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For the lithium (Li) metal anode, constructing a strong and durable protective layer with lithium‐ion permeability is crucial, especially in high donor number (DN) solvent system. High DN solvent‐based electrolytes can support both higher capacity and lower charge overpotential in the rechargeable lithium–oxygen batteries (LOBs). However, Li anodes in high DN solvent system suffer from severe corrosion and uncontrolled dendrite growth due to the unstable solid‐electrolyte interphase (SEI). Typically, this interface is formed in situ through electrochemical processes with complicated component and spatial distribution. Here, a functional molecule is introduced to construct an ion‐wall (IW) on Li surface by prechemical sequential reactions (p‐CSRs), through which the crystalline nanoparticles as bricks and amorphous hybrid compounds as the mortar can be produced to build such a "wall." Different from the conventional SEI, this wall is not only compact and uniform, but also possess high strength, excellent passivation properties and high ionic conductivity. With these properties, the IW could suppress Li dendrites and inhabit the side reaction, supporting highly reversible Li plating/stripping behavior in high DN solvent system. As a result, the cycle stability of LOBs based on the IW protected Li anode is significantly improved. [ABSTRACT FROM AUTHOR]

The occurrence and development of malignant tumors follow an evolutionary trajectory of "mutation ⁃selection ⁃adaption" External and internal carcinogenic factors promote alterations in chromosomes and mutations in the major functional genes of affected cells directly or indirectly via arousing chronic non⁃resolving inflammation. At the stage of precancerous lesion, chronic inflammation facilitates the accumulation of mutation⁃driving forces, of which the transcription and translation of an important tumor suppressor, the fragile histidine triad (FHIT), are seriously inhibited in more than 50% precancerous lesions. External carcinogenic factors induces the promoter CpG methylation and replication stress leads to loss of heterozygosity, both of which result in the defect of FHIT expression. The defect of FHIT expression leads to aneuploidy, resulting in macroevolution characterized by chromosome instability; while the defect of FHIT expression promotes the formation of single⁃stranded DNA, which facilitates the mutagenic effect of APOBEC3B, resulting in microevolution characterized by single base substitutions. Inflammatory factors such as interleukin ⁃6 trans⁃activates the expression of APOBEC3B and trans⁃inactivates the expression of uracil glycosylase (UNG), thus dis⁃balancing APOBEC3B and UNG. This promotes somatic mutations and viral mutations, facilitating cancer evolution. The mutated cells actively transform surrounding fibroblasts into cancer⁃associated fibroblasts that recruit suppressive immune cells to establish tumor microenvironment under hypoxia conditions. The mutated cells are selected and adapted to tumor microenvironment and then retro⁃differentiated into cancer initiation cells, thus facilitat⁃ ing retro⁃development of cancer cells. Based on this theory, FHIT and APOBEC3B/UNG should be novel targets for the prophylaxis and control of malignancies. It will develop a novel avenue for the specific prophylaxis and control of cancers to remove external and internal factors that inhibit the function of FHIT and/or upregulate the expression of AID/APOBEC3s, rectify tumor microenvironment that facilitates cancer retro⁃differentiation via aerobic exercise and immunotherapy, and interrupt the retro⁃development of cancer via targeted therapy. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) can cause nerve paralysis syndrome in mammals and other vertebrates. BoNTs are the most toxic biotoxins known and are classified as Class A biological warfare agents. BoNTs are mainly divided into seven serotypes A-G and new neurotoxins BoNT/H and BoNT/X, which have similar functions. BoNT proteins are 150 kDa polypeptide consisting of two chains and three domains: the light chain (L, catalytic domain, 50 kDa) and the heavy chain (H, 100 kDa), which can be divided into an N-terminal membrane translocation domain (HN, 50 kDa) and a C-terminal receptor binding domain (Hc, 50 kDa). In current study, we explored the immunoprotective efficacy of each functional molecule of BoNT/F and the biological characteristics of the light chain-heavy N-terminal domain (FL-HN). The two structure forms of FL-HN (i.e., FL-HN-SC: single chain FL-HN and FL-HN-DC: di-chain FL-HN) were developed and identified. FL-HN-SC could cleave the vesicle associated membrane protein 2 (VAMP2) substrate protein in vitro as FL-HN-DC or FL. While only FL-HN-DC had neurotoxicity and could enter neuro-2a cells to cleave VAMP2. Our results showed that the FL-HN-SC had a better immune protection effect than the Hc of BoNT/F (FHc), which indicated that L-HN-SC, as an antigen, provided the strongest protective effects against BoNT/F among all the tested functional molecules. Further in-depth research on the different molecular forms of FL-HN suggested that there were some important antibody epitopes at the L-HN junction of BoNT/F. Thus, FL-HN-SC could be used as a subunit vaccine to replace the FHc subunit vaccine and/or toxoid vaccine, and to develop antibody immune molecules targeting L and HN domains rather than the FHc domain. FL-HN-DC could be used as a new functional molecule to evaluate and explore the structure and activity of toxin molecules. Further exploration of the biological activity and molecular mechanism of the functional FL-HN or BoNT/F is warranted. [ABSTRACT FROM AUTHOR]

