High-resolution Electrospray Ionization Mass Spectrometry Research Articles

Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols

The palladium complex [(L1)Pd(μ-OAc)]2[OTf]2 (L1 = neocuproine) is a selective catalyst for the aerobic oxidation of vicinal polyols to α-hydroxyketones, but competitive oxidation of the ligand methyl groups limits the turnover number and necessitates high Pd loadings. Replacement of the neocuproine ligand with 2,2'-biquinoline ligands was investigated as a strategy to improve catalyst performance and explore the relationship between ligand structure and reactivity. Evaluation of [(L2)Pd(μ-OAc)]2[OTf]2 (L2 = 2,2'-biquinoline) as a catalyst for aerobic alcohol oxidation revealed a threefold enhancement in turnover number relative to the neocuproine congener, but a much slower rate. Mechanistic studies indicated that the slow rates observed with L2 were a consequence of precipitation of an insoluble trinuclear palladium species─(L2Pd)3(μ-O)22+─formed during catalysis and characterized by high-resolution electrospray ionization mass spectrometry. Density functional theory was used to predict that a sterically modified biquinoline ligand, L3 = 7,7'-di-tert-butyl-2,2'-biquinoline, would disfavor the formation of the trinuclear (LPd)3(μ-O)22+ species. This design strategy was validated as catalytic aerobic oxidation with [(L3)Pd(μ-OAc)]2[OTf]2 is both robust and rapid, marrying the kinetics of the parent L1-supported system with the high aerobic turnover numbers of the L2-supported system. Changes in ligand structure were also found to modulate regioselectivity in the oxidation of complex glycoside substrates, providing new insights into structure-selectivity relationships with this class of catalysts.

Effects of Different Rootstocks on the Metabolites of Huanglongbing-Affected Sweet Orange Juices Using a Novel Combined Strategy of Untargeted Metabolomics and Machine Learning.

Huanglongbing (HLB) is one of the most destructive citrus diseases, mainly caused by the Gram-negative bacteria Candidatus Liberibacter asiaticus. Aiming at unraveling the mechanisms of different scion/rootstock combinations on improving HLB-affected orange juice quality, the effects of rootstocks on the metabolites of HLB-affected sweet orange juices were investigated using a combined strategy of untargeted metabolomics and machine learning. A total of 2531 ion features were detected using UHPLC-Q-Orbitrap high-resolution electrospray ionization mass spectrometry, and 54 metabolites including amino acids, amines, flavonoids, coumarins, fatty acids, and glycosides were definitely or tentatively identified as the differential markers based on the random forest algorithm. Furthermore, 24 metabolites were verified and semi-quantified using authentic standards. Notably, the presence of specific amino acids and amines, especially polyamines, indicated that different rootstocks might affect glutamate, aspartate, proline, and arginine metabolism to regulate the physiological response against HLB. Meanwhile, the production of flavonoids and prenylated coumarins suggested that rootstocks influenced phenylalanine and phenylpropanoid metabolism. The possible metabolic pathways were proposed, and the important intermediates were verified by authentic standards. These results provide new insights on the effects of rootstocks on the metabolites of HLB-affected sweet orange juices.

Database-assisted, globally optimized targeted secondary electrospray ionization high resolution mass spectrometry (dGOT-SESI-HRMS) and spectral stitching enhanced volatilomics analysis of bacterial metabolites.

Secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) is an innovative analytical technique for the rapid and non-invasive analysis of volatile organic compounds (VOCs). However, compound annotation and ion suppression in the SESI source has hindered feature detection, stability and reproducibility of SESI-HRMS in untargeted volatilomics. To address this, we have developed and optimized a novel pseudo-targeted approach, database-assisted globally optimized targeted (dGOT)-SESI-HRMS using the microbial-VOC (mVOC) database, and spectral stitching methods to enhance metabolite detection in headspace of anaerobic bacterial cultures. Headspace volatiles from representative bacteria strains were assessed using full scan with data dependent acquisition (DDA), conventional globally optimized targeted (GOT) method, and spectral stitching supported dGOT experiments based on a MS peaks list derived from mVOC. Our results indicate that spectral stitching supported dGOT-SESI-HRMS can proportionally fragment peaks with respect to different analysis windows, with a total of 109 VOCs fragmented from 306 targeted compounds. Of the collected spectra, 88 features were confirmed as culture derived volatiles with respect to media blanks. Annotation was also achieved with a total of 25 unique volatiles referenced to standard databases allowing for biological interpretation. Principal component analysis (PCA) summarizing the headspace volatile demonstrated improved separation of clusters when data was acquired using the dGOT method. Collectively, our dGOT-SESI-HRMS method afforded robust capability of capturing unique VOC profiles from different bacterial strains and culture conditions when compared to conventional GOT and DDA modes, suggesting the newly developed approach can serve as a more reliable analytical method for the sensitive monitoring of gut microbial metabolism.

