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Photodynamic therapy (PDT) is a promising cancer treatment modality with advantages of minimal invasiveness, repeatable therapy, and mild systemic toxicity. However, the limited bioavailability of photosensitizer (PS), tumor hypoxia, and the presence of antiapoptotic proteins in cancer cells, has hampered the efficiency of PDT. To address these limitations, herein, we developed a hyaluronic acid (HA) based nanosystem (HA-Ce6-Hemin@DNA-Protamine NPs, HCH@DP) loaded with chlorin e6 (Ce6, as PS), hemin (as mimetic catalase) and antisense oligonucleotide (ASO) of B-cell lymphoma 2 (Bcl-2) anti-apoptosis protein via a simple electrostatic self-assembly method for enhanced PDT of hypoxic solid tumors. The HCH@DP can target deliver the PS and ASO to tumor cells via cancer cell overexpressed HA receptors (i.e., CD44 or RHAMM). The Ce6 was released from HA-ss-Ce6 (HSC conjugates) after the reaction of cleavable disulfide bond with glutathione (GSH), which recovered the fluorescence and phototoxicity of Ce6 upon laser irradiation. Meanwhile, the catalase-mimicking hemin (degradation of HA-eda-hemin by hyaluronidase) decomposed the tumor overdressed endogenous H 2 O 2 to oxygen, which relieved tumor hypoxia and further overcome hypoxia-associated resistance of PDT. Furthermore, the inhibition of Bcl-2 expression by Bcl-2 ASO also greatly improved the cellular sensitivity to PDT. Both in vitro and in vivo results showed the tumor cell targeting ability, hypoxia relief and significantly enhanced antitumor PDT efficacy of HCH@DP for hypoxic tumor cells upon laser irradiation. Thus, by improving the target delivery of PS and ASO, relieving tumor hypoxia, and down-regulation of anti-apoptotic proteins, this HCH@DP nanosystem achieved enhanced PDT efficiency against hypoxic tumors. In general, our work provided a promising strategy to increase the utilization of key components (PS and oxygen) of PDT and the cell sensitivity to PDT by targeting co-delivery PS and oligonucleotides to tumor cells via a biocompatible HA based carrier, thereby achieving efficiently PDT treatment of hypoxic solid tumors with potential translation possibility. The efficiency of PDT against solid tumor is severely restricted by the limited bioavailability of photosensitizer, tumor hypoxia, and the presence of antiapoptotic proteins in cancer cells. Herein, we have developed an activatable hyaluronic acid (HA) based nanosystem (HA-Ce6-Hemin@DNA-Protamine NPs, HCH@DP) via a simple electrostatic self-assembly method for PDT treatment of hypoxic solid tumors. The HCH@DP enabled to target co-delivery of photosensitizer and antisense oligonucleotide to tumor cells, overcoming tumor hypoxia through in situ oxygen production and improving cellular sensitivity by efficiently reducing anti-apoptosis effect of cancer cells for synergistically enhancing PDT efficiency. This work suggests a promising strategy to develop small molecule drug and oligonucleotides co-delivery nanoplatforms for efficiently PDT treatment of hypoxic solid tumor. [Display omitted] [ABSTRACT FROM AUTHOR]

