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Food allergy is a hypersensitive immune reaction to food proteins including cow’s milk protein. Extracellular vesicles (EVs), such as exosomes, are newly discovered intercellular conveyors of functional molecular mechanisms and mediated intercellular interactions involving mast cells and are particularly relevant to allergy. In this study, we investigated whether cow’s milk casein-induced allergy (CIA)-derived EVs can modulate mast cell activation. EVs in CIA mice and control mice were isolated using the ultracentrifugation method and the isolated EVs were quantified using BCA analysis. CIA responses were determined through changes in body temperature and systemic symptom score. The number of EVs was higher in CIA-derived EVs compared to normal EVs. EVs marker proteins such as CD63 and CD9 were elevated in CIA-derived EVs. The levels of EV-associated cytokines such as IL-6, IL-8, and TNF-α were significantly elevated in CIA-derived EVs. In addition, CIA-derived EVs significantly induced degranulation via Lyn kinase activation in mouse bone marrow-derived mast cells and human mast cells. Our results demonstrate that CIA-derived EVs can induce a reaction similar to cow’s milk allergic reaction via mast cell activation. These results provide an insight into the pathology of cow’s milk allergy and a potential therapeutic approach through targeting EV release and/or uptake.

Phytochemical investigation on the dried fruits of Casearia grewiifolia led to the identification of 10 new salicinoyl quinic acid derivatives (1-10), a new benzoyl quinic acid (11), and two known compounds (12 and 13). The structures of the new compounds were elucidated by interpreting 1D and 2D NMR spectroscopic data including HMBC and EXSIDE along with a chemical method for sugar unit analysis. All isolates were evaluated for their inhibitory activities against prostaglandin E2 (PGE2) production in ultraviolet B (UVB)-irradiated HaCat keratinocytes. Of the isolates tested, compounds 6 and 12 were found to inhibit PGE2 production with IC50 values of 20.5 and 28.8 μM, respectively.

Methicillin-resistant Staphylococcus aureus (MRSA) infection on wounds possesses a high risk in increased cases of morbidity and mortality worldwide. Antibiotic-loaded composite biopolymer film wound dressings are one approach to cover the chronic wound area, promote the healing process, and create suitable healing environments. In this study, we developed clindamycin (Cly)-loaded composite biopolymer films using hydrogel-forming biopolymers, such as sodium alginate (SA), pectin (P), and hyaluronic acid (HA) for the treatment of MRSA-infected wounds. Composite films were prepared using a solvent casting method. Cly-loaded composites hydrogel films were evaluated for their physical properties (e.g., film thickness, surface morphology, pH, water vapor transmission, expansion profile, and fluid uptake), in vitro drug release, in vitro bactericidal effects, and in vivo wound healing activity in an ICR mouse model of MRSA-infected wounds. Thin, transparent, and highly absorbent Cly-loaded SA-P (Cly/SA-P) and Cly-loaded SA-P-HA (Cly/SA-P-HA) film dressings were successfully prepared with good physical properties. The Cly/SA-P and Cly/SA-P-HA films exhibited drug release over 12 h under immersed conditions and potent antibacterial activity against MRSA (> 5 log reduction in bacterial viability). Furthermore, compared with the other groups, the Cly/SA-P-HA-treated group significantly accelerated the healing and re-epithelialization of wounds in a mouse model of MRSA-infected wounds. All prepared film dressings were not toxic to healthy fibroblast cells. Thus, the Cly-loaded composite hydrogel film prepared in this study could be a promising wound dressing for the treatment of infected cutaneous wounds.

Although nitric oxide (NO) has been emerging as a novel local anticancer agent because of its potent cytotoxic effects and lack of off-target side effects, its clinical applications remain a challenge because of the short effective diffusion distance of NO that limits its anticancer activity. In this study, we synthesized albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles (Alb-PLP/NO NPs) that possess tumor-penetrating and NO-releasing properties for an effective local treatment of melanoma. Sufficient NO-loading and prolonged NO-releasing characteristics of Alb-PLP/NO NPs were acquired through PLGA-conjugated LP/NO copolymer (PLP/NO) synthesis, followed by nanoparticle fabrication. In addition, tumor penetration ability was rendered by the electrostatic adsorption of the albumin on the surface of the nanoparticles. The Alb-PLP/NO NPs showed enhanced intracellular NO delivery efficiency and cytotoxicity to B16F10 murine melanoma cells. In B16F10-tumor-bearing mice, the Alb-PLP/NO NPs showed improved extracellular matrix penetration and spatial distribution in the tumor tissue after intratumoral injection, resulting in enhanced antitumor activity. Taken together, the results suggest that Alb-PLP/NO NPs represent a promising new modality for the local treatment of melanoma.

This study investigates feasibility in the technical convergence of cold plasma and Fe-impregnated biochar to remove slowly-biodegradable methylene blue (MB) as a model contaminant. A problematic biowastes, spent coffee ground, was reused as a renewable source of biochar, and it impregnates Fe to enhance adsorption performance. Results verify that the cold plasma’s advanced oxidation coupled with the biochar increases overall MB removal efficiency and accelerates degradation kinetics. Experimental data regression verifies that the impregnated Fe significantly enhances the kinetic constants for total organic carbon (0.019–0.045 min−1) and MB (0.050–0.065 min−1). Also, it was confirmed that Fe-impregnation clearly shortens the periods required for almost complete MB degradation to within 1 h. In addition, the higher Fe was impregnated, the stronger synergistic effects on MB degradation rates was observed. The analyses of nitrate, nitrite, and sulfate supports that the MB could be lower down to detection limit by the suggested combination. These results provide useful information about the synergistic combination of physicochemical processes as a viable option to effectively manage slowly-biodegradable pollutants.

