As a third-generation platinum drug, oxaliplatin (OX) is widely used as the first-line chemotherapeutic agent in the treatment of colorectal cancer (CRC). CRC cells acquire resistance to chemotherapy and develop resistance, which is a major challenge for the treatment of advanced CRC. Recent studies have suggested that the therapeutic resistance of tumors is affected by the tumor microenvironment (TME). As a critical role among TME, tumor-associated macrophages (TAMs) play an important role. However, their regulatory mechanism underlying the drug resistance in CRC remains largely unknown. In the present study, we found that the density of macrophages infiltrated into the CRC tissues from OX-resistant patients was significantly higher compared with the OX-sensitive patients. Interestingly, both the total N 6 -methyladenosine (m 6 A) RNA content and the expression of its critical methyltransferase METTL3 were increased in the CRC tissues from OX-resistant patients compared with the OX-sensitive patients. Furthermore, we demonstrated that the M2-polarized TAMs enabled the OX resistance via the elevation of METTL3-mediated m 6 A modification in cells. Through whole-genome CRISPR screening and further validation, we found that TRAF5 contributes to the METTL3-triggered OX resistance in CRC cells. This study unveiled that M2-TAMs were important mediators for the acquisition of OX resistance. Furthermore, we provided evidence that targeting of M2-TAMs and METTL3-mediated m 6 A modification might be a promising adjuvant therapeutic strategy for CRC patients, especially for OX-resistant CRC patients.

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In situ Fourier transform infrared spectroscopy (in situ FTIR) and two-dimensional (2D) correlation analysis were applied to investigate the cyclization pathways of polyacrylonitrile homopolymer (PAN) and poly­(acrylonitrile-co-itaconic acid) (PAI) during thermal treatment under argon atmosphere. The cyclization pathways for PAN and PAI at different temperatures were summarized based on the 2D correlation analysis. According to the cyclization pathways, the cyclization of PAN was divided into three stages. The vital role of the ends of original PAN chains, especially the conjugated nitrile, in initiating cyclization by the free radical mechanism was verified. A part of IA in PAI chains first converted into anhydride, and then the formed anhydride rather than the carboxyl group initiated cyclization first. The ionic mechanism mainly initiated cyclization at 220 °C and below. Both for PAN and PAI, the length of cyclic structures from the free radical mechanism was ca. three repeated six-membered rings, but that from the ionic mechanism was ca. eight repeated six-membered rings.

Cancer immunotherapy suppresses and destroys tumors by reactivating and sustaining the tumorimmune process, and thus improving the immune response of the body to the tumor. Immunotherapeutic strategies are showing promising results in pre-clinical and clinical trials, however, tumor microenvironment (TME) is extremely immunosuppressive. Thus, their translation from labs to clinics still faces issues. Recently, nanomaterial-based strategies have been developed to modulate the TME for robust immunotherapeutic responses. The combination of nanotechnology with immunotherapy potentiates the effectiveness of immunotherapy by increasing delivery and retention, and by reducing immunomodulation toxicity. This review aims to highlight the barriers offered by TME for hindering the efficiency of immunotherapy for cancer treatment. Next, we highlight various nano-carriers based strategies for modulating those barriers for achieving better therapeutic efficacy of cancer immunotherapy with higher safety. This review will add to the body of scientific knowledge and will be a good reference material for academia and industries.