The yellowing of postharvest broccoli is the immediate manifestation of its quality deterioration, which can cause the loss of commodity value. This study employs a comprehensive analysis integrating transcriptomics and metabolomics to elucidate the effects and potential molecular mechanisms of exogenous leucine on pigment metabolism in postharvest broccoli stored at 10 ± 0.5 °C. Results demonstrate that leucine treatment significantly inhibited the decrease of chlorophyll content and the increase of carotenoid content. Leucine treatment also inhibited the respiration rate and maintained higher vitamin C content, total phenols content and DPPH radical scavenging activity of broccoli. Leucine treatment promoted chlorophyll biosynthesis by up-regulating UROD , PPOX , MC , CHLM , POR , DCVR , MT , and CAS expression while inhibiting chlorophyll liberation and degradation by up-regulating CABs expression and down-regulating NYC1 , CLH2 , PAO , and PPD expression. Additionally, exogenous leucine alleviated the damage of photosystem I, photosystem II, and photosynthetic electron transport chains in the thylakoid membrane. Furthermore, leucine treatment results in a lower transcriptional level of PDS , LCYB , crtZ , and ZEP , leading to reduced lycopene, zeaxanthin, and β-carotene content. Leucine treatment promotes the biosynthesis of carlactone, a strigolactone (SL) precursor, by up-regulating DWARF27 , CCD7 , and CCD8 expression. Additionally, leucine treatment down-regulated XDH expression and up-regulated CYP707A expression, inhibiting the biosynthesis and accumulation of abscisic acid (ABA). Consequently, our findings suggest that ABA and SLs may serve as crucial signaling factors in regulating chlorophyll and carotenoid metabolism in leucine-treated broccoli. This study introduces a novel method with theoretical support for delaying the yellowing process in postharvest broccoli. [Display omitted] • Multi-omics revealed the mechanism of leucine treatment (LT) on pigment metabolism. • BoCLH2 , not BoCLH1 , is the key to chlorophyll catabolism in postharvest broccoli. • LT delayed the damage of the thylakoid membrane and chlorophyll liberation. • LT inhibited the accumulation of ABA and promoted the biosynthesis of strigolactones. • ABA and strigolactones may be the key factors in regulating pigment metabolism. [ABSTRACT FROM AUTHOR]

To understand the effects and potential regulatory mechanism of leucine treatment on nucleic acid metabolism in yellowing and senescence process of postharvest broccoli, an integration profiling of transcriptome and metabolome was performed. Results showed that 5 mM leucine treatment delayed the increase in malondialdehyde content and inhibited the degradation of DNA and RNA, thus prolonging the shelf life of postharvest broccoli. A total of 92 differentially expressed genes and 9 differentially accumulated metabolites associated with nucleic acid metabolism were identified. Leucine treatment promoted DNA replication and enhanced DNA repair, thereby increasing the genome integrity and stability. Furthermore, leucine treatment augmented transcription and pre-mRNA processing by upregulating the expression of RNA polymerases , transcription factors , and splicing factors. The metabolomics results showed that the building blocks of DNA and RNA in leucine-treated broccoli were increased. In addition, exogenous leucine promoted mRNA translation and its subsequent recycling of mRNA, which upregulated the related protein biosynthesis and enhanced the energy utilization efficiency. Furthermore, leucine treatment enhanced the formation of small interfering RNA by upregulating the transcription of RNA polymerases V , 1 , 5 , and 6 , thus increasing the resistance of broccoli against RNA viruses. The results of this study shed light on nucleic acid metabolism in postharvest broccoli and its regulatory mechanism and provide a theoretical basis for studying broccoli preservation. [Display omitted] • Multi-omics revealed the mechanism of leucine on nucleic acid metabolism. • Leucine treatment (LT) promoted the replication and repair of DNA in broccoli. • LT enhanced the resistance against RNA viruses by promoting siRNA biosynthesis. • LT also promoted the pre-mRNA splicing and translation processes. • LT promoted the recycle of mRNA, resulting in alleviating the energy deficient. [ABSTRACT FROM AUTHOR]

In this paper, a new approach of bidirectional electro-migration rehabilitation (BIEM) using pulse currents was proposed. The effect of the duty cycle and frequency of the square wave pulse current on the BIEM was investigated. The results showed that the desalination efficiency was improved by 10 % with the decrease of duty ratio and frequency. Furthermore, With the increase of duty ratio and frequency, the hydrogen permeation of steel bars decreased by 28.5 %. More uniform desalination efficiency was obtained by using pulse current. The half-cell potential of the rebars was also measured and it was higher for the samples using pulse currents than for those using direct currents, indicating a lower risk of corrosion after pulse current treatment. The pH value of the concrete also increased during the BIEM process. • The amount of hydrogen permeation in the rebars of concrete repaired by pulse current is reduced. • Increasing frequency and decreasing duty cycle of pulse current make the desalination efficiency distributed more evenly. • Decreasing frequency and duty cycle of pulse current will increase the efficiency of chloride ions removal. [ABSTRACT FROM AUTHOR]

