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Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.

Chiral materials with circularly polarized luminescence (CPL) have garnered significant attention owing to their distinctive luminescent properties and wide array of applications. CPL enables the selective emission of left and right circularly polarized light. The fluorescence quantum yield and dissymmetry factor play pivotal roles in the generation of CPL. Helical polymers exhibit immense promise as CPL materials due to their inherent chirality, structural versatility, modifiability, and capacity to incorporate diverse chromophores. This Review provides a brief review of the synthesis of CPL materials based on helical polymers. The CPL can be realized by aggregation‐induced CPL of non‐emissive helical polymers, and helices bearing chromophores on the pendants and on the chain end. Furthermore, future challenges and potential applications of CPL materials are summarized and discussed. [ABSTRACT FROM AUTHOR]

Cyclic polymers have very unique structure and properties, and thus have drawn intense research attention. However, controlled synthesis of cyclic polymers with predictable molar mass and narrow distribution is still a challenging task. In this study, we developed a novel cyclic catalyst that initiates the ring-expansion polymerisation of isocyanides, producing a series of cyclic helical polymers with predictable molecular weight and low dispersity. Interestingly, the ring-expansion polymerization of the isocyanide macromonomers gives well-defined cyclic bottlebrush polymers. The cyclic topology was demonstrated using transmission electron microscopy. [ABSTRACT FROM AUTHOR]

This study aimed at elucidating some characteristics of the shock wave overpressure generated by a non-traditional layered charge comprising an inner high-energy explosive and an outer polymer matrix composite. Two models for predicting the peak overpressure (Δpm) of the charge were established, namely, a model based on the initial parameters of the blast wave, and a model considering the weakening of the explosion energy through the introduction of polymer matrix cladding. The overpressure of a typical layered charge was experimentally measured for model validation. It was found that the difference between the Δpm predicted by the two models and the experimental data is less than 15.12% and 14.17%, respectively. The model that was established based on the conservation of energy law, is in best agreement with the experimental data under different cladding/charge mass ratios (αm). The model that was based on the initial parameters of the blast wave obtained a low predicted value when αm was 0.4–0.8, which is attributed to the non-uniformity of the gas-solid mixture during the explosive dispersion stage. [ABSTRACT FROM AUTHOR]