Amino acid analogues provide multiple plausible pathways to prebiotic peptides.

Prebiotic peptide synthesis has consistently been a prominent topic within the field of the origin of life. While research predominantly centres on the 20 classical amino acids, the synthesis process encounters significant thermodynamic barriers. Consequently, amino acid analogues are being explored as potential building blocks for prebiotic peptide synthesis. This review delves into the pathway of polypeptide formation, identifying specific amino acid analogues that might have existed on early Earth, potentially participating in peptide synthesis and chemical evolution. Moreover, considering the complexity and variability of the environment on early Earth, we propose the plausibility of coevolution between amino acids and their analogues.

[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Heat flows enrich prebiotic building blocks and enhance their reactivity.

The emergence of biopolymer building blocks is a crucial step during the origins of life1-6. However, all known formation pathways rely on rare pure feedstocks and demand successive purification and mixing steps to suppress unwanted side reactions and enable high product yields. Here we show that heat flows through thin, crack-like geo-compartments could have provided a widely available yet selective mechanism that separates more than 50 prebiotically relevant building blocks from complex mixtures of amino acids, nucleobases, nucleotides, polyphosphates and 2-aminoazoles. Using measured thermophoretic properties7,8, we numerically model and experimentally prove the advantageous effect of geological networks of interconnected cracks9,10 that purify the previously mixed compounds, boosting their concentration ratios by up to three orders of magnitude. The importance for prebiotic chemistry is shown by the dimerization of glycine11,12, in which the selective purification of trimetaphosphate (TMP)13,14 increased reaction yields by five orders of magnitude. The observed effect is robust under various crack sizes, pH values, solvents and temperatures. Our results demonstrate how geologically driven non-equilibria could have explored highly parallelized reaction conditions to foster prebiotic chemistry.

Symmetry breaking and chiral amplification in prebiotic ligation reactions.

The single chirality of biological molecules is a signature of life. Yet, rationalizing how single chirality emerged remains a challenging goal1. Research has commonly focused on initial symmetry breaking and subsequent enantioenrichment of monomer building blocks-sugars and amino acids-that compose the genetic polymers RNA and DNA as well as peptides. If these building blocks are only partially enantioenriched, however, stalling of chain growth may occur, whimsically termed in the case of nucleic acids as "the problem of original syn"2. Here, in studying a new prebiotically plausible route to proteinogenic peptides3-5, we discovered that the reaction favours heterochiral ligation (that is, the ligation of L monomers with D monomers). Although this finding seems problematic for the prebiotic emergence of homochiral L-peptides, we demonstrate, paradoxically, that this heterochiral preference provides a mechanism for enantioenrichment in homochiral chains. Symmetry breaking, chiral amplification and chirality transfer processes occur for all reactants and products in multicomponent competitive reactions even when only one of the molecules in the complex mixture exhibits an imbalance in enantiomer concentrations (non-racemic). Solubility considerations rationalize further chemical purification and enhanced chiral amplification. Experimental data and kinetic modelling support this prebiotically plausible mechanism for the emergence of homochiral biological polymers.

Oldest thylakoids in fossil cells directly evidence oxygenic photosynthesis.

Today oxygenic photosynthesis is unique to cyanobacteria and their plastid relatives within eukaryotes. Although its origin before the Great Oxidation Event is still debated1-4, the accumulation of O2 profoundly modified the redox chemistry of the Earth and the evolution of the biosphere, including complex life. Understanding the diversification of cyanobacteria is thus crucial to grasping the coevolution of our planet and life, but their early fossil record remains ambiguous5. Extant cyanobacteria include the thylakoid-less Gloeobacter-like group and the remainder of cyanobacteria that acquired thylakoid membranes6,7. The timing of this divergence is indirectly estimated at between 2.7 and 2.0 billion years ago (Ga) based on molecular clocks and phylogenies8-11 and inferred from the earliest undisputed fossil record of Eoentophysalis belcherensis, a 2.018-1.854 Ga pleurocapsalean cyanobacterium preserved in silicified stromatolites12,13. Here we report the oldest direct evidence of thylakoid membranes in a parallel-to-contorted arrangement within the enigmatic cylindrical microfossils Navifusa majensis from the McDermott Formation, Tawallah Group, Australia (1.78-1.73 Ga), and in a parietal arrangement in specimens from the Grassy Bay Formation, Shaler Supergroup, Canada (1.01-0.9 Ga). This discovery extends their fossil record by at least 1.2 Ga and provides a minimum age for the divergence of thylakoid-bearing cyanobacteria at roughly 1.75 Ga. It allows the unambiguous identification of early oxygenic photosynthesizers and a new redox proxy for probing early Earth ecosystems, highlighting the importance of examining the ultrastructure of fossil cells to decipher their palaeobiology and early evolution.

Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury.

Acute lung injury (ALI) is one of the most common complications in COVID-19 and also a syndrome of acute respiratory failure with high mortality rates, but lacks effective therapeutic drugs. Natural products provide inspiration and have proven to be the most valuable source for bioactive molecule discovery. In this study, the chemical evolution of the natural product Tanshinone IIA (Tan-IIA) to achieve a piperidine-fused scaffold through a synthetic route of pre-activation, multi-component reaction, and post-modification is presented. Through biological evaluation, it is pinpointed that compound 8b is a standout candidate with remarkable anti-inflammation and anti-oxidative stress properties, coupled with low toxicity. The mechanistic study unveils a multifaceted biological profile of 8b and shows that 8b is highly efficient in vivo for the treatment of ALI. Therefore, this work not only provides an effective strategy for the treatment of ALI, but also offers a distinctive natural product-inspired drug discovery.

Gas-Phase vs. Grain-Surface Formation of Interstellar Complex Organic Molecules: A Comprehensive Quantum-Chemical Study.

Several organic chemical compounds (the so-called interstellar complex organic molecules, iCOMs) have been identified in the interstellar medium (ISM). Examples of iCOMs are formamide (HCONH2), acetaldehyde (CH3CHO), methyl formate (CH3OCHO), or formic acid (HCOOH). iCOMs can serve as precursors of other organic molecules of enhanced complexity, and hence they are key species in chemical evolution in the ISM. The formation of iCOMs is still a subject of a vivid debate, in which gas-phase or grain-surface syntheses have been postulated. In this study, we investigate the grain-surface-formation pathways for the four above-mentioned iCOMs by transferring their primary gas-phase synthetic routes onto water ice surfaces. Our objective is twofold: (i) to identify potential grain-surface-reaction mechanisms leading to the formation of these iCOMs, and (ii) to decipher either parallelisms or disparities between the gas-phase and the grain-surface reactions. Results obtained indicate that the presence of the icy surface modifies the energetic features of the reactions compared to the gas-phase scenario, by increasing some of the energy barriers. Therefore, the investigated gas-phase mechanisms seem unlikely to occur on the icy grains, highlighting the distinctiveness between the gas-phase and the grain-surface chemistry.

Assembly-driven protection from hydrolysis as key selective force during chemical evolution.

The origins of biopolymers pose fascinating questions in prebiotic chemistry. The marvelous assembly proficiencies of biopolymers suggest they are winners of a competitive evolutionary process. Sophisticated molecular assembly is ubiquitous in life where it is often emergent upon polymerization. We focus on the influence of molecular assembly on hydrolysis rates in aqueous media and suggest that assembly was crucial for biopolymer selection. In this model, incremental enrichment of some molecular species during chemical evolution was partially driven by the interplay of kinetics of synthesis and hydrolysis. We document a general attenuation of hydrolysis by assembly (i.e., recalcitrance) for all universal biopolymers and highlight the likely role of assembly in the survival of the 'fittest' molecules during chemical evolution.

From autocatalysis to survival of the fittest in self-reproducing lipid systems.

Studying autocatalysis - in which molecules catalyse their own formation - might help to explain the emergence of chemical systems that exhibit traits normally associated with biology. When coupled to other processes, autocatalysis can lead to complex systems-level behaviour in apparently simple mixtures. Lipids are an important class of chemicals that appear simple in isolation, but collectively show complex supramolecular and mesoscale dynamics. Here we discuss autocatalytic lipids as a source of extraordinary behaviour such as primitive chemical evolution, chemotaxis, temporally controllable materials and even as supramolecular catalysts for continuous synthesis. We survey the literature since the first examples of lipid autocatalysis and highlight state-of-the-art synthetic systems that emulate life, displaying behaviour such as metabolism and homeostasis, with special consideration for generating structural complexity and out-of-equilibrium models of life. Autocatalytic lipid systems have enormous potential for building complexity from simple components, and connections between physical effects and molecular reactivity are only just beginning to be discovered.

Chemical Evolution of Amphiphilic Xenopeptides for Potentiated Cas9 Ribonucleoprotein Delivery.