Vindoline (VDL) is an indole alkaloid, possessing hypoglycemic and vasodilator effects, and it is also the prodrug of many vinca alkaloids. In this paper, we analyzed in vivo (including plasma, urine, bile and faeces) and in vitro metabolic profile of VDL in rat with ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The chromatographic separation was performed on a C 18 column with a mobile phase consisted of 3 mM ammonium acetate buffer and acetonitrile at a flow rate of 300 μL/min. The mass spectral analysis was conducted in a positive electrospray ionization mode, and on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) were used in the biological samples analysis to trace all the potential metabolites of VDL. Twenty-five metabolites of VDL were detected by comparing with the blank sample, of which there were 2 sulfate conjugates. These data suggested that the biotransformation of VDL was deacetylation, oxidation, deoxidization, methylation, dealkylation and sulfate conjugation. This study provides useful information for further study of the pharmacology and mechanism of VDL, meanwhile, the research method can be widely applied to speculate structural features of the metabolites of other vinca alkaloids. [ABSTRACT FROM AUTHOR]

Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity ( r >0.995) within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1 (Rh1), and protopanaxatriol (Ppt) in bile, urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were 40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile. Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component. [ABSTRACT FROM AUTHOR]

Relation extraction task aims at detecting the semantic relation between a pair of entities in a given target sentence. However, previous methods lack the description of the relation definition, thus needing to model the implication of relations during training. To tackle this issue, we propose a natural language inference method for relation extraction. Given a premise and a hypothesis, the natural language inference task refers to predicting whether the facts in the premise necessarily imply the facts in the hypothesis. Specifically, for each relation type, we construct a relation description. These relation descriptions are the definition of relation, containing prior knowledge that helps model understand the meaning of relation. The given target sentence is viewed as the premise, and these descriptions are viewed as the hypotheses. Then model infers whether these hypotheses can be concluded from the premise. Based on the inference results, our model selects the relation corresponding to the most confident hypothesis as the prediction. Substantial experiments on SemEval2010 Task8 dataset demonstrate that the proposed method achieves state-of-the-art performance. • We propose a natural language inference method for relation extraction. • Our model is enhanced using prior relation knowledge without extra pre-training. • We design a joint inference and classification loss. • Our model achieves state-of-the-art results on SemEval2010 Task8 and TACRED. [ABSTRACT FROM AUTHOR]

A novel strategy has been developed to prepare hollow structured Nafion-modified-graphene/polyaniline (NGP) composites via interfacial assembly polymerization between an aqueous phase containing oxidant and an organic phase containing aniline monomers and Nafion-modified graphene. Fourier transform infrared (FTIR), Ultraviolet-visible (UV-vis) and X-ray diffraction (XRD) analyses confirmed the generation of polyaniline (PANI) on graphene during the interfacial polymerization. The morphological evolution of the product had been investigated by scanning electron microscopy (SEM) with respect to the reaction time, based on which a conceivable interpretation of the growth mechanism of the sphere architectures with composite component were given. The as-prepared hollow structured composites showed a good rate capability as electrode material for supercapacitor, and the as-designed interfacial assembly preparation strategy for such composites may provide a generic guideline in developing other graphene-base composite hollow spheres with different compositions. [ABSTRACT FROM AUTHOR]

Abstract: A facile method to prepare uniform polypyrrole (PPy) nanospheres is developed by using 3-chloroperbenzoic acid as oxidant, structure-induced reagent and dopant for polymerization of pyrrole without introducing extra acid, template and surfactant. The as-synthesized PPy nanospheres with an average diameter of 100–200 nm and conductivity about 10−2 S cm−1 are characterized by SEM, FTIR, UV–vis spectroscopy, XRD and elemental analysis in an effort to determine the identity of the nanospheres and the mechanism relevant to their formation and stabilization. Influences of experimental conditions on the morphology of the PPy nanospheres have been investigated. Via the high temperature pyrolyzation at 900 °C, the nitrogen-doped carbon nanospheres have been obtained from the PPy nanospheres precursors, which have a high conductivity of 10–100 S cm−1, showing a good potential as the electrode materials for high-performance supercapacitors due to their excellent electrochemical performance. [Copyright &y& Elsevier]

