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Myocardial ischemia-reperfusion injury (MIRI) poses a significant threat to patients with coronary heart disease. Adenosine A2A receptors have been known as a protective role in MIRI by regulating autophagy, so we assumed that activation of adenosine A2B receptor (A2BAR) might exert a similar effect during MIRI and underlying mechanism be related to proteostasis maintenance as well. In situ hearts were subjected to 30 min of ischemia and 120 min of reperfusion (IR), while in vitro cardiomyocytes from neonatal rats experienced 6 h of oxygen-glucose deprivation followed by 12 h of reoxygenation (OGDR). Initially, we observed that post-ischemia-reperfusion induced autophagy flux blockade and ERS both in vivo and in vitro , evident through the increased expression of p62, LC3II, and BIP, which indicated the deteriorated proteostasis. We used a selective A2BAR agonist, Bay 60–6583, to explore the positive effects of A2BAR on cardiomyocytes and found that A2BAR activation rescued damaged cardiac function and morphological changes in the IR group and improved frail cell viability in the OGDR group. The A2BAR agonist also alleviated the blockage of autophagic flux, coupled with augmented ERS in the IR/OGDR group, which was reassured by using an autophagy inhibitor chloroquine (CQ) and ERS inhibitor (4-PBA) in vitro. Additionally, considering cAMP/PKA as a well-known downstream effector of A2BAR, we utilized H89, a selective PKA inhibitor. We observed that the positive efficacy of Bay 60–6583 was inhibited by H89. Collectively, our findings demonstrate that the A2BAR/cAMP/PKA signaling pathway exerts a protective role in MIRI by mitigating impaired autophagic flux and excessive ERS. [Display omitted] • Myocardial I/R injury is related to autophagy and ERS pathogenesis. • A2B receptor activation reduces reperfusion-induced cardiomyocyte injury. • Bay 60–6583 regulates ERS and autophagy flux via the cAMP/PKA signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new graphdiyne based metal-free catalyst was successfully synthesized. • The catalyst triggered highly catalytic performances toward hydrogen evolution. • The unique nanostructure guaranteed the fast proton-electron transfer during HER. • The alkyne-alkene transition induced the excellent catalytic activity of TAGDY. Graphdiyne-based metal-free catalysts demonstrate outstanding performances in electrocatalysis. In order to accurately understand the activity origin of metal-free electrocatalytic hydrogen production at the atomic level, we have successfully designed and prepared a new metal-free catalyst of 1,2,4-triamino-graphdiyne (TAGDY). Structural characterizations showed that TAGDY has unique nanostructure, which guarantees the fast proton-electron transfer during the catalytic process. Experimental studies revealed that TAGDY possesses excellent electrocatalytic activities and long-term durability towards hydrogen evolution in acidic conditions, better than the most reported metal-free electrocatalysts. Density functional theory calculations and Born-Oppenheimer molecular dynamics simulations revealed that the interaction of (H++e−) pair with alkyne bond induces the transition between C C and C C in TAGDY, which effectively enhanced the catalytic activities of initial inert carbon sites. Combination of theory and experiment as well as the structural characterization, a new level of knowledge for the activity origin and catalytic mechanism of graphdiyne-based metal-free electrocatalysts are presented. [ABSTRACT FROM AUTHOR]

Abstract Food spoilage is a global issue, and millions of people suffer from food-borne infections. So it is urgent to search for novel, effective and safe antimicrobial agents. A novel essential oil was obtained from Eremothecium ashbyii H4565, which was identified and conserved in the China Center for Type Culture Collection. The chemical components of the essential oil were analyzed by gas chromatography-mass spectrometry. The results showed that 22 components were identified, and the major compounds were geraniol, citronellol, phenylethyl alcohol, longifolene, linalool and nerolidol. By disc diffusion assay and double-broth dilution method, the essential oil exhibited antibacterial activities against food spoilage microbes, such as Staphylococcus aureus , Bacillus subtilis , Bacillus cereus , Listeria monocytogenes , Escherichia coli , Salmonella typhimurium , Zygosaccharomyces bailii , Saccharomyces cerevisiae , and Candida utilis. The minimum inhibition concentrations of the essential oil against these microorganisms were 15.6, 15.6, 15.6, 15.6, 7.8, 7.8, 31.2, 15.6, and 31.2 μg/mL, respectively. Based on the results of electron microscopy, protein and DNA leakage, and cytoplasmic membrane permeability, the possible antibacterial mechanism was indicated that cell wall and cytoplasmic membrane were destroyed as the targets by the essential oil.. Therefore, it was suggested that essential oil might be used as a potential antimicrobial agent in food. Highlights • A novel essential oil was obtained from the nutrient broth of Eremothecium ashbyii H4565. • The components of the essential oil was analyzed by GC-MS. • The essential oil exhibited strong antibacterial activities. • The targets of the essential oil might be the cell wall and membrane. [ABSTRACT FROM AUTHOR]

