Isochlorogenic acid A ameliorated lead-induced anxiety-like behaviors in mice by inhibiting ferroptosis-mediated neuroinflammation via the BDNF/Nrf2/GPX4 pathways.

Lead (Pb) is a common environmental neurotoxicant that causes behavioral impairments in both rodents and humans. Isochlorogenic acid A (ICAA), a phenolic acid found in a variety of natural sources such as tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including protective effects on the lungs, livers, and intestines. The objective of this study was to investigate the potential neuroprotective effects of ICAA against Pb-induced neurotoxicity in ICR mice. The results indicate that ICAA attenuates Pb-induced anxiety-like behaviors. ICAA reduced neuroinflammation, ferroptosis, and oxidative stress caused by Pb. ICAA successfully mitigated the Pb-induced deficits in the cholinergic system in the brain through the reduction of ACH levels and the enhancement of AChE and BChE activities. ICAA significantly reduced the levels of ferrous iron and MDA in the brain and prevented decreases in GSH, SOD, and GPx activity. Immunofluorescence analysis demonstrated that ICAA attenuated ferroptosis and upregulated GPx4 expression in the context of Pb-induced nerve damage. Additionally, ICAA downregulated TNF-α and IL-6 expression while concurrently enhancing the activations of Nrf2, HO-1, NQO1, BDNF, and CREB in the brains of mice. The inhibition of BDNF, Nrf2 and GPx4 reversed the protective effects of ICAA on Pb-induced ferroptosis in nerve cells. In general, ICAA ameliorates Pb-induced neuroinflammation, ferroptosis, oxidative stress, and anxiety-like behaviors through the activation of the BDNF/Nrf2/GPx4 pathways.

Silencing of cysteine and serine rich nuclear protein 1 inhibits apoptosis, senescence and collagen degradation in human-derived vaginal fibroblasts in response to oxidative stress or DNA damage.

Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H2O2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP.

Lead-induced liver fibrosis and inflammation in mice by the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways: the role of Isochlorogenic acid a.

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor ß1 (TGF-ß1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways.

Relish involved in immunity and larval survival in the willow leaf beetle Plagiodera versicolora.

BACKGROUND: Insects mainly rely on innate immunity against pathogen infection. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. However, the mechanisms behind the immunodeficiency pathway (IMD) remain poorly understood. RESULTS: In this study, we obtained a Relish gene from transcriptome analysis. Tissue and instar expression profiles were subsequently obtained using quantitative real-time polymerase chain reaction analysis. The results showed that Relish has high expression levels in eggs, larvae and adults, and especially in fat bodies. Transcripts of the tested antimicrobial peptides (AMPs), defensin1, defensin2 and attacin2 were downregulated by dsRelish. Knockdown of Relish led to greater mortality in larvae after Staphylococcus aureus infection. In addition, we performed bacterial 16S ribosomal RNA-based high-throughput sequencing. The results showed that the relative abundance of some gut bacteria was significantly altered after dsRelish ingestion. CONCLUSION: This study provides a greater understanding of the IMD signaling pathway, facilitating functional studies of Relish in P. versicolora. Moreover, a genetic pest management technique might be developed using Relish as a lethal gene to control the pest P. versicolora. © 2024 Society of Chemical Industry.

Printing GelMA bioinks: a strategy for buildingin vitromodel to study nanoparticle-based minocycline release and cellular protection under oxidative stress.

