Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic-Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport.

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti-tumor treatment. In addition, central nervous system neoplasm-targeted nanoplatforms are urgently required. To address these issues, a new multi-functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP-TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione-responsive disulfide bond. Mechanistically, ODP-TH crosses the blood-brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down-regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1-α (HIF-1α). The results reveal that ODP-TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP-TH achieves a more efficient tumor-inhibiting effect. This study not only overcomes the hypoxia-related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi-functional targeted and intensive anti-tumor nanoplatform.

KCNN4-mediated Ca2+/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma.

As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.

Selenium Alleviates Inflammation in Staphylococcus aureus-Induced Mastitis via MerTK-Dependent Activation of the PI3K/Akt/mTOR Pathway in Mice.

Mastitis caused by Staphylococcus aureus infection not only causes serious economic losses, but also affects human health. Se plays an important role in body immunity. However, the mechanisms by which Se regulates mastitis induced by S. aureus are still principally unknown. The purpose of this study is to investigate whether Se can inhibit mastitis induced by S. aureus through regulation of MerTK. Sixty BALB/c female mice were fed low, normal, or high Se concentrations for 7 weeks and then randomly divided into six groups (Se-Low Control group (LSN), Se-Normal Control group (NSN), Se-High Control group (HSN), Se-Low S. aureus group (LSS), Se-Normal S. aureus group (NSS), Se-High S. aureus group (HSS)). The regulation of Se on MerTK was detected via histopathological staining, western blot analysis, enzyme-linked immunosorbent assay, and qRT-PCR. With increased selenium concentrations, the levels of IL-1ß, IL-6, and TNF-α decreased, while the phosphorylation levels of MerTK, PI3K, AKT, and mTOR increased. Therefore, this study showed that Se could alleviate S. aureus mastitis by activating MerTK and PI3K/AKT/mTOR pathway.

[Study on Form of Ar/Air ICP and A Microwave Diagnostics Based on the Hß Spectrum Broadening].

The ICP in closed quartz chamber is an effective solution to local stealth of aircraft. The attenuation of the electromagnetic wave is strongly affected by distribution of electron density in incidence direction. In this paper, an experiment that the planar ICP discharged in all-quartz chamber (30.8 cm×30.8 cm×5.8 cm) was conducted. The E-H mode transition of Ar/Air ICP was observed, and the width and the proportion of ICP area versus the RF power were measured. Such physical phenomena were explained rationally by ICP-source theoretical model. A new microwave diagnostics is presented based on the Hß spectrum broadening and the characteristics of planar-coil ICP. It is used to diagnose the spatial electron density distribution of Ar/Air in incidence direction. The parameters of electron density distribution function in the incident direction are separately solved by the fitting results of the Hß stack broadening and microwave interferometer. And the curves of electron density distribution versus RF power are obtained. We obtain a stable ring plasma source with electron density varying from 0.5×1011～3.2×1011 cm-3. The experiment demonstrates that electron density is prominently affected by the RF power and gas species. The peak value of electron density is positioned near the center of ICP. It is shown that the electron density of Ar ICP is higher than the air, but the area of air ICP is larger through comparing the curves of Ar/Air electron density.

[Experimental study on closed plasma discharging under low pressure and spectroscopic diagnosis].

Closed plasma can overcome difficulties of maintaining plasma and excessive energy consumption in open environment. For plasma stealth technology, a closed plasma generator was designed. Using microsecond pulse generator and argon as working gas, discharge experiments were carried out under low pressure environment. The emission spectrum of Ar at different position in discharge chamber was measured. By using collisional-radiative modal (CRM), the distribution of plasma parameters was studied. At a given electron temperature and density with specified discharge parameters, corresponding population distribution could be obtained by CRM. By comparing the line ratio of argon 2p levels acquired from CRM with the line ratio from spectrum measured, the plasma parameters were confirmed after obtaining the minimum difference value. Using the line ratio of argon 2p9 to 2p1 from CRM while the range of electron density was 1-5 eV, the calculating error was analyzed. The results reveal that, the electron density of the closed plasma reaches a magnitude of 10(11) cm(-3) and shows a gradient distribution with small variational amplitude, and the distribution is beneficial to the application of plasma stealth.

[Spectroscopic diagnosis of dielectric barrier discharge in long gap under low presssure].

In the present paper, a dielectric barrier discharge (DBD) plasma was generated at low pressure in a DBD device with the eletrode distance of 10cm and using Ar as working gas. The changes in electronic temperature and density in the discharge cavum were studied by means of emission spectrometry. The changes in electronic temperature measured by using corona model were obtained. The variations in electronic density were analyzed using 750.4 nm line intensity. It was found that the plasma electronic temperature and density is various at different positions in the discharge cavum. With the measuring point moving from cathode to anode, the electronic temperature firstly increases slowly, then decreases quickly. While the electronic density increases slowly at first, and then rapidly.