Carborane-thiol protected copper nanoclusters: stimuli-responsive materials with tunable phosphorescence.

Atomically precise nanomaterials with tunable solid-state luminescence attract global interest. In this work, we present a new class of thermally stable isostructural tetranuclear copper nanoclusters (NCs), shortly Cu4@oCBT, Cu4@mCBT and Cu4@ICBT, protected by nearly isomeric carborane thiols: ortho-carborane-9-thiol, meta-carborane-9-thiol and ortho-carborane 12-iodo 9-thiol, respectively. They have a square planar Cu4 core and a butterfly-shaped Cu4S4 staple, which is appended with four respective carboranes. For Cu4@ICBT, strain generated by the bulky iodine substituents on the carboranes makes the Cu4S4 staple flatter in comparison to other clusters. High-resolution electrospray ionization mass spectrometry (HR ESI-MS) and collision energy-dependent fragmentation, along with other spectroscopic and microscopic studies, confirm their molecular structure. Although none of these clusters show any visible luminescence in solution, bright μs-long phosphorescence is observed in their crystalline forms. The Cu4@oCBT and Cu4@mCBT NCs are green emitting with quantum yields (Φ) of 81 and 59%, respectively, whereas Cu4@ICBT is orange emitting with a Φ of 18%. Density functional theory (DFT) calculations reveal the nature of their respective electronic transitions. The green luminescence of Cu4@oCBT and Cu4@mCBT clusters gets shifted to yellow after mechanical grinding, but it is regenerated after exposure to solvent vapour, whereas the orange emission of Cu4@ICBT is not affected by mechanical grinding. Structurally flattened Cu4@ICBT didn't show mechanoresponsive luminescence in contrast to other clusters, having bent Cu4S4 structures. Cu4@oCBT and Cu4@mCBT are thermally stable up to 400 °C. Cu4@oCBT retained green emission even upon heating to 200 °C under ambient conditions, while Cu4@mCBT changed from green to yellow in the same window. This is the first report on structurally flexible carborane thiol appended Cu4 NCs having stimuli-responsive tunable solid-state phosphorescence.

Biologically active drimane derivatives isolated from submerged cultures of the wood-inhabiting basidiomycete Dentipellis fragilis.

Four previously undescribed drimane sesquiterpenoids were isolated from submerged cultures of the wood-inhabiting basidiomycete Dentipellis fragilis along with two compounds that were previously reported as synthetic or biotransformation compounds but not as natural products. The constitution and relative configuration of these compounds was determined based on high-resolution electrospray ionization mass spectrometry as well as by 1D and 2D nuclear magnetic resonance spectroscopy. The absolute configurations were established based on exemplary calculation of circular dichroism spectra and comparison with measured data as well as on biogenetic considerations. The biological activities of the isolated compounds were assessed in antimicrobial, cytotoxicity and neurotrophic assays. 10-Methoxycarbonyl-10-norisodrimenin (3) exhibited weak activity against the Gram-positive bacterium Staphylococcus aureus and the zygomycete Mucor hiemalis with minimal inhibitory concentrations of 66.7 μg mL-1. In addition, compound 3 showed weak inhibition of the mammalian cell line KB3.1 (human endocervical adenocarcinoma) with a half maximal inhibitory concentration of 21.2 μM. The neurotrophic activities of 15-hydroxyisodrimenin (1) and 10-carboxy-10-norisodrimenin (5) were assed in neurite outgrowth and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. When supplemented with 5 ng mL-1 nerve growth factor (NGF), the drimanes 1 and 5 induced neurite outgrowth in PC-12 (rat pheochromocytoma) cells compared to cells solely treated with NGF. As evaluated by RT-qPCR, compounds 1 and 5 also increased NGF and brain-derived neurotrophic factor expression levels in 1321N1 astrocytoma cells. Interestingly, the current study only represents the second report on neurotrophic activities of this widespread class of terpenoids. The only other available study deals with Cyathus africanus, another basidiomycete that can produce drimanes and cyathanes, but is only distantly related to Dentipellis and the Hericiaceae.