Accurate identification of active sites is critical for elucidating catalytic reaction mechanisms and developing highly efficient and selective electrocatalysts. Herein, we report the atomic-level identification of active sites using atomically well-defined gold nanoclusters (Au NCs) Au 25 , Au 38 , and Au 144 as model catalysts in the electrochemical CO 2 reduction reaction (CO 2 RR). The studied Au NCs exhibited remarkably high CO 2 RR activity, which increased with increasing NC size. Electrochemical and X-ray photoelectron spectroscopy analyses revealed that the Au NCs were activated by removing one thiolate group from each staple motif at the beginning of CO 2 RR. In addition, density functional theory calculations revealed higher charge densities and upshifts of d -states for dethiolated Au sites. The structure-activity properties of the studied Au NCs confirmed that dethiolated Au sites were the active sites and that CO 2 RR activity was determined by the number of active sites on the cluster surface.

Phytochemical investigation of the methanol extract of the aerial parts of Salvia plebeia aided by a proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA expression screening assay in HepG2 cells led to the identification of 19 compounds including one new norsesquiterpene (1), six new eudesmane sesquiterpenoids (2-5, 8, and 11), and 12 known compounds. The structures of all compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and MS data. Furthermore, computational prediction of ECD or chemical shifts was used to propose the absolute configurations of the new structures. All isolates were assessed for their inhibitory activities against PCSK9 mRNA expression and PCSK9-low-density lipoprotein receptor (LDLR) interactions. None of the isolated compounds inhibited PCSK9 and LDLR interactions. However, compounds 1, 9, and 10 downregulated PCSK9 mRNA expression.

A highly fluorinated alternating polymer, P(RFMi-St), possessing improved thermal properties and patterning capabilities over perfluoroalkyl polymethacrylates under high energy radiation was achieved with semi-perfluorododecyl maleimide (RFMi) and styrene (St). RFMi could be synthesised efficiently via a Mitsunobu reaction condition and copolymerised with St by free radical and reversible-deactivation radical polymerisation protocols. P(RFMi-St) showed a satisfactory glass-transition temperature (108 °C) and intermolecular cross-linking behaviour under electron-beam and commercially more important extreme UV (λ = 13.5 nm) irradiation. The exposed regions lost their solubility, resulting in the successful formation of mechanically non-deteriorated negative-tone images down to 50 nm. In addition, P(RFMi-St) could be solution-processed with chemically non-damaging fluorous liquids, which enabled the polymer to be applied effectively on top of an organic semiconductor layer as a dielectric material (dielectric constant 2.7) for the organic field-effect transistor fabrication.

Chemical reactions typically have numerous controllable factors that need to be optimized to yield the desired products. Although traditional experimental methods are limited to explore possible combinations of these factors, artificial intelligence (AI) can provide the optimal solution based on chemical reaction data. In this study, we optimize the non-oxidative conversion of methane to C2 compounds using AI, such as machine learning (ML) to predict experimental results and metaheuristics to optimize reaction conditions. A decision tree-based machine learning method can reasonably predict the reaction outcomes (CH4 conversion, C2 yield, and selectivities for C2 and coke) with an error of < 5%. Trained ML models are applied to maximize the C2 yield by optimizing the reaction parameters with metaheuristics. We can simultaneously enhance the C2 yield and suppress the coke formation by improving the multi-objective function for the optimization. We believe that our method will be helpful to optimize the chemical reaction conditions with multiple targets.

In addition to producing a classical excitatory postsynaptic current via activation of synaptic NMDA receptors (NMDARs), glutamate in the brain also induces a tonic NMDAR current (INMDA) via activation of extrasynaptic NMDARs (eNMDARs). However, since Mg2+blocks NMDARs in nondepolarized neurons, the potential contribution of eNMDARs to the overall neuronal excitatory/inhibitory (E/I) balance remains unknown. Here, we demonstrate that chronic (7 d) salt loading (SL) recruited NR2D subunit-containing NMDARs to generate an Mg2+-resistant tonicINMDAin nondepolarized [Vh(holding potential) −70 mV] vasopressin (VP; but not oxytocin) supraoptic nucleus (SON) neurons in male rodents. Conversely, in euhydrated (EU) and 3 d SL mice, Mg2+-resistant tonicINMDAwas not observed. Pharmacological and genetic intervention of NR2D subunits blocked the Mg2+-resistant tonicINMDAin VP neurons under SL conditions, while an NR2B antagonist unveiled Mg2+-sensitive tonicINMDAbut not Mg2+-resistant tonicINMDA. In the EU group VP neurons, an Mg2+-resistant tonicINMDAwas not generated by increased ambient glutamate or treatment with coagonists (e.g.,d-serine and glycine). Chronic SL significantly increased NR2D expression but not NR2B expression in the SON relative to the EU group or after 3 d under SL conditions. Finally, Mg2+-resistant tonicINMDAselectively upregulated neuronal excitability in VP neurons under SL conditions, independent of ionotropic GABAergic input. Our results indicate that the activation of NR2D-containing NMDARs constitutes a novel mechanism that generates an Mg2+-resistant tonicINMDAin nondepolarized VP neurons, thus causing an E/I balance shift in VP neurons to compensate for the hormonal demands imposed by a chronic osmotic challenge.SIGNIFICANCE STATEMENTThe hypothalamic supraoptic nucleus (SON) consists of two different types of magnocellular neurosecretory cells (MNCs) that synthesize and release the following two peptide hormones: vasopressin (VP), which is necessary for regulation of fluid homeostasis; and oxytocin (OT), which plays a major role in lactation and parturition. NMDA receptors (NMDARs) play important roles in shaping neuronal firing patterns and hormone release from the SON MNCs in response to various physiological challenges. Our results show that prolonged (7 d) salt loading generated a Mg2+-resistant tonic NMDA current mediated by NR2D subunit-containing receptors, which efficiently activated nondepolarized VP (but not OT) neurons. Our findings support the hypothesis that NR2D subunit-containing NMDARs play an important adaptive role in adult brain in response to a sustained osmotic challenge.

