Quantifying isotope parameters associated with carbonyl-water oxygen exchange during sucrose translocation in tree phloem.

Stable oxygen isotope ratio of tree-ring α-cellulose (δ18Ocel) yields valuable information on many aspects of tree-climate interactions. However, our current understanding of the mechanistic controls on δ18Ocel is incomplete, with a knowledge gap existent regarding the fractionation effect characterizing carbonyl-water oxygen exchange during sucrose translocation from leaf to phloem. To address this insufficiency, we set up an experimental system integrating a vapor 18O-labeling feature to manipulate leaf-level isotopic signatures in tree saplings enclosed within whole-canopy gas-exchange cuvettes. We applied this experimental system to three different tree species to determine their respective relationships between 18O enrichment of sucrose in leaf lamina (Δ18Ol_suc) and petiole phloem (Δ18Ophl_suc) under environmentally/physiologically stable conditions. Based on the determined Δ18Ophl_suc-Δ18Ol_suc relationships, we estimated that on average, at least 25% of the oxygen atoms in sucrose undergo isotopic exchange with water along the leaf-to-phloem translocation path and that the biochemical fractionation factor accounting for such exchange is c. 34‰, markedly higher than the conventionally assumed value of 27‰. Our study represents a significant step toward quantitative elucidation of the oxygen isotope dynamics during sucrose translocation in trees. This has important implications with respect to improving the δ18Ocel model and its related applications in paleoclimatic and ecophysiological contexts.

On the Chemical Purity and Oxygen Isotopic Composition of α-Cellulose Extractable from Higher Plants and the Implications for Climate, Metabolic, and Physiological Studies.

The 18O/16O ratio of α-cellulose in land plants has proved of interest for climate, environmental, physiological, and metabolic studies. Reliable application of such a ratio may be compromised by the presence of hemicellulose impurities in the α-cellulose product obtainable with current extraction methods, as the impurities are known to be isotopically different from that of the α-cellulose. We first compared the quality of hydrolysates of "α-cellulose products" obtained with four representative extraction methods (Jayme and Wise; Brendel; Zhou; Loader) and quantified the hemicellulose-derived non-glucose sugars in the α-cellulose products from 40 land grass species using gas chromatography-mass spectrometry (GC/MS). Second, we performed compound-specific isotope analysis of the hydrolysates using GC/Pyrolysis/IRMS. These results were then compared with the bulk isotope analysis using EA/Pyrolysis/IRMS of the α-cellulose products. We found that overall, the Zhou method afforded the highest purity α-cellulose as judged by the minimal presence of lignin and the second-lowest presence of non-glucose sugars. Isotopic analysis then showed that the O-2-O-6 of the α-cellulose glucosyl units were all depleted in 18O by 0.0-4.3 mUr (average, 1.9 mUr) in a species-dependent manner relative to the α-cellulose products. The positive isotopic bias of using the α-cellulose product instead of the glucosyl units stems mainly from the fact that the pentoses that dominate hemicellulose contamination in the α-cellulose product are relatively enriched in 18O (compared to hexoses) as they inherit only the relatively 18O-enriched O-2-O-5 moiety of sucrose, the common precursor of pentoses and hexoses in cellulose, and are further enriched in 18O by the (incomplete) hydrolysis.

Stem water cryogenic extraction biases estimation in deuterium isotope composition of plant source water.

The hydrogen isotope ratio of water cryogenically extracted from plant stem samples (δ2Hstem_CVD) is routinely used to aid isotope applications that span hydrological, ecological, and paleoclimatological research. However, an increasing number of studies have shown that a key assumption of these applications-that δ2Hstem_CVD is equal to the δ2H of plant source water (δ2Hsource)-is not necessarily met in plants from various habitats. To examine this assumption, we purposedly designed an experimental system to allow independent measurements of δ2Hstem_CVD, δ2Hsource, and δ2H of water transported in xylem conduits (δ2Hxylem) under controlled conditions. Our measurements performed on nine woody plant species from diverse habitats revealed a consistent and significant depletion in δ2Hstem_CVD compared with both δ2Hsource and δ2Hxylem Meanwhile, no significant discrepancy was observed between δ2Hsource and δ2Hxylem in any of the plants investigated. These results cast significant doubt on the long-standing view that deuterium fractionation occurs during root water uptake and, alternatively, suggest that measurement bias inherent in the cryogenic extraction method is the root cause of δ2Hstem_CVD depletion. We used a rehydration experiment to show that the stem water cryogenic extraction error could originate from a dynamic exchange between organically bound deuterium and liquid water during water extraction. In light of our finding, we suggest caution when partitioning plant water sources and reconstructing past climates using hydrogen isotopes, and carefully propose that the paradigm-shifting phenomenon of ecohydrological separation ("two water worlds") is underpinned by an extraction artifact.

