Constraints on the emergence of RNA through non-templated primer extension with mixtures of potentially prebiotic nucleotides.

The emergence of RNA on the early Earth is likely to have been influenced by chemical and physical processes that acted to filter out various alternative nucleic acids. For example, UV photostability is thought to have favored the survival of the canonical nucleotides. In a recent proposal for the prebiotic synthesis of the building blocks of RNA, ribonucleotides share a common pathway with arabino- and threo-nucleotides. We have therefore investigated non-templated primer extension with 2-aminoimidazole-activated forms of these alternative nucleotides to see if the synthesis of the first oligonucleotides might have been biased in favor of RNA. We show that non-templated primer extension occurs predominantly through 5'-5' imidazolium-bridged dinucleotides, echoing the mechanism of template-directed primer extension. Ribo- and arabino-nucleotides exhibited comparable rates and yields of non-templated primer extension, whereas threo-nucleotides showed lower reactivity. Competition experiments confirmed the bias against the incorporation of threo-nucleotides. The incorporation of an arabino-nucleotide at the end of the primer acts as a chain terminator and blocks subsequent extension. These biases, coupled with potentially selective prebiotic synthesis, and the templated copying that is known to favour the incorporation of ribonucleotides, provide a plausible model for the effective exclusion of arabino- and threo-nucleotides from primordial oligonucleotides.

Anthropogenic biases in chemical reaction data hinder exploratory inorganic synthesis.

Most chemical experiments are planned by human scientists and therefore are subject to a variety of human cognitive biases1, heuristics2 and social influences3. These anthropogenic chemical reaction data are widely used to train machine-learning models4 that are used to predict organic5 and inorganic6,7 syntheses. However, it is known that societal biases are encoded in datasets and are perpetuated in machine-learning models8. Here we identify as-yet-unacknowledged anthropogenic biases in both the reagent choices and reaction conditions of chemical reaction datasets using a combination of data mining and experiments. We find that the amine choices in the reported crystal structures of hydrothermal synthesis of amine-templated metal oxides9 follow a power-law distribution in which 17% of amine reactants occur in 79% of reported compounds, consistent with distributions in social influence models10-12. An analysis of unpublished historical laboratory notebook records shows similarly biased distributions of reaction condition choices. By performing 548 randomly generated experiments, we demonstrate that the popularity of reactants or the choices of reaction conditions are uncorrelated to the success of the reaction. We show that randomly generated experiments better illustrate the range of parameter choices that are compatible with crystal formation. Machine-learning models that we train on a smaller randomized reaction dataset outperform models trained on larger human-selected reaction datasets, demonstrating the importance of identifying and addressing anthropogenic biases in scientific data.

Diaminopurine in Nonenzymatic RNA Template Copying.

In the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems.

Unusual Base Pair between Two 2-Thiouridines and Its Implication for Nonenzymatic RNA Copying.

2-Thiouridine (s2U) is a nucleobase modification that confers enhanced efficiency and fidelity both on modern tRNA codon translation and on nonenzymatic and ribozyme-catalyzed RNA copying. We have discovered an unusual base pair between two 2-thiouridines that stabilizes an RNA duplex to a degree that is comparable to that of a native A:U base pair. High-resolution crystal structures indicate similar base-pairing geometry and stacking interactions in duplexes containing s2U:s2U compared to those with U:U pairs. Notably, the C═O···H-N hydrogen bond in the U:U pair is replaced with a C═S···H-N hydrogen bond in the s2U:s2U base pair. The thermodynamic stability of the s2U:s2U base pair suggested that this self-pairing might lead to an increased error frequency during nonenzymatic RNA copying. However, competition experiments show that s2U:s2U base-pairing induces only a low level of misincorporation during nonenzymatic RNA template copying because the correct A:s2U base pair outcompetes the slightly weaker s2U:s2U base pair. In addition, even if an s2U is incorrectly incorporated, the addition of the next base is greatly hindered. This strong stalling effect would further increase the effective fidelity of nonenzymatic RNA copying with s2U. Our findings suggest that s2U may enhance the rate and extent of nonenzymatic copying with only a minimal cost in fidelity.

Achieving Ultra-High Selectivity to Hydrogen Production from Formic Acid on Pd-Ag Alloys.