Using molecular networking-guided isolation, three new galloyl ester triterpenoids (1-3), two new hexahydroxydiphenic acid-conjugated triterpenoids (6 and 7), and four known compounds (4, 5, 8, and 9) were isolated from the fruits and leaves of Castanopsis sieboldii. The chemical structures of 1-3, 6, and 7 were elucidated on the basis of interpreting their NMR, HRESIMS, and ECD spectra. All compounds (1-9) were evaluated for their glucose uptake-stimulating activities in differentiated adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose as a fluorescent-tagged glucose probe. Compounds 2 and 9 resulted in a 1.5-fold increase in glucose uptake. Among them, compound 2 from the fruits showed an upregulation of p-AMPK/AMPK ratio in differentiated C2C12 myoblasts to support the mechanism proposed of glucose uptake stimulation.

Herein we designed a catechol-based compound, 4-allyl pyrocatechol (APC), which contains catechol and alkene groups capable of interacting with various metal oxide substrates and being chemically i...

Hierarchical self-assembly of building blocks over multiple length scales is ubiquitous in living organisms. Microtubules are one of the principal cellular components formed by hierarchical self-assembly of nanometer-sized tubulin heterodimers into protofilaments, which then associate to form micron-length-scale, multi-stranded tubes. This peculiar biological process is now mimicked with a fully synthetic molecule, which forms a 1:1 host-guest complex with cucurbit[7]uril as a globular building block, and then polymerizes into linear poly-pseudorotaxanes that associate laterally with each other in a self-shape-complementary manner to form a tubular structure with a length over tens of micrometers. Molecular dynamic simulations suggest that the tubular assembly consists of eight poly-pseudorotaxanes that wind together to form a 4.5 nm wide multi-stranded tubule.

A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey’s analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the d- and once in the l-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.

Designing and preparing highly active and stable nanostructured Pt-based catalysts with ultralow Pt loading are still challenging for electrochemical applications such as water electrolysis and fuel cells. Here we report for the first time an in situ electrochemical process to synthesize Pt-MoO3−x nanoflakes (NFs) overgrown on commercial bulk MoS2 by employing a facile and simple electrochemical method without using any expensive precious metal salts. The overgrowth of Pt-MoO3−x NFs on the bulk MoS2 surface is conducted by applying electrical energy to the bulk MoS2 and using Pt counter electrode dissolution in an acidic solution. In spite of their 10 times lower Pt loadings compared to commercial Pt black (Alfa Aesar), the synthesized Pt-MoO3−x NFs demonstrate excellent catalytic performance with a Pt mass activity of 2.83 A/mgPt at the overpotential of 100 mV for electrochemical hydrogen evolution reaction (HER), an approximately 4 times higher value than the value of 0.76 A/mgPt at the overpotential of 100 mV for commercial Pt black. We hypothesize that the outstanding HER characteristics of Pt-MoO3−x NFs are related to the existence and increase of Pt-MoO3 interfacial sites and oxygen vacancy sites such as Mo5+ in the Pt-MoO3−x NF structures. In addition, our density functional theory (DFT) calculations demonstrate that Pt and O sites at Pt and MoO3 interfaces and O sites at defective MoO3−x in the Pt-MoO3−x NFs contribute to accelerate the HER.

