Large Molecules Research Articles

Extraction of Heracleum dissectum soluble dietary fiber by different methods: Structure and antioxidant properties.

Heracleum dissectum is rich in nutrients, but there is little research on its soluble dietary fiber (SDF). In this study, SDF from H. dissectum was extracted by enzyme extraction (E-SDF), enzyme chemical extraction (EC-SDF), and fermentation extraction (F-SDF). The composition, molecular weight (Mw), structural characterization, and antioxidant activity of SDF extracted by the three methods were compared. This study showed that different extraction methods lead to differences in their structure. The Mw results showed that F-SDF had the largest Mw, the structure of SDF could be destroyed by enzymatic hydrolysis, and large molecules could be converted into small molecules. The monosaccharide composition analysis showed that the main sugars of E-SDF, EC-SDF, and F-SDF were galacturonic acid and galactose, and the main components of the three SDF samples were hemicellulose hydrolyzed pectin and soluble polysaccharide. Notably, E-SDF had the greatest antioxidant effect at the same concentration. In summary, different extraction methods can affect the structure and antioxidant capacity of H. dissectum SDF, among which E-SDF has potential as a functional food ingredient.

Spin-Restricted Descriptions of Singlet Oxygen Reactions from XMS-CASPT2 Benchmarks.

Reactions of singlet oxygen are numerous, some of which are desired but many are unwanted. Therefore, the ability to correctly predict and interpret this reactivity for complex molecular systems is essential to our understanding of singlet oxygen reactions. DFT is widely used for predicting many reactions but is not suited to degenerate electronic structures; application to isolated singlet oxygen often uses the spin-unrestricted formalism, which results in severe spin contamination. In this work, we demonstrate that spin-restricted DFT can correctly describe the reaction pathway for four prototypical singlet oxygen reactions. By careful benchmarking with XMS-CASPT2, we show that, from the first transition state onward, the degeneracy of the 1Δg state is broken due to differing interactions of the (degenerate) π* orbitals with the organic substrate; this result is well replicated with DFT. These findings demonstrate the utility of using spin-restricted DFT to explore reactions, opening the way to confidently use this computationally efficient method for molecular systems of medium to large organic molecules.

One chiral fingerprint to find them all

Molecular fingerprints are indispensable tools in cheminformatics. However, stereochemistry is generally not considered, which is problematic for large molecules which are almost all chiral.Herein we report MAP4C, a chiral version of our previously reported fingerprint MAP4, which lists MinHashes computed from character strings containing the SMILES of all pairs of circular substructures up to a diameter of four bonds and the shortest topological distance between their central atoms. MAP4C includes the Cahn-Ingold-Prelog (CIP) annotation (R, S, r or s) whenever the chiral atom is the center of a circular substructure, a question mark for undefined stereocenters, and double bond cis–trans information if specified. MAP4C performs slightly better than the achiral MAP4, ECFP and AP fingerprints in non-stereoselective virtual screening benchmarks. Furthermore, MAP4C distinguishes between stereoisomers in chiral molecules from small molecule drugs to large natural products and peptides comprising thousands of diastereomers, with a degree of distinction smaller than between structural isomers and proportional to the number of chirality changes. Due to its excellent performance across diverse molecular classes and its ability to handle stereochemistry, MAP4C is recommended as a generally applicable chiral molecular fingerprint.Scientific contribution The ability of our chiral fingerprint MAP4C to handle stereoisomers from small molecules to large natural products and peptides is unprecedented and opens the way for cheminformatics to include stereochemistry as an important molecular parameter across all fields of molecular design.Graphical

Co-hydrothermal carbonization of municipal sludge and agricultural waste to reduce plant growth inhibition by aqueous phase products: Molecular level analysis of organic matter

