Light Fluence Rate and Tissue Oxygenation (StO2) Distributions Within the Thoracic Cavity of Patients Receiving Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma

The distributions of light and tissue oxygenation (S_tO₂) within the chest cavity were determined for 15 subjects undergoing macroscopic complete resection followed by intraoperative photodynamic therapy (PDT) as part of a clinical trial for the treatment of malignant pleural mesothelioma (MPM). Over the course of light delivery, detectors at each of eight different sites recorded exposure to variable fluence rate. Nevertheless, the treatment-averaged fluence rate was similar among sites, ranging from a median of 40–61 mW cm⁻² during periods of light exposure to a detector. S_tO₂ at each tissue site varied by subject, but posterior mediastinum and posterior sulcus were the most consistently well oxygenated (median S_tO₂ >90%; interquartile ranges ~85–95%). PDT effect on S_tO₂ was characterized as the S_tO₂ ratio (post-PDT S_tO₂/pre-PDT S_tO₂). High S_tO₂ pre-PDT was significantly associated with oxygen depletion (S_tO₂ ratio < 1), although the extent of oxygen depletion was mild (median S_tO₂ ratio of 0.8). Overall, PDT of the thoracic cavity resulted in moderate treatment-averaged fluence rate that was consistent among treated tissue sites, despite instantaneous exposure to high fluence rate. Mild oxygen depletion after PDT was experienced at tissue sites with high pre-PDT S_tO₂, which may suggest the presence of a treatment effect.     

Antibody–Prodrug Conjugates with KSP Inhibitors and Legumain-Mediated Metabolite Formation

Many antibody–drug conjugates (ADCs) have failed to achieve a sufficient therapeutic window in clinical studies either due to target-mediated or off-target toxicities. To achieve an additional safety level, a new class of antibody–prodrug conjugates (APDCs) directed against different targets in solid tumors is here described. The tumor-associated lysosomal endopeptidase legumain with a unique cleavage sequence was utilized for APDC metabolism. Legumain-activatable APDCs were as potent as their cathepsin B-activatable analogues. The peptide sequence susceptible to legumain cleavage was optimized for further discrimination of the formation of active metabolites within tumor cells versus healthy tissues, leveraging different tissue-specific legumain activities. Optimized APDCs with slow legumain-mediated conversion reduced preclinically the levels of active metabolite in healthy organs while retaining high activity against different TWEAKR- and B7H3-expressing tumors.     

Two Peculiar Classes of Solvable Systems Featuring 2 Dependent Variables Evolving in Discrete-Time via 2 Nonlinearly-Coupled First-Order Recursion Relations

In this paper we identify certain peculiar systems of 2 discrete-time evolution equations,

which are algebraically solvable. Here l is the “discrete-time” independent variable taking integer values (l = 0, 1, 2, . . .), x_n ≡ x_n(l) are 2 dependent variables, and are the corresponding 2 updated variables. In a previous paper the 2 functions F⁽ⁿ⁾(x₁, x₂), n = 1, 2, were defined as follows: F⁽ⁿ⁾(x₁, x₂) = P₂ (x_n, x_n+1), n = 1, 2 mod[2], with P₂(x₁, x₂) a specific second-degree homogeneous polynomial in the 2 (indistinguishable!) dependent variables x₁(l) and x₂(l). In the present paper we further clarify some aspects of that model and we present its extension to the case when a specific homogeneous function of arbitrary (integer) degree k (hence a polynomial of degree k when k > 0) in the 2 dependent variables x₁(l) and x₂(l).     

Thermal tool to evaluate essential oil composition of different Eucalyptus genotypes in relation to Glycaspis brimblecombei susceptibility (Hemiptera: Aphalaridae)

Journal of Thermal Analysis and Calorimetry - Eucalyptus spp. (Myrtaceae) is economically important worldwide and is native from Australia. Glycaspis brimblecombei (Hemiptera: Aphalaridae) is an...     

Tripeptide Self-Assembly into Bioactive Hydrogels: Effects of Terminus Modification on Biocatalysis

Bioactive hydrogels based on the self-assembly of tripeptides have attracted great interest in recent years. In particular, the search is active for sequences that are able to mimic enzymes when they are self-organized in a nanostructured hydrogel, so as to provide a smart catalytic (bio)material whose activity can be switched on/off with assembly/disassembly. Within the diverse enzymes that have been targeted for mimicry, hydrolases find wide application in biomaterials, ranging from their use to convert prodrugs into active compounds to their ability to work in reverse and catalyze a plethora of reactions. We recently reported the minimalistic l-His–d-Phe–d-Phe for its ability to self-organize into thermoreversible and biocatalytic hydrogels for esterase mimicry. In this work, we analyze the effects of terminus modifications that mimic the inclusion of the tripeptide in a longer sequence. Therefore, three analogues, i.e., N-acetylated, C-amidated, or both, were synthesized, purified, characterized by several techniques, and probed for self-assembly, hydrogelation, and esterase-like biocatalysis. This work provides useful insights into how chemical modifications at the termini affect self-assembly into biocatalytic hydrogels, and these data may become useful for the future design of supramolecular catalysts for enhanced performance.