Occurrence, bioaccumulation and ecological risk of organic ultraviolet absorbers in multiple coastal and offshore coral communities of the South China Sea.

The occurrence of organic ultraviolet absorbers (OUVAs) in coral reef regions has aroused widespread concern. This study focused on the occurrence, distribution, bioaccumulation and ecological risk of ten OUVAs in both coastal and offshore coral reef regions in the South China Sea. While the Σ10OUVAs was 85 % lower in the offshore seawater (15.1 ng/L) than in the coastal seawater (102.1 ng/L), the Σ10OUVAs was 21 % lower in the offshore corals (1.82 µg/g dry weight (dw)) than in the coastal corals (2.31 µg/g dw). This difference was speculated to relate to the high intensity of human activities in the coastal regions. Moreover, the offshore corals showed higher bioaccumulative capability toward OUVAs (log bioaccumulation factors (BAFs): 1.22-5.07) than the coastal corals (log BAFs: 0.17-4.38), which was presumably the influence of varied physiological status under different environmental conditions. The results of the ecological risk assessment showed that BP-3 resulted in 73 % of coastal corals and 20 % of offshore corals at a risk of bleaching. Therefore, the usage and discharge of BP-3 should be managed and controlled by the countries adjacent to the South China Sea for the protection of coral reefs.

Optimization of BAX trigger site activator BTSA1 with improved antitumor potency and in vitro ADMET properties.

Direct activation of the pro-apoptotic protein BAX represents a potential therapeutic strategy to trigger apoptosis in cancer. Herein, structural optimization of the reported BAX trigger site activator BTSA1 turned out into a series of pyrazolone derivatives, where compound 6d exhibited significantly enhanced antiproliferative effects and apoptosis induction ability compared to BTSA1. Mechanism of action studies revealed that compound 6d could initiate the BAX activation cascade, promoting BAX insertion into mitochondrial membranes and activating MOMP, ultimately leading to the release of cytochrome c and apoptosis. Furthermore, 6d showed significantly improved in vitro stability and CYPs profile compared to BTSA1. This work may lay a foundation to develop potent BAX trigger site activators for the treatment of BAX-expressing malignancies.

Metabolomics Characterization of Scleractinia Corals with Different Life-History Strategies: A Case Study about Pocillopora meandrina and Seriatopora hystrix in the South China Sea.

Life-history strategies play a critical role in susceptibility to environmental stresses for Scleractinia coral. Metabolomics, which is capable of determining the metabolic responses of biological systems to genetic and environmental changes, is competent for the characterization of species' biological traits. In this study, two coral species (Pocillopora meandrina and Seriatopora hystrix in the South China Sea) with different life-history strategies ("competitive" and "weedy") were targeted, and untargeted mass spectrometry metabolomics combined with molecular networking was applied to characterize their differential metabolic pathways. The results show that lyso-platelet activating factors (lyso-PAFs), diacylglyceryl carboxyhydroxymethylcholine (DGCC), aromatic amino acids, and sulfhydryl compounds were more enriched in P. meandrina, whereas new phospholipids, dehydrated phosphoglycerol dihydroceramide (de-PG DHC), monoacylglycerol (MAG), fatty acids (FA) (C < 18), short peptides, and guanidine compounds were more enriched in S. hystrix. The metabolic pathways involved immune response, energy metabolism, cellular membrane structure regulation, oxidative stress system, secondary metabolite synthesis, etc. While the immune system (lysoPAF) and secondary metabolite synthesis (aromatic amino acids and sulfhydryl compounds) facilitates fast growth and resistance to environmental stressors of P. meandrina, the cell membrane structure (structural lipids), energy storage (storage lipids), oxidative stress system (short peptides), and secondary metabolite synthesis (guanidine compounds) are beneficial to the survival of S. hystrix in harsh conditions. This study contributes to the understanding of the potential molecular traits underlying life-history strategies of different coral species.

