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Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells. The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot. as expected, the apoptotic cells exposed to Cd apparently increased. The mRNA and protein expression levels of GRP78 and ATF6α, were elevated in the Cd groups. Additional experiments displayed that Cd notably increased IRE1α and JNK phosphorylation, and upregulated XBP-1 mRNA and protein expression. Moreover, p-eIF2α and CHOP expressions were clearly elevated in the Cd groups. Interestingly, PBA almost completely inhibited ER stress and protected spermatogonia against apoptosis induced by Cd. PBA alleviated Cd-induced ER stress and spermatogonia apoptosis, and may have the therapeutic role in Cd-induced male reproductive toxicity. • CdCl 2 induced spermatogonia apoptosis in vitro. • CdCl 2 triggered spermatogonia ER stress. • 4-PBA alleviated CdCl 2 -induced spermatogonia apoptosis. [ABSTRACT FROM AUTHOR]

• 1-MCP + ethylene absorbent (EA) treatment increase shelf-life of 'Fenjiao' banana. • EA does not have the negative effect on the ripening of 'Fenjiao' banana. • 1-MCP+EA repress the enzymes activity related to fruit softening. • 1-MCP +EA modulate the expression of gene related of ripening. • 1-MCP +EA treatment is easy to promote and apply in the banana industry. The 'Fenjiao' banana (Musa ABB Pisang Awak) has a high commercial and nutritional value and is harvested when it is highly plump at between 85 and 90 % commercial maturity. The fruit are less angular at this stage. However, these fruit soften rapidly after harvest. 1-Methylcyclopropene (1-MCP) significantly delays ripening, but it can cause ripening disorders when used improperly. Ethylene absorbent (EA) is also widely used to increase the postharvest life of fruit, but it has less of an effect on 'Fenjiao' banana. This study was conducted to optimize the concentrations of 1-MCP combined with EA to increase the shelf life of these bananas. The results showed that a low concentration of 1-MCP (7 g L−1) combined with EA (2 g kg−1) significantly prolonged the shelf life of the 'Fenjiao' banana and maintained its high quality. The combination of 1-MCP and EA repressed the activities of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase, ACC synthase, pectin methylesterase, polygalacturonase and pectate lyase in the peel and pulp of 'Fenjiao' banana, as well as the corresponding levels of expression of MbACS1, MbACO1, MbPG1, MbPL1 , except for MbPME1 , which are induced by 1-MCP. This study provides a useful technique for preserving 'Fenjiao' fruit with a study on its possible physiological mechanism, which could be applied in the postharvest production of 'Fenjiao' banana. [ABSTRACT FROM AUTHOR]

Background This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300 m. Methods and Results The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K a and C max of norfloxacin were significantly reduced in high altitude group (p < 0.05). However, the MRT, CL, t 1/2 and Vd were significantly increased (p < 0.05). Conclusions These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a common pollutant with reproductive toxicity. Our previous study revealed that Cd triggered spermatogonia ferroptosis. However, the underlying mechanisms remain unclear. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy and specific degradation of ferritin through lysosomes, resulting in the release of ferrous ions. Excessive autophagy can lead to ferroptosis. This study investigated the role of autophagy in Cd-triggered ferroptosis using GC-1 spermatogonial (spg) cells which exposed to CdCl 2 (5 μM, 10 μM, or 20 μM) for 24 without/with CQ. The cells which transfected with Ncoa4-siRNA were used to explore the role of NCOA4-mediated ferritinophagy in Cd-triggered ferroptosis. The results revealed that Cd caused mitochondrial swelling, rupture of cristae, and vacuolar-like changes. The Cd-treated cells exhibited more autophagosomes. Simultaneously, Cd increased intracellular iron, reactive oxygen species, and malondialdehyde concentrations while decreasing glutathione content and Superoxide Dismutase-2 activity. Moreover, Cd upregulated mRNA levels of ferritinophagy-associated genes (Ncoa4, Lc3b and Fth1), as well as enhanced protein expression of NCOA4, LC3B, and FTH1. While Cd decreased the mRNA and protein expression of p62/SQSTM1. These results showed that Cd caused ferritinophagy and ferroptosis. The use of chloroquine to inhibit autophagy ameliorated Cd-induced iron overload and ferroptosis. Moreover, Ncoa4 knockdown in spermatogonia significantly reduced intracellular iron concentration and alleviated Cd-triggered ferroptosis. In conclusion, our findings demonstrate that Cd activates the ferritinophagy pathway mediated by NCOA4, resulting in iron accumulation through ferritin degradation. This causes oxidative stress, ultimately initiating ferroptosis in spermatogonia. Our results may provide new perspectives and potential strategies for preventing and treating Cd-induced reproductive toxicity. [Display omitted] • Cd causes iron overload and triggers ferroptosis in spermatogonia. • Cd induces ferritinophagy in spermatogonia. • CQ antagonizes against Cd-caused iron overload in spermatogonia. • NCOA4-mediated ferritinophagy participates in Cd-triggered ferroptosis. [ABSTRACT FROM AUTHOR]

• Urinary extracellular vesicles miRNAs' expression pattern of RCC patients was examined. • uEV miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p were upregulated in RCC patients. • A three-uEV miRNA panel could discriminate RCC patients from controls with the AUC of 0.785. • An uEV-miRNA panel could also distinguish early-stage RCC patients with the AUC of 0.786. The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729–0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727–0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC. [ABSTRACT FROM AUTHOR]