Owing to its thermoresponsive and photocrosslinking characteristics, gelatin methacryloyl (GelMA)-based biomaterials have gained widespread usage as a novel and promising bioink for three-dimensional bioprinting and diverse biomedical applications. However, the flow behaviors of GelMA during the sol-gel transition, which are dependent on time and temperature, present significant challenges in printing thick scaffolds while maintaining high printability and cell viability. Moreover, the tunable properties and photocrosslinking capabilities of GelMA underscore its potential for localized drug delivery applications. Previous research has demonstrated the successful incorporation of minocycline (MH) into GelMA scaffolds for therapeutic applications. However, achieving a prolonged and sustained release of concentrated MH remains a challenge, primarily due to its small molecular size. The primary aim of this study is to investigate an optimal extrusion printing method for GelMA bioink in extrusion bioprinting, emphasizing its flow behaviors that are influenced by time and temperature. Additionally, this research seeks to explore the potential of GelMA bioink as a carrier for the sustained release of MH, specifically targeting cellular protection against oxidative stress. The material properties of GelMA were assessed and further optimization of the printing process was conducted considering both printability and cell survival. To achieve sustained drug release within GelMA, the study employed a mechanism using metal ion mediation to facilitate the interaction between MH, dextran sulfate (DS), and magnesium, leading to the formation of nanoparticle complexes (MH-DS). Furthermore, a GelMA-basedin vitromodel was developed in order to investigate the cellular protective properties of MH against oxidative stress. The experimental results revealed that the printability and cell viability of GelMA are significantly influenced by the printing duration, nozzle temperature, and GelMA concentrations. Optimal printing conditions were identified based on a thorough assessment of both printability and cell viability. Scaffolds printed under these optimal conditions exhibited exceptional printability and sustained high cell viability. Notably, it was found that lower GelMA concentrations reduced the initial burst release of MH from the MH-dextran sulfate (MH-DS) complexes, thus favoring more controlled, sustained release profiles. Additionally, MH released under these conditions significantly enhanced fibroblast viability in anin vitromodel simulating oxidative stress.

Local delivery of AdipoRon from self-assembled microparticles to inhibit myelin lipid uptake and to promote lipid efflux from rat macrophages.

Objective.Abundant lipid-laden macrophages are found at the injury site after spinal cord injury (SCI). These cells have been suggested to be pro-inflammatory and neurotoxic. AdipoRon, an adiponectin receptor agonist, has been shown to promote myelin lipid efflux from mouse macrophage foam cells. While it is an attractive therapeutic strategy, systemic administration of AdipoRon is likely to exert off-target effects. In addition, the pathophysiology after SCI in mice is different from that in humans, whereas rat and human SCI share similar functional and histological outcomes. In this study, we evaluated the effects of AdipoRon on rat macrophage foam cells and developed a drug delivery system capable of providing sustained local release of AdipoRon to the injured spinal cord.Approach.Rat macrophages were treated with myelin debris to generate anin vitromodel of SCI foam cells, and the effects of AdipoRon treatment on myelin uptake and efflux were studied. AdipoRon was then loaded into and released from microparticles made from dextran sulfate and fibrinogen for sustained release.Main results.AdipoRon treatment not only significantly promotes efflux of metabolized myelin lipids, but also inhibits uptake of myelin debris. Myelin debris alone does not appear to be inflammatory, but myelin debris treatment potentiates inflammation when administered along with pro-inflammatory lipopolysaccharide (LPS) and interferon-γ. AdipoRon significantly attenuated myelin lipid-induced potentiation of inflammation. Bioactive AdipoRon can be released in therapeutic doses from microparticles.Significance.These data suggest that AdipoRon is a promising therapeutic capable of reducing lipid accumulation via targeting both myelin lipid uptake and efflux, which potentially addresses chronic inflammation following SCI. Furthermore, we developed microparticle-based drug delivery systems for local delivery of AdipoRon to avoid deleterious side effects. This is the first study to release AdipoRon from drug delivery systems designed to reduce lipid accumulation and inflammation in reactive macrophages after SCI.

Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.

Temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) may present as comorbid conditions, but treatment options are ineffective. The purpose of this study was to investigate whether valproate (VPA) attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress, which represents a model of pain associated with TMD and FMS comorbidity, and to explore the potential mechanisms. The results showed that VPA inhibited somatic hyperalgesia induced by orofacial inflammation combined with stress, and down-regulated the interleukin-6 (IL-6) expression in the L4-L5 spinal dorsal horn of female rats. The anti-nociceptive effect of VPA was blocked by single or 5 consecutive day intrathecal administration of recombinant rat IL-6. Orofacial inflammation combined with stress up-regulated the ratio of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) to STAT1 (p-STAT1/STAT1) in the spinal cord. VPA did not affect the STAT1 expression, while it down-regulated the ratio of p-STAT1/STAT1. The expression of STAT3 and the ratio of p-STAT3/STAT3 were not affected by orofacial inflammation combined with stress and VPA treatment. Intrathecal administration of exogenous IL-6 up-regulated the ratio of p-STAT1/STAT1. These data indicate that VPA attenuated somatic hyperalgesia induced by orofacial inflammation combined with stress via inhibiting spinal IL-6 in female rats, and the mechanism may involve the alteration of activation status of spinal STAT1. Thus, VPA may be a new candidate analgesic that targets IL-6 and STAT1 for the treatment of pain associated with the comorbidity of TMD and FMS.