Mass spectrometry-based metabolomic signatures of coral bleaching under thermal stress.

Coral bleaching caused by climate change has resulted in large-scale coral reef decline worldwide. However, the knowledge of physiological response mechanisms of scleractinian corals under high-temperature stress is still challenging. Here, untargeted mass spectrometry-based metabolomics combining with Global Natural Product Social Molecular Networking (GNPS) was utilized to investigate the physiological response of the coral species Pavona decussata under thermal stress. A wide variety of metabolites (including lipids, fatty acids, amino acids, peptides, osmolytes) were identified as the potential biomarkers and subjected to metabolic pathway enrichment analysis. We discovered that, in the thermal-stressed P. decussata coral holobiont, (1) numerous metabolites in classes of lipids and amino acids significantly decreased, indicating an enhanced lipid hydrolysis and aminolysis that contributed to up-regulation in gluconeogenesis to meet energy demand for basic survival; (2) pantothenate and panthenol, two essential intermediates in tricarboxylic acid (TCA) cycle, were up-regulated, implying enhanced efficiency in energy production; (3) small peptides (e.g., Glu-Leu and Glu-Glu-Glu-Glu) and lyso-platelet-activating factor (lysoPAF) possibly implicated a strengthened coral immune response; (4) the down-regulation of betaine and trimethylamine N-oxide (TMAO), known as osmolyte compounds for maintaining holobiont homeostasis, might be the result of disruption of coral holobiont.

Organochlorine pesticides (OCPs) in corals and plankton from a coastal coral reef ecosystem, south China sea.

Recent studies have indicated that coral mucus plays an important role in the bioaccumulation of a few organic pollutants by corals, but no relevant studies have been conducted on organochlorine pesticides (OCPs). Previous studies have also indicated that OCPs widely occur in a few coral reef ecosystems and have a negative effect on coral health. Therefore, this study focused on the occurrence and bioaccumulation of a few OCPs, such as dichlorodiphenyltrichloroethanes (DDTs), hexachlorobenzene (HCB) and p,p'-methoxychlor (MXC), in the coral tissues and mucus as well as in plankton and seawater from a coastal reef ecosystem (Weizhou Island) in the South China Sea. The results indicated that DDTs were the predominant OCPs in seawater and marine biota. Higher concentrations of OCPs in plankton may contribute to the enrichment of OCPs by corals. The significantly higher total OCP concentration (∑8OCPs) found in coral mucus than in coral tissues suggested that coral mucus played an essential role in resisting enrichment of OCPs by coral tissues. This study explored the different functions of coral tissues and mucus in OCP enrichment and biodegradation for the first time, highlighting the need for OCP toxicity experiments from both tissue and mucus perspectives.

Discovery and structure-activity relationship studies of novel Bcl-2/Mcl-1 dual inhibitors with indole scaffold.

The Bcl-2 anti-apoptotic proteins were widely overexpressed in diverse tumor cells, especially for Bcl-2 and Mcl-1, which regarding as important targets of apoptosis induction and resistance of chemotherapy. We identified novel Bcl-2/Mcl-1 dual inhibitors with indole scaffold by the optimization of hit 1. Structure modification against several moieties including hydrophobic fragment, side chain and benzoic acid fragment was conducted and the structure-activity relationship was analyzed. The representative compound 12f exhibited sub-micromolar binding affinities to Bcl-2/Mcl-1 without binding affinity to Bcl-XL. Mechanism of action studies suggested that compound 12f dose-dependently triggered apoptosis in HL-60 cells. Compound 12f represents a novel Bcl-2/Mcl-1 dual inhibitor which deserving further study.

Rapid analysis of quinones in complex matrices by derivatization-based wooden-tip electrospray ionization mass spectrometry.