Multi-Omics Profiling Reveals Resource Allocation and Acclimation Strategies to Temperature Changes in a Marine Dinoflagellate.

Temperature is a critical environmental factor that affects the cell growth of dinoflagellates and bloom formation. To date, the molecular mechanisms underlying the physiological responses to temperature variations are poorly understood. Here, we applied quantitative proteomic and untargeted metabolomic approaches to investigate protein and metabolite expression profiles of a bloom-forming dinoflagellate Prorocentrum shikokuense at different temperatures. Of the four temperatures (19, 22, 25, and 28°C) investigated, P. shikokuense at 25°C exhibited the maximal cell growth rate and maximum quantum efficiency of photosystem II (Fv/Fm) value. The levels of particulate organic carbon (POC) and nitrogen (PON) decreased with increasing temperature, while the POC/PON ratio increased and peaked at 25°C. Proteomic analysis showed proteins related to photoreaction, light harvesting, and protein homeostasis were highly expressed at 28°C when cells were under moderate heat stress. Metabolomic analysis further confirmed reallocated amino acids and soluble sugars at this temperature. Both omic analyses showed glutathione metabolism that scavenges the excess reactive oxygen species, and transcription and lipid biosynthesis that compensate for the low translation efficiency and plasma membrane fluidity were largely upregulated at suboptimal temperature. Higher accumulations of glutathione, glutarate semialdehyde, and 5-KETE at 19°C implied their important roles in low-temperature acclimation. The strikingly active nitrate reduction and nitrogen flux into asparagine, glutamine, and aspartic acid at 19°C indicated these three amino acids may serve as nitrogen storage pools and help cells cope with low temperature. Our study provides insights into the effects of temperature on dinoflagellate resource allocation and advances our knowledge of dinoflagellate bloom formation in marine environments. IMPORTANCE Marine phytoplankton is one of the most important nodes in global biogeochemical cycle. Deciphering temperature-associated marine phytoplankton cell stoichiometric changes and the underlying molecular mechanisms are therefore of great ecological concerns. However, knowledge of how phytoplankton adjust the cell stoichiometry to sustain growth under temperature changes is still lacking. This study investigates the variations of protein and metabolite profiles in a marine dinoflagellate across temperatures at which the field blooms usually occur and highlights the temperature-dependent molecular traits and key metabolites that may be associated with rapid cell growth and temperature stress acclimation.

Initiation of efficient C4 pathway in response to low ambient CO2 during the bloom period of a marine dinoflagellate.

Dinoflagellates are important primary producers and major causative agents of harmful algal blooms in the global ocean. Despite the great ecological significance, the photosynthetic carbon acquisition by dinoflagellates is still poorly understood. The pathways of photosynthetic carbon assimilation in a marine dinoflagellate Prorocentrum donghaiense under both in situ and laboratory-simulated bloom conditions were investigated using a combination of metaproteomics, qPCR, stable carbon isotope and targeted metabolomics approaches. A rapid consumption of dissolved CO2 to generate high biomass was observed as the bloom proceeded. The carbon assimilation genes and proteins including intracellular carbonic anhydrase 2, phosphoenolpyruvate carboxylase, phosphoenolpyruvate carboxykinase and RubisCO as well as their enzyme activities were all highly expressed at the low CO2 level, indicating that C4 photosynthetic pathway functioned in the blooming P. donghaiense cells. Furthermore, δ13 C values and content of C4 compound (malate) significantly increased with the decreasing CO2 concentration. The transition from C3 to C4 pathway minimizes the internal CO2 leakage and guarantees efficient carbon fixation at the low CO2 level. This study demonstrates the existence of C4 photosynthetic pathway in a marine dinoflagellate and reveals its important complementary role to assist carbon assimilation for cell proliferation during the bloom period.