The introduction of the CRISPR/Cas9 system in the form of Cas9/sgRNA ribonucleoproteins (RNP) is an efficient, straightforward strategy for genome editing, and potent RNP carriers are in high demand. Here, we report a series of artificial peptides based on novel ionizable amino acids that are able to deliver Cas9 RNP into cells very efficiently. Systematic variation of hydrophobic properties revealed a relationship between the xenopeptide logD7.4 and genome editing potency. By correlating the physicochemical properties with biological activity, individual optima were found for different xenopeptide sequence architectures. The optimized amphiphilic carriers enable ∼88% eGFP knockout at an RNP dose of only 1 nM and up to 40% homology-directed repair (HDR) in eGFP/BFP switchable reporter cells by co-delivery with an ssDNA template. Mechanistic studies demonstrated that hydrophobically balanced xenopeptides are more resistant to ionic stress as well as concentration-dependent dissociation and promote endocytosis by both clathrin- and macropinocytosis-mediated pathways. The systematic study develops a versatile and adjustable carrier platform and highlights impactful structure-activity relationships, providing a new chemical guide for the design and optimization of nonviral Cas9 RNP nanocarriers.

Light-Fueled Primitive Replication and Selection in Biomimetic Chemical Systems.

The concept of chemically evolvable replicators is central to abiogenesis. Chemical evolvability requires three essential components: energy-harvesting mechanisms for nonequilibrium dissipation, kinetically asymmetric replication and decomposition pathways, and structure-dependent selective templating in the autocatalytic cycles. We observed a UVA light-fueled chemical system displaying sequence-dependent replication and replicator decomposition. The system was constructed with primitive peptidic foldamer components. The photocatalytic formation-recombination cycle of thiyl radicals was coupled with the molecular recognition steps in the replication cycles. Thiyl radical-mediated chain reaction was responsible for the replicator death mechanism. The competing and kinetically asymmetric replication and decomposition processes led to light intensity-dependent selection far from equilibrium. Here, we show that this system can dynamically adapt to energy influx and seeding. The results highlight that mimicking chemical evolution is feasible with primitive building blocks and simple chemical reactions.

[Research progress on processing historical evolution, chemical constituents, and pharmacological action of Bombyx Batryticatus].

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.

Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity.

Low activity has been the primary obstacle impeding the use of DNA enzymes (DNAzymes) as gene silencing agents in clinical applications. Here we describe the chemical evolution of a DNAzyme with strong catalytic activity under near physiological conditions. The enzyme achieves ~65 turnovers in 30 minutes, a feat only previously witnessed by the unmodified parent sequence under forcing conditions of elevated Mg2+ and pH. Structural constraints imposed by the chemical modifications drive catalysis toward a highly preferred UGUD motif (cut site underlined) that was validated by positive and negative predictions. Biochemical assays support an autonomous RNA cleavage mechanism independent of RNase H1 engagement. Consistent with its strong catalytic activity, the enzyme exhibits persistent allele-specific knock-down of an endogenous mRNA encoding an undruggable oncogenic KRAS target. Together, these results demonstrate that chemical evolution offers a powerful approach for discovering new chemotype combinations that can imbue DNAzymes with the physicochemical properties necessary to support therapeutic applications.

Prebiotic chemistry: a review of nucleoside phosphorylation and polymerization.

The phosphorylation of nucleosides and their polymerization are crucial issues concerning the origin of life. The question of how these plausible chemical processes took place in the prebiotic Earth is still perplexing, despite several studies that have attempted to explain these prebiotic processes. The purpose of this article is to review these chemical reactions with respect to chemical evolution in the primeval Earth. Meanwhile, from our perspective, the chiral properties and selection of biomolecules should be considered in the prebiotic chemical origin of life, which may contribute to further research in this field to some extent.

Influence of vertical transport on chemical evolution of dicarboxylic acids and related secondary organic aerosol from surface emission to the top of Mount Hua, Northwest China.

