Enhanced photothermal-ferroptosis effects based on RBCm-coated PDA nanoparticles for effective cancer therapy.

Ferroptosis, a type of programmed cell death induced by the iron-dependent lipid hydroperoxide pathway, has attracted widespread attention. However, Fenton response-dependent ferroptosis has many limitations, such as insufficient reaction conditions in the tumor micro-environment. Here, we propose an all-in-one phototherapy nanoplatform consisting of iron-polydopamine (Fe-PDA), a folic acid-modified red blood cell membrane (FA-RBCm), and epirubicin (EPI), namely, Fe-PDA-EPI@FA-RBCm NPs, to achieve enhanced photothermal-ferroptosis effects via overcoming the limitations of the Fenton-like reaction. The results showed that the synthesized biomimetic nanoparticles could decompose hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH), and further induce the non-apoptotic ferroptosis pathway. After irradiation with near-infrared (NIR) light, the uptake of Fe-PDA-EPI@FA-RBCm NPs by cells could be effectively promoted, and it presented impressive in vitro and in vivo photothermal properties. In vitro and in vivo results showed that laser irradiation could enhance ferroptosis by promoting the production of reactive oxygen species (ROS) and lipid peroxides, down-regulating the expression of glutathione peroxidase 4 (GPX4), and reducing the mitochondrial membrane potential. Furthermore, the photothermal-promoted ferroptosis and apoptosis pathways (photothermal therapy and chemotherapy) exhibited outstanding synergistic antitumor efficacy in vitro and in vivo, with an in vivo tumor inhibition rate as high as 76.95%. In conclusion, the construction of tumor-targeted biomimetic nanocarriers utilizing the advantageous properties of RBCm has been investigated as a potential anticancer strategy.

Superoxide Radical-Mediated Self-Synthesized Au/MoO3-x Hybrids with Enhanced Peroxidase-like Activity and Photothermal Effect for Anti-MRSA Therapy.

A rapid increase in methicillin-resistant Staphylococcus aureus (MRSA) induced infection has been noticed in recent years and the biofilm formed by MRSA further delays wound healing, causing a high mortality rate. Hence, a safe and effective superoxide radical (O2•-) mediated self-synthesis strategy is developed to prepare Au-doped MoO3-x (Au/MoO3-x) plasmonic-semiconductor hybrid for the elimination of MRSA mediated wound infection. The synthesis mechanism of Au NPs is systematically investigated, proving that O2•- plays a key role in reduction of HAuCl4 into Au NPs in the presence of H2O and O2. Au-doped MoO3-x exhibits the improved photothermal conversion efficiency (∼52.40%) compared with MoO3-x (∼41.11%). Moreover, the peroxidase (POD)-like activity of Au/MoO3-x hybrid is higher than that of MoO3-x NPs, resulting in increased yield of highly toxic ·OH. In combination with the enhanced photothermal and POD-like properties, Au/MoO3-x hybrid achieves efficient elimination of MRSA bacteria with eradication ratio of ∼99.76%. Additionally, the as-prepared Au/MoO3-x NPs exhibit excellent biosafety, which is verified via in vitro and in vivo experiments. This study provides the basis for exploring MoO3-x-based hybrids via a green O2•--mediated self-synthesis approach.

Near-Infrared Regulated Nanozymatic/Photothermal/Photodynamic Triple-Therapy for Combating Multidrug-Resistant Bacterial Infections via Oxygen-Vacancy Molybdenum Trioxide Nanodots.

Bacterial infections have become a major danger to public health because of the appearance of the antibiotic resistance. The synergistic combination of multiple therapies should be more effective compared with the respective one alone, but has been rarely demonstrated in combating bacterial infections till now. Herein, oxygen-vacancy molybdenum trioxide nanodots (MoO3-x NDs) are proposed as an efficient and safe bacteriostatic. The MoO3-x NDs alone possess triple-therapy synergistic efficiency based on the single near-infrared irradiation (808 nm) regulated combination of photodynamic, photothermal, and peroxidase-like enzymatic activities. Therein, photodynamic and photothermal therapies can be both achieved under the excitation of a single wavelength light source (808 nm). Both the photodynamic and nanozyme activity can result in the generation of reactive oxygen species (ROS) to reach the broad-spectrum sterilization. Interestingly, the photothermal effect can regulate the MoO3-x NDs to their optimum enzymatic temperature (50 °C) to give sufficient ROS generation in low concentration of H2 O2 (100 µm). The MoO3-x NDs show excellent antibacterial efficiency against drug-resistance extended spectrum ß-lactamases producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Animal experiments further indicate that the MoO3-x NDs can effectively treat wounds infected with MRSA in living systems.

