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The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases. [Display omitted] ● Dietary sources, pharmacokinetics and toxicity of kaempferol. ● Kaempferol has the potential to prevent and treat several metabolic diseases. ● Diabetes, obesity, nonalcoholic fatty liver disease/ non-alcoholic steatohepatitis, atherosclerosis. ● NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. ● Future perspectives of kaempferol. [ABSTRACT FROM AUTHOR]

Abstract: The vacuolar H+-pyrophosphatase (VHP) is a proton pump, which energizes transport across the tonoplast. The contributions of VHP to ion, organic acid and sugar storage are unclear in fruit. Here we characterized the role of an apple vacuolar H+-pyrophosphatase gene (MdVHP1) in Na+, malate and soluble sugar accumulation. MdVHP1 expression was consistent with VHP activities in apple fruits at most developmental stages, and highly significantly correlated with Na+ concentration during fruit development. In apple fruits treated in vitro (i.e., fruit-bearing branches were cultured in Hoagland solution containing each of salt, malate and sucrose, respectively, or irradiated by blue light), MdVHP1 expression was significantly correlated with Na+ and malate transporter genes MdNHX1 and MdtDT, while subunit A of the vacuolar H+-ATPase (MdVHA-A) was significantly correlated with MdtDT and sucrose transporter gene (MdSUT1). In addition, MdVHP1 overexpression noticeably promoted Na+ and malate accumulation, but slightly increased soluble sugar accumulation in transgenic apple callus and tomato fruit, partially by regulating transporter genes MdNHX1, MdtDT and MdSUT1. Taken together, it appears that MdVHP1 favorably contributes to Na+, malate and soluble sugar accumulation in apple fruit. [Copyright &y& Elsevier]

Abstract: Cytosolic NAD-dependent malate dehydrogenase (cyMDH) is an enzyme crucial for malate synthesis in the cytosol. The apple MdcyMDH gene (GenBank Accession No. DQ221207) encoding the cyMDH enzyme in apple was cloned and functionally characterized. The protein was subcellularly localized to the cytoplasm and plasma membrane. Based on kinetic parameters, it mainly catalyzes the reaction from oxalacetic acid (OAA) to malate in vitro. The expression level of MdcyMDH was positively correlated with malate dehydrogenase (MDH) activity throughout fruit development, but not with malate content, especially in the ripening apple fruit. MdcyMDH overexpression contributed to malate accumulation in the apple callus and tomato. Taken together, our results support the involvement of MdcyMDH directly in malate synthesis and indirectly in malate accumulation through the regulation of genes/enzymes associated with malate degradation and transportation, gluconeogenesis and the tricarboxylic acid cycle. [Copyright &y& Elsevier]

Abstract: It is well-known that cytosolic NAD-dependent malate dehydrogenase (cyMDH; l-malate:NAD-oxidoreductase; EC 1.1.1.37) is an enzyme crucial for malic acid synthesis in the cytosol. Nothing is known about cyMDH in growth and stress tolerance. Here we characterised the role of the apple cyMDH gene (MdcyMDH, GenBank ID: DQ221207) in growth and tolerance to cold and salt stresses. MdcyMDH transcripts were highly accumulated in vigorously growing apple tissues, organs and suspension cells. In addition, MdcyMDH was sensitive to cold and salt stresses. MdcyMDH overexpression favourably contributed to cell and plant growth and conferred stress tolerance both in the apple callus and tomato. Taken together, our results indicated that MdcyMDH is involved in plant and cell growth as well as the tolerance to cold and salt stresses. [Copyright &y& Elsevier]

Abstract: Malic acid (MA) in apple fruit is the predominant organic acid associated with taste, flavour and juice quality. In this study, three full-length cDNAs of MdPEPC, MdVHA-A and MdcyME were cloned from apple fruit. They encoded cytosolic phosphoenolpyruvate carboxylase (MdPEPC, EC 4.1.1.31), subunit A of vacuolar H+-ATPase (MdVHA, EC 3.6.1.3) and cytosolic NADP-dependent malic enzyme (MdcyME, EC 1.1.1.40), respectively, for MA synthesis, transportation and degradation. Real-time quantitative PCR discovered that the expression levels of three genes varied with development stages, and that their expression patterns differed between low acid (LA) and high acid (HA) genotypes. In addition, enzyme activity assay showed that PEPC and VHA contributed positively to MA accumulation during fruit development both in LA and HA, while cyME did negatively. [Copyright &y& Elsevier]