Abstract: The enantiomers separation of eight pharmaceutical racemates collected in Chinese Pharmacopoeia 2010 (Ch.P2010), including nitrendipine, felodipine, omeprazole, praziquantel, sulpiride, clenbuterol hydrochloride, verapamil hydrochloride and chlorphenamine maleate, was performed on chiral stationary phase of amylose ramification by high performance liquid chromatography (HPLC) on Chiralpak AD-H column and Chiralpak AS-H column with the mobile phase consisted of isopropanol and n-hexane. The detection wavelength and the flow rate were set at 254nm and 0.7mL/min, respectively. The effects of proportion of organic additives, alcohol displacer and temperature on the separation were investigated. The results indicated that eight chiral drugs were separated on chiral stationary phase of amylase ramification in normal phase chromatographic system. The chromatographic retention and resolution of enantiomers were adjusted by factors, including the changes of the concentration of alcohol displacer in mobile phase, organic alkaline modifier and column temperature. It was shown that the resolution was improved with reducing concentration of alcohol displacer. When the concentration of organic alkaline modifier was 0.2%, the resolution and the peak shape were fairly good. Most racemates mentioned above had the best resolution at column temperature of 25°C. The best temperature should be kept unchanged in the process of separation so as to obtain stable separation results. [Copyright &y& Elsevier]

Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease with a cancer-like phenotype. Competing endogenous RNA (ceRNA) networks extensively involve in its pathological processes. But rare ceRNA networks and profound molecular mechanisms have been revealed in PAH. The aim of this study was to illuminate the ceRNA networks in PAH. In this work, we have chosen the idiopathic PAH as an example. GSE15197 (mRNA) and GSE56914 (miRNA) from the Gene Expression Omnibus (GEO) were selected to explore key genes and novel ceRNA networks in PAH by a series of integrated bioinformatic analysis. To be more scientific, a part of pairs in identified ceRNA network were detected in hypoxia-induced HPASMCs. And the dual-luciferase assay was performed to certify the relationship between miRNAs and mRNAs. Totally, 311 differentially expressed genes (DEGs) were identified and functional enrichment analysis illuminated that the majority of DEGs were enriched in proliferation, anti-apoptosis, inflammation and cancer-related pathways. And 10 hub genes were determined via Cytohubba after PPI network construction. Sequentially, with stepwise reverse prediction and pan-cancer co-expression analysis from mRNA to LncRNA in TargetScan, miRNet, ENCORI (Starbase V3.0) databases, a crucially ceRNA network was identified including 14 LncRNAs, 2 miRNAs, and 3 mRNAs. Further, in hypoxia-induced HPASMCs, the alterations of mRNAs, miRNAs and LncRNAs and their relationship were in accordance with the results we identified. Consequently, the unique hub genes and ceRNA network we proposed may advance our understanding of the molecular mechanisms in PAH. [ABSTRACT FROM AUTHOR]

Two-dimensional carbon fiber reinforced silicon carbide (2D-C/SiC) composites are well-known for the high-temperature performance in aeronautical and aerospace fields, but they are susceptible to foreign object damage in service. Therefore, the high-temperature performance of pre-impacted 2D-C/SiC is closely connected with flight security. In this study, the pre-impact testing was conducted using a stress-reversal split Hopkinson bar, and the pre-impact energies were set from 0.1J to 0.9J. Subsequently, the pre-impacted specimens were heated for a period in the temperature-keeping procedure from 20 °C to 1600 °C. Oxidation kinetics of the pre-impacted 2D-C/SiC specimens were obtained based on the weight loss-temperature trends. Finally, the specimens were compressed under high temperatures at the strain rates from 10−4/s to 1000/s, so the residual compressive strength (RCS)-temperature trends were achieved. Hence, the correlation between the weight loss and the RCS was established. Interestingly, the pre-impact strengthening effect on the compressive strength was found. The results revealed that the RCS of 2D-C/SiC is affected by various parameters, providing new sights into the high-temperature damage tolerance of ceramic matrix composites. [Display omitted] • High-temperature damage tolerance of 2D-C/SiC composites. • Oxidation mechanism is not only controlled by the temperature. • Pre-impact gives rise to the increase in strength to some extent. • Strain rate effect on the strength is reduced by the increasing temperature-keeping duration. [ABSTRACT FROM AUTHOR]