Palladium-silver-based alloy catalysts have a great potential for CO-free hydrogen production from formic acid for fuel cell applications. However, the structural factors affecting the selectivity of formic acid decomposition are still debated. Herein, the decomposition pathways of formic acid on Pd-Ag alloys with different atomic configurations have been investigated to identify the alloy structures yielding high H2 selectively. Several PdxAg1-x surface alloys with various compositions were generated on a Pd(111) single crystal; their atomic distribution and electronic structure were determined by a combination of infrared reflection absorption spectroscopy (IRAS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT). It was established that the Ag atoms with Pd neighbors are electronically altered, and the degree of alteration correlates with the number of nearest Pd. Temperature-programmed reaction spectroscopy (TPRS) and DFT demonstrated that the electronically altered Ag domains create a new reaction pathway that selectively dehydrogenates formic acid. In contrast, Pd monomers surrounded by Ag are demonstrated to have a similar reactivity compared to pristine Pd(111), yielding CO and H2O in addition to the dehydrogenation products. However, they bind to the produced CO weaker than pristine Pd, demonstrating an enhancement in resistance to CO poisoning. This work therefore shows that surface Ag domains modified by interaction with subsurface Pd are the key active sites for selective decomposition of formic acid, while surface Pd atoms are detrimental to selectivity. Hence, the decomposition pathways can be tailored for CO-free H2 production on Pd-Ag alloy systems.

Synthesis and Characterization of Corn Stover-Based Cellulose Triacetate Catalyzed by Ionic Liquid Phosphotungstate.

Cellulose triacetate (CTA) was successfully synthesized from corn stover cellulose (CSC) in the presence of [PyPS]3PW12O40 (IL-POM). The effects of IL-POM contents, reaction temperature, and reaction time on the yield and degree of substitution of CTA were investigated. The synthesized CTA was characterized by SEM, FTIR, and TGA, and the degree of polymerization and solubility in various organic solvents were evaluated. Results showed that the optimum reaction conditions were as follows: 0.04 g of IL-POM, reaction temperature of 140 °C, and reaction time of 45 min, for 0.4 g of CSC and 9 mL of glacial acetic acid. The yield of CTA under optimum reaction conditions was as high as 79.27%, and the degree of substitution was 2.95. SEM and FTIR results showed that the cellulose acetylation occurred, and CTA was synthesized. The TGA results revealed that the decomposition temperature of CTA increased by about 30 °C when compared with that of CSC. A simple, environment-friendly, and efficient process for the preparation of CTA from CSC was constructed, which provides a new pathway for the high-value utilization of corn stover.

Facile fabrication of flexible AuNPs@CDA SERS substrate for enrichment and detection of thiram pesticide in water.

Pesticide residues in water is one of the most serious problems in developing countries. Surface enhanced Raman spectroscopy (SERS) is widely used in the detection and monitoring of pesticide and other trace compounds because of its low limits of detection (LODs). However, different SERS substrate synthesis methods have different economic benefits and environmental impacts. In this paper, a flexible AuNPs@CDA SERS substrate was fabricated by the gold nanoparticles (AuNPs) and the biomass-based cellulose diacetate (CDA), which had stable test performance and considerable LODs. The substrates were economically viable and environment friendly. The characterization analysis of the substrate allows us to flexibly select different test methods (drop-test or enrichment-test) as coping strategy in different situation. The results showed that the LODs of thiram pesticide in water by enrichment-test could reach 10-7 g/mL, and had a good linear relationship in the concentration range of 10-7-10-6 g/mL. This strategy can realize the rapid and effective detection and monitoring of thiram pesticide in water.

Numerical Tensile Damage Procedure Analysis of Angle-Ply Laminate Using Multi-Scale RVEs with Smear Crack Models.

This paper reported the tensile failure strengths and damage procedure of composite laminate manufactured from the toughened-epoxy T800 prepreg at multi-scale levels. According to the exterior and interior distinction of each layer in laminate, the macro/mesoscale representative volume element (macro-RVE, meso-RVE) was first constructed, respectively. Then the micro-scale representative volume element (micro-RVE) with a hexagonal fiber-packed pattern in the interior zone of each layer in the laminate was finally determined on the principle of the same fiber volume fraction between the composite laminate and multi-scale RVEs. In the multi-RVEs analysis, the mechanical failure strengths of each scale model were transmitted from the last-scale model's homogenization, such as the meso-RVE from micro-RVE and the macro-RVE from meso-RVE. Based on our previous report, the innovative multi-scale damage and post-damage models on the concept of the smear crack were improved fully and incorporated by user-defined material subroutines (UMATs), such as in the addition of multiple cracks co-coupled, which makes it predict the element damage procedure. The averaged mechanical responses with damage mechanism of multi-scale RVEs under tensile, compressive, or shear loadings were obtained wholly by the homogenization method. The macroscale tensile damage initiation and propagation procedure were analyzed in detail including their global/local responses, being extended to comparison with experimental results.