Abstract: cDNA-AFLP, coupled with bulked segregant analysis (BSA), was used to screen genes expressed differently between low- and high-acid apple fruits from hybrids of ‘Toko’בFuji’ (Malus × domestica Borkh.). Sixty-four combinations of AFLP primers produced 2240 fragments, of which only one showed different expression between low- and high-acid fruits. The specific fragment was cloned and sequenced, and the complete cDNA was achieved by 3′ and 5′ rapid amplification of cDNA ends (RACE). The screened gene, designated as Mal-DDNA (GenBank accession no. DQ417661), showed no significant homology to clones in GenBank. The relatedness between fruit acidity and the transcription level of Mal-DDNA was identified by RT-PCR analysis on 30 hybrids. RT-PCR analysis indicated that Mal-DDNA transcripted in low-acid fruits at both early and ripe stages whereas in high- and mid-acid fruits, it did not transcript at the early stage. RNA gel-blot hybridization indicated that Mal-DDNA transcripted only in fruits and had clear difference between low- and high/mid-acid fruits. There was a good indication that Mal-DDNA existed as one copy in apple genome by Southern blot. Possible regulation of Mal-DDNA in apple fruit acidity is also discussed in the paper. [Copyright &y& Elsevier]

Grafting grapevines on resistant rootstocks is an effective tool to overcome biotic and abiotic stress constraints. The increasing consumer attention for fruit quality makes it indispensable to evaluate the impacts of resistant rootstocks on fruit quality. In this paper, berry quality modifications induced by the rootstocks were determined in the ‘Summer Black’ grape. Compared to the own-rooted vines, berry and cluster weights, berry texture and skin color were altered by the rootstocks to varying extents. Beta maintained TSS/TA and the contents of fructose, glucose and sucrose; in contrast, SO4, 5BB and 101–14 M impaired these parameters. The rootstocks modified berry nutrition and flavor by affecting the contents of cations and free amino acids. Aroma amount and components were largely modified by the rootstocks; Beta largely enhanced the amount of total aroma volatiles and ester compounds while SO4 imparted the reverse influence. Hence, berry nutrition and flavor were widely modified by the rootstocks; the Beta rootstock favored berry quality, and SO4 impaired berry quality; the effects of 5BB and 101–14 M on berry quality varied according to the different parameters. [ABSTRACT FROM AUTHOR]

In order to solve the performance limitations of traditional ship-type and cylindrical FPSO, this paper presents a new concept of sandglass-type FPSO. For the new sandglass-type floating model, firstly by using classic boundary element method based on wave potential theory, the effects of shape parameters on motion performance of sandglass-type model are studied. Then the wave frequency versus minimum heave motion RAO is selected as the critical design parameter to control heave motion of new floating model, and its convenient engineering estimation expression is theoretically and mathematically deduced. Furthermore, on this basis the design guideline for sandglass shape is analyzed and proposed. Next according to the information of a cylindrical FPSO, a sandglass-type floating model with the same basic function has been designed. Finally, by analyzing the numerical solution and experimental data, the numerical boundary element method and design guideline in this paper can be validated to be effective and accurate. Furthermore, it can be found that the sandglass-type design can obviously improve the hydrodynamic performance of FPSO. Thus this paper can provide an innovative engineering platform and a design proposal for the development of ocean oil and gas exploitation. [ABSTRACT FROM AUTHOR]

Abstract: Different concentrations of a sodium chloride spray were applied to the grapevine cultivar Kyoho to determine the effects of salinity on berry quality. The fruit’s fresh weight, relative water content, hardness and titratable acid were gradually enhanced with increased salt concentrations. Anthocyanin and soluble solids increased after treatment with moderate salinity (20 and 60mM); however, the results were reversed under high salinity (100 and 150mM). The soluble sugars glucose, fructose and sucrose increased after treatment with moderate salinity, whereas glucose and fructose declined under high salinity. For the six organic acids tested, their total levels were elevated by salinity, which increased the production of tartaric and malic acids. The aroma of the berry was extremely sensitive to salinity and showed a considerable decline in abundance and variety at 20mM NaCl. In summary, moderate salinity enhanced the overall berry quality, but decreased the aroma quality, whereas high salinity decreased the berry quality. [Copyright &y& Elsevier]

Summary: Vacuole H+-ATPases (VHAs) are plant proton pumps, which play a crucial role in plant growth and stress tolerance. In the present study, we demonstrated that the apple vacuolar H+-ATPase subunit A (MdVHA-A) is highly conserved with subunit A of VHA (VHA-A) proteins from other plant species. MdVHA-A was expressed in vegetative and reproductive organs. In apple in vitro shoot cultures, expression was induced by polyethylene glycol (PEG)-mediated osmotic stress. We further verified that over-expression of MdVHA-A conferred transgenic tobacco seedlings with enhanced vacuole H+-ATPase (VHA) activity and improved drought tolerance. The enhanced PEG-mimic drought response of transgenic tobacco seedlings was related to an extended lateral root system (dependent on auxin translocation) and more efficient osmotic adjustment. Our results indicate that MdVHA-A is a candidate gene for improving drought tolerance in plants. [Copyright &y& Elsevier]

