No abstract

Aberrant vascular network is a hallmark of cancer. However, the role of vascular endothelial cells (VECs)-expressing PD-L1 in tumor immune microenvironment and antiangiogenic therapy remains unclear. In this study, we used the specimens of cancer patients for immunohistochemical staining to observe the number of PD-L1 + CD34 + VECs and infiltrated immune cells inside tumor specimens. Immunofluorescence staining and flow cytometry were performed to observe the infiltration of CD8 + T cells and FoxP3 + T cells in tumor tissues. Here, we found that PD-L1 expression on VECs determined CD8 + T cells', FoxP3 + T cells' infiltration, and the prognosis of patients with lung adenocarcinoma. Anlotinib downregulated PD-L1 expression on VECs through the inactivation of AKT pathway, thereby improving the ratio of CD8/FoxP3 inside tumor and remolding the immune microenvironment. In conclusion, our results demonstrate that PD-L1 high expression on VECs inhibits the infiltration of CD8 + T cells, whereas promotes the aggregation of FoxP3 + T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth.

Fe3O4-TiO2 nanosheets (Fe3O4-TNS) were synthesized by means of lamellar reverse micelles and solvothermal method, which were characterized by TEM, XRD, XPS, BET, and magnetic property analysis. It can be found that Fe3O4-TNS nanosheets exhibited better photocatalytic antibacterial activity toward Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus than pure Fe3O4 and TNS, and the antibacterial efficiency could reach 87.2% and 93.7% toward E. coli and S. aureus with 100 μg/mL Fe3O4-TNS after 2 h of simulated solar light illumination, respectively. The photocatalytic destruction of bacteria was further confirmed by fluorescent-based cell live/dead test and SEM images. It was uncovered that Fe3O4-TNS inactivated G- E. coli and G+ S. aureus by different mechanisms: the destruction of outer membranes and ruptured cell bodies were responsible for the bactericidal effect against E. coli, while the antibacterial effect toward S. aureus were due to the fact that the cells were adsorbed in form of clusters by massive Fe3O4-TNS, which could restrict their activities and cause malfunction of the selective permeable barriers. Furthermore, the antibacterial mechanism was studied by employing scavengers to understand exact roles of different reactive species, indicating the key roles of h(+) and H2O2. The recovery and reusability experiments indicated that Fe3O4-TNS still retained more than 90% bacteria removal efficiency even after five cycles. Considering the easy magnetic separation, bulk availability, and high antibacterial activity of Fe3O4-TNS, it is a promising candidate for cleaning the microbial contaminated water environment.

Ag-CoFe2O4-graphene oxide (Ag-CoFe2O4-GO) nanocomposite was synthesized by doping silver and CoFe2O4 nanoparticles on the surface of GO, which was used to purify both bacteria and Pb(II) contaminated water. The Ag-CoFe2O4-GO nanomaterial was characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman, X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), cyclic voltammetry (CV), and magnetic property tests. It can be found that Ag-CoFe2O4-GO nanocomposite exhibited excellent antibacterial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus compared with CoFe2O4, Ag-CoFe2O4, and CoFe2O4-GO composite. This superior disinfecting effect was possibly attributed to the combination of GO nanosheets and Ag nanoparticles. Several antibacterial factors including temperature, time, and pH were also investigated. It was obvious that E. coli was more susceptible than S. aureus toward all the four types of nanomaterials. The structural difference of bacterial membranes should be responsible for the resistant discrepancy. We also found that Ag-CoFe2O4-GO inactivated both bacteria in an irreversibly stronger manner than Ag-CoFe2O4 and CoFe2O4-GO. The Pb(II) removal efficiency with all the nanomaterials showed significant dependence on the surface area and zeta potential of the materials. In this work, not only did we demonstrate the simultaneous superior removal efficiency of bacteria and Pb(II) by Ag-CoFe2O4-GO but also the antibacterial mechanism was discussed to have a better understanding of the interaction between Ag-CoFe2O4-GO and bacteria. In a word, taking into consideration the easy magnetic separation, bulk availability, and irreversibly high antibacterial activity of Ag-CoFe2O4-GO, it is the very promising candidate material for advanced antimicrobial or Pb(II) contaminated water treatment.

TiO2-Bi2WO6 binanosheet (TBWO), synthesized by a facile two-step hydrothermal method, was used as an effective visible-light-driven photocatalyst for the inactivation of E. coli and was characterized by TEM, SEM, XRD, FTIR, XPS, and BET. A series of TBWOs with different doping ratios of TiO2 loading from 10 to 55 wt % were synthesized. Among all of the TBWOs, 40% TBWO exhibited the best bacteria disinfection efficiency, and the quantity of viable bacteria could reach 10° with 40% TBWO (100 μg/mL) after being illuminated for 4 h. Furthermore, the confocal fluorescent-based cell live/dead test and the SEM technology were applied to verify the photocatalytically lethal effect toward E. coli and the rupture of bacterial membranes. The leak of bacterial contents, including the bacterial genome represented by relevant 16srDNA, and total protein were detected by PCR and bicinchoninic acid assay. In this work, the antibacterial mechanism was studied by employing photoelectrochemical techniques, electron spin resonance (ESR), and scavengers of different reactive species, revealing the pivotal roles of electron hole (h(+)) and electron (e(-)) in the photocatalytic process. In addition, the •O2(-) and •OH radicals were also detected in the TBWOs system by ESR. It was found that the adsorption of visible light and separation of photogenerated carriers within TiO2 have been largely promoted after being coupled with Bi2WO6, which should be responsible for the improved bactericidal effect.