Novel Position-Specific 18O/16O Measurement of Carbohydrates. II. The Complete Intramolecular 18O/16O Profile of the Glucose Unit in a Starch of C4 Origin.

Information about plant photosynthetic carbon assimilation, physiology, and biochemistry is locked in the 18O/16O ratios of the individual positions of higher plants carbohydrates but is under-utilized, because of the difficulty of making these determinations. We report the extension of the wet chemistry approach we used to access the 18O/16O ratio of O-3 of glucose with a novel GC/Pyrolysis/IRMS-based method, to determine the 18O/16O ratios of O-4, O-5, and O-6. The O atoms (OH groups) at positions 1, 2, 5, and 6 of glucose were protected by acetonation (converting to 1,2;5,6-di-O-isopropylidene-glucofuranose, DAGF). The DAGF was then converted to 6-bromo-6-deoxy-1,2;3,5-di-O-isopropylidene-glucofuranose (6-bromoDAGF) with the simultaneous removal of O-6 with N-bromosuccinimide and triphenylphosphine. The DAGF was also methylated at O-3 with CH3I under the catalysis of NaH to 3-methylDAGF, which was then deacetonated to 1,2-O-isopropylidene-3-O-methyl-glucofuranose (3-methylMAGF). O-5 and O-6 were then removed as a whole from 3-methylMAGF by I2 oxidization under the catalysis of Ph3P and imidazole. Isotope mass balance was then applied to calculate the 18O/16O of O-5 and O-6 as a whole and O-6, respectively. Sampling at different stages of substrate conversion to product and applying a Rayleigh-type fractionation model were employed, when quantitative conversion of substrate was unachievable to calculate the δ18O of the converted substrate. Quantitative conversion of glucose with phenylhydrazine to phenylglucosazone also allowed for the calculation of δ18O2 by applying isotope mass balance between the two. A C4 starch-derived glucose intramolecular δ18O profile is now determined: O-3 is relatively enriched (by 12.16 mUr), O-4 is relatively depleted (by 20.40-31.11 mUr), and O-2 is marginally enriched (by 2.40 mUr) against the molecular average.

Novel GC/Py/GC/IRMS-Based Method for Isotope Measurements of Nitrate and Nitrite. I: Converting Nitrate to Benzyl Nitrate for δ18O Analysis.

The 18O/16O (and 15N/14N) ratio of natural nitrate (NO3-) and nitrite (NO2-) can be used to extract valuable information about their source and fate as environmental contaminants, their metabolism as macronutrients in plants and animals, and their behavior in the N biogeochemical cycle. We developed an accurate, precise, sensitive (minimum sample size: 0.2 µg NO3--equivalent), and reliable (minimal oxygen exchange, loss, or gain) method to selectively isolate and purify nitrate and nitrite from natural water, soil, air, and plant materials by strong anion exchange (SAX) for low- to normal-salinity samples or strong cation exchange (SCX) for high-salinity samples, followed by quantitative conversion to their respective benzyl esters, which can be separated and individually analyzed for δ18O (and potentially δ15N) by gas chromatography (GC)/pyrolysis/GC/isotope-ratio mass spectrometry (IRMS). The method compares favorably with the currently popular bacterial denitrification and chemical reduction methods, in terms of sensitivity and reliability, and has the potential to simultaneously measure δ15N and δ18O of nitrate and nitrite from natural samples of various origins.

Leaf transition from heterotrophy to autotrophy is recorded in the intraleaf C, H and O isotope patterns of leaf organic matter.