Pediatric Hepatoblastoma After Neoadjuvant Chemotherapy: Diagnostic Performance of MR in Staging POSTTEXT and Vascular Involvement.

BACKGROUND: The assessment of resectability after neoadjuvant chemotherapy of hepatoblastoma is dependent on Post-Treatment EXTENT of Disease (POSTTEXT) staging and its annotation factors P (portal venous involvement) and V (hepatic venous/inferior vena cava [IVC] involvement), but MR performance in assessing them remains unclear. PURPOSE: To assess the diagnostic performance of contrast-enhanced MR imaging for preoperative POSTTEXT staging and diagnosing vascular involvement in terms of annotation factors P and V in pediatric hepatoblastoma following neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Thirty-five consecutive patients (17 males, median age, 24 months; age range, 6-98 months) with proven hepatoblastoma underwent preoperative MR imaging following neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 3.0 T; T2-weighted imaging (T2WI), T2WI with fat suppression, diffusion weighted imaging, radial stack-of-the-star/Cartesian 3D Dixon T1-weighted gradient echo imaging. ASSESSMENT: Three radiologists independently assessed the POSTTEXT stages and annotation factors P and V based on the 2017 PRE/POSTTEXT system. The sensitivities and specificities were calculated for 1) diagnosing each POSTTEXT stage; 2) discrimination of stages III and IV (advanced) from those stages I and II (non-advanced) hepatoblastomas; and 3) annotation factors P and V. The combination of pathologic findings and surgical records served as the reference standard. STATISTICAL TESTS: Sensitivity, specificity, Fleiss kappa test. RESULTS: The sensitivity and specificity ranges for discriminating advanced from non-advanced hepatoblastomas were 73.3%-80.0% and 80.0%-90.0%, respectively. For annotation factor P, they were 66.7%-100.0% and 90.6%, respectively. For factor V, they were 75.0% and 67.7%-83.9%, respectively. There was excellent, substantial, and moderate agreement on POSTTEXT staging (Fleiss kappa = 0.82), factors P (Fleiss kappa = 0.64), and factors V (Fleiss kappa = 0.60), respectively. DATA CONCLUSION: MR POSTTEXT provides reliable discrimination between advanced and non-advanced tumors, and MR has moderate to excellent specificity at identifying portal venous and hepatic venous/IVC involvement. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Transcriptome analysis and expression profiles of odorant binding proteins and chemosensory proteins in Orius sauteri.

The flower bug Orius sauteri (Heteroptera: Anthocoridae), is a polyphagous predator and a natural enemy widely used in biological pest control to micro-pests including aphids, spider mites, thrips and so on. In the present study, the transcriptome analysis of adult heads in O. sauteri were performed and identified a total of 38 chemosensory genes including 24 odorant binding proteins (OBPs) and 14 chemosensory proteins (CSPs). Subsequently, we conducted quantitative real-time PCR to detect the tissue expression level of 18 OBPs and 8 CSPs. The results showed that almost all OsauOBPs and OsauCSPs have a high expression level in the adult heads of both sexes. In addition, 5 OsauOBPs (OBP1, OBP2, OBP3, OBP4 and OBP14) have a significantly higher expressed in male heads than female, indicating that these chemosensory proteins might be involved in the male-specific behaviors such as pheromone reception and mate-seeking. This study will provide helpful reference for subsequent understanding of chemoreception mechanism in O. sauteri.

Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China.