Quinones are important components participating in various biological processes as well as hazardous substances to human health. Rapid determination of quinones in environmental samples and biofluids is the basis for assessing their health effect. Here, we presented a rapid, straightforward, highly sensitive and environmental-friendly wooden-tip electrospray ionization mass spectrometry (ESI-MS) method for the determination of quinones in PM2.5, urine and serum. An amine group "tag" was introduced to the quinone structure through in situ derivatization with cysteamine to improve ionization efficiency of quinones in wooden-tip ESI-MS. The toothpicks were treated by sharpening and acidification with HNO3. Experimental parameters, including sample volume, spray voltage, and spray solvent composition were optimized to be 1 µL, 3.5 kV, and ACN/CH3COOC2H5 (v/v, 9:1), respectively. The limits of detection for the determination of 1,4-benzoquinone, methyl-p-benzoquinone, 1,4-naphthoquinone and 1,4-anthraquinone in ACN under the optimal conditions were 1.00, 0.96, 0.13, 0.16 ng (1.00, 0.96, 0.13, 0.16 µg/mL, sample volume, 1 µL), respectively. This approach was successfully applied to the determination of 1,4-naphthoquinone and 1,4-anthraquinone in complex matrices, including PM2.5, urine and serum without or with minimal sample preparation (LOD range: 0.22-1.48 ng).

The impact of national energy structure on the concentrations, environmental behavior, and sources of polycyclic aromatic hydrocarbons in riverine and coastal sediments of the Beibu Gulf, China.

In this study, polycyclic aromatic hydrocarbons (PAHs) were measured in sediments of the Beibu Gulf in 2017 to investigate sources and a risk assessment. The results showed the total PAH concentration (∑16PAHs) in sediments of the Beibu Gulf in 2017 (17.6 ± 16.7 ng g-1) was significantly lower than that in 2010 (47.8 ± 27.4 ng g-1). The ∑16PAHs concentrations varied spatially within the Beibu Gulf, impacted by point source pollution. The results of adsorption/desorption and water-air partitioning suggest that the environmental behavior of PAHs in the Beibu Gulf is affected by atmospheric deposition and sediment-water partitioning. A risk assessment showed that the PAHs in sediments were within a safety threshold. Three source apportionment methods show that oil spills and oil and biomass burning were the most important (>83.8%) sources of PAHs in sediments of the Beibu Gulf.

Reaction Tracking and High-Throughput Screening of Active Compounds in Combinatorial Chemistry by Tandem Mass Spectrometry Molecular Networking.

Combinatorial synthesis has been widely used as an efficient strategy to screen for active compounds. Mass spectrometry is the method of choice in the identification of hits resulting from high-throughput screenings due to its high sensitivity, specificity, and speed. However, manual data processing of mass spectrometry data, especially for structurally diverse products in combinatorial chemistry, is extremely time-consuming and one of the bottlenecks in this process. In this study, we demonstrated the effectiveness of a tandem mass spectrometry molecular networking-based strategy for product identification, reaction dynamics monitoring, and active compound targeting in combinatorial synthesis. Molecular networking connects compounds with similar tandem mass spectra into a cluster and has been widely used in natural products analysis. We show that both the expected and side products can be readily characterized using molecular networking based on their mass spectrometry fragmentation patterns. Additionally, time-dependent molecular networking was integrated to track reaction dynamics to determine the optimal reaction time to maximize target product yields. We also present a proof-of-concept experiment that successfully identified and isolated active molecules from a dynamic combinatorial library. These results demonstrated the potential of using molecular networking for identifying, tracking, and high-throughput screening of active compounds in combinatorial synthesis.

Ambient Ionization Mass Spectrometry Today and Tomorrow: Embracing Challenges and Opportunities.