Engineering ligand chemistry on Au25 nanoclusters: from unique ligand addition to precisely controllable ligand exchange.

Au25 nanoclusters (NCs) protected by 18 thiol-ligands (Au25SR18, SR is a thiolate ligand) are the prototype of atomically precise thiolate-protected gold NCs. Studies concerning the alteration of the number of surface ligands for a given Au25SR18 NC are scarce. Herein we report the conversion of hydrophobic Au25PET18 (PET = 2-phenylethylthiolate) NCs to Au25SR19 [Au25PET18(metal complex)1] induced by ligand exchange reactions (LERs) with thiolated terpyridine-metal complexes (metal complex, metal = Ru, Fe, Co, Ni) under mild conditions (room temperature and low amounts of incoming ligands). Interestingly, we found that the ligand addition reaction on Au25PET18 NCs is metal dependent. Ru and Co complexes preferentially lead to the formation of Au25SR19 whereas Fe and Ni complexes favor ligand exchange reactions. High-resolution electrospray ionization mass spectrometry (HRESI-MS) was used to determine the molecular formula of Au25SR19 NCs. The photophysical properties of Au25PET18(Ru complex)1 are distinctly different from Au25PET18. The absorption spectrum is drastically changed upon addition of the extra ligand and the photoluminescence quantum yield of Au25PET18(Ru complex)1 is 14 times and 3 times higher than that of pristine Au25PET18 and Au25PET17(Ru complex)1, respectively. Interestingly, only one surface ligand (PET) could be substituted by the metal complex when neutral Au25PET18 was used for ligand exchange whereas two ligands could be exchanged when starting with negatively charged Au25PET18. This charge dependence provides a strategy to precisely control the number of exchanged ligands at the surface of NCs.

Cisplatin binding to angiogenin protein: new molecular pathways and targets for the drug's anticancer activity.

Cisplatin (CisPt), a platinum-based chemotherapeutic widely used in the treatment of various cancers, has multiple mechanisms of action, including nuclear DNA (nDNA) and mitochondrial DNA (mDNA) damage and cytoskeletal perturbations affecting, in turn, the membrane transporter activity. CisPt binding to proteins and enzymes may modulate its biochemical mechanism of action and is associated with cancer cell resistance to the drug. In this work, we investigate the interaction between cisplatin and angiogenin (Ang), a protein strongly expressed in many types of cancer and a potent angiogenic factor. The adduct formed upon reaction of CisPt with Ang (Ang@CisPt) was characterized by X-ray crystallography to evidence the exact platination site and by UV-visible (UV-vis) absorption and circular dichroism (CD) spectroscopies to shed light on any possible change in the protein conformation. Furthermore, high-resolution electrospray ionization (ESI) mass spectrometry was utilized to evaluate the Ang : CisPt stoichiometry of the Ang@CisPt adduct. The effect of the Ang@CisPt adduct on a prostate cancer cell line (PC-3) was tested by colorimetric assays in terms of cell viability, at both levels of nuclear and mitochondrial damage, and reactive oxygen species (ROS) production. Cellular imaging by laser scanning confocal microscopy (LSM) was utilized to scrutinize the cytoskeleton actin reorganization and the lysosome and mitochondria organelle perturbation. These studies highlight the possibility of new molecular pathways and targets for CisPt activity.

Multimodal high-resolution nano-DESI MSI and immunofluorescence imaging reveal molecular signatures of skeletal muscle fiber types.

The skeletal muscle is a highly heterogeneous tissue comprised of different fiber types with varying contractile and metabolic properties. The complexity in the analysis of skeletal muscle fibers associated with their small size (30-50 μm) and mosaic-like distribution across the tissue tnecessitates the use of high-resolution imaging to differentiate between fiber types. Herein, we use a multimodal approach to characterize the chemical composition of skeletal fibers in a limb muscle, the gastrocnemius. Specifically, we combine high-resolution nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) with immunofluorescence (IF)-based fiber type identification. Computational image registration and segmentation approaches are used to integrate the information obtained with both techniques. Our results indicate that the transition between oxidative and glycolytic fibers is associated with shallow chemical gradients (<2.5 fold change in signals). Interestingly, we did not find any fiber type-specific molecule. We hypothesize that these findings might be linked to muscle plasticity thereby facilitating a switch in the metabolic properties of fibers in response to different conditions such as exercise and diet, among others. Despite the shallow chemical gradients, cardiolipins (CLs), acylcarnitines (CAR), monoglycerides (MGs), fatty acids, highly polyunsaturated phospholipids, and oxidized phospholipids, were identified as molecular signatures of oxidative metabolism. In contrast, histidine-related compounds were found as molecular signatures of glycolytic fibers. Additionally, the presence of highly polyunsaturated acyl chains in phospholipids was found in oxidative fibers whereas more saturated acyl chains in phospholipids were found in glycolytic fibers which suggests an effect of the membrane fluidity on the metabolic properties of skeletal myofibers.