Toward benchmarking theoretical computations of elementary rate constants on catalytic surfaces: formate decomposition on Au and Cu.

With the emergence of methods for computing rate constants for elementary reaction steps of catalytic reactions, benchmarking their accuracy becomes important. The unimolecular dehydrogenation of adsorbed formate on metal surfaces serves as a prototype for comparing experiment and theory. Previously measured pre-exponential factors for CO2 formation from formate on metal surfaces, including Cu(110), are substantially higher than expected from the often used value of k B T/h, or ∼6 × 1012 s-1, suggesting that the entropy of the transition state is higher than that of the adsorbed formate. Herein, the rate constant parameters for formate decomposition on Au(110) and Cu(110) are addressed quantitatively by both experiment and theory and compared. A pre-exponential factor of 2.3 × 1014 s-1 was obtained experimentally on Au(110). DFT calculations revealed the most stable configuration of formate on both surfaces to be bidentate and the transition states to be less rigidly bound to the surface compared to the reactant state, resulting in a higher entropy of activation and a pre-exponential factor exceeding k B T/h. Though reasonable agreement is obtained between experiment and theory for the pre-exponential factors, the activation energies determined experimentally remain consistently higher than those computed by DFT using the GGA-PBE functional. This difference was largely erased when the metaGGA-SCAN functional was applied. This study provides insight into the underlying factors that result in the relatively high pre-exponential factors for unimolecular decomposition on metal surfaces generally, highlights the importance of mobility for the transition state, and offers vital information related to the direct use of DFT to predict rate constants for elementary reaction steps on metal surfaces.

Emerging advances in identifying signal transmission molecules involved in the interaction between Mycobacterium tuberculosis and the host.

Tuberculosis caused by Mycobacterium tuberculosis (MTB) is an ancient chronic infectious disease and is still the leading cause of death worldwide due to a single infectious disease. MTB can achieve immune escape by interacting with host cells through its special cell structure and secreting a variety of effector proteins. Innate immunity-related pattern recognition receptors (PPR receptors) play a key role in the regulation of signaling pathways. In this review, we focus on the latest research progress on related signal transduction molecules in the interaction between MTB and the host. In addition, we provide new research ideas for the development of new anti-tuberculosis drug targets and lead compounds and provide an overview of information useful for approaching future tuberculosis host-oriented treatment research approaches and strategies, which has crucial scientific guiding significance and research value.

Nylon membranes modified by gold nanoparticles as surface-enhanced Raman spectroscopy substrates for several pesticides detection.

Surface enhanced Raman spectroscopy (SERS) is an attractive means for trace compound detection because of its high sensitivity, however, the poor reproducibility is a major challenge. Herein, we propose a facile SERS strategy employing the several developed test processes to improve the repeatability of the SERS analysis based on regular nylon membranes as substrates to detect trace compounds. Various methods, including in situ reduction, immersion adsorption, and filtration, were first compared to prepare composite substrates using nylon membranes and gold nanoparticles. The substrates prepared by filtration showed the best test parallelism (RSD = 7.85%). Its limit of detection (LOD) could reach 10-8 g mL-1 with a good linear relationship in the range 10-8 to 10-7 g mL-1. Finally, three pesticide solutions were tested to verify the substrate applicability. A superior LOD of 10-8 g mL-1 was observed for thiram, whereas the LODs of both phorate and benthiocarb could reach 10-6 g mL-1. Overall, modifying nylon membrane substrates with gold nanoparticles improves the repeatability and economic viability of SERS and favors its wider commercial application for detecting trace compounds.

Enhancing physical properties of chitosan/pullulan electrospinning nanofibers via green crosslinking strategies.

In this study, electrospun chitosan/pullulan composite nanofiber films were crosslinked by two green methods (heating and cinnamaldehyde). With the increase of chitosan content, the morphology results indicated that the nanostructures of thermal crosslinking chitosan/pullulan (TCP) and cinnamaldehyde crosslinking chitosan/pullulan (CCP) nanofiber films became more stable. The decreases in weight loss (83.65 % to 43.85 % for TCP and 23.42 % to 15.58 % for CCP) and the increases in water contact angle (31.8° to 54.1° for TCP and 83.65 % to 43.85 % for CCP) confirmed the improved water stability. The decreases in water vapor permeability indicated that the crosslinking processes significantly improved the barrier properties of the films. Mechanical and thermal properties of TCP and CCP films were enhanced respectively. Furthermore, the corresponding properties of CCP films were more excellent than TCP films. FTIR results indicated the occurrence of Maillard reaction during the thermal crosslinking process and Schiff base reaction during the cinnamaldehyde crosslinking process.