Ambient ionization mass spectrometry (AIMS) has grown into a group of emerging analytical techniques that allow rapid, real-time, high-throughput, in situ, and in vivo analysis in many scientific fields including biomedicine, pharmaceuticals, and forensic sciences. While dozens of AIMS techniques have been introduced over the past two decades, their broad commercial and industrial use is still restricted by multiple challenges. In this Perspective, we discuss the most relevant technical challenges facing AIMS, i.e., reproducibility, quantitative ability, molecular coverage, sensitivity, and data complexity, and scientists' recent attempts to overcome these hurdles. Furthermore, we present future directions of AIMS from our perspective, including the necessity that efforts should be made to unravel blind biomolecules in routine analysis, the construction of a data depository for AIMS users, the full automation of pipelines for prospect integration in a robotic laboratory, the movement toward on-site tests, and the expansion of outreach to motivate government officials in policymaking. We anticipate that, with progress in these critical but immature areas, AIMS technology will keep evolving to become a more robust and user-friendly set of technologies and, consequently, be translated into everyday life practice.

Mass Spectrometry-Inspired Degradation of Disinfection By-Product, 2,6-Dichloro-1,4-benzoquinone, in Drinking Water by Heating.

2,6-Dichloro-1,4-benzoquinone (DCBQ), a highly toxic and carcinogenic disinfection by-product, was degraded during the electrospray process by elevating the source temperature. This unexpected finding inspired us to use heating to degrade DCBQs in drinking water. The results show that about 99% of DCBQs in the drinking water were degraded in one minute by heating to 100°C with room light irradiation. Therefore, a conclusion can be drawn that heating enables the degradation of DCBQs in drinking water.

Sensitive Determination of Quinones by High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry with Methanol Derivatization.

Quinones are a class of compounds having substantial toxicity and pharmacological function. This work has produced a derivatization method for quinone detection with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). Through introducing tags (methoxy) to the quinone structures, the ionization efficiencies of five quinones (p-benzoquinone (BQ), methyl-p-benzoquinone (MBQ), 1,4-naphthoquinone (1,4-NQ), 1,2-naphthoquinone (1,2-NQ), and 1,4-anthraquinones (AQ)) were greatly improved during ESI. The limit of detections (LODs) for quinone determination could be flexibly adjusted by changing the reaction time or the solvent composition. While lower LODs (<0.02 - 2.06 pg for five quinones) were achieved with methanol as the derivatization reagent, the reaction time was substantially shortened (from 27 to 3 h or 11 h) with methanol/water (v/v, 1:1) as the derivatization reagent. Finally, the proposed method was successfully used for quinone determination in airborne particulates.

Occurrence and distribution of antibiotics in mariculture farms, estuaries and the coast of the Beibu Gulf, China: Bioconcentration and diet safety of seafood.

The occurrence, distribution, bioconcentration and diet safety via seafood consumption of 19 antibiotics were investigated in eight closed mariculture ponds, four estuaries, two nearshore areas and one offshore area from the Beibu Gulf. Seventeen, 16, 15 and 7 antibiotics were detected at total concentrations of 43.2 - 885 ng L-1, 22.4 - 118 ng L-1, 22.7 - 24.5 ng L-1, and 1.81-3.23 ng L-1 in the water of the above different areas, respectively. This indicates that the mariculture ponds are important sources of antibiotic pollution on the coast of the Beibu Gulf. Ten antibiotics were detected in feed samples with concentrations ranging from 0.03 to 95.4 ng g-1, demonstrating the presence of antibiotics in the feed and/or residual antibiotics in the raw material of the feed. The field bioconcentration factors (BCFs) of the antibiotics calculated in different culture organisms ranged from 0.55 to 10,774 L kg-1. The estimated daily intakes (EDIs) of sulphonamides, fluoroquinolones, macrolides and chloramphenicols via aquatic products were 19.8-105, 33.7-178, 34.9-186 and 6.9-37.1 ng d-1, respectively. According to the acceptable daily intakes (ADIs) and maximum residue limits (MRLs) proposed by different organisations, these aquatic products (shrimp, crab and oyster) reached the standard of safe consumption and could not pose a health risk to humans. However, a potential elevated risk to humans may remain because of the occurrence of multiple antibiotics in the cultured organisms, particularly for sensitive populations, such as pregnant women, the elderly and children.