Objective: In developed countries, midday napping and nighttime sleep duration have been linked to long-term survival; however, little is known about such effects in less developed regions. Therefore, this study aimed to assess the associations of midday napping and nocturnal sleep with mortality in middle-aged and older Chinese adults. Methods: A nationwide cohort of 15,524 adults aged ≥ 45 years was enrolled from 28 provincial regions across mainland China and followed up from 2011 to 2018, using data from the Chinese Health and Retirement Longitudinal Study. Midday napping and nighttime sleep duration were assessed using standardized questionnaires. Cox proportional hazards models with random intercepts for the surveyed provinces were used to estimate hazard ratios ( HRs) of all-cause mortality, adjusting for sociodemographic characteristics, behavioral factors, and health status. Results: A total of 1,745 deaths occurred during a median follow-up of 7.1 years, and the mean (standard deviation) age was 59 (10.1) years at baseline. Compared with non-nappers, over 60 min nappers had a higher risk of all-cause mortality [ HR: 1.35, 95% confidence interval ( CI): 1.17-1.56], while no significant associations were observed among < 30 min nappers. Compared with sleep duration of 6-8 h/night, both short (< 6 h) and long (≥ 8 h) sleep duration were significantly associated with increased mortality, with corresponding HR (95% CI) estimates of 1.21 (1.05-1.38) and 1.26 (1.10-1.44), respectively. We observed significant patterns for greater risks associated with longer nap duration, with a P trend value < 0.001 for all-cause mortality. No significant evidence of an additive interaction was identified between midday napping and nighttime sleep. Conclusion: Long midday napping and inappropriate nighttime sleep were independently associated with an increased risk of all-cause mortality in middle-aged and older Chinese populations. Biological studies are needed to validate our findings and clarify the mechanisms underlying this association.

[Effects of Modified Biochar-Supported Zero-Valent Iron on the Removal of Trichloroethylene and Responses of Microbial Community in Soil].

Trichloroethylene is a typical organic contaminant that has widely existed in industry sites and groundwater. Biochar-supported zero-valent iron material has been used to remove trichloroethylene in groundwater; however, it could affect the microbial communities in aquifer soil, leading to changes in the environmental behavior of trichloroethylene. In this study, biochar was prepared under oxygen-limited conditions and modified by NaOH and HNO3 agents. Then, a modified biochar-supported zero-valent iron composite (BC composites) was synthesized using ball milling technology. The effects of BC composites on the removal of trichloroethylene and the responses of the microbial community were investigated under the condition of simulated aquifer soil. The results showed that the specific surface areas of BC composites were increased after the modification with NaOH. The highest removal rate of trichloroethylene was observed in the BC_2 treatment, up to 90.01%. Except in the BC_1 treatment, the diversity and abundance of soil microorganisms were increased, and the microbial community structure was changed after the addition of different BC composites, in which Bacillus, Thiobacillus, and Pseudomonas might have been the potential degrading bacteria of trichloroethylene. The abundance of Thiobacillus and Pseudomonas increased under the BC_2 treatment, which was favorable to the removal of trichloroethylene. The stabilization of the microbial community structure was probably maintained by Nocardioideas, Thermincola, Lysobacter, Gemmatimonas, Microvirga, and Pseudomonas. According to the predictive analysis of microbial metabolic pathways, the abundance of xenobiotics biodegradation and metabolism genes and the folding, sorting, and degradation of genes were the highest under the BC_2 treatment. Thus, the NaOH-modified BC composite could prompt the removal of trichloroethylene in simulated aquifer soil, probably due to the increase in the abundance of soil-degrading bacteria and the expression of degradation genes, demonstrating that the NaOH-modified BC composite could be used for the remediation of the organic-contaminated industry sites as a new composite material.

Comparative microbiome analysis reveals the variation in microbial communities between 'Kyoho' grape and its bud mutant variety.