Atomic layer deposition (ALD) is an efficient technique that allows atomic-level surface control of metal catalysts for the design and development of electrocatalytic materials. Herein, we report a strategy for efficient catalyst design using a particle ALD method to enhance the electrocatalytic glycerol-oxidation-reaction (GOR) performance. Atomically controlled thin SnO2 layers were deposited on a carbon-supported Pt nanoparticle (Pt/C) surface using the ALD technique. The resulting SnO2 overcoated Pt/C (ALD(SnO2)–Pt/C) was then heat-treated at 400 °C under a N2 atmosphere. The onset potential as a kinetic parameter decreased with ALD (SnO2) coatings. The turnover frequency (TOF) for the GOR showed similar values for the tested samples (TOF of Pt/C: 74.86 h−1 and TOF of ALD(SnO2)–Pt/C: 91.29 h−1). Interestingly, interactions between the ALD SnO2 overcoating and Pt nanoparticles improved the catalytic stability for the GOR, preventing sintering of Pt nanoparticle catalysts. This demonstrates that an ALD SnO2 coating on defect sites of Pt can diminish Pt sintering for the GOR. From the GOR in an electrochemical batch reactor, the ALD(SnO2)–Pt/C catalyst also generated more glyceraldehyde (GAD) product than uncoated Pt/C at a similar glycerol conversion level. The density functional theory (DFT) calculations suggest that the binding energies of glycerol and reaction intermediates change at the interface of the SnO2-coated Pt surface compared to those at the Pt surface only, thus affecting the reaction chemistry for the electrocatalytic GOR. This work highlights how we can control reaction performance measures such as catalytic stability and product selectivity by using the particle ALD technique for electrocatalytic reactions such as glycerol oxidation.

Gastric motility is controlled by slow waves. In general, the activation of the ATP-sensitive K+ (KATP) channels in the smooth muscle opposes the membrane excitability and produces relaxation. Since metabolic inhibition and/or diabetes mellitus are accompanied by dysfunctions of gastric smooth muscle, we examined the possible roles of KATP channels in human gastric motility. We used human gastric corpus and antrum smooth muscle preparations and recorded the mechanical activities with a conventional contractile measuring system. We also identified the subunits of the KATP channels using Western blot. Pinacidil (10 μM), a KATP channel opener, suppressed contractions to 30% (basal tone to -0.2 g) of the control. The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 μM), a KATP channel blocker. The relaxation by pinacidil was not affected by a pretreatment with L-arginine methyl ester, tetraethylammonium, or 4-aminopyridine. Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). Other KATP channel openers such as diazoxide, cromakalim and nicorandil also inhibited the spontaneous and ACh-induced contractions. Calcitonin gene-related peptide (CGRP), a gastric neuropeptide, induced muscle relaxation by the activation of KATP channels in human gastric smooth muscle. Finally, we have found with Western blot studies, that human gastric smooth muscle expressed KATP channels which were composed of Kir 6.2 and SUR2B subunits.

Microbial specialized metabolites are an important source of and inspiration for many pharmaceutical, biotechnological products and play key roles in ecological processes. However, most bioactivity-guided isolation and identification methods widely employed in metabolite discovery programs do not explore the full biosynthetic potential of an organism. Untargeted metabolomics using liquid chromatography coupled with tandem mass spectrometry is an efficient technique to access metabolites from fractions and even environmental crude extracts. Nevertheless, metabolomics is limited in predicting structures or bioactivities for cryptic metabolites. Linking the biosynthetic potential inferred from (meta)genomics to the specialized metabolome would accelerate drug discovery programs. Here, we present a k-nearest neighbor classifier to systematically connect mass spectrometry fragmentation spectra to their corresponding biosynthetic gene clusters (independent of their chemical compound class). Our pipeline offers an efficient method to link biosynthetic genes to known, analogous, or cryptic metabolites that they encode for, as detected via mass spectrometry from bacterial cultures or environmental microbiomes. Using paired data sets that include validated genes-mass spectral links from the Paired Omics Data Platform, we demonstrate this approach by automatically linking 18 previously known mass spectra to their corresponding previously experimentally validated biosynthetic genes (i.e., via NMR or genetic engineering). Finally, we demonstrated that this new approach is a substantial step towards making in silico (and even de novo) structure predictions for peptidic metabolites and a glycosylated terpene. Altogether, we conclude that NPOmix minimizes the need for culturing and facilitates specialized metabolite isolation and structure elucidation based on integrative omics mining.SignificanceThe pace of natural product discovery has remained relatively constant over the last two decades. At the same time, there is an urgent need to find new therapeutics to fight antibiotic-resistant bacteria, cancer, tropical parasites, pathogenic viruses, and other severe diseases. Here, we introduce a new machine learning algorithm that can efficiently connect metabolites to their biosynthetic genes. Our Natural Products Mixed Omics (NPOmix) tool provides access to genomic information for bioactivity, class, (partial) structure, and stereochemistry predictions to prioritize relevant metabolite products and facilitate their structural elucidation. Our approach can be applied to biosynthetic genes from bacteria (used in this study), fungi, algae, and plants where (meta)genomes are paired with corresponding mass fragmentation data.

