Biological reproduction rests ultimately on chemical autocatalysis. Autocatalytic chemical cycles are thought to have played an important role in the chemical complexification en route to life. There are two, related issues: what chemical transformations allow such cycles to form, and at what speed they are operating. Here we investigate the latter question for solitary as well as competitive autocatalytic cycles in resource-unlimited batch and resource-limited chemostat systems. The speed of growth tends to decrease with the length of a cycle. Reversibility of the reproductive step results in parabolic growth that is conducive to competitive coexistence. Reversibility of resource uptake also slows down growth. Unilateral help by a cycle of its competitor tends to favour the competitor (in effect a parasite on the helper), rendering coexistence unlikely. We also show that deep learning is able to predict the outcome of competition just from the topology and the kinetic rate constants, provided the training set is large enough. These investigations pave the way for studying autocatalytic cycles with more complicated coupling, such as mutual catalysis.

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce-Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce-Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce-Aln gel. In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2- as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV-vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes\' (or ketones) generation.

Many people wonder whether biology, including humans, will benefit or experience harm from new developments in information such as artificial intelligence (AI). Here, it is proposed that biological and non-biological information might be components of a unified process, \'Panevolution\' or \'Pan-Evo\', based on four basic operations-innovation, transmission, adaptation, and movement. Pan-Evo contains many types of variable objects, from molecules to ecosystems. Biological innovation includes mutations and behavioural changes; non-biological innovation includes naturally occurring physical innovations and innovation in software. Replication is commonplace in and outside biology, including autocatalytic chemicals and autonomous software replication. Adaptation includes biological selection, autocatalytic chemicals, and \'evolutionary programming\', which is used in AI. The extension of biological speciation to non-biological information creates a concept called \'Panspeciation\'. Panevolution might benefit or harm biology, but the harm might be minimal if AI and humans behave intelligently because humans and the machines in which an AI resides might split into vastly different environments that suit them. That is a possible example of Panspeciation and would be the first speciation event involving humans for thousands of years. This event will not be particularly hostile to humans if humans learn to evaluate information and cooperate better to minimise both human stupidity and artificial simulated stupidity (ASS-a failure of AI).

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here, we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamic simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Biosurfactants account for about 12% of the global value of the surfactant market, which is currently dominated by synthetic surfactants obtained from fossil sources. Yet, the production of biosurfactants from renewable feedstock is bound to increase, driven by the increasing pressure from both society and governments for chemistry-based industries to become more ecofriendly and economically sustainable. A photo-chemical oxidation process is reported here, yielding new biosurfactants from urban biowaste in water that perform as a solvent and terminal oxidant reagent at room temperature without the addition of conventional oxidants and catalysts. Products with 200-500 kDa molecular weight are obtained. They lower the surface tension of water down to 34 mN/m at 0.5-2 g/L concentration. The estimated cost is rather low (0.1-1.5 EUR/kg), which is competitive with the cost of synthetic surfactants but much lower than the cost of the best-performing bacterial surfactants. For the implementation of the photo-chemical oxidation process at the industrial level, the results suggest that the new biosurfactants obtained in the present work may not reach the performance level of the best-performing bacterial surfactants capable of lowering the surface tension of water down to 28 mN/m. Yet, the biosurfactants produced by the photo-chemical process have a greater chance of being marketed on large scales.

The paper discusses the perspectives of further implementation of the autocatalytic properties of a soluble biopolymer (SBP) derived from municipal biowastes for the realisation of a biorefinery producing value-added bio-products for consumer use. The reaction of an SBP and water is reported to cause the depolymerisation and oxidation of the pristine SBP organic matter with the formation of carboxyl-functionalised polymers having lower molecular weight and CO2. These findings demonstrate the oxidation of the SBP via water, which could only occur through the production of O and OH radicals catalysed by the SBP. According to the adopted experimental plan, the anaerobic digestate supplied by an Italian municipal biowaste treatment plant was hydrolysed in pH 13 water at 60 °C. The dry product was re-dissolved in plain water at pH 10 and used as a control against the same solution with hydrogen peroxide at 0.1-3 H2O2 moles per SBP carbon mole added. The control and test solutions were kept at room temperature, in the dark or in a climatic chamber under irradiation with simulated solar light, until the pH of the solutions remained constant. Afterwards, the solutions were processed to recover and analyse the crude soluble products. The present work reports the results obtained for the control solution and for the test solutions treated in the presence and absence of H2O2, with and without pH control, in the dark and under irradiation with simulated solar light.

Natural chiral amino acids typically adopt an L structural configuration. While a preference for specific molecular chiralities is observed throughout biology and cellular chemistry, the origins of this preference are unclear. In a previous report the origin of enantiomeric selectivity was analyzed in terms of an \"RNA World\" model, and a pathway to a chiral preference for d-ribose was proposed based on the autocatalytic transformation of glyceraldehyde as a precursor to the formation of sugars. Metal-ion-promoted catalysis allows the parity non-conserving (PNC) weak nuclear interaction to influence the chirality of a nascent chiral carbon center. Since the PNC effect is the only natural property with an inherent handedness, it is an obvious candidate to influence enantiomeric preference from a catalytic reaction performed over geologically relevant time scales. The PNC influence requires and emphasizes the important role of catalytic metal ions in primordial chemistry. In this study, the impact of geologically available divalent calcium and higher Z alkaline earth elements are examined as mediators of chiral preference. Detailed calculations of the magnitude of the effect are presented, including the influence of time, temperature, pH, and metal ion identity. It is concluded that metal ions can direct chiral preference for amino acid synthesis via a metal-promoted autocatalytic Strecker reaction within a relatively short geological timeframe, thereby providing a pool of l-amino acids for catalytic chemistry evolving either from an RNA-world model of molecular evolution or alternative pathways to protein synthesis.

Peptide cyclization improves conformational rigidity, providing favorable pharmacological properties, such as proteolytic resistance, target specificity, and membrane permeability. Thus, many synthetic and biosynthetic peptide circularization strategies have been developed. PatG and related natural macrocyclases process diverse peptide sequences, generating millions of cyclic derivatives. However, the application of these cyclases is limited by low yields and the potential presence of unwanted intermediates. Here, we designed a covalently fused G macrocyclase with substrates that efficiently and spontaneously release cyclic peptides. To increase the fidelity of synthesis, we developed an orthogonal control mechanism enabling precision synthesis in Escherichia coli. As a result, a library comprising 4.8 million cyclic derivatives was constructed, producing an estimated 2.6 million distinct cyclic peptides with an improved yield and fidelity.

Selection among autocatalytic species fundamentally depends on their growth law: exponential species, whose number of copies grows exponentially, are mutually exclusive, while sub-exponential ones, whose number of copies grows polynomially, can coexist. Here we consider competitions between autocatalytic species with different growth laws and make the simple yet counterintuitive observation that sub-exponential species can exclude exponential ones while the reverse is, in principle, impossible. This observation has implications for scenarios pertaining to the emergence of natural selection.