features. Through the coassembly of mGBCPs with diversely sized inorganic fillers such as metal ions (ca. 0.1 nm), metal oxide clusters (0.5-2 nm), and metallic nanoparticles (>2 nm), we create three-dimensional filler arrays with controlled interfiller separation and arrangement. Multiple types of inorganic fillers are simultaneously integrated into the mGBCP matrix by introducing orthogonal interactions between distinct fillers and mGBCP side chains. This results in nanocomposites where each type of filler is selectively segregated into specific nanodomains with matrix-defined orientations. The developed coassembly strategy offers a versatile and scalable pathway for hierarchically structured nanocomposites, unlocking new possibilities for advanced materials in the fields of optoelectronics, sensing, and catalysis.

Hierarchically engineered nanostructures from compositionally anisotropic molecular building blocks.

The inability to synthesize hierarchical structures with independently tailored nanoscale and mesoscale features limits the discovery of next-generation multifunctional materials. Here we present a predictable molecular self-assembly strategy to craft nanostructured materials with a variety of phase-in-phase hierarchical morphologies. The compositionally anisotropic building blocks employed in the assembly process are formed by multicomponent graft block copolymers containing sequence-defined side chains. The judicious design of various structural parameters in the graft block copolymers enables broadly tunable compositions, morphologies and lattice parameters across the nanoscale and mesoscale in the assembled structures. Our strategy introduces advanced design principles for the efficient creation of complex hierarchical structures and provides a facile synthetic platform to access nanomaterials with multiple precisely integrated functionalities.

Rapid Access to Diverse Multicomponent Hierarchical Nanostructures from Mixed-Graft Block Copolymers.

Multicomponent nanostructured materials assembled from molecular building blocks received wide attention due to their precisely integrated multifunctionalities. However, discovery of these materials with desirable composition and morphology was limited by their low synthetic scalability and narrow structural tuning window with given building blocks. Here, we report a scalable and diversity-oriented synthetic approach to hierarchically structured nanomaterials based on a few readily accessible building blocks. Mixed-graft block copolymers containing sequence-defined side chains were prepared through ring-opening metathesis copolymerization of three or four types of macromonomers. Intramolecularly defined interfaces promoted the formation of ordered hierarchical structures with lattice sizes tunable across multiple length scales. The same set of macromonomers were arranged and combined in different ways, providing access to diverse morphologies in the resultant structures.

PEG-stabilized coaxial stacking of two-dimensional covalent organic frameworks for enhanced photocatalytic hydrogen evolution.

Two-dimensional covalent organic frameworks (2D COFs) featuring periodic frameworks, extended π-conjugation and layered stacking structures, have emerged as a promising class of materials for photocatalytic hydrogen evolution. Nevertheless, the layer-by-layer assembly in 2D COFs is not stable during the photocatalytic cycling in water, causing disordered stacking and declined activity. Here, we report an innovative strategy to stabilize the ordered arrangement of layered structures in 2D COFs for hydrogen evolution. Polyethylene glycol is filled up in the mesopore channels of a ß-ketoenamine-linked COF containing benzothiadiazole moiety. This unique feature suppresses the dislocation of neighbouring layers and retains the columnar π-orbital arrays to facilitate free charge transport. The hydrogen evolution rate is therefore remarkably promoted under visible irradiation compared with that of the pristine COF. This study provides a general post-functionalization strategy for 2D COFs to enhance photocatalytic performances.

Adsorption Behavior of Polymer Chain with Different Topology Structure at the Polymer-Nanoparticle Interface.

The effect of the polymer chain topology structure on the adsorption behavior in the polymer-nanoparticle (NP) interface is investigated by employing coarse-grained molecular dynamics simulations in various polymer-NP interaction and chain stiffness. At a weak polymer-NP interaction, ring chain with a closed topology structure has a slight priority to occupy the interfacial region than linear chain. At a strong polymer-NP interaction, the "middle" adsorption mechanism dominates the polymer local packing in the interface. As the increase of chain stiffness, an interesting transition from ring to linear chain preferential adsorption behavior occurs. The semiflexible linear chain squeezes ring chain out of the interfacial region by forming a helical structure and wrapping tightly the surface of NP. In particular, this selective adsorption behavior becomes more dramatic for the case of rigid-like chain, in which 3D tangent conformation of linear chain is absolutely prior to the 2D plane orbital structure of ring chain. The local packing and competitive adsorption behavior of bidisperse matrix in polymer-NP interface can be explained based on the adsorption mechanism of monodisperse (pure ring or linear) case. These investigations may provide some insights into polymer-NP interfacial adsorption behavior and guide the design of high-performance nanocomposites.