Orientin and vitexin, 4’-hydroxyl-2-phenylchromen-4-one, are both major flavones derivatives found in Trollius ledebourii possessing definite pharmacological activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on Male Sprague Dawley rats of orientin and vitexin were tested, respectively. A systematic method based on ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was developed to characterize metabolites by means of electrospray ionization (ESI) mass spectrometry in positive ion mode. An on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was developed to observe probable relevant metabolites. By comparison of chromatographic behaviors with reference substances, exact protonated ions, MS/MS fragment ions and relevant literature, a total of 12 metabolites of orientin and 23 metabolites of vitexin were detected, respectively, which suggested that orientin is more metabolically stable than vitexin. Oxidation, methylation, acetylation, reduction, loss of C 6 H 10 O 5 and glucuronide conjugation were the major biotransformation routes of both of them in rats. More significant, glutamine conjugation, loss of CO and loss of CH 2 O were the unique metabolic pathways of vitexin compared with that of orientin for the first time. Besides, most metabolites were observed in rat urine and feces, implying that urine and feces were the active metabolic places for flavones. This is the first study on metabolisms of orientin and vitexin in vitro and in vivo simultaneously and the proposed metabolic pathways of them might provide further understanding of their pharmacological mechanisms and later study on their excretion. [ABSTRACT FROM AUTHOR]

Sophoricoside (SOPH) is an isoflavone glycoside isolated from Fructus Sophorae , and it has the effects on reproductive system. Currently, a strategy was firstly developed to identify the metabolites of SOPH in vitro and in vivo using ultra high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC–Q–TOF–MS/MS). Based on the proposed method, 60 metabolites were structurally characterized in vivo including 22 phase I and 38 phase II metabolites, and 4 metabolites in vitro were detected containing 2 phase I and 2 phase II metabolites. The results indicated that the metabolic pathways mainly included oxidation, reduction, hydrolysis, methylation, sulfate, glucuronide, glutamine and glycine conjugation. These results will provide basic data for future pharmacological and toxicology studies of SOPH and other isoflavone glycoside. [ABSTRACT FROM AUTHOR]

Nucleic acids (DNA and RNA) play crucial roles in guiding protein synthesis and plant resistance to biotic and abiotic stresses, but our current available understanding concerning on the role and function of nucleic acid metabolism, transcription and translation processes in postharvest fruit and vegetables remains largely unclear. In this study, an iTRAQ-based proteomics was used to investigate changes of protein abundance in postharvest broccoli under 40% O 2 + 5% CO 2 , 20% O 2 + 5% CO 2 and 5% O 2 + 5% CO 2 treatments. A total of 128 differentially expressed proteins (fold change ≥ 1.2) were identified. High O 2 stress reduced the DNA level by down-regulating the expression of proteins involved in DNA replication and up-regulating the expression of proteins DNA degradation. The decrease of DNA content, inhibition of transcription and promotion of RNA degradation induced by high O 2 stress further led to the mass loss of RNA content in postharvest broccoli. Additionally, high O 2 stress suppressed RNA processing, transport and translation and activated the expression of 20 S and 26 S proteasome, thereby accelerating the decrease of protein levels in postharvest broccoli. The decrease of DNA and RNA content might be related to the early yellowing and senescence in postharvest broccoli. This study revealed that the effect and mechanism of high O 2 stress on DNA and RNA metabolism, transcription and translation processes, and the role of these metabolic pathway on senescence in postharvest broccoli. [Display omitted] • Proteomic revealed the effects of high O 2 stress on DNA, RNA and protein metabolism. • High O 2 stress accelerated the degradation of DNA and RNA. • High O 2 stress decreased protein by activating 20 S and 26 S proteasomes activities. • The decrease of DNA and RNA might be the key reason for broccoli senescence. [ABSTRACT FROM AUTHOR]