Enhanced piezo-photocatalytic performance by piezoelectric and visible light photoexcitation coupling through piezoelectric Na0.5Bi0.5TiO3 micron crystals.

The unique piezoelectric potential of piezoelectrics could lead to performance gains for electrochemical catalysis. Here, a cuboid-like Na0.5Bi0.5TiO3 (NBTO) piezoelectric micron crystal was synthesized by a hydrothermal process. The piezocatalytic and visible light assisted piezo-photocatalytic activities of NBTO were investigated. Surprisingly, under ultrasonic vibration and visible light irradiation, the NBTO exhibited four times faster degradation rate than that under ultrasonic vibration only, although the NBTO doesn't absorb visible light. An efficient coupling between piezoelectric effect and visible light photoexcitation in NBTO was directly demonstrated. The improved piezo-photocatalytic performance is attributed to the piezoelectric potential and the decrease of bandgap of NBTO micron crystal due to strain induced by ultrasonic vibration. A new fundamental mechanism for the improved degradation of organic dye has been proposed for piezoelectric and photoexcitation coupling. This work extends the application of wide band gap piezoelectric materials in the visible light area.

Histopathological changes of Ceroplastes japonicus infected by Lecanicillium lecanii.

The infection process and pathological changes of Japanese wax scale, Ceroplastes japonicus Green, by the hyphomycete Lecanicillium lecanii (Zimmermann) Gams & Zare were investigated by light, scanning and transmission electron microscopy. The results showed that L. lecanii generally infected the wax scale by penetrating the integument. The anal area, the body margin, around the base of mouthparts and legs, over the stigmatic furrow and the area around the vulva were susceptible places, while the wax test had an inhibitory effect on L. lecanii. Within 24h after inoculation, conidia became attached to the cuticle, and within 48h, hyphae adhered to the integument of the scale and their tips differentiated into specialized infection pegs. Penetration of the cuticle occurred within 72h of inoculation; the fungus caused the insect cuticle to rupture and hyphae entered the insect body through these openings. Within 72h after inoculation, L. lecanii entered the hemocoele of the scale and formed blastospores. After 96h, blastospores were dispersed throughout the hemolymph and completely disrupted the hemocytes, resulting in damage of the cell nucleus and agglutination of chromatin. Concomitant to colonization of the hemolymph, the internal organs and tissues, e.g., tracheae, malpighian tubules and muscle fibers, were also infected. As the infection progressed, the wax test and body changed color from white and red, respectively, to yellowish. After 144h, the internal tissue structure was totally compromised and the insects died. After this time, new conidiophores bearing conidia were produced on the surface of the cadavers.

[The characterization of scaffold made of N,O-carboxymethyl chitosan and tricalcium phosphate].

PURPOSE: To study the mechanical and chemical characterization of scaffold made of N,O-carboxymethyl chitosan (N,O-CMCS) and tricalcium phosphate(TCP) with various weight ratios. METHODS: Three composites of N,O-CMCS/TCP with weight ratios of 2:1,1:1 and 1:2 were mixed using the same volume of distilled water. The characteristic bands, morphologic structure, compressive strength and Young modulus of the composites were analyzed by infrared spectroscopy (IR),scanning electron microscopy(SEM) and universal testing machine respectively. RESULTS: The shift of IR characteristic bands of -COO(-)and -NH(2) to lower wave number was observed in three composites gradually, which resulted from the complexation of -COO(-) and -NH(2) with calcium ions. The pores of the three-dimensional porous structure and compressive strength of the composite increased when there were more N,O-CMCS in the composite. When there were more TCP in the composite, its porosity became less and Young modulus increased, so that the composite demonstrated more rigidity. CONCLUSIONS: N,O-CMCS had the capability of complexing with calcium ions. The scaffold made of N,O-CMCS and TCP had the properties of three-dimensional porous structure, flexible remolding and mechanical strength, so it will be a promising biomaterial for bone substitute.

[Effects of lead exposure to rat placenta and pups during different gestation periods].

