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Background: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated. Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo. Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice. Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.

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Results Synthesis and Characterizations of PolymerBefore encapsulation of Gef and complexation of YAP-siRNA, we developed a novel amphiphilc block dendritic polymer, ployOEGMA-block-poly [Dendron-Ppa] (Polymer), as a nanocarrier for Gef and YAP-siRNA. Polymer was composed of: 1) a hydrophilic polymer of OEGMA, 2) a reduction-sensitive peptide dendron, and 3) a hydrophobic polymer of Ppa. We first synthesized low molecular weight dendron (Py-SS-Dendron)

The aim of this study was to investigate how mesenchymal stromal cells (MSCs) modulate metabolic balance and attenuate hepatic lipotoxicity in the context of non‐alcoholic fatty liver disease (NAFLD). In vivo, male SD rats were fed with high‐fat diet (HFD) to develop NAFLD; then, they were treated twice by intravenous injections of rat bone marrow MSCs. In vitro, HepG2 cells were cocultured with MSCs by transwell and exposed to palmitic acid (PA) for 24 hours. The endoplasmic reticulum (ER) stressor thapsigargin and sarco/ER Ca2+‐ATPase (SERCA2)–specific siRNA were used to explore the regulation of ER stress by MSCs. We found that MSC administration improved hepatic steatosis, restored systemic hepatic lipid and glucose homeostasis, and inhibited hepatic ER stress in HFD‐fed rats. In hepatocytes, MSCs effectively alleviated the cellular lipotoxicity. Particularly, MSCs remarkably ameliorated the ER stress and intracellular calcium homeostasis induced by either PA or thapsigargin in HepG2 cells. Additionally, long‐term HFD or PA stimulation would activate pyroptosis in hepatocytes, which may contribute to the cell death and liver dysfunction during the process of NAFLD, and MSC treatment effectively ameliorates these deleterious effects. SERCA2 silencing obviously abolished the ability of MSCs against the PA‐induced lipotoxicity. Conclusively, our study demonstrated that MSCs were able to ameliorate liver lipotoxicity and metabolic disturbance in the context of NAFLD, in which the regulation of ER stress and the calcium homeostasis via SERCA has played a key role.

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Background: Gold nanoparticles (AuNPs) have shown great promise in various biomedical applications, but their effects on male reproductive function remain to be ascertained. The aim of this study was to investigate the uptake, cytotoxicity and testosterone production inhibition of AuNPs in mouse Leydig cells, as well as their accumulation in the testes of male mice and their effects on male reproductive function. Results: AuNPs (5 nm) were able to be internalized into the endosomes/lysosomes of TM3 Leydig cells, induce the formation of autophagosomes, increase the production of reactive oxygen species (ROS), and disrupt the cell cycle in S phase, resulting in concentrationdependent cytotoxicity and DNA damage. Interestingly, AuNPs significantly reduced testosterone production in TM3 cells by inhibiting the expression of 17α-hydroxylase, an important enzyme in androgen synthesis. After repeated intravenous injection, AuNPs gradually accumulated and retained in the testes of male BALB/c mice in a dosedependent manner. One week after withdrawal, the level of plasma testosterone in the 0.5 mg/kg AuNPs group was significantly reduced compared to that in the PBS control group, accompanied by the decreased expression of 17α-hydroxylase in the testes. In addition, AuNPs treatment significantly increased the rate of epididymal sperm malformation, but without affecting fertility. Conclusion: Our results suggest that AuNPs can accumulate in the testes and reduce testosterone production in Leydig cells by down-regulating the expression of 17αhydroxylase, thus affecting the quality of epididymal sperm.

In this work, the interfacial properties of a series of metal-free organic naphthodithienothiophene (NDTT)-based photosensitizers adsorbed on TiO2 surfaces were investigated by a combination of ab initio calculations and experimental measurements. The calculations and experiments reveal that because of the efficient charge transfer from the adsorbed dyes to TiO2 nanocrystal surface there is an upward shift for the energy levels of dyes and a downward shift for the conduction band of surface TiO2 and that the band gaps for both of them are also reduced. Such electronic level alignments at the interface would lead to increased light absorption range by adsorbed dyes and increased driving force for charge injection but reduced open-circuit potential (V(oc)). More interestingly, we found that molecule engineering of the donor group and introducing additional electron-withdrawing unit have little effect on the electronic level alignments at the interface (because band gaps of the dyes adsorbed on TiO2 surfaces become approximately identical when compared with those of the dyes measured in solution) but that they can affect the steric effect and the charge separation at the interface to tune V(oc) and the short-circuit current density (J(sc)) effectively. All these findings suggest that optimizing the interfacial properties of dyes adsorbed on TiO2 surfaces by synchronously modifying steric effects of dye molecules anchored on TiO2 and charge-transfer and separation properties at the interfaces is important to construct efficient dye-sensitized solar cells.