RATIONALE: Quantitatively relating 13 C/12 C, 2 H/1 H and 18 O/16 O ratios of plant α-cellulose and 2 H/1 H of n-alkanes to environmental conditions and metabolic status should ideally be based on the leaf, the plant organ most sensitive to environmental change. The fact that leaf organic matter is composed of isotopically different heterotrophic and autotrophic components means that it is imperative that one be able to disentangle the relative heterotrophic and autotrophic contributions to leaf organic matter. METHODS: We tackled this issue by two-dimensional sampling of leaf water and α-cellulose, and specific n-alkanes from greenhouse-grown immature and mature and field-grown mature banana leaves, taking advantage of their large areas and thick waxy layers. Leaf water, α-cellulose and n-alkane isotope ratios were then characterized using elemental analysis isotope ratio mass spectrometry (IRMS) or gas chromatography IRMS. A three-member (heterotrophy, autotrophy and photoheterotrophy) conceptual linear mixing model was then proposed for disentangling the relative contributions of the three trophic modes. RESULTS: We discovered distinct spatial leaf water, α-cellulose and n-alkane isotope ratio patterns that varied with leaf developmental stages. We inferred from the conceptual model that, averaged over the leaf blade, only 20% of α-cellulose in banana leaf is autotrophically laid down in both greenhouse-grown and field-grown banana leaves, while approximately 60% and 100% of n-alkanes are produced autotrophically in greenhouse-grown and field-grown banana leaves, respectively. There exist distinct lateral (edge to midrib) gradients in autotrophic contributions of α-cellulose and n-alkanes. CONCLUSIONS: Efforts to establish quantitative isotope-environment relationships should take into account the fact that the evaporative leaf water 18 O and 2 H enrichment signal recorded in autotrophically laid down α-cellulose is significantly diluted by the heterotrophically formed α-cellulose. The δ2 H value of field-grown mature banana leaf n-alkanes is much more sensitive than α-cellulose as a recorder of the growth environment. Quantitative isotope-environment relationship based on greenhouse-grown n-alkane δ2 H values may not be reliable.

The effect of processing medium on the 2 H/1 H of carbon-bound hydrogen in α-cellulose extracted from higher plants.

RATIONALE: Although the 2 H/1 H ratio of the carbon-bound hydrogens (C-Hs) in α-cellulose extracted from higher plants has long been used successfully for climate, environmental and metabolic studies, the assumption that bleaching with acidified NaClO2 to remove lignin before pure α-cellulose can be obtained does not alter the 2 H/1 H ratio of α-cellulose C-Hs has nonetheless not been tested. METHODS: For reliable application of the 2 H/1 H ratio of α-cellulose C-H, we processed plant materials representing different phytochemistries and photosynthetic carbon assimilation modes in isotopically contrasting bleaching media (with an isotopic difference of 273 mUr). All the isotope ratios were measured by elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). RESULTS: Our results show that H from the bleaching medium does appear in the final pure α-cellulose product, although the isotopic alteration to the C-H in α-cellulose due to the incorporation of processing H from the medium is small if isotopically "natural" water is used to prepare the processing medium. However, under prolonged bleaching such an isotope effect can be significant, implying that standardizing the bleaching process is necessary for reliable 2 H/1 H measurement. CONCLUSIONS: The currently adopted method for removing lignin for α-cellulose extraction from higher plant materials with acidified NaClO2 bleaching is considered acceptable in terms of preserving the isotopic fidelity if isotopically "natural" water is used to prepare the bleaching solution.

Novel Position-Specific 18O/16O Measurement of Carbohydrates. I. O-3 of Glucose and Confirmation of 18O/16O Heterogeneity at Natural Abundance Levels in Glucose from Starch in a C4 Plant.

The 18O/16O ratio at both molecular and positional levels in the carbohydrates of higher plants is a reliable proxy for the plant growth environment, and a potential indicator of the plant photosynthetic carbon assimilation mode, and its physiological, biochemical and metabolic status. The lack of exploitable nuclear resonance in 18O and 16O and the extremely low 17O abundance make the NMR-based PSIA (position-specific isotopic analysis) a significant challenge. In this Article, an alternative three-step wet chemistry based method for accessing the 18O/16O of glucose O-3 is presented. The O atoms (OH groups) at positions 1, 2, 5, and 6 were first protected by acetonation (converting glucose to 1,2;5,6-di- O-isopropylidene-glucofuranose). The protected glucose was then esterified at O-3 by thionoformylation. Subsequent Barton-McCombie deoxygenation quantitatively removed the O-3 from the protected sugar. Mass balance was then applied to calculate the 18O/16O of O-3 using the isotopic values of the protected sugar before and after the deoxygenation step. The method is innovative in that (i) isolation and purification of individual compounds for 18O by EA/Pyrolysis/IRMS analysis is unnecessary as the reaction mixture can be analyzed on a GC/Pyrolysis/IRMS; (ii) sample quantity is dramatically reduced; and (iii) the approach to access the O-3 isotopic signal can be easily expanded to other positions within glucose and other sugars. It was shown that O-3 is enriched by 12 mUr relative to the molecular average (O-2-O-6) for a glucose of C4 photosynthetic origin. We highlighted the potential applications of the intramolecular O isotopic heterogeneity of glucose this method revealed.