The objective of the present experiment was to determine ME concentrations and amino acid (AA) digestibility in various hatchery byproducts (HBPs) for broiler chickens. In experiment 1, a total of forty 60-day-old female broiler chickens were allotted to 1 of 5 dietary treatments with 8 replicates and used to measure ME concentrations in HBPs. The basal diet was prepared to contain corn, soybean meal, corn oil, and other non-energy ingredients. Additional 4 experimental diets were prepared to contain 10% of infertile eggs (IFE), unhatched eggs (UHE), low-grade or dead chicks (LDC), and mixture (MIX; 55% IFE, 10% UHE, 10% LDC, and 25% hatched eggshells). In experiment 2, a total of seven hundred and sixteen 1-day-old mixed-sex broiler chickens (1:1 ratio of males and females) were allotted to 1 of 5 dietary treatments with 7 replicates per treatment and used to determine apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of AA in HBPs. The experimental diets consisted of a nitrogen-free diet and 4 diets containing IFE, UHE, LDC, or MIX as a sole source of AA. Results indicated that AME and AMEn values were greater (P < 0.05) for LDC than for IFE, which had greater (P < 0.05) AME and AMEn values for UHE and MIX. The AID and SID of most AA in LDC were greater (P < 0.05) than those in MIX, whereas IFE and UHE had intermediate AID and SID of those AA as compared to LDC and MIX. Average SID of essential AA in LDC was greater (P < 0.05) than in UHE and MIX, but the average SID of nonessential AA did not differ among 4 HBPs. In conclusion, LDC has the greatest ME concentrations and AA digestibility among 3 individual HBPs (IFE, UHE, and LDC). The mixture of HBPs has the least ME concentrations and AA digestibility in broiler chickens. The ME and AA digestibility of HBPs are likely affected by inclusion amounts of hatched eggshells. However, high concentrations of ME and available AA demonstrate that individual HBPs and their mixture are potential protein ingredients for broiler diets.

Tonic extrasynaptic GABAA receptor (GABAA R) activation is under the tight control of tonic GABA release from astrocytes to maintain the brain's excitation/inhibition (E/I) balance; any slight E/I balance disturbance can cause serious pathological conditions including epileptic seizures. However, the pathophysiological role of tonic GABA release from astrocytes has not been tested in epileptic seizures. Here, we report that pharmacological or genetic intervention of the GABA-permeable Bestrophin-1 (Best1) channel prevented the generation of tonic GABA inhibition, disinhibiting CA1 pyramidal neuronal firing and augmenting seizure susceptibility in kainic acid (KA)-induced epileptic mice. Astrocyte-specific Best1 over-expression in KA-injected Best1 knockout mice fully restored the generation of tonic GABA inhibition and effectively suppressed seizure susceptibility. We demonstrate for the first time that tonic GABA from reactive astrocytes strongly contributes to the compensatory shift of E/I balance in epileptic hippocampi, serving as a good therapeutic target against altered E/I balance in epileptic seizures.

The major class of bioactive metabolites in Gymnema sylvestre, a popular Ayurvedic medicinal plant for the treatment of diabetes mellitus, is oleanane triterpenoids. In this study, a targeted, biosynthesis-inspired approach using UHPLC-qTOF/MS was implemented to elucidate the whole chemical profile of this plant for the standardization of the Vietnamese G. sylvestre variety. The known compounds were first determined to identify the building blocks of the biosynthetic intermediates and the construction rules for synthesizing oleanane triterpenoids in the plant. These blocks were recombined to build a virtual library of all reasonable compounds consistent with the deduced construction rules. Various techniques, including relative mass defect filtering, multiple key ion analysis, mass fragmentation analysis, and comparison with standard references, were applied to determine the presence of these predicted compounds. Conventional isolation and structure elucidation of six of the new compounds were carried out to identify the new building blocks and validate the assignments. Consequently, 119 peaks were quickly assigned to oleanane triterpenoids, and among them, 77 peaks were predicted to be new compounds based on their molecular formulas and mass fragmentation patterns. All the identified metabolites were then classified into different layers to analyze their logical relationships, and a multilayered chemical profile of the oleanane triterpenoids was constructed. This new approach is expected to be practical for characterizing structures of modular secondary metabolites, such as triterpenoid saponins, and for proposing biosynthetic relationships among compounds of the same class of metabolites in medicinal plants.

The purpose of this study was to develop a microcapsule-type self-healing coating system that could self-heal cracks and then maintain the healed state even upon crack expansion. Mixtures consisting of a photoinitiator and two methacrylate components, bismethacryloxypropyl-terminated polydimethylsiloxane (BMT-PDMS) and monomethacryloxypropyl-terminated PDMS (MMT-PDMS), were transformed into viscoelastic semi-solids through photoreaction. The viscoelasticity of the reacted mixtures could be controlled by varying the mass ratio of the two methacrylates. Through a stretchability test, the optimal composition mixture was chosen as a healing agent. Microcapsules loaded with the healing agent were prepared and dispersed in a commercial undercoating to obtain a self-healing coating formulation. The formulation was applied onto mortar specimens, and then cracks were generated in the coating by using a universal testing machine (UTM). Cracks with around a 150-μm mean width were generated and were allowed to self-heal under UV light. Then, the cracks were expanded up to 650 μm in width. By conducting a water sorptivity test at each expanded crack width, the self-healing efficiency and capability of maintaining the healed state were evaluated. The B-M-1.5-1-based coating showed a healing efficiency of 90% at a 150-μm crack width and maintained its healing efficiency (about 80%) up to a 350-μm crack width. This self-healing coating system is promising for the protection of structural materials that can undergo crack formation and expansion.