Highlights • Low temperature reduced banana fruity note volatiles such as esters. • Low temperatures affected volatile-related amino acids and fatty acid compositions. • Chilling temperature affected the key enzymes and genes in volatile biosynthesis. • Low temperatures repressed the LOX pathway and amino acid metabolic pathway. Abstract Banana fruit is sensitive to chilling injury, which not only causes physical damage but also dramatically reduces fruit flavor. In this work, we evaluated the influence of non-chilling low temperature (NCT, 13 °C) and chilling temperature (CT, 5 °C) storage on volatiles production in banana in comparison to control conditions (20 °C) and evaluated the possible mechanisms. We found that CT storage caused chilling injury, which negatively affected the physical appearance of the fruit and dramatically reduced volatiles production, especially fruity note volatiles, such as esters. In contrast, NCT storage only reduced the production of a few specific volatiles. Both NCT and CT affected volatile-related amino acid and biosynthetic precursors of fatty acid compositions. The expression levels of the volatiles biosynthesis-related genes, MaHPL, MaLOX, and MaAAT, were repressed by low temperature (NCT and CT), particularly chilling temperature, while MaADH and MaPDC were up-regulated. These results suggest that CT significantly reduces volatiles production by regulating different key enzymes and genes involved in volatiles biosynthetic pathways and is mainly mediated via the repression of the lipoxygenase and amino acid metabolic pathways. [ABSTRACT FROM AUTHOR]

Background Different gene expression profiles are observed in intracranial aneurysm tissues. Understanding these genes and what regulates their expression will provide insight into the pathogenesis of intracranial aneurysms. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms. Methods We compared 20 intracranial aneurysm tissue specimens with 20 matched specimens from the superficial temporal artery as controls. We identified the gene expression profiles in these samples using the GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications using the Infinium HumanMethylation450 BeadChip Kit. Results A total of 11,022 differentially methylated sites between aneurysm tissues and matched control tissues were identified, and 2142 differentially expressed gene transcripts were detected based on the 2 gene expression profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and verification analysis showed that the MYH11 , LIFR , and TLR4 genes were associated with the occurrence and development of intracranial aneurysms. These genes mainly encode cell adhesion molecules or are involved in the NF-κB, JAK-STAT, and ERK/JNK signaling pathways. Conclusions In the development of intracranial aneurysms, DNA methylation plays an important role in the regulation of genetic expression involved in immune and inflammatory reactions, cell function, cell maintenance, and cell signal transduction. [ABSTRACT FROM AUTHOR]

Gene expression is epigenetically regulated through DNA methylation and covalent chromatin modifications, such as acetylation, phosphorylation, ubiquitination, sumoylation, and methylation of histones. Histone methylation state is dynamically regulated by different groups of histone methyltransferases and demethylases. The trimethylation of histone 3 (H3K4) at lysine 4 is usually associated with the activation of gene expression, whereas trimethylation of histone 3 at lysine 27 (H3K27) is associated with the repression of gene expression. The polycomb repressive complex contains the H3K27 methyltransferase Ezh2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3). The Jumonji domain containing-3 (Jmjd3, KDM6B) and ubiquitously transcribed X-chromosome tetratricopeptide repeat protein (UTX, KDM6A) have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3. The role and mechanisms of both JMJD3 and UTX have been extensively studied for their involvement in development, cell plasticity, immune system, neurodegenerative disease, and cancer. In this review, we will focus on recent progresses made on understanding JMJD3 in the regulation of gene expression in development and diseases. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease. [ABSTRACT FROM AUTHOR]

• It is a novel report on the effects of BPA on ovarian development in adolescent mice. • 4266 differentially expressed genes (DEGs) in the ovary of adolescent mice due to BPA exposure were identified by RNA-Seq. • BPA exposure has far-reaching effects on ovarian development in adolescent mice. Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways. [ABSTRACT FROM AUTHOR]

Flower odor is often essential for attracting pollinators, and this is especially true for species-specific mutualism such as the one between Ficus species and their pollinating wasps. Receptive figs emit a stage and species specific odor composed of a mix of volatile organic compounds (VOC) that is attractive to their pollinators. Histological studies suggest that the ostiolar bracts are the main locus of fig floral VOC synthesis. To confirm a major role of the ostiole in VOC synthesis, detect the genes involved in VOC synthesis and analyze differences between closely related species, we compare the transcriptomes of pre-receptive and receptive figs of two closely related species, F. hirta and F. triloba. The two species presented similar numbers of expressed genes and similar annotation, classification results, and their up-regulated unigenes belonged to similar biosynthetic pathways. However, phenylpropanoid and terpene synthesis were the main enriched VOC pathways in receptive figs of F. hirta while terpene and jasmonate synthesis were the main enriched VOC pathways in F. triloba. The shift in gene expression between pre-receptive and receptive figs was much more marked in the ostiolar bracts than in the flowers of F. hirta , and in the fig wall, confirming an important role of the ostiole in receptive fig odor emission. Only one unigene directly involved in VOC synthesis presented signatures of positive selection, further supporting that the source of interspecific receptive fig odor differentiation is based on gene regulation rather than on gene differentiation. Regulation based receptive fig odor differentiation between species suggests a potential for rapid evolution of this interspecific barrier. • F. hirta and F. triloba presented similar numbers of expressed genes and similar annotation. • F. hirta and F. triloba had different enriched VOC pathways related to pollinator attraction. • The important role of the ostiole in receptive fig odor emission was conformed. • The source of interspecific fig odor differentiation is based on gene regulation rather than on gene differentiation. [ABSTRACT FROM AUTHOR]