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil–water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management. [ABSTRACT FROM AUTHOR]

A growing theme in chemistry is the joining of multiple organic molecular building blocks to create functional molecules. Diverse derivatizable structures—here termed “scaffolds” comprised of “hubs”—provide the foundation for systematic covalent organization of a rich variety of building blocks. This review encompasses 30 tri- or tetra-armed molecular hubs (e.g., triazine, lysine, arenes, dyes) that are used directly or in combination to give linear, cyclic, or branched scaffolds. Each scaffold is categorized by graph theory into one of 31 trees to express the molecular connectivity and overall architecture. Rational chemistry with exacting numbers of derivatizable sites is emphasized. The incorporation of water-solubilization motifs, robust or self-immolative linkers, enzymatically cleavable groups and functional appendages affords immense (and often late-stage) diversification of the scaffolds. Altogether, 107 target molecules are reviewed along with 19 syntheses to illustrate the distinctive chemistries for creating and derivatizing scaffolds. The review covers the history of the field up through 2020, briefly touching on statistically derivatized carriers employed in immunology as counterpoints to the rationally assembled and derivatized scaffolds here, although most citations are from the past two decades. The scaffolds are used widely in fields ranging from pure chemistry to artificial photosynthesis and biomedical sciences.

Botulinum neurotoxins (BoNTs) can cause nerve paralysis syndrome in mammals and other vertebrates. BoNTs are the most toxic biotoxins known and are classified as Class A biological warfare agents. BoNTs are mainly divided into seven serotypes A-G and new neurotoxins BoNT/H and BoNT/X, which have similar functions. BoNT proteins are 150 kDa polypeptide consisting of two chains and three domains: the light chain (L, catalytic domain, 50 kDa) and the heavy chain (H, 100 kDa), which can be divided into an N-terminal membrane translocation domain (HN, 50 kDa) and a C-terminal receptor binding domain (Hc, 50 kDa). In current study, we explored the immunoprotective efficacy of each functional molecule of BoNT/F and the biological characteristics of the light chain-heavy N-terminal domain (FL-HN). The two structure forms of FL-HN (i.e., FL-HN-SC: single chain FL-HN and FL-HN-DC: di-chain FL-HN) were developed and identified. FL-HN-SC could cleave the vesicle associated membrane protein 2 (VAMP2) substrate protein in vitro as FL-HN-DC or FL. While only FL-HN-DC had neurotoxicity and could enter neuro-2a cells to cleave VAMP2. Our results showed that the FL-HN-SC had a better immune protection effect than the Hc of BoNT/F (FHc), which indicated that L-HN-SC, as an antigen, provided the strongest protective effects against BoNT/F among all the tested functional molecules. Further in-depth research on the different molecular forms of FL-HN suggested that there were some important antibody epitopes at the L-HN junction of BoNT/F. Thus, FL-HN-SC could be used as a subunit vaccine to replace the FHc subunit vaccine and/or toxoid vaccine, and to develop antibody immune molecules targeting L and HN domains rather than the FHc domain. FL-HN-DC could be used as a new functional molecule to evaluate and explore the structure and activity of toxin molecules. Further exploration of the biological activity and molecular mechanism of the functional FL-HN or BoNT/F is warranted.