The organic matter molecular mechanism by which combined hydrothermal carbonization (co-HTC) of municipal sludge (MS) and agricultural wastes (rice husk, spent mushroom substrate, and wheat straw) reduces the inhibitory effects of aqueous phase (AP) products on pak choi (Brassica campestris L.) growth compared to HTC of MS alone is not clear. Fourier-transform ion cyclotron resonance mass spectrometry was used to characterize the differences in organic matter at the molecular level between AP from MS HTC alone (AP-MS) and AP from co-HTC of MS and agricultural waste (co-Aps). The results showed that N-bearing molecules of AP-MS and co-Aps account for 70.6 % and 54.2 %–64.1 % of all molecules, respectively. Lignins were present in the highest proportion (56.3 %–78.5 %) in all APs, followed by proteins and lipids. The dry weight of co-APs hydroponically grown pak choi was 31.6 %–47.6 % higher than that of the AP-MS. Molecules that were poorly saturated and with low aromaticity were preferentially consumed during hydroponic treatment. Molecules present before and after hydroponics were defined as resistant molecules; molecules present before hydroponics but absent after hydroponics were defined as removed molecules; and molecules absent before hydroponics but present after hydroponics were defined as produced molecules. Large lignin molecules were broken down into more unsaturated molecules, but lignins were the most commonly resistant, removed, and produced molecules. Correlation analysis revealed that N- or S-bearing molecules were phytotoxic in the AP. Tannins positively influenced the growth of pak choi. These results provide new insights into potential implementation strategies for liquid fertilizers produced from AP arising from HTC of MS and agricultural wastes.

Electric Field Gradient in Chiral and Tetrahedral Molecules within High-Order LRESC Formalism.

In this work, we present the electric field gradient (EFG) given by the linear response elimination of the small component (LRESC) scheme up to the 1/c4 order (c is the speed of light in vacuum) in CHFClX (X = Br, I, At) chiral molecules, together with CHF2Br and CH2FX (X = Br, I, At) tetrahedral systems. The former could be good candidates for further parity violation studies, especially when heavy atoms are surrounding. In this context, the LRESC scheme demonstrates effective applicability to large tetrahedral and chiral molecules that incorporate heavy elements, with relativistic effects playing a crucial role. The LRESC results of EFG exhibit an excellent agreement with those calculated at the four-component level, giving differences of only hundredths order in a.u. (atomic units) for the bromine nucleus and less than 0.1 a.u. for the iodine nucleus. Regarding the other nuclei, for the chiral molecules, there is a heavy atom effect on the light atom (HALA) for chlorine and fluorine atoms as the substituent halogen atom becomes heavier. Furthermore, the electronic part of the EFG for the central carbon and the fluorine nuclei presents an important dependence with the environment in the molecules under study. With accurate calculations of the EFG and tabulated nuclear quadrupole moment, the nuclear quadrupole coupling constant is obtained within the LRESC scheme, including for the first time correlation effects on the spin-dependent corrections with this methodology, providing results close to the experimental ones for Cl, Br, and I atoms. At the Hartree-Fock level, the differences are around 6% for Br and I nuclei, and at the density functional theory level with the LDA and PBE0 functionals, the differences are no more than 2%.

Direct Observation of Covalently Bound Clusters in Resonantly Stabilized Radical Reactions and Implications for Carbonaceous Particle Growth.

Based on quantum mechanically guided experiments that observed elusive intermediates in the domain of inception that lies between large molecules and soot particles, we provide a new mechanism for the formation of carbonaceous particles from gas-phase molecular precursors. We investigated the clustering behavior of resonantly stabilized radicals (RSRs) and their interactions with unsaturated hydrocarbons through a combination of gas-phase reaction experiments and theoretical calculations. Our research directly observed a sequence of covalently bound clusters (CBCs) as key intermediates in the evolution from small RSRs, such as benzyl (C7H7), indenyl (C9H7), 1-methylnaphthyl (1-C11H9), and 2-methylnaphthyl (2-C11H9), to large polycyclic aromatic hydrocarbons (PAHs) consisting of 28 to 55 carbons. We found that hydrogen abstraction and RSR addition drive the formation and growth of CBCs, leading to progressive H-losses, the generation of large PAHs and PAH radicals, and the formation of white smoke (incipient carbonaceous particles). This mechanism of progressive H-losses from CBCs (PHLCBC) elucidates the crucial relationship among RSRs, CBCs, and PAHs, and this study provides an unprecedentedly seamless path of observed assembly from small RSRs to large nanoparticles. Understanding the PHLCBC mechanism over a wide temperature range may enhance the accuracy of multiscale models of soot formation, guide the synthesis of carbonaceous nanomaterials, and deepen our understanding of the origin and evolution of carbon within our galaxy.

