We designed a cascade nanozyme with both superoxide dismutase– and catalase-mimicking activities for anti-inflammation therapy.

Oral microecological agents show potential in reshaping intestinal microbiota and treating inflammatory bowel disease (IBD), but their clinical application is hindered by gastrointestinal challenges, antioxidant instability, and ineffective targeted delivery. In this study, we proposed a protective modification strategy utilizing a nanozyme coating and an alginate microsphere system to enhance the delivery efficiency, effectiveness, and precision of probiotics. By incorporating Mn into CeO₂, Mn@CeO₂ nanozyme was synthesized, significantly boosting ROS scavenging activity both in vitro and in vivo at safe dosages. Following the coincubation of Mn@CeO₂ with Limosilactobacillus reuteri, the nanozymes were successfully distributed onto the surface of the probiotics. MnCe@LR/AMs were then fabricated using the electrostatic spray method, enhancing their tolerance to the acidic environment of the stomach. Notably, sodium alginate (SA), through electrostatic interactions and binding to mannose receptors highly expressed at inflamed sites, conferred a dual-targeting property to MnCe@LR/AMs. In the treatment of colitis in mice, MnCe@LR/AMs were shown to function through the synergistic antioxidant and anti-inflammatory activities of their components. They also effectively reinforced the intestinal barrier, while improving gut microbial diversity and increasing the relative abundance of probiotics. Furthermore, we demonstrated that MnCe@LR/AMs contribute to the maintenance of intestinal homeostasis by enhancing the absorption of amino acids in the gut and modulating macrophage polarization to regulate the immune response. These findings suggest that MnCe@LR/AMs hold significant promise for developing advanced IBD therapies, offering improved precision and efficacy in probiotic delivery.

Thioesters and thioacetic acid (TAA) have been invoked as key reagents for the origin of life as activated forms of acetate analogous to acetyl-CoA. These species could have served as high-energy group-transfer reagents and allowed carbon insertions to form higher molecular weight compounds such as pyruvate. The apparent antiquity of the Wood-Ljungdahl CO₂ fixation pathway and its presence in organisms which inhabit hydrothermal (HT) environments has also led to suggestions that there may be a connection between the abiotic chemistry of compounds similar to TAA and the origins of metabolism. These compounds’ apparent chemical simplicity has made their prebiotic availability assumed, however, although the kinetic behavior and thermochemical properties of TAA and analogous esters have been preliminarily explored in other contexts, the geochemical relevance of these compounds merits further evaluation. Therefore, the chemical behavior of the simplest thiolated acetic acid derivatives, TAA and methylthioacetate (MTA) were explored here. Using laboratory measurements, literature data and thermochemical models, we examine the plausibility of the accumulation of these compounds in various geological settings. Due to the high free energy change of their hydrolysis and corresponding low equilibrium constants, it is unlikely that these species could have accumulated abiotically to any significant extant.

Contents 1. Introduction 1.1. A workshop and this document 1.2. Framing origins of life science 1.2.1. What do we mean by the origins of life (OoL)? 1.2.2. Defining life 1.2.3. How should we characterize approaches to OoL science? 1.2.4. One path to life or many? 2. A Strategy for Origins of Life Research 2.1. Outcomes—key questions and investigations 2.1.1. Domain 1: Theory 2.1.2. Domain 2: Practice 2.1.3. Domain 3: Process 2.1.4. Domain 4: Future studies 2.2. EON Roadmap 2.3. Relationship to NASA Astrobiology Roadmap and Strategy documents and the European AstRoMap Appendix I Appendix II Supplementary Materials References

An abiotic formation of meso- and d l-tartrates in 80% yield via the cyanide-catalyzed dimerization of glyoxylate under alkaline conditions is demonstrated. A detailed mechanism for this conversion is proposed, supported by NMR evidence and ¹³C-labeled reactions. Simple dehydration of tartrates to oxaloacetate and an ensuing decarboxylation to form pyruvate are known processes that provide a ready feedstock for entry into the citric acid cycle. While glyoxylate and high hydroxide concentration are atypical in the prebiotic literature, there is evidence for natural, abiotic availability of each. It is proposed that this availability, coupled with the remarkable efficiency of tartrate production from glyoxylate, merits consideration of an alternative prebiotic pathway for providing constituents of the citric acid cycle.