Abstract Valsa pyri , an ascomycete pathogen that is a member of the Valsaceae family (Sordariomycetes, Diaporthales), which causes pear or apple canker and leads to tree death and massive yield losses. Here, we selected two V. pyri isolates (Vp14 and Vp297) that exhibited different invasion abilities for transcriptomics analyses. Compared toVp297, Vp14 had stronger virulence and spread faster on host-like nutrients. Four samples, including mycelium or infectious mycelium, of the two isolates were sequenced. Clean reads were mapped to the V. pyri genome, and 12490 transcripts and 178 new genes were identified. There were dramatically fewer differentially expressed genes (DEGs) in Vp14 than in Vp297. According to GO and COG annotations, there were both more up- and down-regulated genes in Vp297 than in Vp14 except for genes involved in amino acid transport and metabolism, carbohydrate transport and metabolism, peroxidases and so on. Specific up-regulated DEGs, including genes encoding cell wall degrading enzymes and genes involved in nitrogen metabolism and peroxidases which play crucial roles in virulence and infectious growth, were especially enriched inVp14. These results indicate that the Vp14 isolate may infect its host and take up nutrition more efficiently, reflecting a stronger ability for invasion or infectious growth. Our analysesindicate that a successful V. pyri infection involves multiple instances of transcriptome remodeling to regulate gene functions. Comparative transcriptomics between isolates of V. pyri may aid in our understanding of the virulence mechanism of this pathogen. Highlights • The two Valsa pyri isolates differ in their utilization of mineral or host nutrition in vitro. • Greater specific genes were upregulated in the stronger virulence isolate Vp14, involve in cell wall degrading enzymes, peroxidases and nitrogen metabolism, which are required for virulence and necrotrophic growth of fungi.. • This is the first comparative transcriptomics research uncovering the difference between Valsa pyri isolates. [ABSTRACT FROM AUTHOR]

The carbon dioxide (dry) reforming of methane (DRM) (CH 4  + CO 2  → 2CO + 2H 2 ) on La and La 2 O 3 modified Ni(1 1 1) has been investigated theoretically. As promoters, La and La 2 O 3 strengthen the adsorption of the intermediates compared with pure Ni(1 1 1). The strong adsorption of CO 2 on La 2 O 3 modified Ni(1 1 1) deforms La 2 O 3 , and the complex intermediate CO 2 (La 2 O 2 -O) is formed. The CO 2 (La 2 O 2 -O) participates in the DRM reaction and reduces the carbon deposition on the catalyst surface. For La and La 2 O 3 modified Ni(1 1 1), the reactions of CH 4  + CO 2  → CH + 3H + CO + O → CHO + 3H + CO → 2CO + 2H 2 and CH 4  + CO 2  + La 2 O 3  → CH + CO 2 (La 2 O 2 -O) + 3H → CHO + CO 2 (La 2 O 2 ) + 3H → 2CO + 2H 2  + La 2 O 3 are the most favorable pathways for DRM, respectively. Both the density functional study and microkinetic analysis support that compared with pure Ni(1 1 1), La and La 2 O 3 modified Ni(1 1 1) improve the reaction both thermodynamically and kinetically. The carbon deposition is suppressed on La 2 O 3 modified Ni(1 1 1) due to the lower rate in the reaction CH → C + H, compared with La modified Ni(1 1 1). [ABSTRACT FROM AUTHOR]

The 2-amino-3-methyl-imidazole [4,5-f] quinoline (IQ) is a compound generated during the Maillard reaction while heating protein-rich foods and has been classified as a class 2A possible human carcinogen that has attracted ongoing public concern. However, the formation mechanism of IQ remains unknown. Herein, we investigated the formation mechanism of IQ in the Maillard reaction model system under various reaction conditions (temperature, time, and pH). The results showed that various conditions significantly influenced the precursors, reactive carbonyl species, and IQ formation (P < 0.05). There was regularity between IQ and various conditions, and the R 2 in the fitting curves were between 0.90 and 0.99. To further explore the relationship between IQ and various conditions, a partial least squares (PLS) prediction model was constructed. The model indicates that temperature is a significant contributor to the formation of IQ during the Maillard reaction. Further analysis indicated that crotonaldehyde plays a vital role. Crotonaldehyde could promote IQ formation at low addition levels but inhibit its formation at high addition levels. Possible effects of crotonaldehyde on the formation of IQ were proposed. Overall, this research will help to identify more effective ways to reduce the formation of IQ in meat products, which can improve their safety for human consumption. [Display omitted] • The formation of IQ in the Maillard reaction model system was studied. • The regularity between the formation of IQ and various conditions was proposed. • The partial least squares (PLS) model was constructed for the prediction of IQ formation. • The effects of crotonaldehyde during the formation of IQ were illustrated. [ABSTRACT FROM AUTHOR]