Time-resolved method to distinguish protein/peptide oxidation during electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) is one of the most prevalent techniques used to monitor protein/peptide oxidation induced by reactive oxygen species (ROSs). However, both corona discharge (CD) and electrochemistry (EC) can also lead to protein/peptide oxidation during ESI. Because the two types of oxidation occur almost simultaneously, determining the extent to which the two pathways contribute to protein/peptide oxidation is difficult. Herein, a time-resolved method was introduced to identify and differentiate CD- and EC-induced oxidation. Using this approach, we separated the instantaneous CD-induced oxidation from the hysteretic EC-induced oxidation, and the effects of the spray voltage and flow rate of the ESI source on both oxidation types were investigated with a homemade ESI source. For angiotensin II analogue (b-DRVYVHPF-y), the dehydrogenation and oxygenation species were the detected EC-induced oxidation products, while the oxygenation species were the major CD-induced oxidation products. This time-resolved approach was also applicable to a commercial HESI source, in which both CD and EC were responsible for hemoglobin and cytochrome c oxidation with upstream grounding while CD dominated the oxidation without upstream grounding.

Occurrence, sources and transport of antibiotics in the surface water of coral reef regions in the South China Sea: Potential risk to coral growth.

Laboratory research has indicated that antibiotics had negative effects on coral growth by disturbing natural microbiota; however, no field studies have reported antibiotic contamination levels and their influence on coral growth in natural coral reef regions (CRRs). This study investigated antibiotic occurrence and sources in the surface water from CRRs that have suffered from rapid coral degradation and evaluated their risk to coral growth. These regions are in the South China Sea, including four coastal and two offshore CRRs. The results show that 13 antibiotics were detected in the coastal CRRs with concentrations ranging from 10-2-100 ng L-1, while 5 antibiotics occurred in offshore CRRs (300-950 km from the mainland), with concentrations ranging from 10-2 to 10-1 ng L-1. Their concentrations decreased gradually from the coast to offshore in the transport process. However, Yongxing Island, which is approximately 300 km from the mainland, was an exception with relatively higher concentrations than the surrounding reefs because of the ever-increasing human activity on the island. The presence of anthropogenic contaminants antibiotics in CRRs may be a potential risk to coral growth.

Unexpected Reduction of Iminoquinone and Quinone Derivatives in Positive Electrospray Ionization Mass Spectrometry and Possible Mechanism Exploration.

Unexpected reduction of iminoquinone (IQ) and quinone derivatives was first reported during positive electrospray ionization mass spectrometry. Upon increasing spray voltage, the intensities of IQ and quinone derivatives decreased drastically, accompanying the increase of the intensities of the reduction products, amodiaquine (AQ) and phenol derivatives. To gain more insight into the mechanism of such reduction, we explored the experimental factors that are influential to corona discharge (CD). The results show that experimental parameters that favor severe CD, including metal spray emitter, using water as spray solvent, sheath gas with low dielectric strength (e.g., nitrogen), and shorter spray tip-to-mass spectrometer inlet distance, facilitated the reduction of IQ and quinone derivatives, implying that the reduction should be closely related to CD in the gas phase. Graphical Abstract ᅟ.

Oxidation of the antibacterial agent norfloxacin during sodium hypochlorite disinfection of marine culture water.