Hyperxylones A and B, two polycyclic polyprenylated acylphloroglucinols with a benzoyl substituted bicyclo[3.2.1]octane core from Hypericum beanii

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs) possessing a rare benzoyl substituted bicyclo[3.2.1]octane core, hyperxylones A (1) and B (2), along with three new dearomatized isoprenylated acylphloroglucinols (DIAPs), hyperxylones C − E (3–5), were isolated from the roots of Hypericum beanii. The structures of 1–5 were determined by high-resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were biomimetically semi-synthesized starting from 5 and 4, respectively, enabling the correct stereochemical assignment of 5 and 4. Moreover, compounds 1 and 2 showed anti-nonalcoholic steatohepatitis (NASH) activity by inhibiting lipid deposition in L02 cells; compounds 3 and 5 exhibited nitric oxide (NO) inhibitory activity in lipopolysaccharides (LPS)-induced RAW264.7 cells.

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

Effects of a Volatile Organic Compound Filter on Breath Profiles Measured by Secondary Electrospray High-Resolution Mass Spectrometry.

Environmental volatile organic compounds (VOCs) from the ambient air potentially influence on-line breath analysis measurements by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). The aim of this study was to investigate how inhaling through a VOC filter affects the detected breath profiles and whether it is feasible to integrate such filters into routine measurements. A total of 24 adult participants performed paired breath analysis measurements with and without the use of an activated carbon filter for inspiration. Concordance correlation coefficients (CCCs) and the Bland−Altman analysis were used to assess the agreement between the two methods. Additionally, the effect on a selection of known metabolites and contaminants was analyzed. Out of all the detected features, 78.3% showed at least a moderate agreement before and after filter usage (CCC > 0.9). The decrease in agreement of the remaining m/z features was mostly associated with reduced signal intensities after filter usage. Although a moderate-to-substantial concordance was found for almost 80% of the m/z features, the filter still had an effect by decreasing signal intensities, not only for contaminants, but also for some of the studied metabolites. Operationally, the use of the filter complicated and slowed down the conductance of measurements, limiting its applicability in clinical studies.

Purification of Two Taxanes from Taxus cuspidata by Preparative High-Performance Liquid Chromatography

In the present study, an effective method of preparative high-performance liquid chromatography (Prep-HPLC) was established to purify two taxanes in Taxus cuspidata. During the experimental operation, the effects of flow rate, injection volume, and column temperature on the purity of 10-deacetyltaxol (10-DAT) and paclitaxel (PTX) were investigated, and the optimized conditions were as follows: flow rate of 10 mL/min, injection volume of 0.5 mL, and column temperature of 30 °C. Under these conditions, the purity of 10-DAT and PTX reached 95.33% and 99.15%, respectively. The purified products were characterized by scanning electron microscopy (SEM), high-performance liquid chromatography (HPLC), and electrospray ionization-high resolution mass spectrometry (ESI-HRMS). The results demonstrated that preparative HPLC can effectively purify 10-DAT and PTX from Taxus cuspidata with a purity of &gt;95%, which was suitable for the large-scale preparation of 10-DAT and PTX.

