Microstructures of an Ultrafine Grained SS400 Steel in an Industrial Scale

The microstructures of a SS400 steel after thermomechanical control process（TMCP） in an industrial production were observed by optical microscope,scanning electron microscope（SEM） and transmission electron microscope（TEM）.The results indicated that the size of ferrite grains was 4-5μm,and transmission of ferrite was around 70%.The types of the ultrafine ferrite grains were analyzed and the strengthening mechanisms were discussed.The results show that the ultrafine ferrite grains came from three processes,i.e.deformation induced ferrite transformation（DIFT）.dynamic recrystallization of ferrite and accelerated cooling process.The increase in the strength of the material was mainly due to the grain refining.

Bispecific antibody and its clinical applications in cancer

Bispecific antibody (BsAb) usually consists of two different antigen-binding arms, by which it is capable of simultaneously binding to target cells and effector cells, and can directly mediate the killing of target cells by retargeting and activating effector cells. The development of BsAb research goes through three main stages: chemical cross-linking of murine-derived monoclonal antibody, hybrid hy-bridomas and engineered BsAb. Among them, engineered BsAb has more formats than the other two, such as diabody, ScdHLX, ScZip, ScCH3, ScFab and BsIgG, etc. Compared with former murine-derived BsAbs, engineered BsAb has lower immunogenicity and stronger penetrating capacity, and currently, some of them appear suitable for clinical application in yields and qualities. Up to now, several phase I and phase II clinical studies of BsAb, for instance, some (Fab’)2 and Diabodies, have been performed. Among those BsAbs, anti-CD3/anti-tumor BsAbs is most common, they not only can activate T cell and induce CD3AK

Tumor microenvironment-responsive MnSiO_(3)-Pt@BSA-Ce6 nanoplatform for synergistic catalysis-enhanced sonodynamic and chemodynamic cancer therapy

Compared with traditional photodynamic therapy(PDT),ultrasound(US)triggered sonodynamic therapy(SDT)has a wide application prospect in tumor therapy because of its deeper penetration depth.Herein,a novel MnSiO_(3)-Pt(MP)nanocomposite composed of Mn Si O_(3)nanosphere and noble metallic Pt was successfully constructed.After modification with bovine serum albumin(BSA)and chlorine e6(Ce6),the multifunctional nanoplatform Mn SiO_(3)-Pt@BSA-Ce6(MPBC)realized the magnetic resonance imaging(MRI)-guided synergetic SDT/chemodynamic therapy(CDT).In this nanoplatform,sonosensitizer Ce6 can generate singlet oxygen(^(1)O_(2))to kill cancer cells under US irradiation.Meanwhile,the loaded Pt has the ability to catalyze the decomposition of overexpressed hydrogen peroxide(H_(2)O_(2))in tumor microenvironment(TME)to produce oxygen(O_(2)),which can conquer tumor hypoxia and promote the SDT-induced^(1)O_(2)production.In addition,MP can degrade in mildly acidic and reductive TME,causing the release of Mn^(2+).The released Mn^(2+) not only can be used for MRI,but also can generate hydroxyl radical(^·OH)for CDT by Fenton-like reaction.The multifunctional nanoplatform MPBC has high biological safety and good anticancer effect,which displays the great latent capacity in biological application.

Modulating multidrug resistance through inhibiting of protein kinase C activity by phenothiazines

In the present study, actions of phenothiazines(PTZ) in reversing multidrug resistance(MDR) and inhibiting PKC activity were investigated. It was found that the three PTZs caused 2.49, 36.58 and 75.78 fold reversal of K562/AO2 MDR cells resistant to adriamycin, respectively, while the chemosensitizer verapamil caused 40 fold reversal in the same condition, indicating that PTZ11 is a novel reversal agent of MDR and a potential chemotherapeutic reagent for tumor therapy. PKC activity analysis in the presence of PTZs showd that PTZ6 and PTZ11 inhibited rat brain protein kinase C activity in a manner of dose_dependent. The IC 50 values were (489.77±31.4) and (113±9.64) μmol/L, respectively. PTZ7 had no inhibition on PKC activity. Further study showed that PTZ11 could reduce PMA_mediated activation of PKC in a manner of dose_dependent, suggesting that PTZ11 might compete for the high_affinity phorbol ester binding site within PKC molecule. Recently, an X_ray structure of PMA in complex with PKC Cys2 activator_binding domain was solved. We therefore decided to explore the possible binding model of PTZ11 with PKC molecule using SYBYL 6.02 program. It was shown that the binding site of PTZ11 with PKC molecule partially overlapped with that of PMA, providing for the first time new data for designing PKC inhibitors and MDR reversal drugs.