Chlorination disinfection and antibiotic addition are two universal processes of marine culture. The generation of disinfection byproducts (DBPs) is unavoidable. Antibiotic residue not only pollutes water but also acts as a precursor to the production of new DBPs. The fate of antibiotic norfloxacin (NOR) in chlorination disinfection was investigated. It was observed that NOR could be oxidized by disinfection agent sodium hypochlorite, but the oxidation rate varied considerably with the type of disinfected water. For fresh water, marine culture water and sea water, the reaction rate constant was 0.066 min-1, 0.466 min-1 and 1.241 min-1, respectively. The difference was primarily attributed to the promotion role of bromide ions in seawater and marine culture water. Moreover, the bromide ions could result in the generation of brominated DBPs (Br-DBPs). The kinetics, products, reaction centers and mechanisms were investigated. The active site of NOR was found to be the N4 atom on piperazinyl in fresh water. During marine culture water and sea water disinfection, the carboxyl on NOR was oxidized and two Br-DBPs were formed. This was attributed to the lowering of the reaction's required activation energy when performed in the presence of bromide ions. The Br-DBPs were also confirmed in real shrimp pond brackish water. Quantitative structure activity relationships and the total organic halogen analysis showed that the DBPs in marine culture water possessed stronger toxicological properties than the DBPs in fresh water. The toxicity increase was attributed to the production of Br-DBPs in the disinfection process of marine culture water.

Direct sequencing of a disulfide-linked peptide with electrospray ionization tandem mass spectrometry.

Dissociation of disulfide is normally mandatory prior to disulfide peptide sequencing via electrospray ionization collision induced dissociation mass spectrometry (ESI-CID-MS). Herein, a facile method for directly sequencing intact disulfide peptides was proposed. The basic principles involved were electrolyte-enhanced corona discharge in ESI and the following oxidative cleavage reaction.

Alleviation of electrochemical oxidation for peptides and proteins in electrospray ionization: obtaining more accurate mass spectra with induced high voltage.

Accurate mass spectrometry (MS) signal for peptide/protein analysis, which could be affected by various MS conditions, plays an essential role in identification and quantification of biological samples. Herein, we tried to alleviate the possible interferences from electrochemical oxidations during electrospray ionization (ESI). Three most common electrochemical oxidation reactions in ESI include oxidation of analyte, solvent, and electrode. With introduction of induced electrospray ionization (IESI) (a variant form of ESI), these interferences were significantly alleviated for peptides/proteins. That effect was also tested with flow injection experiments with different solution flow rates, electrolyte concentrations and solvent compositions, which was to simulate various chromatography conditions in conventional liquid chromatography (LC) separations. For all chromatography conditions tested, electrochemical oxidation was significantly alleviated for the absence of physical contact between spray solution and electrode.

Reactive paper spray mass spectrometry for in situ identification of quinones.

RATIONALE: The polycyclic aromatic hydrocarbons quinones are reported to be harmful and could cause mutations and cancer via the generation of reactive oxygen species through their redox cycle in human body. For detection by gas chromatography and high-performance liquid chromatography mass spectrometry (MS), sample pretreatments and chromatographic separation prior to MS are generally required, which makes the whole analytical process laborious and time-consuming, resulting in difficulties for fast screening targets from complicated matrices. Thus facile, rapid and reliable MS methods for detection of quinones in complicated matrices are in great demand. METHODS: Reactive paper spray mass spectrometry is reported for rapid identification and quantification of quinones in complicated matrices. The method is based on an in situ derivatization reaction between cysteamine and quinones prior to analysis with paper spray mass spectrometry. With the addition of an easily charged chemical tag, the ionization efficiency of analysts is greatly improved. Due to the high ionization efficiency of the drivatives, quinones in complicated matrices could be detected rapidly without any pretreatment. RESULTS: Under the optimized experimental conditions, the linear dynamic ranges for both 1,4-benzoquinone and 1,4-naphthoquinone are 0.4-40 ng and that for 1,4-anthraquinone is 0.4-20 ng. Limits of detection for these three analytes were measured to be 160, 40 and 200 pg using methyl-p-benzoquinone as internal standard. The capability to conduct MS analysis under ambient pressure is illustrated by identification of 1,4-naphthoquinone and 1,4-anthraquinone in raw urine, raw serum and cell culture medium. CONCLUSIONS: Reactive paper spray could be applied to fast screening of quinones from complicated matrices. Therefore, we believe that reactive paper spray mass spectrometry might be potentially useful in the fields of environmental sciences, metabolomics and clinic analysis.