Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.

The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-ceramide, a bioactive sphingolipid that mediates several biological functions. Upon binding to cell surfaces, CGSPGWVRC triggers ceramide-rich platform formation, activates acid sphingomyelinase and ceramide production, without the associated downstream apoptotic signaling. We also show that the lung selectivity of CGSPGWVRC homing peptide is dependent on ceramide production in vivo. Finally, we demonstrate two potential applications for this lipid vascular targeting system: i) as a bioinorganic hydrogel for pulmonary imaging and ii) as a ligand-directed lung immunization tool against COVID-19. Thus, C16-ceramide is a unique example of a lipid-based receptor system in the lung vascular endothelium targeted in vivo by circulating ligands such as CGSPGWVRC.

A serine carboxypeptidase-like acyltransferase catalyzes consecutive four-step reactions of hydrolyzable tannin biosynthesis in Camellia oleifera.

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. CONCLUSIONS: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Microscopic and submicroscopic exploration of diplolepideae peristome structures in hygroscopic movement.

BACKGROUND: The Diplolepideae are the larger group within the Arthrodontae mosses, characterized by peristomes formed from residual cell walls. It is now understood that these peristomes exhibit diverse hygroscopic movements, playing a crucial role in spore release. However, the exact mechanism behind this movement remains unclear, lacking direct evidence. This study investigated the microscopic and submicroscopic structures of the peristomes in three Diplolepideae species: Hypopterygium fauriei (Besch.), Pylaisia levieri (Müll. Hal.) Arikawa and Regmatodon declinatus (Hook.) Brid. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to reveal the differences in their hygroscopic movement mechanisms. RESULTS: The three species exhibited distinct responses upon wetting: H. fauriei's exostome closed inwards, P. levieri' opened outwards, and R. declinatus' elongated significantly. These differences are attributed to the varying microfibril deposition in the exostome layers. Uniform deposition in the inner layer and minimal deposition in the outer layer enabled exostome opening upon wetting and closing when dry. Our findings suggest that the diastole and contraction of fine microfibrils in the exostome plates and ridges are the key drivers of hygroscopic movement. CONCLUSIONS: This study provides further evidence at both the structural and submicroscopic levels, contributing to the unraveling of the hygroscopic movement mechanism in Diplolepideae peristomes. This enhanced understanding sheds light on the relationship between peristome structure and function.

Exploring the role of biotic factors in regulating the spatial variability in land surface phenology across four temperate forest sites.

Land surface phenology (LSP), the characterization of plant phenology with satellite data, is essential for understanding the effects of climate change on ecosystem functions. Considerable LSP variation is observed within local landscapes, and the role of biotic factors in regulating such variation remains underexplored. In this study, we selected four National Ecological Observatory Network terrestrial sites with minor topographic relief to investigate how biotic factors regulate intra-site LSP variability. We utilized plant functional type (PFT) maps, functional traits, and LSP data to assess the explanatory power of biotic factors for the start and end of season (SOS and EOS) variability. Our results indicate that PFTs alone explain only 0.8-23.4% of intra-site SOS and EOS variation, whereas including functional traits significantly improves explanatory power, with cross-validation correlations ranging from 0.50 to 0.85. While functional traits exhibited diverse effects on SOS and EOS across different sites, traits related to competitive ability and productivity were important for explaining both SOS and EOS variation at these sites. These findings reveal that plants exhibit diverse phenological responses to comparable environmental conditions, and functional traits significantly contribute to intra-site LSP variability, highlighting the importance of intrinsic biotic properties in regulating plant phenology.

Resolved Raman sideband cooling of a single optically trapped cesium atom.

We developed a resolved Raman sideband cooling scheme that can efficiently prepare a single optically trapped cesium (Cs) atom in its motional ground states. A two-photon Raman process between two outermost Zeeman sublevels in a single hyperfine state is applied to reduce the phonon number. Our scheme is less sensitive to the variation in the magnetic field than the commonly used scheme where the two outermost Zeeman sublevels belonging to the two separate ground hyperfine states are taken. Fast optical pumping with less spontaneous emission guarantees the efficiency of the cooling process. After cooling for 50 ms, 82% of the Cs atoms populate their three-dimensional ground states. Our scheme improves the long-term stability of Raman sideband cooling in the presence of magnetic field drift and is thus suitable for cooling other trapped atoms or ions with abundant magnetic sublevels.

Detection of two homologous major QTLs and development of diagnostic molecular markers for sucrose content in peanut.