Cryo2StructData: A Large Labeled Cryo-EM Density Map Dataset for AI-based Modeling of Protein Structures

The advent of single-particle cryo-electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological molecules and their complexes at atomic resolution. The high-resolution structures of biological macromolecules and their complexes significantly expedite biomedical research and drug discovery. However, automatically and accurately building atomic models from high-resolution cryo-EM density maps is still time-consuming and challenging when template-based models are unavailable. Artificial intelligence (AI) methods such as deep learning trained on limited amount of labeled cryo-EM density maps generate inaccurate atomic models. To address this issue, we created a dataset called Cryo2StructData consisting of 7,600 preprocessed cryo-EM density maps whose voxels are labelled according to their corresponding known atomic structures for training and testing AI methods to build atomic models from cryo-EM density maps. Cryo2StructData is larger than existing, publicly available datasets for training AI methods to build atomic protein structures from cryo-EM density maps. We trained and tested deep learning models on Cryo2StructData to validate its quality showing that it is ready for being used to train and test AI methods for building atomic models.

Scanning Electron Microscopy Imaging of Large DNA Molecules Using a Metal-Free Electro-Stain Composed of DNA-Binding Proteins and Synthetic Polymers.

This paper presents the first scanning electron microscopy (SEM)-based DNA imaging in biological samples. This novel approach incorporates a metal-free electro-stain reagent, formulated by combining DNA-binding proteins and synthetic polymers to enhance the visibility of 2-nm-thick DNA under SEM. Notably, DNA molecules stain with proteins and polymers appear as dark lines under SEM. The resulting DNA images exhibit a thickness of 15.0±4.0nm. As SEM is the primary platform, it integrates seamlessly with various chemically functionalized large surfaces with the aid of microfluidic devices. The approach allows high-resolution imaging of various DNA structures including linear, circular, single-stranded DNA and RNA, originating from nuclear and mitochondrial genomes. Furthermore, quantum dots are successfully visualized as bright labels that are sequence-specifically incorporated into DNA molecules, which highlights the potential for SEM-based optical DNA mapping. In conclusion, DNA imaging using SEM with the novel electro-stain offers electron microscopic resolution with the ease of optical microscopy.

Fractionation of biomass-burning smoke-derived dissolved organic matters on the surface of clay minerals: Variations of molecular properties and components

Biomass burning (e.g., wildfire) frequently occurs globally, inevitably produces abundant biomass-burning smoke-derived dissolved organic matters (BBS-DOMs) which eventually deposits on the surface environment. The adsorption and fractionation of BBS-DOMs on clays inevitably alter their biogeochemical process and environmental behaviors in the surface environment. It is therefore important to clarify the adsorption and fractionation of BBS-DOM on clay surfaces. This study found that the fractionation of BBS-DOMs on clays (montmorillonite and kaolinite) were controlled by their functional groups, aromaticity, molecular size and organic components. The spectral indexes (SUVA254 and S275–295) of BBS-DOMs in solution after clays adsorption suggested that with the increasing DOC concentration, the primary interaction between BBS-DOMs and clays changed from hydrogen bond to hydrophobic/pore filling effects, and the adsorption ratio of the large molecules increased, which were very different from natural fulvic acid. Furthermore, various BBS-DOMs and fulvic acid had different component fractionation behaviors during clay adsorption, because they had different abundances of protein-like matters (hydrogen bond donors), pyridine-N/pyrimidine-N (positive charge doners of electrostatic interaction), and fulvic-like matters (hydrophobic interaction and pore filling effect). Additionally, the increasing pH weakened the adsorption of bulk BBS-DOMs and enhanced the adsorption ratio of aromatic matters and smaller BBS-DOM molecules. Meanwhile, at a higher pH, the adsorption ratio of protein-like matters increased, while the adsorption ratio of humic- and fulvic-like matters decreased. The result was ascribed to the enhanced hydrogen bond between protein-like matters and clays as well as the enhanced electrostatic repulsion between humic−/fulvic-like matters and clays. This study is helpful for deeply understanding the multimedia-crossing environmental behavior of BBS-DOMs in the surface environment.