Rapid and Simultaneous Quantification of Short- and Ultrashort-Chain Perfluoroalkyl Substances in Water and Wastewater

Per- and polyfluoroalkyl substances (PFASs) are a class of chemicals of growing concern. Recently, there has been a shift toward the use of short- and ultrashort-chain PFASs, which are difficult to measure with current analytical methods and rarely included in environment monitoring studies. In this research, we developed and optimized online solid-phase extraction, high-performance liquid chromatography, and electrospray ionization high-resolution mass spectrometry methods for the rapid and simultaneous quantification of 10 short- and ultrashort-chain PFASs. We applied our method to water samples collected from a variety of natural, engineered, industrial, and commercial water systems. We detected ultrashort-chain PFASs in every sample, including hydraulic fracturing water and wastewater samples and wastewater from electronic fabrication facilities for the first time, identifying previously unknown sources of ultrashort-chain PFASs. We also measured ultrashort-chain PFASs in a variety of drinking water sources, including what was thought to be pristine groundwater and surface water sources. The measurement of ultrashort-chain PFASs in every sample type studied here raises concern over the potential ubiquity of these compounds in the environment and highlights the need for further monitoring studies, especially as longer-chain PFASs become regulated, and the industrial shift to short- and ultrashort-chain PFASs increases.

Chemical constituents of Pteris excelsa and their antioxidant activity

Pteris excelsa Gaud. is a perennial evergreen herbaceous plant belonging to the Pteridaceae family. In the present study, the chemical constituents of this species were obtained by utilizing MCI, C18 and silica gel and Sephadex LH-20 gel column chromatography. A new flavonol glycoside was identified, kaempferol-4′,7-dimethyl-3-O-β-D-glucosyl-(1 → 4)-α-L-rhamnoside (1), together with fourteen known compounds (2–15), kaempferol-4′-methyl-3-O-β-D-glucoside (2), kaempferol-4′,7-dimethyl-3-O-glucoside (3), kaempferol-3-O-β-D-glucoside (4), kaempferol- 4′-methyl-3,7-α-O-L-dirhamnoside (5), kaempferol-3,7-di-O-α-L-rhamnoside (6), pterosin B (7), 3β-hydroxycinnamolide (8), N-(3-carboxypropyl)-2-acetylpyrrole (9), vanillic acid (10), sauropunol C/D (11), 6-anhydro-2-deoxy-β-O-furanosides (12), aquilegiolide (13), menisdaurilide (14), 2-(D-glycerol-1,2-dihydroxyethyl) furan (15). The structures of these compounds were established based on their high-resolution electrospray ionization mass spectrometry results and nuclear magnetic resonance spectroscopy data and by comparing their spectroscopic data with those reported in the literature. Importantly, we found that the antioxidant activity of PE, EtOAc and n-BuOH fractions of 98% methanol extract of P. excelsa (mediated by scavenging free radicals) was 33.57 ± 0.67%, 52.98 ± 1.55% and 45.25 ± 1.10% at a concentration of 400 μg/mL, respectively. Besides, compounds 1–6 displayed an antioxidant effect against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical.

An interoperability framework for multicentric breath metabolomic studies.

Exhaled breath contains valuable information at the molecular level and offers promising potential for precision medicine. However, few breath tests transition to routine clinical practice, partly because of the missing validation in multicenter trials. Therefore, we developed and applied an interoperability framework for standardized multicenter data acquisition and processing for breath analysis with secondary electrospray ionization-high resolution mass spectrometry. We aimed to determine the technical variability and metabolic coverage. Comparison of multicenter data revealed a technical variability of ∼20% and a core signature of the human exhaled metabolome consisting of ∼850 features, corresponding mainly to amino acid, xenobiotic, and carbohydrate metabolic pathways. In addition, we found high inter-subject variability for certain metabolic classes (e.g., amino acids and fatty acids), whereas other regions such as the TCA cycle were relatively stable across subjects. The interoperability framework and overview of metabolic coverage presented here will pave the way for future large-scale multicenter trials.

A pair of new sesquiterpene isomers containing spiro heterocyclic skeleton from plant-derived fungus Botryosphaeria dothidea

A pair of new sesquiterpene isomers containing a spiro heterocyclic skeleton, dothimes A ( 1 ) and B ( 2 ), together with six known compounds, quindoline ( 3 ), ( S )-3-(3-indolyl)lactic acid methyl ester ( 4 ), dankasterone B ( 5 ), dibutyl phthalate ( 6 ), (1 S ,3 R ,4 R ,7 S )-3,4-dihydroxy- α -bisabolol ( 7 ), and p -hydroxybenzaldehyde ( 8 ), were isolated from the plant-derived fungus Botryosphaeria dothidea . The structures of all isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D nuclear magnetic resonance (NMR), and high resolution electrospray ionization mass spectrometry (HRESIMS) data, as well as by comparison with literature reports. Compounds 1 and 2 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC 50 values of 63.66 and 58.29 μM, respectively. • A pair of new sesquiterpene isomers was isolated from Botryosphaeria dothidea . • The structures of 1 and 2 were elucidated by spectroscopic analyses. • Compounds 1 and 2 showed weak anti-inflammatory activity.

