Extracellular vesicles mediated proinflammatory macrophage phenotype induced by radiotherapy in cervical cancer.

BACKGROUND: Radiotherapy is a highly effective treatment for cervical cancer. Recent studies focused on the radiotherapy induced anti-tumor immunity. Whether tumor-derived extracellular vesicles (EVs) play roles in radiotherapy induced tumor associated macrophage (TAM) polarization remains unclear. MATERIALS AND METHODS: This study analysed the phenotype of macrophages in cancer tissue and peripheral blood of cervical cancer patients using flow cytometry analysis. The role of EVs from plasma of post-irradiated patients on M2-like transformed macrophages was assessed. The M1- and M2-like macrophages were assessed by expression of cell surface markers (CCR7, CD163) and intracellular cytokines (IL-10, TNFα and iNOS). The capacity of phagocytosis was assessed by PD-1 expression and phagocytosis of pHrodo Red E. coli bioparticles. RESULTS: Our results demonstrated that radiotherapy of cervical cancer induced an increase in the number of TAMs and a change in their subtype from the M2-like to the M1-like phenotype (increased expression of CCR7 and decreased expression of CD163). The EVs from plasma of post-irradiated patients facilitated the M2-like to the M1-like phenotype transition (increased expression of CCR7, TNFα and iNOS, and decreased expression of CD163 and IL-10) and increased capacity of phagocytosis (decreased PD-1 expression and increased phagocytosis of pHrodo Red E. coli bioparticles). CONCLUSIONS: Our data demonstrated that irradiation in cervical cancer patients facilitated a proinflammatory macrophage phenotype which could eventually able to mediate anti-tumor immune responses. Our findings highlight the importance of EV in the crosstalk of tumor cells and TAM upon irradiation, which potentially leading to an increased inflammatory response to cancer lesions.

Isotactic-Alternating, Heterotactic-Alternating, and ABAA-Type Sequence-Controlled Copolyester Syntheses via Highly Stereoselective and Regioselective Ring-Opening Polymerization of Cyclic Diesters.

Synthesizing different types of sequence-controlled copolyesters can enrich the diversity of copolyesters and modify their properties more precisely, but it is still a challenge to synthesize a complicated sequence-controlled copolyester using different hydroxy acids in a living polymerization manner. In this work, a highly regioselective and stereoselective catalytic system was developed to synthesize biorenewable and biodegradable copolyesters of mandelic acid and lactic acid with isotactic-alternating, heterotactic-alternating, and ABAA-type precise and complicated sequences. Because of the regular incorporation of mandelic acid into polylactide, these sequence-controlled copolymers of mandelic acid and lactic acid show higher glass-transition temperatures than polylactide and a random copolymer. A stereocomplexation interaction between two opposite enantiomeric isotactic polymer chains was also discovered in the isotactic-alternating copolymer.

Highly isoselective ring-opening polymerization of rac-O-carboxyanhydrides using a zinc alkoxide initiator.

The stereoselective ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs) remains a major challenge due to the easy epimerization of monomers. In this work, using a zinc alkoxide initiator, highly efficient ROP of enantiopure 5-methyl-1,3-dioxolane-2,4-dione (LacOCA), 5-benzyl-1,3-dioxolane-2,4-dione (PheOCA), and 5-(4-(benzyloxy)benzyl)-1,3-dioxolane-2,4-dione (Try(Bn)OCA) was achieved without obvious epimerization. Moreover, highly isoselective ROP of rac-LacOCA, rac-PheOCA, and rac-Try(Bn)OCA was successful with the highest isoselectivity of Pm = 0.97 at -70 °C.

Mononuclear Salen-Sodium Ion Pairs as Catalysts for Isoselective Polymerization of rac-Lactide.

A series of mononuclear salen-sodium anions, as the first examples, were synthesized with tetra-alkyl ammonium as a counterpart cation. These complexes are efficient catalysts for the isoselective ring-opening polymerization of rac-lactide; the molecular weights of polymers are under control and molecular weight distributions are narrow when five equivalents of BnOH is used as an initiator. The best isoselectivity value of Pm = 0.82 was achieved at -70 °C. The experimental results together with a density functional theory calculation show that a ligand-assisted activated monomer mechanism is more reasonable than an activated monomer mechanism for this system.

Isoselective Polymerization of rac-Lactide Catalyzed by Ion-Paired Potassium Amidinate Complexes.

Three potassium crown ether complexes supported with bulky amidinate ligands were synthesized for the ring-opening polymerization (ROP) of rac-lactide. The side polymerization reaction initiated directly by ligand anion was suppressed well in the presence of alcohol as our design, and the synthesis of linear polylactide with a molecular weight as high as 117.7 kg/mol was successful together with an isoselectivity value of Pm = 0.88 at -70 °C. In this system, lactide can be deprotonated by amidinate anion to give lactide enolate, which can initiate the ROP of lactide as a side reaction in the absence of alcohol; however, this side reaction can also be suppressed well in the presence of alcohol by a decrease in temperature. An interesting anti-Arrhenius-like behavior in the polymerization was discovered, which can be attributed to the fact that the active catalyst can be converted to a less active lactide enolate potassium complex at a high temperature.

A thermo-responsive supramolecular gel and its luminescence enhancement induced by rare earth Y3.

A new acylhydrazone-functionalized dual benzimidazole derivative gelator (L) was synthesized. L can self-assemble in DMSO-EG (ethylene glycol) or DMF-water mixtures to form a thermo-responsive supramolecular organogel (L-gel). In order to increase the fluorescence intensity of L-gel (DMSO-EG system), L-gel slowly turned into a clear solution upon addition of one equivalent of RE (rare earth) Y3+. Interestingly, this gelator L and Y3+ can be assembled into an enhanced blue-light-emitting supramolecular metallogel (Y@gel) in DMF-water mixtures.

Correction: Photoswitchable ring-opening polymerization of lactide catalyzed by azobenzene-based thiourea.

Correction for 'Photoswitchable ring-opening polymerization of lactide catalyzed by azobenzene-based thiourea' by Zhongran Dai et al., Chem. Commun., 2016, 52, 8826-8829.

Photoswitchable ring-opening polymerization of lactide catalyzed by azobenzene-based thiourea.

The reactivity of a catalytic polymerization system using photoresponsive azobenzene-based thiourea/PMDETA as a catalyst could be switched between slow and fast states by alternating exposure to UV and ambient light, because the active site of azobenzene thiourea is blocked via intramolecular hydrogen bonding when the azobenzene thiourea transfers from the E isomer to the Z isomer under UV irradiation.

Different mechanisms at different temperatures for the ring-opening polymerization of lactide catalyzed by binuclear magnesium and zinc alkoxides.

Two binuclear magnesium and zinc alkoxides supported by a bis-salalen type dinucleating heptadentate Schiff base ligand were synthesized and fully characterized. The two complexes are efficient initiators for the ring-opening polymerization (ROP) of L-lactide, affording polymers with narrow polydispersities and desirable molecular weights. Interestingly, the mechanisms for the ROP of lactide are different at different temperatures. At a high temperature of 130 °C, a coordination-insertion mechanism is reasonable for the bulk melt polymerization of lactide. At a low temperature, the alkoxide cannot initiate the ROP reaction; however, upon the addition of external benzyl alcohol into the system, the ROP of lactide can smoothly proceed via an "activated monomer" mechanism. In addition, these complexes display slight stereo-selectivity for the ring-opening polymerization of rac-lactide, affording partially isotactic polylactide in toluene with a Pm value of 0.59.