Abstract PO2-01-04: Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis

Abstract Background: Human epidermal growth factor receptor-2 overexpression or gene amplification (HER2+) breast cancer is considered to be a highly aggressive, dangerous and even fatal subtype..In recent years, with the application of large molecule anti-HER2 monoclonal antibody and its biosimilar in neoadjuvant therapy of HER2-positive breast cancer, small molecule tyrosine kinase inhibitors (TKIs) have also performed strong advantages of antineoplastic activity in breast cancer. At present, there is no direct evidence to demonstrate the differences in neoadjuvant efficacy of anti-HER2 monoclonal antibody and tyrosine kinase inhibitors (TKIs) in this subtype of breast cancer.We conducted a preliminary network meta-analysis to explore the difference of efficacy and safety between anti-HER2 monoclonal antibody and TKIs for neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer. Method: A systematic literature search in the Cochrane Central Register of Controlled Trials, PubMed, Embase and Web of Science was performed.Randomized or non-randomized controlled studies of neoadjuvant therapy for HER2-positive breast cancer including large molecules trastuzumab, pertuzumab and small molecules TKIs (pyrotinib, lapatinib, nenatinib, etc.) were screened.Studies had to satisfy the following criteria: i) randomized or non-randomized controlled trials, ii) at least one treatment group received an anti-HER2 agent, iii) available information of any efficacy end-point. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR) were the efficacy end-points of interest, and selected safety end-points were also analysed. Results: A total of 5885 published manuscripts were identified,and 19 studies including 6517 patients were finally included in our analysis. and 19 different regimens were evaluated. Dual anti-HER2-therapy,trastuzumab with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab or TKIs and chemotherapy in terms of pCR(OR=2.20, 95%CI=1.92-2.52).In the comparison of dual-target treatment regiments, the efficacy of pyrotinib plus trastuzumab combined chemotherapy was superior to that of pertuzumab plus trastuzumab combined chemotherapy (OR=1.20, 95%CI=0.85-1.70), but the difference was not statistically significant.In addition, compared with pertuzumab combined with trastuzumab and chemotherapy,there was no significant difference in the efficacy aspect of TKIs combined with trastuzumab and chemotherapy (OR=1.15, 95%CI=0.88-1.51). Conclusion:For the selection of neoadjuvant treatment for HER2-positive early or locally advanced breast cancer, trastuzumab plus pertuzumab combined with chemotherapy is still the preferred strategy at present.As our study showed that pyrotinib combined with trastuzumab and chemotherapy maybe could provide another option for neoadjuvant target therapy for HER2-positive breast cancer. Keywords: breast cancer, HER2-positive, neoadjuvant, network meta-analysis, target therapy. Characteristics of eligible studies. NAC=Neoadjuvant chemotherapy;T=nab-paclitaxel,paclitaxel or Docetaxel;F= fluorouracil;E=epirubicin;A=doxorubicin;C=cyclophosphamide; Cb=carboplatin;tzmb=trastuzumb;pzmb=pertuzumab;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% CIs for pCR among different experimental arms. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Cross-comparison odds ratios (ORs) and their respective 95% confidence intervals (CIs) for pathologic complete response (pCR) in HR-positive and HR-negative subgroups. CT=chemotherapy;tzmb=trastuzumb;pzmb=pertuzumab;TKI=tyrosine kinase inhibitors;Py=pyrotinib;lpnb=lapatinib;Ne=neratinib. Citation Format: Lu Gan, Fangxuan Li, Jialin Su. Efficacy and safety of anti-HER2 therapy in neoadjuvant therapy for HER2-positive breast cancer: a network meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-04.

Gas-phase formation of fullerene/9-hydroxyfluorene cluster cations

Abstract In interstellar environment, fullerene species readily react with large molecules (e.g. PAHs and their derivatives) in the gas phase, which may be the formation route of carbon dust grains in space. In this work, the gas-phase ion-molecule collision reaction between fullerene cations (Cn +, n = 32, 34, …, 60) and functionalized PAH molecules (9-hydroxyfluorene, C13H10O) are investigated both experimentally and theoretically. The experimental results show that fullerene/9-hydroxyfluorene cluster cations are efficiently formed, leading to a series of large fullerene/9-hydroxyfluorene cluster cations (e.g. [(C13H10O)C60]+, [(C13H10O)3C58]+, and [(C26H18O)(C13H10O)2C48]+). The binding energies and optimized structures of typical fullerene/9-hydroxyfluorene cluster cations were calculated. The bonding ability plays a decisive role in the cluster formation processes. The reaction surfaces, modes and combination reaction sites can result in different binding energies, which represent the relative chemical reactivity. Therefore, the geometry and composition of fullerene/9-hydroxyfluorene cluster cations are complicated. In addition, there is an enhanced chemical reactivity for smaller fullerene cations, which is mainly attributed to the newly formed deformed carbon rings (e.g. 7 C-ring). As part of the coevolution network of interstellar fullerene chemistry, our results suggest that ion-molecule collision reactions contribute to the formation of various fullerene/9-hydroxyfluorene cluster cations in the ISM, providing insights into different chemical reactivity caused by oxygenated functional groups (e.g. hydroxyl, OH, or ether, C-O-C) on the cluster formations.

