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Tumor-resident lymphocytes can mount a response against neoantigens expressed in microsatellite-stable gastrointestinal (GI) cancers, and adoptive transfer of neoantigen-specific lymphocytes has demonstrated antitumor activity in selected patients. However, whether peripheral blood could be used as an alternative minimally invasive source to identify lymphocytes targeting neoantigens in patients with GI cancer with relatively low mutation burden is unclear. We used a personalized high-throughput screening strategy to investigate whether PD-1 expression in peripheral blood could be used to identify CD8+ or CD4+ lymphocytes recognizing neoantigens identified by whole-exome sequencing in 7 patients with GI cancer. We found that neoantigen-specific lymphocytes were preferentially enriched in the CD8+PD-1+/hi or CD4+PD-1+/hi subsets, but not in the corresponding bulk or PD-1- fractions. In 6 of 7 individuals analyzed we identified circulating CD8+ and CD4+ lymphocytes targeting 6 and 4 neoantigens, respectively. Moreover, neoantigen-reactive T cells and a T cell receptor (TCR) isolated from the CD8+PD-1+ subsets recognized autologous tumor, albeit at reduced levels, in 2 patients with available cell lines. These data demonstrate the existence of circulating T cells targeting neoantigens in GI cancer patients and provide an approach to generate enriched populations of personalized neoantigen-specific lymphocytes and isolate TCRs that could be exploited therapeutically to treat cancer.

Background Oncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of oncolytic viruses by forming a barrier that blocks efficient viral penetration and spread. The stroma also plays a critical role in progression, immunosuppression and invasiveness of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and T cell-mediated cytotoxicity against the tumor stroma to improve therapeutic activity. Methods The bispecific T-cell Engager against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro . In vivo , T-cell biodistribution and antitumor efficacy studies were conducted in NOD/ scid / IL2rg − / − (NSG) mice. Results FBiTE expression did not decrease the infectivity and replication potency of the armed virus . FBiTE-mediated binding of CD3 + effector T cells and FAP + target cells led to T-cell activation, proliferation, and cytotoxicity of FAP-positive cells in vitro . In vivo , FBiTE expression increased intratumoral accumulation of T cells and decreased the level of FAP, a marker of CAFs, in tumors. The antitumor activity of the FBiTE-armed adenovirus was superior to the parental virus. Conclusions Combination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development.

This review article focuses on the application of microwave-assisted techniques in various processes, including microwave-assisted extraction, microwave-assisted pyrolysis, microwave-assisted acid hydrolysis, microwave-assisted organosolv, and microwave-assisted hydrothermal pretreatment. This article discusses the mechanisms behind these techniques and their potential for increasing yield, producing more selectivity, and lowering reaction times while reducing energy usage. It also highlights the advantages and disadvantages of each process and emphasizes the need for further research to scale the processes and optimize conditions for industrial applications. A specific case study is presented on the pretreatment of coffee waste, demonstrating how the choice of microwave-assisted processes can lead to different by-products depending on the initial composition of the biomass.

A thermodynamic and kinetic study of the adsorption process of Zn (II) and Pb (II) ions from aqueous solution on the surface of graphene oxide (GO) to establish the mechanisms of adsorbate–adsorbent interaction on this surface. The effect of pH on the retention capacity was studied and adsorption isotherms were determined from aqueous solution of the ions; once the experimental data was obtained, the kinetic and thermodynamic study of the sorption process was carried out. The data were fitted to the Langmuir, Freundlich, Dubinin-Raduskevich and Temkin isotherm models. The results showed that Zn(II) and Pb(II) on the GO adsorbing surface fitted the Langmuir model with correlation coefficients (R2) of 0.996. Kinetic models studied showed that a pseudo-second-order model was followed and thermodynamically, the process was spontaneous according to the values of Gibbs free energy (ΔGo). N2 adsorption isotherms were determined and modeled with the NLDFT (nonlocal density functional theory) and QSDFT (quenched solid density functional theory) kernels.

All tumors accumulate genetic alterations, some of which can give rise to mutated, non-self peptides presented by human leukocyte antigen (HLA) molecules and elicit T-cell responses. These immunogenic mutated peptides, or neoantigens, are foreign in nature and display exquisite tumor specificity. The correlative evidence suggesting they play an important role in the effectiveness of various cancer immunotherapies has triggered the development of vaccines and adoptive T-cell therapies targeting them. However, the systematic identification of personalized neoantigens in cancer patients, a critical requisite for the success of these therapies, remains challenging. A growing amount of evidence supports that only a small fraction of all tumor somatic non-synonymous mutations (NSM) identified represent neoantigens; mutated peptides that are processed, presented on the cell surface HLA molecules of cancer cells and are capable of triggering immune responses in patients. Here, we provide an overview of the existing strategies to identify candidate neoantigens and to evaluate their immunogenicity, two factors that impact on neoantigen identification. We will focus on their strengths and limitations to allow readers to rationally select and apply the most suitable method for their specific laboratory setting.