Thermal gelling properties and structural properties of myofibrillar protein including thermo-reversible and thermo-irreversible curdlan gels.

This study investigated the gelling and structural properties of composite gels prepared with myofibrillar protein (MP) and different concentrations of thermo-reversible curdlan gels (TRC) and thermo-irreversible curdlan gels (TIRC). The gel strength, water holding capacity, and whiteness of MP gels were significantly increased with increasing TRC and TIRC content (P < 0.05). Dynamic rheological testing upon temperature sweeping indicated that the G' and G″ values of MP were significantly enhanced with added TRC or TIRC, which were positively related to the lower particle size of composite MP sols. Moreover, the presence of TRC or TIRC changed the secondary structure of MP gels, as well as altered the tertiary structure of MP sols. The micrographs of MP gels indicated that TRC prompted the formation of more dense and stable protein matrix. Our results revealed that TRC or TIRC had distinctive effects on the gelling properties and secondary structure of MP.

Using a stable pre-emulsified canola oil system that includes porcine plasma protein hydrolysates and oxidized tannic acid to partially replace pork fat in frankfurters.

The objective of this study was to evaluate the effect of two different forms of canola oil (pure liquid form or a pre-emulsified form that includes porcine plasma protein hydrolysates modified by oxidized tannic acid) used for pork back-fat substitutions on the physico-chemical characteristics of frankfurters. When compared to the control group, partial replacement of pork back-fat using a pre-emulsified canola oil system exhibited excellent water and fat binding capacities, quicker relaxation times and lower amounts of saturated fatty acids (SFAs) (P < .05), as well as increased hardness, gumminess, and chewiness (P < .05) when verified by dynamic rheology analysis. Additionally, higher replacement ratio of pre-emulsified canola oil did significantly decrease the overall acceptability than the control group (P < .05). Our results indicate that pre-emulsified canola oil provided greater improvement with respect to the physical characteristics of partial pork back-fat replaced frankfurters, when compared to pure canola oil inclusion.

Honeycomb-structured carbon aerogels from nanocellulose and skin secretion of Andrias davidianus for highly compressible binder-free supercapacitors.

Nanocellulose-derived carbon is a promising material in energy storage because of its sustainability, low environmental impact, and large specific surface area. Herein, the skin secretion of Andrias davidianus (SSAD) is applied for the first time as the bio-nitrogen source to dope carbon aerogels from nanocellulose. Cellulose nanocrystal (CNC) is discovered to be very effective to address the dispersion problem of SSAD in water. After being homogeneously mixed with cellulose nanofiber (CNF), honeycomb-structured nanofibrous carbon aerogels are obtained via unidirectional freeze-drying of the SSAD/CNC/CNF mixture followed by high-temperature carbonization. Impressively, unlike those fragile carbon aerogels in many early works, the present ones exhibit outstanding elasticity in repeated compression and release tests. Moreover, a symmetric binder-free supercapacitor is assembled from the carbon aerogels, which exhibits improved electrochemical capacitive properties and cycling stability. And even after 500 compression and release cycles, the supercapacitor can still maintain high capacitive performance, indicating its superiorities in durability and electrochemical stability.

Fast dissolving oral films for drug delivery prepared from chitosan/pullulan electrospinning nanofibers.

In this study, Chitosan/pullulan composite nanofiber fast dissolving oral films (FDOFs) were prepared via electrospinning technology. The ratio of chitosan/pullulan (C/P) had an influence on solution property and nanofiber morphology, with the increase of chitosan, viscosity and conductivity of solutions increased, the morphology obtained by scanning electron microscopy indicated that the diameter of nanofibers decreased initially then increased. The Fourier transform infrared spectra indicated hydrogen bond interactions between chitosan and pullulan molecules. X-ray diffraction analysis proved that electrospinning process decreased the crystallinity of materials. Thermal analysis showed that melting point, degradation temperature and glass transition temperature increased with the addition of chitosan content in the FDOF. Water solubility test proved that the FDOF can dissolve in water completely within 60 s. Finally, in order to prove its practicability in future, a model drug of aspirin was encapsulated in the FDOF successfully.