Electronic-rich large conjugated molecules dispersing through ionic liquid solution process for fluorescent detection of iodine gas

Materials containing large conjugated structures have good applications prospects in multiple fields due to their electron-rich properties. Nevertheless, the rigid structures of such materials make them difficult to process, making them difficult to be utilized adequately, which limits further development of their performance potentials. Herein, through ionic liquid solution process (ILSP), the electron-rich and fluorescent properties of pentacene have been successfully liberated to detect iodine vapor. Pentacene can be dissolved in BmimNTf2 to form (Ph)5@BmimNTf2 solution with excellent fluorescence. (Ph)5@BmimNTf2 solution was loaded onto polyamide membranes to prepare composite membrane detectors, which can detect iodine vapors, showing rapid response, portability and low cost. Theoretical calculations indicate a charge-transfer complex is formed between pentacene and iodine. The amount of charge transfer (δQ) between pentacene and iodine monomer molecules can be up to 0.115e. This study provides potential for exploiting the applications of large conjugated materials utilizing ILSP.

Catalytic Cracking of Oily Sludge using Nickel Metal Catalyst Embedded in Silica Derived from Adsorbent in a Gas Process Plant

Abstract. One of the Oily Sludge (OS) recycling methods is through catalytic cracking. This process involves the reaction breaking down large molecules into smaller ones with the help of a catalyst. Nickel (Ni) metal is often used as a catalyst because it can increase fuel liquid yield while reducing the coke formation. To enhance its performance, Ni metal can be embedded in a carrier material like Silica to form the Ni-Silica catalyst. In this research, OS sourced from a Gas Process Plant is treated with catalytic cracking using Ni-Silica, where the Silica used is derived from an Adsorbent activated with NaOH. Optimization of the cracking conditions is carried out using Response Surface Methodology (RSM) with a Box-Behnken design. The optimized cracking reaction conditions include temperature (713 K, 723 K, and 733 K), time (50 min, 60 min, and 70 min), and catalyst-to-OS ratio of 1:5, 1:6, and 1:7. Statistical analysis indicates that the relationship between the reaction condition variables and the Oil Liquid Product (OLP) falls into the moderate category, as shown by the coefficient of determination (R²) of 0.5. The calculated F-value for the deviation from the mathematical model is smaller than the F-Table value (9.2) at both 5% and 1% significance levels, with a value of 0.6. This indicates that the mathematical model generated can be accepted as the mathematical model within the range of reaction conditions in this study. Calculus analysis reveals that the optimum reaction conditions are a temperature of 717.34 K, a time of 58.58 min, and a catalyst-to-OS ratio of 1:6, 15. Canonical analysis indicates that for OLP, λ1= [-12.38], λ2= [-2.27], and λ3= [4.50], where lambda values indicate that the most sensitive response surface parameter for OLP is temperature, followed by the catalyst-to-sample ratio, and the least sensitive is reaction time.   Keywords: Catalytic Cracking, Ni Metal, OS, RSM, Silica

Cluster-in-Cluster Approach for Computing MP2-Level Vibrational Infrared Spectra of Large Molecular Clusters.

Constructing the Hessian matrix (HM) for large molecules demands huge computational resources. Here, we report a cluster-in-cluster (CIC) procedure for efficiently evaluating HM and dipole derivatives for large molecular clusters by employing the second-order Møller-Plesset perturbation (MP2) theory. The highlight of the proposal is the separation of the estimations of Hartree-Fock (HF) and post-HF components. The parent cluster with n molecules is divided (virtually) into n subclusters centering each monomer and accommodating its near neighbors decided by a distance cutoff. The HF-level HM is obtained by doing full calculation (FC), while the correlation part is approximated by the respective subclusters. A software automating the procedure [followed by calculating infrared (IR) frequencies and intensities] is applied to deduce the IR spectrum for a variety of molecular clusters, particularly water clusters of various sizes, containing up to ∼2000 basis functions. The accuracy of the IR spectrum constructed using CIC is remarkable, with a substantial time advantage (with respect to its FC counterpart). The reduced computational resources and the tractability of the computations are other major benefits of the procedure.