Dicarboxylic acids are strong hygroscopic organic compounds in the atmosphere, and thus significantly affect the cloud formation process and radiative forcing on a regional scale. So far, the evolution of dicarboxylic acids during vertical transport from the surface to the mountaintop has yet to be explicitly understood. In this study, the molecular distribution and stable carbon isotopic (δ13C) compositions of dicarboxylic acids and related organic compounds (DCRCs) in PM2.5 were measured simultaneously at the top (c. 2060 m a.s.l.) and foot (c. 400 m a.s.l.) of Mount (Mt.) Hua during the summer of 2020. Due to the strong anthropogenic emissions at ground level, the concentrations of DCRCs at foot of Mt. Hua were generally higher than those at the top. Oxalic acid (C2) was the predominant diacid in both sites, whose concentrations at foot and top of Mt. Hua were 87-852 and 40-398 ng m-3, respectively. Ratios of adipic acid to azelaic acid (C6/C9), phthalic aid to azelaic acid (pH/C9), glyoxal to methylglyoxal (Gly/mGly), and lower δ13C values (-21.0 ± 2.3 ‰ and - 21.9 ± 2.7 ‰) of C2 indicated that the contributions of anthropogenic sources to DCRCs in PM2.5 in the mountain region are more significant than biogenic sources. Aerosols from the foot of Mt. Hua could affect the atmosphere on the top of the mountain via vertical transport under the influence of daytime valley wind, even though the altitude of Mt. Hua is beyond the boundary layer most of time. The value δ13C of C2 is linearly correlated with C2/mGly, C2/pyruvic acid (Pyr), C2/glyoxylic acid (ωC2) at the top of the mountain, and C2/Gly, C2/ωC2 at the foot of the mountain, indicating that the formation pathway of C2 is mGly-Pyr-ωC2-C2 at the top of Mt. Hua and Gly-ωC2-C2 at the foot of Mt. Hua.

Research progress on processing historical evolution, chemical constituents, and pharmacological action of Bombyx Batryticatus / 中国中药杂志

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.

Natural Radioactivity and Chemical Evolution on the Early Earth: Prebiotic Chemistry and Oxygenation.

It is generally recognized that the evolution of the early Earth was affected by an external energy source: radiation from the early Sun. The hypothesis about the important role of natural radioactivity, as a source of internal energy in the evolution of the early Earth, is considered and substantiated in this work. The decay of the long-lived isotopes 232Th, 238U, 235U, and 40K in the Global Ocean initiated the oxygenation of the hydro- and atmosphere, and the abiogenesis. The content of isotopes in the ocean and the kinetics of their decay, the values of the absorbed dose and dose rate, and the efficiency of sea water radiolysis, as a function of time, were calculated. The ocean served as both a "reservoir" that collected components of the early atmosphere and products of their transformations, and a "converter" in which further chemical reactions of these compounds took place. Radical mechanisms were proposed for the formation of simple amino acids, sugars, and nitrogen bases, i.e., the key structures of all living things, and also for the formation of oxygen. The calculation results confirm the possible important role of natural radioactivity in the evolution of terrestrial matter, and the emergence of life.

[Research progress on processing history evolution, chemical constituents, and pharmacological effects of Hirudo].

As a traditional animal drug, Hirudo is slightly toxic and has the effects of breaking blood stasis, dredging meridians, expelling stasis, and resolving mass. It has a long history of processing, and the early boiling records can be traced back to the Han Dynasty. More than ten processing methods such as frying, roasting, and lime processing appeared later. After processing, Hirudo is deodorized and modified in taste and becomes crispy, which is conducive to crushing and clinical application. At present, the reported components in Hirudo mainly include protein polypeptides, pteridines, and lipids, which have anti-coagulant, anti-thrombotic, anti-atherosclerotic, anti-tumor, and other pharmacological effects. This study reviewed the processing history evolution, chemical consti-tuents, and pharmacological effects of Hirudo to provide a reference for the related research on Hirudo.

Thymine Adsorption onto Cation Exchanged Montmorillonite Clay: Role of Biogenic Divalent Metal Cations in Prebiotic Processes of Chemical Evolution.

The adsorption of thymine, a key pyrimidine base of deoxyribonucleic acid (DNA) on montmorillonite clay (Mnt) exchanged with metal ions (Mnt-M2+, M2+ = Fe2+, Co2+, Cu2+, Ca2+, and Mg2+) over a range of concentration (7.0 × 10-5 M to 12.0 × 10-5 M) and pH (4.0 - 9.0) at ambient temperature has been investigated in aqueous environment spectrophotometrically (UV, FTIR, XRD, SEM-EDX). The effectiveness of various adsorbents was determined in terms of percent (%) binding and Langmuir constants (KL and Xm) using Langmuir adsorption isotherm at their respective pH of maximum adsorption. Transition metal ions incorporated Mnt, particularly Fe2+ have shown better adsorption ability than alkaline earth metal ions. The present study reveals the significant role of divalent metal cation exchanged Mnt clay in the chemical evolution of biomolecules of genetic continuity and self-replication which might have occurred through the adsorption of thymine on and between their silicate layers to protect and achieve biocompatibility.