Microbes are an important part of the vineyard ecosystem, which significantly influence the quality of grapes. Previously, we identified a bud mutant variety (named 'Fengzao') from 'Kyoho' grapes. The variation of microbial communities in grape and its bud mutant variety has not been studied yet. So, in this study, with the samples of both 'Fengzao' and 'Kyoho', we conducted high-throughput microbiome sequencing and investigated their microbial communities in different tissues. Obvious differences were observed in the microbial communities between 'Fengzao' and 'Kyoho'. The fruit and the stem are the tissues with relatively higher abundance of microbes, while the leaves contained less microbes. The fruit and the stem of 'Kyoho' and the stem of 'Fengzao' had relatively higher species diversity based on the alpha diversity analysis. Proteobacteria, Enterobacteriaceae and Rhodobacteraceae had significantly high abundance in 'Fengzao'. Firmicutes and Pseudomonas were highly abundant in the stems of 'Kyoho', and family of Spirochaetaceae, Anaplasmataceae, Chlorobiaceae, and Sphingomonadaceae, and genera of Spirochaeta, Sphingomonas, Chlorobaculum and Wolbachia were abundant in the fruits of 'Kyoho'. These identified microbes are main components of the microbial communities, and could be important regulators of grapevine growth and development. This study revealed the differences in the microbial compositions between 'Kyoho' and its bud mutant, and these identified microbes will be significant resources for the future researches on the quality regulation and disease control of grapevines.

Traumatic dislocation of the iris into the vitreous cavity with intact lens: a case report.

BACKGROUND: Traumatic aniridia occurs when the iris is extruded from the eye and is often accompanied by lens injuries. However, traumatic aniridia due to dislocation of the iris into the vitreous cavity without lens damage has never been reported. CASE PRESENTATION: A 30-year-old man presented with visual loss and pain for 6 h after a thin wire injured his right eyeball. Ophthalmologic examinations manifested a 2 mm full-thickness corneal laceration and total hyphema. An intact clear lens, healthy attached retina, and almost complete iris tissue in the vitreous cavity were found after resolution of hyphema the next day. Further examination revealed that the defect in the zonule below the corneal wound was the path for the iris to enter the vitreous cavity. The patient opted for nonsurgical treatment until pigment granules and opacity were observed in the vitreous cavity after 50 days. Vitrectomy was performed to remove the dislocated iris. CONCLUSIONS: The presentation of this unique case indicates that the torn iris was displaced to the vitreous cavity with an intact lens and missing local zonula instead of out the corneal laceration after a penetrating injury. The type of injury, mechanism, and force on the spot may contribute to the occurrence of this rare condition. Instead of artificial irises, tinted glasses were more appropriate treatment option for this patient. Peripheral retinal examination was essential in the management of this case. In such cases, the iris in the vitreous cavity should be resected to prevent complications.

Identification of watermelon H3K4 and H3K27 genes and their expression profiles during watermelon fruit development.

BACKGROUND: The ClaH3K4s and ClaH3K27s gene families are subfamilies of the SET family, each with a highly conserved SET structure domain and a PHD structural domain. Both participate in histone protein methylation, which affects the chromosome structure and gene expression, and is essential for fruit growth and development. METHODS AND RESULTS: In order to demonstrate the structure and expression characteristics of ClaH3K4s and ClaH3K27s in watermelon, members of the watermelon H3K4 and H3K27 gene families were identified, and their chromosomal localization, gene structure, and protein structural domains were analyzed. The phylogeny and covariance of the gene families with other species were subsequently determined, and the expression profiles were obtained by performing RNA-Seq and qRT-PCR. The watermelon genome had five H3K4 genes with 3207-8043 bp nucleotide sequence lengths and four H3K27 genes with a 1107-5499 bp nucleotide sequence. Synteny analysis revealed the close relationship between watermelon and cucumber, with the majority of members displaying a one-to-one covariance. Approximately half of the 'Hua-Jing 13 watermelon' ClaH3K4s and ClaH3K27s genes were expressed more in the late fruit development stages, while the changes were minimal for the remaining half. H3K4-2 expression was observed to be slightly greater on day 21 compared to other periods. Moreover, ClaH3K27-1 and ClaH3K27-2 were hardly expressed throughout the developing period, and ClaH3K27-4 exhibited the highest expression. CONCLUSION: These results serve as a basis for further functional characterization of the H3K4 and H3K27 genes in the fruit development of watermelon.