Yellowing is always accompanied by chlorophyll degradation and carotenoid accumulation, which is an important indicator for evaluating the quality and commercial value of postharvest broccoli. Elevated CO 2 treatment was applied in broccoli heads to investigate its effect and mechanism on pigment metabolism. The results demonstrated that 30% CO 2 treatment maintained higher nutritional quality by increasing phenols and flavonoids contents and delayed the yellowing by alleviating chlorophyll loss and carotenoid accumulation. The chlorophyll molecule could also be continuously synthesized in postharvest broccoli. The up-regulation of chlorophyll synthesis genes (BoMCase , BoChlM , BoChlE , BoPOR , BoDVR and BoChlG) and chlorophyll combination genes (BoCAB1 and BoCAB2) and the down-regulation of chlorophyll degradation genes (BoSGR1 , BoNYC1 , BoPPH , BoPAO and BoRCCR) were observed in postharvest broccoli treated with 30% CO 2. Additionally, 30% CO 2 treatment down-regulated the expression of BoPSY , BoLCYB , BoCHYB and BoVDE , thereby inhibiting zeaxanthin and β-carotene biosynthesis. This study provided new insights into chlorophyll biosynthesis after harvest and the regulation of elevated CO 2 on pigment metabolism in postharvest broccoli. • This study revealed the effect of CO 2 treatment on yellowing of postharvest broccoli. • Proper CO 2 delayed chlorophyll degradation by suppressing chlorophyll catabolism. • The expression of chlorophyll anabolic genes and BoCAB was induced by 30% CO 2. • 30% CO 2 inhibited the accumulation of zeaxanthin and β-carotene. • Broccoli yellowing is due to the of chlorophyll decrease and carotenoid increase. [ABSTRACT FROM AUTHOR]

• Proteomic analysis was used to reveal the senescence mechanism under elevated O 2. • A total of 54 proteins related to broccoli senescence were identified and classified. • Elevated O 2 up-regulated the EMP, the TCA cycle, and OXPHOS to produce more ATP. • Elevated O 2 destroyed the vesicle transport system of synthetic proteins and lipids. • Energy waste is responsible for rapid broccoli senescence under high O 2 stress. Ripening and senescence of horticultural products involve in different metabolic processes, but the understanding of these processes at the proteomics level remains unknown. In this study, a proteomic technique was used for investigating the expression changes of proteins in broccoli heads under 5% O 2 + 5% CO 2 , 20% O 2 + 5% CO 2 and 40% O 2 + 5% CO 2 treatments. A total of 54 differentially expressed proteins (fold change ≥1.5) associating with ripening and senescence were identified. The results indicated that high O 2 treatment promoted the degradation of carbohydrate, lipid, amino acid and protein, thereby providing more substrates for energy production, in turn, accelerated the biosynthesis of lipid, amino acid, and protein. However, high O 2 treatment disrupted vesicle and transmembrane transport and inhibited the transport of these metabolites to specific organelles, thereby resulting in energy waste in postharvest broccoli heads. Therefore, we concluded that energy waste caused by the damage of transmembrane transport might be responsible for broccoli head ripening and senescence under high O 2 stress. In summary, this study revealed a comprehensive and interacting metabolic network of postharvest broccoli head ripening and senescence under high O 2 stress, which could be used for the development of postharvest preservation technologies to control ripening and senescence of horticultural products. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Amino acid metabolism in broccoli was revealed by proteomics under high O 2 stress. • High O 2 stress induced amino acid degradation to support the TCA cycle. • High O 2 stress disrupted the urea cycle , thereby aggravating ammonium toxicity. • Amino acids, the precursors of glucosinolate, were reduced under high O 2 stress. • High O 2 stress induced ethylene anabolism and methionine catabolism. To better understand the global changes of amino acid catabolism and anabolism in broccoli in response to high O 2 stress, iTRAQ-based proteomics combined with amino acid analysis was used to investigate the broccoli proteome at 0 and 4 d after treatment with different O 2 concentrations (5% O 2 + 5% CO 2 , 20% O 2 + 5% CO 2 and 40% O 2 + 5% CO 2) at 20℃. A total of 106 proteins with changes ≥ 1.2-fold in abundance were observed. Amino acid anabolism was significantly suppressed by high O 2 stress, while catabolism was enhanced. High O 2 stress-induced amino acid metabolism promoted the conversion of Met to ethylene and the degradation of amino acids to intermediate metabolites of the TCA cycle, thereby suppressing glucosinolate biosynthesis. However, the up-regulation of arginase and urease induced by high O 2 stress aggravated ammonium toxicity. These findings enhance our understanding of high O 2 stress-induced amino acid metabolism, as well as the effects of amino acid metabolism on broccoli senescence. [ABSTRACT FROM AUTHOR]