Peritendinous adhesion mainly occurs between proliferating fibrous tissues and adjacent normal organs after surgery. Many physical barriers are applied to the implanted site to prevent peritendinous adhesion. However, these barriers often trigger inflammatory responses. Therefore, our study sought to develop phlorotannins-loaded cartilage acellular matrix films as a physical barrier and investigate their inhibitory effect on inflammatory responses, which are associated with the induction of postoperative peritendinous adhesion. Our findings indicated that incorporating phlorotannin into the cartilage acellular matrix film did not affect its unique characteristics including its thermal and spectroscopic properties. Moreover, the phlorotannins-loaded cartilage acellular matrix films suppressed the expression of inflammatory mediators on RAW 264.7 macrophages stimulated using Escherichia coli lipopolysaccharides and exhibited an anti-inflammatory effect when implanted subcutaneously in rats. Therefore, our results highlssssssssssssight the potential of phlorotannins-loaded cartilage acellular matrix films as a promising physical barrier to prevent postoperative peritendinous adhesion. This article is protected by copyright. All rights reserved.

Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes; however, their causal associations and potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may elevate TMB levels in cancer genomes accompanying APOBEC overactivity and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated they can be reconstructed using known causal features such as APOBEC overexpression, MLH1 underexpression, POLE mutations, and the level of homologous recombination deficiency. We further demonstrated, that tumor hypoxia-related mutation signatures are similar to those associated with APOBEC suggesting that APOBEC-related mutagenic activity mediates hypoxia-related mutational consequences in cancer genomes, and also, that mutation signatures can be further used to predict hypoxic tumors. Taken together, our study advances mutation signature-level mechanistic insights in cancer genomes, extending categories of cancer-relevant mutation signatures and their potential biological implications.Author summaryMutation signature analysis is powerful in deciphering the causative mutagenic events and their contributions in individual cancer genomes, but the causal relationship of individual mutation signatures are still largely unknown. PanCancer-scaled correlative analysis revealed mutation resource candidates in cancer genomes such as NHEJ1 and ALKBH3 deficiencies that may facilitate the accumulation of mutations in the setting of APOBEC overactivity and DNA mismatch repair deficiency, respectively. A feature-driven mutation discovery approach was employed to identify the mutation signatures representing homologous recombination deficiency and tumor hypoxia, the extent of which may serve as mutation-based phenotypic measures, previously estimated by DNA copy number alterations and mRNA expression signatures, respectively. Our study advances our understanding into the mechanistic insights of mutation signatures and proposes a method to utilize somatic mutations as a molecular proxy in terms of mutation signatures.

Three undescribed 8,3′-neolignans, corynol (1), 3-methoxy-corynol (2) and 3′-deoxy-corynol (3), together with two bergenin derivatives, three flavonoids, two hydrolysable tannins and six simple phenolic compounds, were isolated from the twigs of Corylopsis coreana Uyeki. The structures of the 8,3′-neolignans were elucidated by analyzing their NMR, HRESIMS and ECD spectra. All the isolated compounds were evaluated for their SIRT1 stimulatory activity, and 3′-deoxy-corynol (3) showed SIRT1 stimulation activity. Furthermore, a docking study of 3 was performed with three representative binding pockets of SIRT1.

Carcinogens such as heterocyclic amine (HCA), produced during meat cooking, pose a risk of digestive and reproductive cancers in humans. Nevertheless, the exact mechanisms for HCA formation in meat and the control of HCA formation are not known. In this review, we provide an overview of the main cause of HCA formation in cooked meat, fundamental data on natural materials to inhibit HCA carcinogenicity, and methods to analyze HCA in cooked meat. Related past studies has shown that natural substances contain various components that act as antioxidants, and these antioxidants can prevent HCA and mutagenic factors. Free radicals and DNA adducts produced by HCA metabolism have carcinogenic properties. Antioxidants have been found to inhibit oxidative stress caused by free radicals and DNA adducts. Therefore, we can be hypothesized that various natural materials can inhibit HCA carcinogens and mutagens.

This paper proposes a lane detection algorithm using a laser range finder (LRF) for the autonomous navigation of a mobile robot. There are many technologies for ensuring the safety of vehicles, such as airbags, ABS, and EPS. Further, lane detection is a fundamental requirement for an automobile system that utilizes the external environment information of automobiles. Representative methods of lane recognition are vision-based and LRF-based systems. In the case of a vision-based system, the recognition of the environment of a three-dimensional space becomes excellent only in good conditions for capturing images. However, there are so many unexpected barriers, such as bad illumination, occlusions, vibrations, and thick fog, that the vision-based method cannot be used for satisfying the abovementioned fundamental requirement. In this paper, a three-dimensional lane detection algorithm using LRF that is very robust against illumination is proposed. For the three-dimensional lane detection, the laser reflection difference between the asphalt and the lane according to color and distance has been utilized with the extraction of feature points. Further, a stable tracking algorithm is introduced empirically in this research. The performance of the proposed algorithm of lane detection and tracking has been experimentally verified.

As our understanding of the structure and diversity of the microbial world grows, interpreting its function is of critical interest for understanding and managing the many systems microbes influence. Despite advances in sequencing, lack of standardization challenges comparisons among studies that could provide insight into the structure and function of microbial communities across multiple habitats on a planetary scale. Technical variation among distinct studies without proper standardization of approaches prevents robust meta-analysis. Here, we present a multi-omics, meta-analysis of a novel, diverse set of microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry), centering our description on relationships and co-occurrences of microbially-related metabolites and microbial taxa across environments. Standardized protocols and analytical methods for characterizing microbial communities, including assessment of molecular diversity using untargeted metabolomics, facilitate identification of shared microbial and metabolite features, permitting us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of a community resource that will become more valuable with time. To provide examples of applying this database, we outline important ecological questions that can be addressed, and test the hypotheses that every microbe and metabolite is everywhere, but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment. The relative abundances of microbially-related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner, and highlight the power of certain chemistry – in particular terpenoids – in distinguishing Earth’s environments.