Hepatoprotective effect of avicularin on lead-induced steatosis, oxidative stress, and inflammation in mice associated with the MAPK/HSP60/NLRP3 and SREBP1c pathway.

Lead (Pb), an environmental hazard, causes severe diseases in the liver, kidney, cardiovascular system, hematopoietic system, reproductive system, and nervous system. Avicularin (AVI), the main dietary flavonoid found in many citrus fruits, exhibited potential protective properties on organs. However, the molecular mechanisms of these protective actions are currently not clear. In our study, the effects of AVI on Pb-induced hepatotoxicity were evaluated using ICR mice. Changes in oxidative stress, inflammation, lipid metabolism, and related signaling were evaluated. We found for the first time that treatment with AVI significantly reduced hepatic steatosis, inflammation, and oxidative stress induced by Pb. AVI attenuated Pb-induced liver dysfunction and lipid metabolism disorder in mice. AVI decreased the serum biochemical indicators of lipid metabolism. AVI decreased the expression levels of lipid metabolism-related protein SREBP-1c, acetyl-CoA carboxylase (ACC), and FAS. AVI suppressed Pb-induced inflammation in livers, as indicated by decreasing the TNF-α and IL-1ß levels. AVI suppressed oxidative stress by increasing the activation of SOD, CAT, and GPx. Furthermore, AVI inhibited the activities of JNK, ERK, p38, and NF-κB. AVI further decreased the levels of HSP60, NLRP3, p-IκBα, and p-p65 in the livers of mice. Collectively, this study indicated that AVI mitigated Pb-induced hepatic steatosis, oxidative stress, and inflammation by regulating the SREBP-1c and MAPK/HSP60/NLRP3 signaling pathways.

Proteome-Wide Identification of Non-histone Lysine Methylation during Grape Berry Ripening.

To gain a comprehensive understanding of non-histone methylation during berry ripening in grape (Vitis vinifera L.), the methylation of non-histone lysine residues was studied using a 4D label-free quantitative proteomics approach. In total, 822 methylation sites in 416 methylated proteins were identified, with xxExxx_K_xxxxxx as the conserved motif. Functional annotation of non-histone proteins with methylated lysine residues indicated that these proteins were mostly associated with "ripening and senescence", "energy metabolism", "oxidation-reduction process", and "stimulus response". Most of the genes encoding proteins subjected to methylation during grape berry ripening showed a significant increase in expression during maturation at least at one developmental stage. The correlation of methylated proteins with QTLs, SNPs, and selective regions associated with fruit quality and development was also investigated. This study reports the first proteomic analysis of non-histone lysine methylation in grape berry and indicates that non-histone methylation plays an important role in grape berry ripening.

Genome-wide characterization of long terminal repeat retrotransposons provides insights into trait evolution of four cucurbit species.

Cucurbits are a diverse plant family that includes economically important crops, such as cucumber, watermelon, melon, and pumpkin. Knowledge of the roles that long terminal repeat retrotransposons (LTR-RTs) have played in diversification of cucurbit species is limited; to add to understanding of the roles of LTR-RTs, we assessed their distributions in four cucurbit species. We identified 381, 578, 1086, and 623 intact LTR-RTs in cucumber (Cucumis sativus L. var. sativus cv. Chinese Long), watermelon (Citrullus lanatus subsp. vulgaris cv. 97103), melon (Cucumis melo cv. DHL92), and Cucurbita (Cucurbita moschata var. Rifu), respectively. Among these LTR-RTs, the Ale clade of the Copia superfamily was the most abundant in all the four cucurbit species. Insertion time and copy number analysis revealed that an LTR-RT burst occurred approximately 2 million years ago in cucumber, watermelon, melon, and Cucurbita, and may have contributed to their genome size variation. Phylogenetic and nucleotide polymorphism analyses suggested that most LTR-RTs were formed after species diversification. Analysis of gene insertions by LTR-RTs revealed that the most frequent insertions were of Ale and Tekay and that genes related to dietary fiber synthesis were the most commonly affected by LTR-RTs in Cucurbita. These results increase our understanding of LTR-RTs and their roles in genome evolution and trait characterization in cucurbits.