Evaluation of Patient-Centric Sample Collection Technologies for Pharmacokinetic Assessment of Large and Small Molecules.

Low-volume sampling devices offer the promise of lower discomfort and greater convenience for patients, potentially reducing patient burden and enabling decentralized clinical trials. In this study, we determined whether low-volume sampling devices produce pharmacokinetic (PK) data comparable to conventional venipuncture for a diverse set of monoclonal antibodies (mAbs) and small molecules. We adopted an open-label, non-randomized, parallel-group, single-site study design, with four cohorts of 10 healthy subjects per arm. The study drugs, doses, and routes of administration included: crenezumab (15 mg/kg, intravenous infusion), etrolizumab (210 mg, subcutaneous), GDC-X (oral), and hydroxychloroquine (HCQ, 200 mg, oral). Samples were collected after administration of a single dose of each drug using conventional venipuncture and three low-volume capillary devices: TassoOne Plus for liquid blood, Tasso-M20 for dry blood, both applied to the arm, and Neoteryx Mitra® for dry blood obtained from fingertips. Serum/plasma concentrations from venipuncture and TassoOne Plus samples overlapped and PK parameters were comparable for all drugs, except HCQ. After applying a baseline hematocrit value, the dry blood concentrations and PK parameters for the two monoclonal antibodies were comparable to those obtained from venipuncture. For the two small molecules, two bridging strategies were evaluated for converting dry blood concentrations to equivalent plasma concentrations. A baseline hematocrit correction and/or linear regression-based correction was effective for GDC-X, but not for HCQ. Additionally, the study evaluated the bioanalytical data quality and comparability from the various collection methods, as well as patient preference for the devices.

Different effects of mesophilic and thermophilic anaerobic digestion on subsequent pyrolysis: Characteristics, kinetics and thermodynamic analysis

Anaerobic digestion (AD) combined with pyrolysis has been used as an innovative sludge-to-energy process that enhances energy recovery. This study investigated the different impacts of mesophilic and thermophilic AD on subsequent pyrolysis. The pyrolysis characteristics, kinetics, and thermodynamics of raw sludge (RS) and digested sludge (DS) after both mesophilic and thermophilic AD were investigated using thermogravimetric analysis (TGA) and three kinetic models (Starink, Flynn–Wall–Ozawa, Kissinger–Akahira–Sunose). TGA results indicated that thermophilic AD reduced the weight loss from 71.2-75.6 % for RS to 55.0–59.1 % for DS, more considerably than mesophilic AD (reducing from 70.6-75.2 % to 61.3–69.5 %), indicating higher organic matter removal. Kinetic analysis showed that the activation energy (E) of RS and DS pyrolysis ranged from 128.9 to 399.9 kJ/mol and 117.3 to 470.4 kJ/mol, respectively. Mesophilic AD generally increased the E, while thermophilic AD did not markedly alter E at low conversion rates (0.2–0.5) but increased it at high conversion rates (0.6–0.8), changing from 203.7–399.9 kJ/mol for RS to 248.9–470.4 kJ/mol for DS. Thermodynamic analysis showed that mesophilic AD generally enhanced pyrolysis favorability and reactivity but impeded activated complex formation. Thermophilic AD enhanced favorability and favored complex formation at low conversion rates but hindered it at high conversion rates. Reactivity varied with thermophilic AD extent, with excessive AD reducing reactivity. Pyrolysis–gas chromatography/mass spectrometry analysis confirmed that AD, on the one hand, decomposed biodegradable organics into low-molecular-weight organics, retained them in the DS, and facilitated subsequent pyrolysis. On the other hand, AD could accumulate large bio-refractory molecules, rendering DS less prone to pyrolytic decomposition. This effect of thermophilic AD was more significant than that of mesophilic AD. Given more favorable change was observed in kinetics and thermodynamics at lower conversion rates, low-temperature pyrolysis to produce biochar might be a promising strategy for DS treatment. The insights gained in this study may guide the optimization of AD conditions to maximize the efficiency of subsequent pyrolysis, providing more insight into the thermochemical conversion of DS and pyrolysis design.

'Gel-Stacks' gently confine or reversibly immobilize arrays of single DNA molecules for manipulation and study.

