BCL2A1 neoepitopes-elicited cytotoxic T lymphocytes are a promising individualized immunotherapy of pancreatic cancer.

Conventional treatments have shown a limited efficacy for pancreatic cancer, and immunotherapy is an emerging option for treatment of this highly fatal malignancy. Neoantigen is critical to improving the efficacy of tumor-specific immunotherapy. The cancer and peripheral blood specimens from human leukocyte antigen (HLA)-A0201 positive pancreatic cancer patient were subjected to next-generation sequencing and bioinformatics analyses were performed to screen high-affinity and highly stable neoepitopes. The activation of cytotoxic T lymphocytes (CTLs) by the mutBCL2A111-20 neoepitope targeting B-cell lymphoma 2-related protein A1 (BCL2A1) mutant epitope was investigated, and the cytotoxicity of mutBCL2A111-20 neoepitope-specific CTLs to pancreatic cancer cells was evaluated. The mutBCL2A111-20 neoepitope was found to present a high immunogenicity and induce CTLs activation and proliferation, and was cytotoxic to mutBCL2A111-20 neoepitope-loaded T2 cells and pancreatic cancer PANC-1-Neo and A2-BxPC-3-Neo cells that overexpressed mutBCL2A111-20 neoepitopes, appearing a targeting neoepitope specificity. In addition, high BCL2A1 expression correlated with a low 5-year progress free interval (PFI) among pancreatic cancer patients. Our findings provide experimental supports to individualized T-cell therapy targeting mutBCL2A111-20 neoepitopes, and provide an option of immunotherapy for pancreatic cancer.

Coupling harmful algae derived nitrogen and sulfur co-doped carbon nanosheets with CeO2 to enhance the photocatalytic degradation of isothiazolinone biocide.

Removing the algae from water bodies is an effective treatment toward the worldwide frequently occurred harmful algae blooms (HAB), but processing the salvaged algae waste without secondary pollution places another burden on the economy and environment. Herein, a green hydrothermal process without any chemical addition was developed to resource the HAB algae (Microcystis sp.) into autogenous nitrogen and sulfur co-doped carbon nanosheet materials C-CNS and W-CNS, whose alga precursors were collected from pure culture and a wild bloom pond, respectively. After coupling with CeO2, the obtained optimal C-CNS/CeO2 and W-CNS/CeO2 composites photocatalytically degraded 95.4% and 88.2% of the marine pollutant 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) in 90 min, significantly higher than that of pure CeO2 (63.15%). DCOIT degradation on CNS/CeO2 was further conducted under different conditions, including pH value, coexisting cations and anions, and artificial seawater. Although different influences were observed, the removal efficiencies were all above 76%. Along with the ascertained good stability and reusability in five consecutive runs, the great potential of CNS/CeO2 for practical application was validated. UV-vis DRS showed the increased light absorption of CNS/CeO2 in comparison to pure CeO2. PL spectra and photoelectrochemical measurements suggested the lowered charge transfer resistance and thereby inhibited charge recombination of CNS/CeO2. Meanwhile, trapping experiments and electron paramagnetic resonance (EPR) detection verified the primary roles of hydroxyl radical (OH) and superoxide radical (O2-) in DCOIT degradation, as well as their notably augmented generation by CNS. Consequently, a mechanism of CNS enhanced photocatalytic degradation of DCOIT was proposed. The intermediates involved in the reaction were identified by LC-QTOF-MS, giving rise to a deduced degradation pathway for DCOIT. This study offers a new approach for resourceful utilization of the notorious HAB algae waste. Besides that, photocatalytic degradation has been explored as an effective measure to remove DCOIT from the ocean.

Selecting the Best Performing Modified Asphalt Based on Rheological Properties and Microscopic Analysis of RPP/SBS Modified Asphalt.