A collection of 29 cultivable fungal strains isolated from deep-sea sediments of the Gulf of Mexico were cultivated under the “one strain, many compounds” approach to explore their chemical diversity and antimicrobial potential. From the 87 extracts tested, over 50% showed antimicrobial activity, and the most active ones were those from cultures grown at 4 °C in darkness for 60 days (resembling deep-sea temperature). PCA analysis of the LC-MS data of all the extracts confirmed that culture temperature is the primary factor in the variation of the 4462 metabolite features, accounting for 21.3% of the variation. The bioactivity-guided and conventional chemical studies of selected fungal strains allowed the identification of several active and specialized metabolites. Finally, metabolomics analysis by GNPS molecular networking and manual dereplication revealed the biosynthetic potential of these species to produce interesting chemistry. This work uncovers the chemical and biological study of marine-derived fungal strains from deep-sea sediments of the Gulf of Mexico.

The marine-facultative Aspergillus sp. MEXU 27854, isolated from the Caleta Bay in Acapulco, Guerrero, Mexico, has provided an interesting diversity of secondary metabolites, including a series of rare dioxomorpholines, peptides, and butyrolactones. Here, we report on the genomic data, which consists of 11 contigs (N50~3.95 Mb) with a ~30.75 Mb total length of assembly. Genome annotation resulted in the prediction of 10,822 putative genes. Functional annotation was accomplished by BLAST searching protein sequences with different public databases. Of the predicted genes, 75% were assigned gene ontology terms. From the 67 BGCs identified, ~60% belong to the NRPS and NRPS-like classes. Putative BGCs for the dioxomorpholines and other metabolites were predicted by extensive genome mining. In addition, metabolomic molecular networking analysis allowed the annotation of all isolated compounds and revealed the biosynthetic potential of this fungus. This work represents the first report of whole-genome sequencing and annotation from a marine-facultative fungal strain isolated from Mexico.

This article provides an overview of various microwave-assisted techniques, such as microwave-assisted extraction (MAE), microwave-assisted organic synthesis (MAOS), microwave-assisted pyrolysis (MAP), microwave-assisted hydrothermal treatment (MAHT), microwave-assisted acid hydrolysis (MAAH), microwave-assisted organosolv (MAO), microwave-assisted alkaline hydrolysis (MAA), microwave-assisted enzymatic hydrolysis (MAEH), and microwave-assisted fermentation (MAF). Microwave-assisted biomass pretreatment has emerged as a promising method to improve the efficiency of biomass conversion processes, in particular microwave-assisted pyrolysis (MAP). The focus is on microwave-assisted pyrolysis, detailing its key components, including microwave sources, applicators, feedstock characteristics, absorbers, collection systems, and reactor designs. Based on different studies reported in the literature and a mathematical model, a mechanical design of a microwave oven adapted for pyrolysis is proposed together with a computer-aided design and a finite element analysis. The semi-continuous system is designed for a 40 L capacity and a power of 800 W. The material with which the vessel was designed is suitable for the proposed process. The challenges, opportunities, and future directions of microwave-assisted technologies for the sustainable use of biomass resources are presented.

Hydrothermal processing has emerged as a promising clean technology for managing the substantial amounts of agro-industrial waste generated worldwide. This study aims to introduce a clean technology approach to biomass valorization processes by exploring the hydrothermal conversion of two distinct biomass feedstocks, peapods and coffee cherries, into valuable platform chemicals through the use of homogeneous acid catalysts. The hydrothermal valorization experiments were conducted in a 500 mL reactor at 180 °C for 1 h with a 1:20 biomass–acid solution ratio, utilizing a set of organic and inorganic acids as catalysts. The chemical compositions of the biomass feedstocks were analyzed, revealing significant differences in their cellulose (20.2 wt% in peapods; 27.6 wt% in coffee cherries), hemicellulose (17.4 wt% in peapods; 12.5 wt% in coffee cherries), and lignin (5.0 wt% in peapods; 13.7 wt% in coffee cherries) contents. Without the use of catalysts, peapods yielded 45.128 wt% platform chemicals, outperforming coffee cherries, which produced 32.598 wt%. The introduction of various acid catalysts influenced the yields and selectivity of platform chemicals. Sulfuric acid enhanced sugar production, yielding 62.936 wt% from peapods and 51.236 wt% from coffee cherries. Hydrochloric acid selectively favored sugar production but resulted in decreased overall yields. Nitric acid facilitated the conversion of both biomass types, yielding 35.223 wt% from coffee cherries and 40.315 wt% from peapods. Adipic acid achieved the highest overall yields, with 53.668 wt% for coffee cherries and 65.165 wt% for peapods, while also increasing levulinic acid production. Acetic acid significantly increased sugar yields, which reached 50.427 wt% with peapods. The findings highlight the potential of hydrothermal valorization as a clean technology for biomass conversion and underscores the importance of tailoring catalyst selection and process conditions to optimize the valorization of biomass feedstocks.

Ultrasonic pretreatment is a crucial step in the bioconversion of lignocellulosic biomass, such as peapods, into valuable products. Ultrasonic pretreatment is a highly effective physical method that utilizes ultrasonic waves to enhance various processes. Biomass pretreatment is achieved through physical effects such as acoustic cavitation, which disrupts the biomass structure, and chemical effects like radical formation, which breaks down complex molecules. This article focuses on the characteristics, types, and applications of ultrasonic pretreatment in peapods, with a particular emphasis on its role in lignin removal and ultrasound design. An innovative mechanical design in a CAD application of a continuous ultrasound treatment with a capacity of 5 L and an FEA analysis of the equipment are presented as results, providing insights for the design and optimization of ultrasonic pretreatment processes.