Abstract: The survival of plant cells strongly depends on maintaining or adjusting the activity of the V-ATPase under drought conditions. In this study, a V-ATPase gene, VHA-B, was identified in an apple cDNA library, and an analysis of the deduced MdVHA-B protein sequence showed that it clusters with VHA-B proteins of other species. The expression of MdVHA-B was induced by abiotic stress, including abscisic acid (ABA), salinity, drought and low and high temperatures. Furthermore, the over-expression of MdVHA-B in transgenic tomato plants resulted in a high tolerance to drought stress, reduced relative water loss and malondialdehyde contents and increased levels of free proline and H+-ATPase activity compared to the wild-type plants (WT). Additionally, it has similar sensibility to exogenous ABA in transgenic MdVHA-B tomato seeds and seedlings, while more sensitive to polyethylene glycol in transgenic tomato compared with WT. This study indicates that MdVHA-B plays an important role in drought stress, yet may act independently of the ABA signaling pathway. [Copyright &y& Elsevier]

Abstract: The products of the FIS genes play important regulatory roles in diverse developmental processes, especially in seed formation after fertilization. In this study, a FIS-class gene MhFIE was isolated from apple. It encoded a predicted protein highly similar to polycomb group (PcG) protein FERTILIZATION-INDEPENDENT ENDOSPERM (FIE). MhFIE functioned as an Arabidopsis FIE homologue, as indicated by functional complementation experiment using Arabidopsis fie mutant. In addition, BiFC assay showed that MhFIE protein interacted with AtCLF. Furthermore, transgenic Arabidopsis ectopically expressing MhFIE produced less APETALA3 (AtAP3) and AGAMOUS (AtAG) transcripts than WT control, and therefore exhibited abnormal flower, seed development. These results suggested that polycomb complex including FIE and CLF proteins played an important role in reproductive development by regulating the expression of its downstream genes. In addition, it was found that MhFIE constitutively expressed in various tissues tested. Its expression levels were lower in apomictic apple species than the sexual reproductive species, suggested it was possibly involved into apomixis in apple. Furthermore, the hybrids of tea crabapple generated MhFIE transcripts at different levels. The parthenogenesis capacity was negatively correlated with MhFIE expression level in these hybrids. These results suggested that MhFIE was involved into the regulation of flower development and apomixis in apple. [Copyright &y& Elsevier]

Abstract: DELLA proteins are essential components of GA signal transduction. MhGAI1 was isolated from the tea crabapple (Malus hupehensis Redh. var. pingyiensis), and it was found to encode a DELLA protein. Mhgai1 is a GA-insensitive allele that was artificially generated via a bridge-PCR approach. Ectopic expression of Mhgai1 reduced plant stature, decreased spontaneous fruit-set-ratio and enhanced drought-tolerance in transgenic tomatoes. In addition, we examined the long-distance movement of Mhgai1 mRNAs by grafting experiments and SqRT-PCR analysis. It was found that the wild-type scions accumulated Mhgai1 transcripts trafficked from the transgenic rootstocks and therefore exhibited dwarf phenotypes. Furthermore, transgenic tomato plants produced more soluble solids, sugars and organic acids compared to wild-type tomatoes, suggesting an involvement of GA signaling in the regulation of fruit quality. Despite noticeable accumulation in the leaves and stems of WT scions, Mhgai1 transcripts were undetectable in flowers and fruit. Therefore, fruit quality was less influenced by the grafting of WT scions onto transgenic rootstocks than they were by the ectopic expression of Mhgai1 in transgenic rootstocks. Taken together, MhGAI1, which functions as a repressor in the GA signaling pathway, and its GA-insensitive allele, Mhgai1, could turn out to be useful targets for the genetic improvement of dwarfing rootstocks in apples. [Copyright &y& Elsevier]

Abstract: Vacuolar H+-translocating inorganic pyrophosphatase (VHP, EC 3.6.1.1) is an electrogenic proton pump, which is related to growth as well as abiotic stress tolerance in plants. In this study, a VHP gene MdVHP1 was isolated from apple. The alignment of nucleotide and amino acid sequences showed that it encoded a type I VHP protein. It expressed in vegetative and reproductive organs, and its expression was induced by salt, PEG-mediated osmotic stress, cold and heat in apple in vitro shoot cultures. MdVHP1 expression showed a similar pattern in different apple tissues, but different change dynamics in response to abiotic stresses, compared with MdVHP2 (another MdVHP gene in apple). MdVHP1 overexpression enhanced tolerance to salt, PEG-mimic drought, cold and heat in transgenic apple calluses, which was related to an increased accumulation of proline and decreased MDA content compared with control calluses. In addition, MdVHP1 overexpression confers improved tolerance to salt and drought in transgenic tomato, along with an increased ion accumulation, high RWC and low solute potential compared with wild type. These results indicate that MdVHP1 is an important regulator for plant tolerance to abiotic stresses by modulating internal stores of ions and solutes. [Copyright &y& Elsevier]