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.

Molten carbonate fuel cells (MCFCs) are regarded as the closest fuel cell to commercialization due to their high capacity and energy efficiency. However, they are operated at a high temperature (620 °C or higher), where liquid electrolyte loss occurs during operation; hence, their lifetime is limited. For the long-term operation of MCFCs, it is essential to develop a novel method to replenish the electrolyte during operation. However, it is very difficult to directly inject the electrolyte, (Li0.62K0.38)2CO3, into each unit cell of the stack unless it is supplemented through liquid or gas phase at low temperature. It was verified whether LiI and KI, which have low melting points and high vapor pressures, could replenish the lost electrolyte in MCFCs. In this study, the LiI and KI injected into the unit cell in liquid phase showed a similar tendency to the Li/K carbonate electrolyte. This is because LiI and KI react with the CO2/O2 gases supplied to the cathode during MCFC operation to form Li/K carbonate electrolytes.

The chlorination of methane (CH4) is an attractive route to convert CH4 into more valuable chemicals. The selective formation of methyl chloride (CH3Cl) is a key process, but it is rather difficult to achieve with high selectivity due to a radical reaction. Catalytic ionic processes can be a solution. Herein, sulfated tin oxide (STO) was employed in the gas-phase catalytic chlorination of CH4. The STO catalyst exhibited high selectivity to CH3Cl (>96%) even at high CH4 conversion. By applying a suite of physicochemical characterizations, it is shown that the strong Lewis acid sites on STO generated by the interaction of Sn and surface sulfate groups are mainly responsible for the highly selective CH4 conversion. DFT calculations further revealed that STO surface can activate more Cl2 molecules in a heterolytic manner, leading to better catalytic performances as compared to SnO2 and sulfated zirconia catalysts.

In this study, Al-foam as a support material is used to reinforce the mechanical strength of the matrix. The use of an Al-foam supported matrix improves mechanical strength but has lower cell performance than using a conventional matrix. The main reasons for the low performance of the cell using the Al-foam supported matrix are short circuit due to leakage current through the Al-foam support and low electrolyte retention capability because of low wettability of aluminum to the liquid electrolytes. To solve these problems, we have developed a process to oxidize the surface of Al-foam reinforced matrix. By observing the unit cell performances, electrochemical analyses and morphological changes according to various oxide thicknesses of the Al-foam support, we have confirmed the optimal oxidation conditions for the Al-foam reinforced matrix. As a result, it was confirmed that the use of an oxidized Al-foam reinforced matrix of about 30 vol% can achieve a cell performance of more than 0.8 V under the current load of 150 mA/cm2 and improve long-term stability.

For a stable methane to olefins, aromatics, and hydrogen (MTOAH) reaction, 0.27–0.43 wt % Fe-containing silica catalysts were synthesized through various preparation methods and tested. The presenc...

In Alzheimer's disease, amyloid-β (Aβ) accumulation in the brain results in neuronal cell death and is one of the major causes of dementia. Because the current therapeutic agents are not yet sufficiently effective or safe, there have been attempts to find new neuroprotective chemicals against Aβ-induced cytotoxicity. A 70% EtOH extract of whole plants of Ambrosia artemisiifolia (common ragweed) was selected after the screening of a natural extract library. Seven new eudesmane-type glycosides (1-7) and seven known compounds (8-14) were obtained through bioactivity-guided fractionation from the aerial parts of this plant. Their structures were determined on the basis of their nuclear magnetic resonance spectra, high-resolution electrospray ionization mass spectrometry analysis, and electronic circular dichroism calculations. Among them, compounds 1, 2, 4-6, 8, 9, 11, 13, and 14 showed protective effects against Aβ-induced cytotoxicity in Aβ42-transfected HT22 cells. The most active compounds, 5 and 6, exhibited moderate protective activity dose-dependently (10, 20, and 40 μM).

Volatile fatty acids (VFAs) are representative odorous compounds. This study was carried out to decompose VFAs using electron beam irradiation. Acetic acid, propionic acid, butyric acid, isovaleric acid, and valeric acid were used as target VFAs. In order to confirm the decomposition efficiency and characteristics by various influential factors, experiments on the absorbed dose, background gas, and initial concentration were performed. The results confirmed that the removal efficiency increased with an increase of the absorbed dose. In addition, the removal efficiency was increased with an increase of the molecular weight of these compounds (in the following order: acetic acid

This study evaluated the recovery rate of Fatty Acids Methyl Ester (FAME) using various waste cooking greases from local restaurants. The productivity of biodiesel was analyzed based on the FAME contents and profiles according to the source of greases. Adapting a statistical approach, Response Surface Methodology (RSM), various transesterification based on the ratio of catalyst (KOH) and methanol was evaluated experimentally. Results presented a significant difference in total FAME recovery depending on reaction condition. RSM revealed the optimal blending condition of methanol (59−100 ml) and KOH (2.2−3.2 g) for waste cooking greases of bovine, swine, and poultry, which presented similar FAME characteristics when compared with other biodiesels. Optimal conditions for bovine, swine and poultry made the potential of biodiesel recovery from greases as high as 57.0%, 55.3%, and 53.7%, respectively. Overall, suggested optimized transesterification of waste cooking grease prevents unnecessary resource waste and enables the concept of waste-to-energy. It is also eco-friendly due to reduced pollutant emission and fossil fuel substitution.