• Proteomic analysis was used to reveal the yellowing mechanism under elevated O 2. • 189 proteins related to broccoli yellowing were identified and classified. • Elevated O 2 might damage the thylakoid structure and thus to promote yellowing. • Elevated O 2 destroyed the photosystem and led to chlorophyll photobleaching. • The oxidative damage of chloroplast was aggravated by high O 2 stress. Controlled atmosphere storage has been proved to be an effective measure to regulate chlorophyll degradation. The obvious inhibitory effect of CO 2 on chlorophyll degradation was widely studied, but information available on the promotion of chlorophyll degradation by elevated O 2 was limited. The present work aimed to investigate the regulation of different O 2 concentrations on yellowing of broccoli heads during storage by physiology and proteomics. As expected, 40% O 2 + 5% CO 2 treatment promoted the chlorophyll degradation and carotenoid synthesis, and thus to accelerate the yellowing of broccoli heads. In addition, elevated O 2 decreased the ascorbic acid, glucosinolate, and flavonoid contents and increased the MDA content. A total of 189 proteins related to the yellowing of broccoli heads were identified as differentially expressed proteins (fold change ≥1.20 or ≤0.83). These proteins were mainly associated with pigment metabolism, thylakoid structure, photosynthetic system, chloroplast ribosome, antioxidant substance metabolism, and antioxidant enzyme metabolism. The proteomics results showed 40% O 2 + 5% CO 2 treatment disrupted antioxidant metabolism and aggravated oxidative stress compared with 5% O 2 + 5% CO 2 and 20% O 2 + 5% CO 2 treatments, thus leading to the destruction of photosystems I and II, thylakoid membrane, and chloroplast ribosome in broccoli heads. In addition, 40% O 2 + 5% CO 2 treatment accelerated the yellowing of postharvest broccoli heads by down-regulating chlorophyll b iosynthetic pathway and the expression of apolipoproteins (light-harvesting complex I, II, and oxygen-evolving enhancer protein) and ribulose-1,5-bisphosphate carboxylase (Rubisco), and up-regulating chlorophyll degradation and carotenoid biosynthetic pathways. This study might improve our understanding of yellowing acceleration mechanisms of broccoli heads by elevated O 2 , thereby promoting the development of new broccoli heads preservation technology. [ABSTRACT FROM AUTHOR]

Abstract: Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20. This compound significantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen–glucose deprivation in vitro. Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood–brain barrier of rats. [Copyright &y& Elsevier]