Possible mechanism underlying the effect of Heshouwuyin, a tonifying kidney herb, on sperm quality in aging rats.

BACKGROUND: Herb mixtures are used as alternatives to hormone therapy in China for the treatment of partial androgen deficiency in aging men. However, the compositions of these herb mixtures are complex and their mechanisms are often unknown. This study investigates the effect of Heshouwuyin, a Chinese herbal compound for invigorating the kidney, on the control of testosterone secretion and sperm function. METHODS: Aged Wistar rats were administered with Heshouwuyin. A Shouwu pill group and young group were used as controls. RESULTS: Morphology, chemiluminescence, fluorescence immunohistochemistry, and western blot showed that the epididymal sperm of naturally aged rats had intact plasma membranes. They also had abnormal mitochondrial function and DNA integrity, a significant decline in serum testosterone levels, and significant pathological changes in the structure of testicular tissues. Heshouwuyin significantly improved sperm function and serum testosterone levels, and improved testicular morphology. Moreover, the curative efficacy of Heshouwuyin after 60 days was better than that of Heshouwuyin after 30 days and the Shouwu pill group. CONCLUSION: Heshouwuyin exerts an important role in controlling testosterone secretion and sperm function.

[Effect of Heshouwuyin on the expression of Cox7a2 protein in testis tissue of exercised-induced fatigue rat].

OBJECTIVE: To explore the effect of Heshouwuyin on the expression of cytochrome C oxidase7a2 (Cox7a2) in testis tissue of rats with exercised-induced fatigue. METHODS: Fifty SD rats were divided into normal control group (A group), Heshouwuyin administered normal group (B group), model control group (C group), Heshouwuyin treated group (D group) and Heshouwuyin prevented group (E group) randomly with 10 rats for each. The exercise-induced fatigue models in rats of C, D, E groups were established. The rats in D group were treated with Heshouwuyin [20 g/(kg x d), contained crude drug 9.6 g/mL] for 60 days (during the 42 days of modeling and after the 18 days of modeling). The rats in E group were also treated with Heshouwuyin for 60 days (but before the 18 days of modeling and during the 42 days of modeling). Beckmancoulter Unicel Dxl 800 was used to detect the level of serum testosterone, according to the manufacture's instructions. Western blot and RT-PCR were used to observe the differential expression of Cox7a2. RESULTS: The level of serum testosterone in C group was decreased compared with A group (P < 0.05), which implied the success of modeling. Compared with group A, the level of serum testosterone in B, D, E groups were increased (P < 0.05). Cox7a2 protein was expressed mainly in leydig cell and spermatocyte. Compared with A,B, D, E groups, the expression of Cox7a2 protein and mRNA in C group increased (P < 0.05), and there no significant difference was observed between group A and B, as well as group D and E. CONCLUSION: The expression of Cox7a2 was down-regulated by Heshouwuyin.

Effects of moderate exercise over different phases on age-related physiological dysfunction in testes of SAMP8 mice.

Oxidative stress and chronic inflammation have been implicated in the testicular aging process. Different types and moderate-intensity of regular exercise may reduce age-related physiological dysfunction associated with inflammation and oxidative stress, but such effects of moderate-intensity of exercise over different phases of life in testes have not been reported. In this study, male SAMP8 mice, a senescence-accelerated strain, were maintained as sedentary (sed) or subjected to daily 15-min periods of swimming exercise between ages of 2-7 months (lifelong), 2-4 months (earlier) or 5-7 months (late). Age-related changes, including serum testosterone levels and biomarkers of inflammation and oxidative stress were analyzed at the end of the experiment. All exercise groups showed significantly greater serum testosterone levels and decreased age-related inflammation and oxidative stress compared with the sedentary group. Exercise also increased expression and activity of the nuclear factor erythroid 2-related factor (Nrf2), a transcriptional regulator of the cellular anti-oxidant system, and decreased expression and activity of nuclear factor kappa beta (NF-κB), a mediator of inflammatory molecules, in the nucleus of testicular cells. However, lifelong and earlier groups generally showed significantly better protective effects than the late group against age-related physiological dysfunction in testes. Thus, lifelong exercise and earlier phase exercise were most effective in counteracting oxidative stress and inflammation and in preserving testes function through regulation of Nrf2 and NF-κB. These results advocate the benefits of lifelong exercise and emphasize a greater protection against male aging by instituting exercise earlier rather than late in life.