KEY MESSAGE: We identified two stable and homologous major QTLs for sucrose content in peanut, and developed breeder-friendly molecular markers for marker-assisted selection breeding. Sucrose content is a crucial quality trait for edible peanuts, and increasing sucrose content is a key breeding objective. However, the genetic basis of sucrose content in peanut remains unclear, and major quantitative trait loci (QTLs) for sucrose content have yet to be identified. In this study, a high-density genetic map was constructed based on whole-genome re-sequencing data from a peanut RIL population. This map consisted of 2,042 bins and 24,142 SNP markers, making it one of the most comprehensive maps to date in terms of marker density. Two major QTLs (qSCA06.2 and qSCB06.2) were identified, explaining 31.41% and 24.13% of the phenotypic variance, respectively. Notably, these two QTLs were located in homologous genomic regions between the A and B subgenomes. The elite allele of qSCA06.2 was exclusive to Valencia-type, while the elite allele of qSCB06.2 existed in other peanut types. Importantly, the distribution of alleles from two homologous QTLs in the RIL population and diverse germplasm accessions consistently demonstrated that only the combination of elite allelic genotypes from both QTLs/genes resulted in a significantly dominant phenotype, accompanied by a substantial increase in sucrose content. The newly developed diagnostic markers for these QTLs were confirmed to be reliable and could facilitate future breeding efforts to enhance sucrose content using marker-assisted selection techniques. Overall, this study highlights the co-regulation of sucrose content by two major homologous QTLs/genes and provides valuable insights into the genetic basis of sucrose in peanuts.

Identification of QTLs associated with very-long chain fatty acid (VLCFA) content via linkage mapping and BSA-seq in peanut.

KEY MESSAGE: Three major QTLs qA01, qB04.1 and qB05 for VLCFA content and their corresponding allele-specific markers will benefit peanut low VLCFA breeding, and a candidate gene Arahy.IF1JV3 was predicted. Peanut is a globally significant oilseed crop worldwide, and contains a high content (20%) of saturated fatty acid (SFA) in its seeds. As high level SFA intake in human dietary may increase the cardiovascular disease risk, reducing the SFA content in peanut is crucial for improving its nutritional quality. Half of the SFAs in peanut are very long-chain fatty acids (VLCFA), so reducing the VLCFA content is a feasible strategy to decrease the total SFA content. Luoaowan with extremely low VLCFA (4.80%) was crossed with Jihua16 (8.00%) to construct an F2:4 population. Three major QTLs including qA01, qB04.1 and qB05 for VLCFA content were detected with 4.43 ~ 14.32% phenotypic variation explained through linkage mapping. Meanwhile, three genomic regions on chromosomes B03, B04 and B05 were identified via BSA-seq approach. Two co-localized intervals on chromosomes B04 (100.10 ~ 103.97 Mb) and B05 (6.39 ~ 10.90 Mb) were identified. With markers developed based on SNP/InDel variations in qA01 between the two parents, the remaining interval was refined to 103.58 ~ 111.14 Mb. A candidate gene Arahy.IF1JV3 encoding a ß-ketoacyl-CoA synthase was found in qA01, and its expression level in Luoaowan was significantly lower than that in Jihua16. Allele-specific markers targeting qA01, qB04.1 and qB05 were developed and validated in F4 population, and an elite line with high oleic, low VLCFA (5.05%) and low SFA (11.48%) contents was selected. This study initially revealed the genetic mechanism of VLCFA content, built a marker-assisted selection system for low VLCFA breeding, and provided an effective method to decrease the SFA content in peanut.

Palladium-Catalyzed Cycloaddition Reactions of π-Allylpalladium 1,4-Dipoles with 1,3,5-Triazinanes: Access to Hexahydropyrimidines, 1,3-Oxazinanes, and 1,5-Diazocanes.

Palladium-catalyzed decarboxylation of 5-methylene-1,3-oxazinan-2-ones and 5-methylene-1,3-dioxan-2-ones to generate aza-π-allylpalladium and oxa-π-allylpalladium 1,4-dipoles for [4 + 2] cycloaddition reaction with 1,3,5-triazinanes was developed, affording a wide range of hexahydropyrimidine and 1,3-oxazinane derivatives in good to excellent yields (up to 99%). The acyclic sulfonamido-substituted allylic carbonates as aza-π-allylpalladium 1,4-dipole precursors also apply to the developed synthesized strategy, achieving the synthesis of hexahydropyrimidines. Moreover, the in situ-generated aza-π-allylpalladium 1,4-dipoles undergoing dimeric [4 + 4] cycloaddition were also demonstrated by the construction of 1,5-diazocane derivatives.

Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.

An overview of characteristic factors of biochar as a soil improvement tool in rice growth- A review.

Biochar is a growing tool for bioremediation and soil improvement applications. Researchers are focusing on biochar due to its efficacy, eco-friendly composition, and cost-effective solutions to a variety of environmental issues. In recent times biochar has been used in enhancing the soil, increasing nutrient content, and sequestering carbon in paddy cultivation soils. India and Southeast Asian countries consume paddy as a major source of food in large quantities. Therefore, improving the growth condition of paddy fields using an easily available and safe technique will help increase the production rate. This will fulfill the needs of the growing population. Biochar is developed by the thermal decomposition of organic materials in low or no oxygen through pyrolysis, gasification, and co-pyrolysis methods. It improves paddy soil fertility due to its special physicochemical properties such as porosity, high surface area, efficient slow release, nutrient holding capacity, and maintenance of soil microbiota. Considering the importance of biochar in paddy soil fertility, the present work reviews the sources of biochar, functionalization of biochar, mechanism, and beneficial role of biochar.

Removal of potentially toxic elements from water with the moss-tufa micro-filtration system.

Mosses are an integral component in the tufa sedimentary landscape. In this study, we investigated the use of the porous moss-tufa structure as a filtration system for removing potentially toxic elements (PTEs) from water samples. Three species of mosses that commonly grow on tufa were selected, and the PTEs filtered by the moss-tufa system were identified by inductively coupled plasma mass spectrometry. The bioconcentration factor (BCF) of mosses was calculated to compare the enrichment effects of different mosses on PTEs. Likewise, the level of PTEs flowing through the moss-tufa system was measured, and the water quality removal rate (C) was calculated accordingly. The results revealed that the moss-tufa system was mainly composed of Fissidens grandifrons Brid., Hydrogonium dixonianum P. C. Chen, and Cratoneuron filicinum (Hedw.) Spruce var. filicinum. Among these, Fissidens grandifrons Brid. reported the highest retention capacity for PTEs. Collectively, the moss-tufa filtration system displayed a strong retention capacity and removal rate of Mn, Pb, and Ni from the water sample. The removal of PTEs by the moss-tufa system was mainly based on the enrichment of mosses and the adsorption-retention ability of tufa. In conclusion, the moss-tufa micro-filtration system displayed the effective removal of PTEs from water samples and could be applied to control the levels of toxic elements in karst water bodies.

Influence of silver doping on pro-inflammatory and pro-fibrogenic effects of nano-titanium dioxide in murine lung.

Silver is usually loaded on nano-titanium dioxide (TiO2 ) through photodeposition method to enhance visible-light catalytic functions for environment purification. However, little is known about how the toxicity changes after silver doping and how the physicochemical properties of loaded components affect nanocomposite toxicity. In this study, Ag-TiO2 with different sizes and contents of silver particles were obtained by controlling photodeposition time (PDT) and silver addition amount. Pro-inflammatory and pro-fibrogenic responses of these photocatalysts were evaluated in male C57BL/6J murine lung. As a result, silver was well assembled on TiO2 , promoting visible-light catalytic activity. Notably, the size of silver particles increased with PDT. Meanwhile, toxicity results showed that pure TiO2 (P25) mainly caused neutrophil infiltration, while 2 wt/wt% silver-loaded TiO2 recruited more types of inflammatory cells in the lung. Both of them caused the increase of proinflammatory cytokines while decreasing the anti-inflammatory cytokine in bronchoalveolar lavage fluid. However, 2 wt/wt% silver doping also accelerated the lung pro-fibrogenic response of photocatalysts in the subacute phase from evidence of collagen deposition and hydroxyproline concentrations. Mechanistically, the overactivation of TGFBR2 receptors in TGF-ß/smads pathways by silver-loaded TiO2 rather than pure TiO2 may be the reason why silver-loaded TiO2 can promote pro-fibrogenic effect response. Intriguingly, the increased toxicity caused by silver doping can be rescued by increasing the size of the loaded silver or decreasing the silver amount. These results may be important for the new understanding of the toxicity of TiO2 -based photocatalysts.

Evaluation of the Reliability of the CCM-300 Chlorophyll Content Meter in Measuring Chlorophyll Content for Various Plant Functional Types.