• Elevated O 2 concentration accelerated chlorophyll degradation. • H 2 O 2 content decreased along with O 2 concentration elevated. • H 2 O 2 down-regulated the expression of BoSGR1, BoNYC, BoPPH, BoPAO , and BoRCCR. • Elevated O 2 concentration enhanced Chl-POX activity at the transcription level. • Chl oxidative dominated the Chl degradation under elevated O 2 concentration. Postharvest broccoli heads undergo yellowing quickly in unsuitable conditions, which diminishes their quality and commercial value. We investigated the pattern and molecular regulatory mechanism of chlorophyll (Chl) degradation in broccoli under elevated O 2 controlled atmosphere. As results, the 40% O 2 + 5% CO 2 treatment accelerated the Chl degradation and the change in color of postharvest broccoli heads, while the 5% O 2 + 5% CO 2 treatment delayed the yellowing. The results indicated that Chl degradation pattern of postharvest broccoli heads concurrently involved the Pheide a oxygenase (PAO)/phyllobilin and oxidative degradation pathways, and the latter might be the dominant pathway of Chl degradation. The regulatory mechanism of elevated O 2 on Chl degradation may be related to its ability to accelerate cell damage and death, destroy the light-harvesting complex II, and promote up-regulation of genes in the PAO/phyllobilin and oxidative degradation pathways. In contrast, low O 2 treatment may down-regulate the expression of Chl degradation-related genes by increasing H 2 O 2 content, thus delaying the yellowing of broccoli heads. [ABSTRACT FROM AUTHOR]

Exsomes play a significant role in increasing pathophysiological processes by delivering their content. Recently, a variety of studies have showed exosomal microRNAs (miRNAs) are involved in pulmonary hypertension (PH) notably. In this study, we found that exosomal miR-211 was overexpressed in hypoxia-induced PH rats but its intrinsic regulation was unclear. Therefore, our aim was to reveal the underlying mechanism which overexpressed exosomal miR-211 targeted in the development of PH. 18 male SD rats were randomly divided into normoxia and hypoxia group, housed in normal or hypoxic chamber for 3 weeks respectively. Then, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index(RV/(LV + S)), the percentage of medial wall area (WA%) and the percentage of medial wall thickness (WT%) were measured. Expression of miR-211 in exosomes was detected by qRT-PCR. Expression of Ca2+/calmodulin-dependent kinase1(CaMK1)and peroxisome proliferator-activated receptors-γ(PPAR-γ)in lung tissue were detected by Western blot(WB); After miR-211 overexpressed exosomes were injected to rats through caudal vein, mPAP, PVR, RV/(LV + S), WA% and WT% were also measured. Sequentially, hypoxia rats were injected with lentivirus riched in miR-211 inhibitor via tail vein, and PH-related indicators were measured. In vitro, after miR-211 was positively or negatively regulated in pulmonary arterial smooth muscle cell (PASMC) by plasmid transfection, proliferation of PASMC was detected by CCK8, as well as the expression of CaMK1 and PPAR- γ. Further, the relationship between CaMK1 and miR-211 was verified by Dual-Luciferase assay. And the regulatory relationship of CaMK1/PPAR- γ aixs was demonstrated in PASMC. Evident increases of mPAP, PVR, RVHI, WT% and WA% were observed with hypoxia administration. And the concentration of plasma exosomes in hypoxia rats was increased and positively correlated with the above indexes. miR-211 in exosomes of PH was upregulated while the expression of CaMK1 and PPAR-γ decreased in lung tissues. Further, injection of exosomes overexpressed with miR-211 demonstrated that exosomal miR-211 aggravated PH while inhibition of miR-211 attenuated PH in rats. In vitro, overexpression of miR-211 promoted the proliferation of PASMC and inhibited expression of CaMK1 and PPAR-γ in PASMC. And Dual-luciferase assay demonstrated that CaMK1 was a downstream gene of miR-211. Plasmid transfection experiments indicated that CaMK1 can promote PPAR-γ expression. Exosomal miR-211 promoted PH via inhibiting CaMK1/PPAR-γ axis, promoting PASMC proliferation in rats. Unlabelled Image • miR-211 overexpression along with plasma exosomes increase in hypoxia-induced PAH rats. • miR-211 overexpression promoted the proliferation of PASMC. • miR-211 down-regular expression of CaMK1, CaMK 1 further inhibits PPAR-γ expression. [ABSTRACT FROM AUTHOR]