Histone modifications in FASN modulated by sterol regulatory element-binding protein 1c and carbohydrate responsive-element binding protein under insulin stimulation are related to NAFLD.

Non-alcoholic fatty liver disease (NAFLD) and its causal factors of hepatic insulin resistance (IR) and type 2 diabetes are rapidly growing worldwide. Developing new therapeutic methods for these conditions requires a comprehensive understanding between hepatic lipid metabolism and IR. Sterol regulatory element-binding transcription factor 1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis. They are induced by insulin, which directly binds to the sterol regulatory elements (SRE) or carbohydrate-responsive elements (ChORE) of the FASN promoter to induce its expression. The insulin pathway involved in NAFLD has well studied, but the role of histone modification in NAFLD is just beginning to be investigated, and there is minimal data regarding its involvement. In the current study, we investigated histone modifications in FASN under insulin stimulation. H3K4 hypertrimethylation and H3, H4 hyperacetylation in the FASN promoter was found in HepG2 cells and primary hepatocytes following insulin stimulation. We also found that insulin treatment induced the transcription factor SREBP-1c, ChREBP and could accelerate FASN expression by enhancing SREBP-1c, SRE, and ChREBP ChORE binding and inducing H3, H4 hyperacetylation at SRE, ChORE, or transcription start site (TSS) regions of the FASN promoter in hepatocellular carcinoma cell line (HepG2) and primary hepatocytes. Finally, histone acetylation could influence FASN expression by impairing SREBP-1c SRE and ChREBP ChORE binding.

Hydrogen isotopic differences between C3 and C4 land plant lipids: consequences of compartmentation in C4 photosynthetic chemistry and C3 photorespiration.

The 2 H/1 H ratio of carbon-bound H in biolipids holds potential for probing plant lipid biosynthesis and metabolism. The biochemical mechanism underlying the isotopic differences between lipids from C3 and C4 plants is still poorly understood. GC-pyrolysis-IRMS (gas chromatography-pyrolysis-isotope ratio mass spectrometry) measurement of the 2 H/1 H ratio of leaf lipids from controlled and field grown plants indicates that the biochemical isotopic fractionation (ε2 Hlipid_biochem ) differed between C3 and C4 plants in a pathway-dependent manner: ε2 HC4 > ε2 HC3 for the acetogenic pathway, ε2 HC4 < ε2 HC3 for the mevalonic acid pathway and the 1-deoxy-D-xylulose 5-phosphate pathway across all species examined. It is proposed that compartmentation of photosynthetic CO2 fixation into C4 mesophyll (M) and bundle sheath (BS) cells and suppression of photorespiration in C4 M and BS cells both result in C4 M chloroplastic pyruvate - the precursor for acetogenic pathway - being more depleted in 2 H relative to pyruvate in C3 cells. In addition, compartmentation in C4 plants also results in (i) the transferable H of NADPH being enriched in 2 H in C4 M chloroplasts compared with that in C3 chloroplasts for the 1-deoxy-D-xylulose 5-phosphate pathway pathway and (ii) pyruvate relatively 2 H-enriched being used for the mevalonic acid pathway in the cytosol of BS cells in comparison with that in C3 cells.

Clinical and Neuroimaging Features of Acute Ischemic Stroke in Cancer Patients.