Chlorophyll fluorescence is a well-established method to estimate chlorophyll content in leaves. A popular fluorescence-based meter, the Opti-Sciences CCM-300 Chlorophyll Content Meter (CCM-300), utilizes the fluorescence ratio F735/F700 and equations derived from experiments using broadleaf species to provide a direct, rapid estimate of chlorophyll content used for many applications. We sought to quantify the performance of the CCM-300 relative to more intensive methods, both across plant functional types and years of use. We linked CCM-300 measurements of broadleaf, conifer, and graminoid samples in 2018 and 2019 to high-performance liquid chromatography (HPLC) and/or spectrophotometric (Spec) analysis of the same leaves. We observed a significant difference between the CCM-300 and HPLC/Spec, but not between HPLC and Spec. In comparison to HPLC, the CCM-300 performed better for broadleaves (r = 0.55, RMSE = 154.76) than conifers (r = 0.52, RMSE = 171.16) and graminoids (r = 0.32, RMSE = 127.12). We observed a slight deterioration in meter performance between years, potentially due to meter calibration. Our results show that the CCM-300 is reliable to demonstrate coarse variations in chlorophyll but may be limited for cross-plant functional type studies and comparisons across years.

Enhanced and Sustainable Removal of Indoor Formaldehyde by Naturally Porous Bamboo Activated Carbon Supported with MnOx: Synergistic Effect of Adsorption and Oxidation.

Novel bamboo activated carbon (BAC) catalysts decorated with manganese oxides (MnOx) were prepared with varying MnOx contents through a facile one-step redox reaction. Due to the physical anchoring effect of the natural macropore structure for catalyst active components, homogeneous MnOx nanoparticles (NPs), and high specific surface area over catalyst surface, the BAC@MnOx-N (N = 1, 2, 3, 4, 5) catalyst shows encouraging adsorption and catalytic oxidation for indoor formaldehyde (HCHO) removal at room temperature. Dynamic adsorption and catalytic activity experiments were conducted. The higher Smicro (733 m2/g) and Vmicro/Vt (82.6%) of the BAC@MnOx-4 catalyst could facilitate its excellent saturated and breakthrough adsorption capacity (5.24 ± 0.42 mg/g, 2.43 ± 0.22 mg/g). The best performer against 2 ppm HCHO is BAC@MnOx-4 catalyst, exhibiting a maximum HCHO removal efficiency of 97% for 17 h without any deactivation as RH = 0, which is higher than those of other MnOx-based catalysts. The average oxidation state and in situ DRIFTS analysis reveal that abundant oxygen vacancies on the BAC@MnOx-4 catalyst could be identified as surface-active sites of decomposing HCHO into the intermediate species (dioxymethylene and formate). This study provides a potential approach to deposit MnOx nanoparticles onto the BAC surface, and this hybrid BAC@MnOx material is promising for indoor HCHO removal at room temperature.

Identification of histopathological classification and establishment of prognostic indicators of gastric adenocarcinoma based on deep learning algorithm.

The aim of this study is to establish a deep learning (DL) model to predict the pathological type of gastric adenocarcinoma cancer based on whole-slide images(WSIs). We downloaded 356 histopathological images of gastric adenocarcinoma (STAD) patients from The Cancer Genome Atlas database and randomly divided them into the training set, validation set and test set (8:1:1). Additionally, 80 H&E-stained WSIs of STAD were collected for external validation. The CLAM tool was used to cut the WSIs and further construct the model by DL algorithm, achieving an accuracy of over 90% in identifying and predicting histopathological subtypes. External validation results demonstrated the model had a certain generalization ability. Moreover, DL features were extracted from the model to further investigate the differences in immune infiltration and patient prognosis between the two subtypes. The DL model can accurately predict the pathological classification of STAD patients, and provide certain reference value for clinical diagnosis. The nomogram combining DL-signature, gene-signature and clinical features can be used as a prognostic classifier for clinical decision-making and treatment.

Insights into acylation mechanisms: co-expression of serine carboxypeptidase-like acyltransferases and their non-catalytic companion paralogs.