As an asphalt modifier, waste polypropylene (RPP) can not only optimize the performance of asphalt but also greatly alleviate the problem of waste plastic treatment, effectively reducing environmental pollution and resource waste. In order to evaluate the influence of RPP and styrene butadiene styrene (SBS) on asphalt performance, the application of RPP in modified asphalt pavement has been expanded. In this study, a dynamic shear rheometer (DSR), bending beam rheometer (BBR) and other instruments were used to evaluate the rheological properties of composite-modified asphalt. Fourier infrared spectroscopy (FTIR) and fluorescence microscopy (FM) was employed to conduct a microscopic analysis of the modified asphalt, and the layer analysis method was adopted to determine the optimal RPP content. The test results show that the rheological properties of asphalt are significantly improved by the composite modification of RPP and SBS. In addition, the cross-linking between polymer and asphalt is further enhanced by the composite addition of RPP and SBS. The comprehensive performance of modified asphalt is optimized at the RPP content of 2%, which is suitable for applications in the cold temperate zone. The RPP/SBS composite-modified asphalt is able to improve the utilization rate of RPP and has good environmental and economic benefits, thus exhibiting excellent comprehensive performance. However, the optimal asphalt content in the mixture was not investigated, and the economic benefits brought by the utilization of RPP were not evaluated and require further study.

Altered MUC1 epitope-specific CTLs: A potential target for immunotherapy of pancreatic cancer.

The efficacy of conventional treatments for pancreatic cancer remains unsatisfactory, and immunotherapy is an emerging option for adjuvant treatment of this highly deadly disorder. The tumor-associated antigen (TAA) MUC1 is expressed in a variety of human cancers and is overexpressed in more than 90% of pancreatic cancer, which makes it an attractive target for cancer immunotherapy. As a self-protein, MUC1 shows a low immunogenicity because of immune tolerance, and the most effective approach to breaking immune tolerance is alteration of the antigen structure. In this study, the altered MUC11068-1076Y1 epitope (YLQRDISEM) by modification of amino acid residues in sequences presented a higher immunogenicity and elicited more CTLs relative to the wild-type (WT) MUC11068-1076 epitope (ELQRDISEM). In addition, the altered MUC11068-1076Y1 epitope was found to cross-recognize pancreatic cancer cells expressing WT MUC1 peptides in an HLA-A0201-restricted manner and trigger stronger immune responses against pancreatic cancer via the perforin/granzyme apoptosis pathway. As a potential HLA-A0201-restricted CTL epitope, the altered MUC11068-1076Y1 epitope is considered as a promising target for immunotherapy of pancreatic cancer. Alteration of epitope residues may be feasible to solve the problem of the low immunogenicity of TAA and break immune tolerance to induce immune responses against human cancers.

Research on the Ability of Bio-rejuvenators to Disaggregate Oxidized Asphaltene Nanoclusters in Aged Asphalt.

A real rejuvenator must have the ability to disaggregate oxidized asphaltene nanoclusters. However, few studies pay attention to the topic, and there is a lack of comparison of the disaggregation ability of different rejuvenators. Thus, the disaggregation ability and regeneration mechanism of three bio-rejuvenators (waste cooking oil (WCO), waste wood oil (WWO), and straw liquefied residue oil (SLRO)) on oxidized asphaltene nanoclusters were studied in this paper. Laboratory tests and molecular dynamics (MD) simulation were used to compare the effectiveness of the three bio-rejuvenators and reveal its corresponding mechanism. It is found that these bio-rejuvenators have a softening effect on aged asphalt binder, but not all of them can disaggregate oxidized asphaltene nanoclusters. The introduction of WWO and WCO can effectively disturb the nanoclusters caused by the increase of polar functional groups during the oxidation process. The effect of WWO is more significant, but neither of them can restore the asphaltene dispersion to the virgin asphalt binder. SLRO has an adverse effect on the disaggregation of oxidized asphaltene nanoclusters. WCO, WWO, and SLRO showed different disaggregation mechanisms, including ″pull-out, intercalation, and compression″, respectively. WCO and WWO can increase the activation energy reduced by aging in a short aging time, and SLRO makes the activation energy lower. Such findings can help enterprises screen more reasonable rejuvenators to facilitate the recycling of reclaimed asphalt pavement (RAP) materials and promote the sustainable development of the construction industry.