Algicidal characteristics of novel algicidal compounds, cyclic lipopeptide surfactins from Bacillus tequilensis strain D8, in eliminating Heterosigma akashiwo blooms.

Heterosigma akashiwo blooms have caused severe damage to marine ecosystems, the aquaculture industry and human health worldwide. In this study, Bacillus tequilensis D8 isolated from an H. akashiwo bloom area was found to exert high algicidal activity via extracellular metabolite production. This activity remained stable after exposure to different temperatures and light intensities. Scanning electron microscopy observation and fluorescein diacetate staining indicated that the algicidal substances rapidly destroyed algal plasma membranes and decreased esterase activity. Significant decreases in the maximum photochemical quantum yield and relative electron transfer rate were observed, which indicated photosynthetic membrane destruction. Subsequently, the algicidal compounds were separated and purified by high-performance liquid chromatography and identified as three surfactin homologues by interpreting high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy data. Among these, surfactin-C13 and surfactin-C14 exhibited strong algicidal activity against three HAB-causing species, namely, H. akashiwo, Skeletonema costatum, and Prorocentrum donghaiense, with 24 h-LC50 values of 1.2-5.31 μg/ml. Surfactin-C15 showed strong algicidal activity against S. costatum and weak algicidal activity against H. akashiwo but little activity against P. donghaiense. The present study illuminates the algicidal characteristics and mechanisms of action of surfactins on H. akashiwo and their potential applicability in controlling harmful algal blooms.

Biotransformation of 18β-Glycyrrhetinic Acid by Human Intestinal Fungus Aspergillus niger RG13B1 and the Potential Anti-Inflammatory Mechanism of Its Metabolites.

18β-Glycyrrhetinic acid (GA) is a triterpenoid possessing an anti-inflammatory activity in vivo, while the low bioavailability limits its application due to its intestinal accumulation. In order to investigate the metabolism of GA in intestinal microbes, it was incubated with human intestinal fungus Aspergillus niger RG13B1, finally leading to the isolation and identification of three new metabolites (1-3) and three known metabolites (4-6) based on 1D and 2D NMR and high-resolution electrospray ionization mass spectroscopy spectra. Metabolite 6 could target myeloid differentiation protein 2 (MD2) to suppress the activation of nuclear factor-kappa B (NF-κB) signaling pathway via inhibiting the nuclear translocation of p65 to downregulate its target proteins and genes in lipopolysaccharide (LPS)-mediated RAW264.7 cells. Molecular dynamics suggested that metabolite 6 interacted with MD2 through the hydrogen bond of amino acid residue Arg90. These findings demonstrated that metabolite 6 could serve as a potential candidate to develop the new inhibitors of MD2.

Orchestrated Response of Intracellular Zwitterionic Metabolites in Stress Adaptation of the Halophilic Heterotrophic Bacterium Pelagibaca bermudensis.

Osmolytes are naturally occurring organic compounds that protect cells against various forms of stress. Highly polar, zwitterionic osmolytes are often used by marine algae and bacteria to counteract salinity or temperature stress. We investigated the effect of several stress conditions including different salinities, temperatures, and exposure to organic metabolites released by the alga Tetraselmis striata on the halophilic heterotrophic bacterium Pelagibaca bermudensis. Using ultra-high-performance liquid chromatography (UHPLC) on a ZIC-HILIC column and high-resolution electrospray ionization mass spectrometry, we simultaneously detected and quantified the eleven highly polar compounds dimethylsulfoxonium propionate (DMSOP), dimethylsulfoniopropionate (DMSP), gonyol, cysteinolic acid, ectoine, glycine betaine (GBT), carnitine, sarcosine, choline, proline, and 4-hydroxyproline. All compounds are newly described in P. bermudensis and potentially involved in physiological functions essential for bacterial survival under variable environmental conditions. We report that adaptation to various forms of stress is accomplished by adjusting the pattern and amount of the zwitterionic metabolites.

Discovery of natural polyphenols from the wild vegetable Suaeda salsa L. with potential cardioprotective functions

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1–14), eight phenolic acids (15–22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27–29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1–5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3–5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.