Large DNA molecules (>20kb) are difficult analytes prone to breakage during serial manipulations and cannot be 'rescued' as full-length amplicons. Accordingly, to present, modify and analyze arrays of large, single DNA molecules, we created an easily realizable approach offering gentle confinement conditions or immobilization via spermidine condensation for controlled delivery of reagents that support live imaging by epifluorescence microscopy termed 'Gel-Stacks.' Molecules are locally confined between two hydrogel surfaces without covalent tethering to support time-lapse imaging and multistep workflows that accommodate large DNA molecules. With a thin polyacrylamide gel layer covalently bound to a glass surface as the base and swappable, reagent-infused, agarose slabs on top, DNA molecules are stably presented for imaging during reagent delivery by passive diffusion.

Endogenous Antimicrobial-Immunomodulatory Molecules: Networking Biomolecules of Innate Immunity.

Endogenous antimicrobial-immunomodulatory molecules (EAIMs) are essential to immune-mediated human health and evolution. Conventionally, antimicrobial peptides (AMPs) have been regarded as the dominant endogenous antimicrobial molecule; however, AMPs are not sufficient to account for the full spectrum of antimicrobial-immunomodulatory duality occurring within the human body. The threat posed by pathogenic microbes is pervasive with the capacity for widespread impact across many organ systems and multiple biochemical pathways; accordingly, the host needs the capacity to react with an equally diverse response. This can be attained by having EAIMs that traverse the full range of molecular size (small to large molecules) and structural diversity (including molecules other than peptides). This review identifies multiple molecules (peptide/protein, lipid, carbohydrate, nucleic acid, small organic molecule, and metallic cation) as EAIMs and discusses the possibility of cooperative, additive effects amongst the various EAIM classes during the host response to a microbial assault. This comprehensive consideration of the full molecular diversity of EAIMs enables the conclusion that EAIMs constitute a previously uncatalogued structurally diverse and collectively underappreciated immuno-active group of integrated molecular responders within the innate immune system's first line of defence.

Numerical Analysis of the Influence of a Magnetic Field on the Group Dynamics of Iron-Doped Carbon Nanotori

Columnar phases consisting of a group of carbon toroidal molecules (C120, C192, C252, C288) are studied numerically. Each nanotorus was previously doped with an iron atom. This made it possible to use an external magnetic field as a tool for influencing both an individual molecule and a linear fragment of the columnar phase. A high-precision scheme for calculating the dynamics of large molecules with a rigid frame structure is proposed to solve the problem. The group dynamics of nanotori clusters under the influence of an external magnetic field has been studied using classical molecular dynamics methods. The influence of the molecular cluster size, temperature, magnetic moment of the molecule, and magnetic field direction on the collective behavior of iron-doped toroidal molecules with different contents of carbon atoms is analyzed. Molecular dynamics calculations showed that systems of nanotori doped with a single iron atom retain a columnar structure both in the absence and in the presence of an external magnetic field. The columnar fragment behaves as a stable linear association of molecules even at sufficiently high values of magnetic induction, performing a coordinated collective orbital rotation around a common center of mass on a nanosecond time scale.

Metabolic Control During Macrophage Polarization by a Citrate-Functionalized Scaffold for Maintaining Bone Homeostasis.

Metabolites, as markers of phenotype at the molecular level, can regulate the function of DNA, RNA, and proteins through chemical modifications or interactions with large molecules. Citrate is an important metabolite that affects macrophage polarization and osteoporotic bone function. Therefore, a better understanding of the precise effect of citrate on macrophage polarization may provide an effective alternative strategy to reverse osteoporotic bone metabolism. In this study, a citrate functional scaffold to control the metabolic pathway during macrophage polarization based on the metabolic differences between pro-inflammatory and anti-inflammatory phenotypes for maintaining bone homeostasis, is fabricated. Mechanistically, only outside M1 macrophages are accumulated high concentrations of citrate, in contrast, M2 macrophages consume massive citrate. Therefore, citrate-functionalized scaffolds exert more sensitive inhibitory effects on metabolic enzyme activity during M1 macrophage polarization than M2 macrophage polarization. Citrate can block glycolysis-related enzymes by occupying the binding-site and ensure sufficient metabolic flux in the TCA cycle, so as to turn the metabolism of macrophages to oxidative phosphorylation of M2 macrophage, largely maintaining bone homeostasis. These studies indicate that exogenous citrate can realize metabolic control of macrophage polarization for maintaining bone homeostasis in osteoporosis.