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil–water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.

Density functional theory has been used to investigate the adsorption and dissociation of 5-hydroxy-3-hexanediol-1,4-naphthaquinone (Jug-C4-thiol) at a coverage of p(4 × 4) on a Au(111) surface. Both physisorption and chemisorption processes are investigated. For each process, the surface energy potential is explored by an exhaustive test of the adsorption site. The most favorable site is found to be face-centered cubic. The adsorption energies are less than − 0.20 eV in the case of physisorption, while they range from − 1.70 to − 1.92 eV for chemisorption. The effect of the naphthoquinone function is negligible in the adsorption process. The alkyl chain inhibits electron delocalization between the surface and the conjugated head of the molecule. Analysis of the bonding shows the formation of two ionocovalent bonds between the sulfur and the gold atoms. The thermodynamics and kinetics of S–H bond dissociation are studied. The results reveal that adsorption involves a dissociation path in which a hydrogen atom moves to the most neighboring site and a hydrogen atom migrates to its most stable site. The maximum barrier energy of the first step is less than 2.7 eV while the migration barrier does not exceed 0.5 eV. [ABSTRACT FROM AUTHOR]

Background: Plant extracts contain a huge variety of pharmacologically active substances. Conventionally, various chromatographic methods must be applied several times to purify functional compounds to measure their functional activity. However, conventional purification methods are time-consuming and expensive due to the laborious purification process. Recently, a high-throughput discovery method that replaces such time-consuming purification processes was introduced; this method uses 15 T ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (15 T FT-ICR MS) and a high-throughput screening method. This 15 T FT-ICR MS provides unparalleled resolution and sub-ppm accuracy in mass measurements, while simultaneously detecting multiple compounds without separation. The high-throughput, simultaneous multi-component discovery method known as Scaling of Correlations between Activity and Mass Profiles (SCAMP) was used to detect functional compounds in a plant extract. We validated the performance of SCAMP using 33 fractions from antioxidant-rich mulberry ethyl acetate extract and known standard antioxidants. Results: The mulberry fruit was first separated into 33 fractions by LC and analyzed using high-resolution mass spectrometry. The antioxidative strength of the 33 fractions and standard antioxidants was measured. To validate the efficiency of this antioxidant discovery method, correlations between the antioxidation activity profile and changes in mass intensity of components within the 33 fractions were calculated to provide relative scores for the antioxidant candidate list. Enrichment curves and area under the curve (AUC) values were then calculated to compare the performance of the methods. Using this improved scoring method, five strong antioxidants, chlorogenic acid (14.2 ng), dihydoxy quercetin (46.2 ng), rutin (154.0 ng), quercetin (71.7 ng) and luteolin (3.5 ng) in 2 kg mulberry fruit, were found within the top 20 candidates. Conclusions: We calculated AUCs in order to compare scoring methods quantitatively. Scoring systems were compared and calculated AUCs, where the AUCs for new scoring systems (0.98 and 0.99) were higher than the previously used correlation coefficient (AUC = 0.89). Using the new scoring algorithms, we successfully enriched thirteen unknown strong antioxidant candidates in addition to known antioxidants, methyl syringin and naringenin (3.5 ng) in mulberry extract. Targeted purification of these unknown candidates will significantly reduce purification time and labor. [ABSTRACT FROM AUTHOR]

Surface modification is an important and predominant technique for obtaining biofunction in metals for biomedical use including dentistry. One surface modification technique is a process that changes the surface composition, structure, and morphology of a material, leaving the bulk mechanical properties intact. A tremendous number of surface modification techniques to improve the hard tissue compatibility of titanium have been developed. Hydroxyapatite layer, titanium oxide layer, and calcium titanate layer with various morphologies are deposited using electrochemical treatment including micro-arc oxidation. Also, surface modification layers without hydroxyapatite and calcium phosphate are chemically formed that accelerate bone formation. Other approach is the immobilization of biofunctional molecules such as poly(ethylene glycol) to the metal surface to control the adsorption of proteins and adhesion of cells, platelets, and bacteria. In the case of immobilization of biomolecules such as collagen and peptide, bone formation and soft tissue adhesion are improved.