Serine carboxypeptidase-like acyltransferases (SCPL-ATs) play a vital role in the diversification of plant metabolites. Galloylated flavan-3-ols highly accumulate in tea (Camellia sinensis), grape (Vitis vinifera), and persimmon (Diospyros kaki). To date, the biosynthetic mechanism of these compounds remains unknown. Herein, we report that two SCPL-AT paralogs are involved in galloylation of flavan-3-ols: CsSCPL4, which contains the conserved catalytic triad S-D-H, and CsSCPL5, which has the alternative triad T-D-Y. Integrated data from transgenic plants, recombinant enzymes, and gene mutations showed that CsSCPL4 is a catalytic acyltransferase, while CsSCPL5 is a non-catalytic companion paralog (NCCP). Co-expression of CsSCPL4 and CsSCPL5 is likely responsible for the galloylation. Furthermore, pull-down and co-immunoprecipitation assays showed that CsSCPL4 and CsSCPL5 interact, increasing protein stability and promoting post-translational processing. Moreover, phylogenetic analyses revealed that their homologs co-exist in galloylated flavan-3-ol- or hydrolyzable tannin-rich plant species. Enzymatic assays further revealed the necessity of co-expression of those homologs for acyltransferase activity. Evolution analysis revealed that the mutations of the CsSCPL5 catalytic residues may have taken place about 10 million years ago. These findings show that the co-expression of SCPL-ATs and their NCCPs contributes to the acylation of flavan-3-ols in the plant kingdom.

Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection.

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.

Genome-wide analysis of UDP-glycosyltransferase gene family and identification of a flavonoid 7-O-UGT (AhUGT75A) enhancing abiotic stress in peanut (Arachis hypogaea L.).

BACKGROUND: Glycosylation, catalyzed by UDP-glycosyltransferase (UGT), was important for enhancing solubility, bioactivity, and diversity of flavonoids. Peanut (Arachis hypogaea L.) is an important oilseed and cash crop worldwide. In addition to provide high quality of edible oils and proteins, peanut seeds contain a rich source of flavonoid glycosides that benefit human health. However, information of UGT gene family was quite limited in peanut. RESULTS: In present study, a total of 267 AhUGTs clustered into 15 phylogenetic groups were identified in peanut genome. Group I has greatly expanded to contain the largest number of AhUGT genes. Segmental duplication was the major driving force for AhUGT gene family expansion. Transcriptomic analysis of gene expression profiles in various tissues and under different abiotic stress treatments indicated AhUGTs were involved in peanut growth and abiotic stress response. AhUGT75A (UGT73CG33), located in mitochondria, was characterized as a flavonoid 7-O-UGT by in vitro enzyme assays. The transcript level of AhUGT75A was strongly induced by abiotic stress. Overexpression of AhUGT75A resulted in accumulating less amount of malondialdehyde (MDA) and superoxide, and enhancing tolerance against drought and/or salt stress in transgenic Arabidopsis. These results indicated AhUGT75A played important roles in conferring abiotic stress tolerance through reactive oxygen species scavenging. CONCLUSIONS: Our research only not provides valuable information for functional characterization of UGTs in peanut, but also gives new insights into potential applications in breeding new cultivars with both desirable stress tolerance and health benefits.

LATS-regulated nuclear-cytoplasmic translocation of SREBP2 inhibits hepatocellular carcinoma cell migration and invasion via epithelial-mesenchymal transition.

Abnormal cholesterol synthesis plays a crucial role in the development of hepatocellular carcinoma (HCC). Sterol regulatory element-binding protein 2 (SREBP2) is involved in cholesterol synthesis by translocating to the nucleus where it stimulates the transcription of genes encoding enzymes involved in the cholesterol synthesis pathway. However, the function and regulatory mechanism of SREBP2 in HCC remain unclear. In this study, we aimed to gain a better understanding of the effects of SREBP2 and its functional mechanism in HCC. In 20 HCC patients, we demonstrated that SREBP2 was highly expressed in HCC specimens, relative to their peritumoral tissue, and that higher expression correlated positively with a poor prognosis in these patients. Moreover, higher SREBP2 levels in the nucleus enhanced the occurrence of microvascular invasion, whereas inhibition of SREBP2 nuclear translocation by fatostatin markedly suppressed the migration and invasion of HCC cells via the epithelial-mesenchymal transition (EMT) process. The effects of SREBP2 were subject to functional activity of large tumor suppressor kinase (LATS), whereas inhibition of LATS promoted nuclear translocation of SREBP2, as observed in hepatoma cells and a subset of subcutaneous tumor samples from nude mice. In conclusion, SREBP2 enhances the invasion and metastasis of HCC cells by promoting EMT, which can be strengthened by the repression of LATS. Therefore, SREBP2 may serve as a novel therapeutic target for HCC.