In addition to attaining strong charge transport capability, field-effect transistors based on conjugated polymer thin films should be processed using non-chlorinated solvents for device fabrication, to avoid adverse impacts on human health and the environment. Although many high-performance diketopyrrolopyrrole (DPP) based conjugated polymers have been studied, few DPP based polymers that can be processed in non-chlorinated solvents have been reported to date. In this work, ambipolar polymeric semiconductors based on a DPP backbone that can be solution-processed using non-chlorinated solvents are reported. The DPP backbone combined with asymmetric conjugated segments results in high solubility and processability in non-chlorinated solvents, such as toluene and o-xylene, without disruption in the conjugation and molecular ordering of the main backbone. The polymer films fabricated with a high-boiling-point additive show ambipolar charge transport characteristics and highly enhanced electrical performance due to greatly enhanced intermolecular interactions and the resulting aggregated nanostructures. The combination of non-chlorinated solution processing with the green additive, along with ambipolar characteristics, enables high-performance environmentally friendly complementary logic circuit integration to be achieved.

This study demonstrates the development of a nitric oxide (NO)-releasing hydrogel wound dressing and its efficacy at accelerating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. A DETA/NONOate-doped alginate (Alg-DETA/NO) hydrogel was synthesized using alginate as a hydrogel-forming wound dressing material and diethylenetriamine/diazeniumdiolate (DETA/NONOate) as an NO donor. Alg-DETA/NO exhibited a prolonged NO release profile over a period of 4 days. The rheological properties of Alg-DETA/NO did not differ significantly from those of pure alginate. Importantly, Alg-DETA/NO showed potent antibacterial activity against MRSA, with minimal toxicity to mouse fibroblasts. The application of Alg-DETA/NO to MRSA-infected wounds in a mouse model showed a favorable wound healing with accelerated wound-size reduction and reduced skin bacterial infection. Additionally, histological examination revealed that Alg-DETA/NO reduced inflammation at the wound site and promoted re-epithelialization, angiogenesis, and collagen deposition. Thus, Alg-DETA/NO presented herein could serve as a safe and potent hydrogel dressing for the treatment of MRSA-infected wounds.

Fabrication of plasmonic nanostructures in a precise and reliable manner is a topic of huge interest because their structural details significantly affect their plasmonic properties. Herein, we present nanotip indentation lithography (NTIL) based on atomic force microscopy (AFM) indentation for the patterning of plasmonic nanostructures with precisely controlled size and shape. The size of the nanostructures is controlled by varying the indentation force of AFM tips into the mask polymer; while their shapes are determined to be nanodisks (NDs) or nanotriangles (NTs) depending on the shapes of the AFM tip apex. The localized surface plasmon resonance of the NDs is tailored to cover most of the visible-wavelength regime by controlling their size. The NTs show distinct polarization-dependent plasmon modes consistent with full-wave optical simulations. For the demonstration of the light–matter interaction control capability of NTIL nanostructures, we show that photoluminescence enhancement from MoS2 layers can be deliberately controlled by tuning the size of the nanostructures. Our results pave the way for the AFM-indentation-based fabrication of plasmonic nanostructures with a highly precise size and shape controllability and reproducibility.

Glucagon-like peptide-1 (GLP-1) is a peptide hormone with tremendous therapeutic potential for treating type 2 diabetes mellitus. However, the short half-life of its native form is a significant drawback. We previously prolonged the plasma half-life of GLP-1 via site-specific conjugation of human serum albumin (HSA) at position 16 of recombinant GLP-1 using site-specific incorporation of p-azido-phenylalanine (AzF) and strain-promoted azide-alkyne cycloaddition (SPAAC). However, the resulting conjugate GLP1_8G16AzF-HSA showed only moderate in vivo glucose-lowering activity, probably due to perturbed interactions with GLP-1 receptor (GLP-1R) caused by the albumin-linker. To identify albumin-conjugated GLP-1 variants with enhanced in vivo glucose-lowering activity, we investigated the conjugation of HSA to a C-terminal region of GLP-1 to reduce steric hindrance by the albumin-linker using two different conjugation chemistries. GLP-1 variants GLP1_8G37AzF-HSA and GLP1_8G37C-HSA were prepared using SPAAC and Michael addition, respectively. GLP1_8G37C-HSA exhibited a higher glucose-lowering activity in vivo than GLP1_8G16AzF-HSA, while GLP1_8G37AzF-HSA did not. Another GLP-1 variant, GLP1_8A37C-HSA, had a glycine to alanine mutation at position 8 and albumin at its C-terminus and exhibited in vivo glucose-lowering activity comparable to that of GLP1_8G37C-HSA, despite a moderately shorter plasma half-life. These results showed that site-specific HSA conjugation to the C-terminus of GLP-1 via Michael addition could be used to generate GLP-1 variants with enhanced glucose-lowering activity and prolonged plasma half-life in vivo.