BACKGROUND: The occurrence of acute ischemic stroke in cancer patients is not unusual. In clinical practice, acute ischemic stroke with cancer usually cannot be diagnosed promptly due to lack of specific markers. But for cancer patients, advanced prevention, accurate diagnosis and proper treatment of acute ischemic stroke are very important. The aim of the present study was to investigate the clinical and neuroimaging features of acute ischemic stroke in patients with cancer. METHODS: We conducted a retrospective review of all cancer-associated acute ischemic stroke patients (n = 46) admitted to the Affiliated Hospital of Academy of Military Medical Sciences between October 2011 and March 2015. A group of non-cancer acute ischemic stroke patients (n = 50) at the same period were selected randomly as control. The clinical and neuroimaging data were collected and compared between the 2 groups. RESULTS: Patients with cancer-associated stroke (CS) had a lower body mass index (23.26 ± 3.70 vs. 24.88 ± 2.83, p = 0.021) compared to non-cancer stroke (NC) patients. A lower proportion of CS patients suffered from hypertension (45.7 vs. 68.0%, p = 0.039) and hyperlipidemia (10.9 vs. 72.0%, p = 0.000) than the NC group. A higher proportion of CS patients had deep vein catheter (24.0 vs. 0%) before the onset of stoke than that of the NC group. Levels of hemoglobin, albumin and triglyceride were lower in CS groups compared with that of the NC group (p < 0.05). The prothrombin time, international normalized ratio, D-dimer and fibrinogen levels were significantly higher in the CS group than in the NC group (p < 0.05). As to the neuroimaging patterns, disperse lesions (OR 7.01; 95% CI 1.17-42.12; p < 0.05) was independently associated with CS. CONCLUSIONS: Cancer-associated ischemic stroke was different form conventional ischemic stroke in the aspect of clinical and neuroimaging manifestation. This phenomenon might be because of the embolic etiology of CS. These features together could become a clue to CS.

Capping the hydroxyl groups (-OH) of α-cellulose to reduce Hy-groscopicity for accurate 18O/16O measurement by EA/Py/IRMS.

Obtaining an accurate measurement of 18O/16O at natural abundance level for land plants-derived α-cellulose with the currently popular EA/Py/IRMS (elemental analysis/pyrolysis/isotope ratio mass spectrometry) method is a challenge due to the hygroscopic nature of the exposed hydroxyl groups, as the 18O/16O of adsorbed moisture is usually different from that of the α-cellulose and the relative amount of adsorbed moisture is sample- and relative humidity-dependent. To minimize the hygroscopicity-related measurement error, we capped the hydroxyl groups of α-cellulose by benzylation to various degrees and found that the 18O/16O ratio of α-cellulose increased with the degree of benzyl substitution (DS), consistent with the theoretical prediction that a reduced presence of exposed hydroxyl groups should lead to a more accurate (and therefore more reliable) α-cellulose 18O/16O measurement. We propose the establishment of a moisture adsorption-degree of substitution or percentage of oxygen-18O/16O ratio equation, based on the measurement of C%, O% and δ18O of variably capped α-cellulose, so that a robust correction can be made in a plant species- and laboratory conditions-specific manner. Failure to do so will lead to an average underestimate of α-cellulose δ18O by 3.5 mUr under "average" laboratory conditions.

Effect of antibiotic monensin on cell proliferation and IGF1R signaling pathway in human colorectal cancer cells.

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin. METHODS: Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1. RESULTS: We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells. CONCLUSION: Monensin could suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.

Dissolved organic nitrogen cycling revealed at the molecular level in the Bohai and Yellow Sea.

Marginal seas play a crucial role in the cycling of dissolved organic nitrogen (DON) between the terrestrial and marine environments. However, very few studies have considered the molecular transformation of DON in marginal seas, leaving the DON molecular modifications in its cycling largely unknown. Therefore, this study examined DON cycling in the Bohai Sea and Yellow Sea, two semi-closed marginal seas in northern China, using stable isotopes (δ15N and δ13C), optical characteristics, and molecular compositions. Compared to the Yellow Sea, the Bohai Sea had a weaker exchange with the open ocean, resulting in higher concentrations, lower δ15N, and more recalcitrant properties in DON. The DON cycling showed significant differences inside and outside the Yellow Sea Cold Water (YSCW). Degradation was the major sink of DON in the YSCW, during which more highly unsaturated compounds and carboxyl-rich alicyclic molecules were produced. Nitrogen atoms were found to be removed from the molecules with more N atoms to those with fewer ones during the DON degradation. This study discovered the molecular modifications in DON cycling and highlighted the intrinsic mechanisms in the cycling of DON in marginal seas.