OBJECTIVE: To investigate the effects of lead exposure to rat placenta and pups during different gestation periods. METHODS: All 108 Wistar rats (72 females, 36 males) were randomly divided into four groups. All rats were orally fed with 0.025% lead acetate during different gestation periods. Blood was obtained from the abdominal vena cava and the lead level in maternal blood was measured by means of atomic absorption spectrometry at the end of the pregnancy. The number of pups, their body weight, body length and tail length were measured. The effects of lead to rat placenta were observed by level of microscopy, optical microscopy and electronic microscopy. RESULTS: Experimental groups the blood lead level at the end of gestation were above 0.483 micromol/L. There were significant differences among, of pups, during different groups (P < 0.01). Among them the drinking lead group of whole distant was the lowest in placenta weight [(0.31 +/- 0.13) g] body weight of pups [(2.08 +/- 0.88) g] length and tail length of pups [(2.37 +/- 0.32) cm, (0.98 +/- 0.09) cm]. There were significantly differences between the experimental groups and controls. Maternal blood lead level was negatively related to placenta weight (r = 0.652, P < 0.01), and had no relation with the body weight of pups (r = -0.107, P = 0.46). In the experimental groups of lead poisoned rats, the placenta showed focus necrosis in the deciduas, and increased the trophoblastic giant cells and light staining cells in the trophospongium. Trophoblast in the labyrinth and trophospongium showed degeneration; fibrin deposition around the villi was increased. Microvilli around the trophoblast were shorter and less, mitochondrion was swollen and decreased in number, rough endoplasmic reticulum was distended and ribosomal number on membrane decreased. CONCLUSION: Lead exposure during different gestation periods should have a traumatic effect on the trophoblast, leading to interference of nutrition and oxygen exchange. Furthermore, the blood supply to the placenta and nutrition and oxygen exchange between mother and pups were also interfered, leading to reduction of placenta weight and retardation of development of pups.

[Observation on the ultrastructure of Pneumocystis carinii].

OBJECTIVE: To study the life cycle and morphology of Pneumocystis carinii by ultrastructural observation. METHODS: Wistar rat model of P. carinii infection was established by subcutaneous injection with dexamethasone. Lung tissue of the infected rats was used for the transmission electron microscopical study. RESULTS: The organisms were mainly present in the lung alveolar cavity, and also in the alveolar septum, pulmonary macrophages and neutrophils. More trophozoites of P. carinii attached to the type I alveolar epithelial cells, and rarely to the type II alveolar epithelial cells. Most of these trophozoites showed pseudopodial evaginations on their pellicles. The nucleus-associated organelle and spindle microtubules were observed in some trophozoites. The precyst phase was in three forms: early, intermediate and late form. Synaptonemal complexes indicating meiotic nuclear divisions and a clump of mitochondria were also observed in the precyst. The pellicle of the cyst has a thickened portion with a pore. There were nucleus with nucleolus, mitochondrion, vesicles, endoplasmic reticulum and numerous ribosomes in the organisms, and tubular expansions on its surface. CONCLUSION: The life cycle of P. carinii consists of trophozoite, precyst and cyst stages. The presence of a single pore in the cyst wall reveals that pore formation may be a mode of excystation for intracystic bodies of P. carinii.

Inhibitory effect of polypeptide from Chlamys farreri on UVA-induced apoptosis in human keratinocytes.

Polypeptide from Chlamys farreri (PCF, Mr = 879) is a novel marine active product isolated from gonochoric Chinese scallop Chlamys farreri which has been served as sea food for several thousand years. As an octapeptide, PCF consists of 8 amino acids, namely, Pro, Asn, Ser, Thr, Arg, Hyl, Cys, and Gly. PCF had been identified as a marine chemopreventive drug that protected hairless mice's epidermis against UV-induced damage in our previous study. However, the molecular mechanisms that underlie the effect of PCF on ultraviolet A-induced apoptosis in ketatinocytes are not well understood yet. In the present study, PCF was investigated as a potential inhibitory agent for UVA-induced apoptosis in a human keratinocyte cell line, HaCaT. The effects of PCF on UVA-induced generation of ROS and MDA, DNA damage, apoptosis rate were examined. We also investigated whether PCF could inhibit UVA-induced decreasing of mitochondrial membrane potential and the changing of morphology of the cells. We found that, compared with UVA only group, PCF attenuated UVA-induced generation of ROS and MDA, increased the mitochondrial membrane potential, and decreased the apoptosis rate. These results indicate that PCF may protect HaCaT keratinocytes against UVA-induced apoptosis.