Abstract: A novel cyclic dimer based on oleanolic acid was synthesized using click chemistry and it showed remarkable selectivity and affinity to bind fluoride ion through C–H⋯F hydrogen bond interactions which involved the delocalization of proton in methylene. [Copyright &y& Elsevier]

Summary: Surface modification is an important and predominant technique for obtaining biofunction in metals for biomedical use including dentistry. One surface modification technique is a process that changes the surface composition, structure, and morphology of a material, leaving the bulk mechanical properties intact. A tremendous number of surface modification techniques to improve the hard tissue compatibility of titanium have been developed. Hydroxyapatite layer, titanium oxide layer, and calcium titanate layer with various morphologies are deposited using electrochemical treatment including micro-arc oxidation. Also, surface modification layers without hydroxyapatite and calcium phosphate are chemically formed that accelerate bone formation. Other approach is the immobilization of biofunctional molecules such as poly(ethylene glycol) to the metal surface to control the adsorption of proteins and adhesion of cells, platelets, and bacteria. In the case of immobilization of biomolecules such as collagen and peptide, bone formation and soft tissue adhesion are improved. [Copyright &y& Elsevier]

Although small water clusters (SWCs) are important in many research fields, efficient methods of preparing SWCs are still rarely reported, which is mainly due to the lack of related materials and understanding of the molecular interaction mechanisms. In this study, a series of functional molecules were added in water to obtain small water cluster systems. The decreasing rate of the half-peak width in a sodium dodecyl sulfate (SDS)–water system reaches ≈20% at 0.05 mM from 17O nuclear magnetic resonance (NMR) results. Based on density functional theory (DFT) and molecular dynamics (MD) simulation calculation, it can be concluded that functional molecules with stronger negative electrostatic potential (ESP) and higher hydrophilicity have a stronger ability to destroy big water clusters. Notably, the concentrations of our selected molecule systems are one to two magnitudes lower than that of previous reports. This study provides a promising way to optimize aqueous systems in various fields such as oilfield development, protein stability, and metal anti-corrosion. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of human placental extracts (HPE) on the protection from acute liver injury (ALI) induced by D-GalN and analyze the components of HPE. Methods: (1)Fourty male mice were randomly divided into five groups (Blank, Model, MgIG, HPE and HPE+ MgIG) for the ALI model and treatments.The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) were determined by biochemical assays.Nitric monoxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) in serum and hepatic tissue were detected by assay kits.The extent of liver damage was evaluated by histological examination.(2)Relative molecular mass of HPE was determined by SDS-PAGE.(3) Component identification was performed by using LCMS-TOF.(4)Selected functional molecules in HPE were detected by protein array. Results: (1) A lower level of NO and MDA and a higher SOD and T-AOC were observed in rats treated with HPE compared to the non-treated rats in an acute liver failure disease model.(2) The size of HPE was about 1 200-4 600 by electrophores.(3) 7 peaks of HPE were identified, including uracil, hypoxanthine, tyrosine, phenylalanine, tryptophan, xanthine and thymine.(4) Comparable high concentrations of TGF-β, IGF-1, IL-9, IL-29 and TNF-α of HPE were revealed by protein array. Conclusions: (1) HPE protects rat from liver damage induced by D-GalN. (2) HPE contains Uracil, hypoxanthine, xanthine, thymine, and functional proteins as TGF-β, IGF-1, IL-9, IL-29 and TNF-α.