Valsa pyri is a fatal pathogenic fungus that causes pear and apple canker disease. To date, its cellular development and pathogenicity have been poorly understood. In this study, a V . pyri Ca 2+ /calcineurin-dependent transcription factor CRZ1 (VpCRZ1) is identified and functionally characterized. The △VpCRZ1 mutant exhibits impaired pathogenicity and is no longer able to form fruiting body. Interestingly, this mutant also exhibits enhanced pigment deposition and increased resistance to cell wall perturbing agents including SDS, Congo red and calcofluor white (CFW). The expression levels of Congo red resistance genes ( VpRCR1 and VpRCR2 ) and chitin synthetase genes ( VpCHS2 and VpCHS6 ) are upregulated in the △VpCRZ1 mutant compared to the wild type. Furthermore, We show that a VpCRZ1: eGFP fusion protein localizes to the nucleus in a Ca 2+ -dependent manner similar to its homologs in other fungi, and that the VpFKS1 , VpPMC1 , VpPMC2 , VpPMR1 , and VpPMA1 genes are regulated by VpCRZ1 in response to Ca 2+ levels. Together, these results suggest that VpCRZ1 is a Ca 2+ -dependent transcription factor and required for regulating mycelial morphology, fruiting body formation, and virulence of this important pear and apple pathogen. [ABSTRACT FROM AUTHOR]

Abstract: Cytochrome P450c17-II (cyp17-II) gene is an important factor affecting the growth, gonad differentiation and development, and other reproductive traits of fish. There are three CpG rich regions in the coding region of cyp17-II gene in Japanese flounder (Paralichthys olivaceus). The aim of this study was to understand whether mutations in exons of the cyp17-II gene occured at CpG sites, and mutations and methylation status of those CpG sites were involved in regulation of the expression level of cyp17-II gene and the reproductive endocrine of Japanese flounder. The results showed that three single nucleotide polymorphisms (SNPs) were identified. SNP1 [(c. G594A (p.Gly 188Arg)] located in exon 4 of L1 locus, and SNP2 (c.A939G) and SNP3 (c.C975T) of L2 locus located in CpG rich region of the exon 6 of cyp17-II gene. Furthermore, the A to G transition at 939bp position added a new methylation site to the cyp17-II coding region. According to multiple-comparison analysis, two loci (L1 and L2) were significantly associated with serum testosterone (T) level (P< 0.05) and the expression of cyp17-II in ovary (P< 0.01). Intriguingly, individuals with GG genotype of L2 locus containing eight CpG methylation sites had significantly lower serum testosterone level and cyp17-II mRNA expression than those with AA genotype containing seven CpG methylation sites. Moreover, the CpG site was highly methylated (⩾77.8%) at 938bp position of individuals with GG genotype of L2 locus. These implied that the mutation and methylation status of the coding region of cyp17-II could influence the gene expression and the reproductive endocrine levels in female Japanese flounder and L2 locus could be regarded as a candidate genetic or epigenetic marker for Japanese flounder breeding programs. [Copyright &y& Elsevier]

Abstract: Carboxymethyl cellulose (CMC) can facilitate in situ delivery of zero-valent iron (ZVI) nanoparticles in contaminated aquifer. This work investigated transport of CMC-stabilized ZVI nanoparticles (CMC-Fe) using column breakthrough experiments and model simulations. The nanoparticles (18.1±2.5nm) were transportable through four saturated model porous media: coarse and fine glass beads, clean sand, and sandy soil. The transport data were interpreted using both classical filtration theory and a modified convection–dispersion equation with a first-order removal rate law. At full breakthrough, a constant concentration plateau (C e /C 0) was reached, ranging from 0.99 for the glass beads to 0.69 for the soil. While Brownian diffusion was the predominant mechanism for particle removal in all cases, gravitational sedimentation also played an important role, accounting for 30% of the overall single-collector contact efficiency for the coarse glass beads and 6.7% for the soil. The attachment efficiency for CMC-Fe was found to be 1–2 orders of magnitude lower than reported for ZVI nanoparticles stabilized with other commercial polymers. The particle removal and travel distance are strongly dependent on interstitial flow velocity, but only modestly affected by up to 40mM of calcium. Simulation results indicate that once delivered, 99% of the nanoparticles will be removed by the soil matrix within 16cm at a groundwater flow velocity of 0.1m/day, but may travel over 146m at flow velocity of 61m/day. [Copyright &y& Elsevier]

[Display omitted] • Novel ferulic acid derivatives with oxadiazole were designed and synthesized. • The synthesized compounds showed significantly antiviral activity. • Compound 6 h can intensify the activities of some defensive enzymes. • 6 h regulates phenylpropanoid biosynthesis pathway and chloroplast function. • Some of the synthesized compounds could be used as potential elicitors. A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans -ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6 h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a , 6b , 6e , 6f and 6 h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6 h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV. [ABSTRACT FROM AUTHOR]

Abstract: DNA synthesis during S-phase and upon DNA repair is accompanied by chromatin assembly. The chromatin assembly factor CAF-1 has been biochemically well-characterized to deposit histones onto newly synthesized DNA. To gain insights into the in vivo functions of CAF-1 in Drosophila, we generated null mutants of the largest subunit of dCAF-1, dCAF-1-p180. We show that, unlike CAF-1 mutant yeast, dCAF-1-p180 mutant flies are hemizygous lethal. Removal of maternal dCAF-1-p180 activity by germline clones blocks oogenesis. Tissue-specific deletion of dCAF-1-p180 in the eye primordia disrupts eye development. In addition, reduction of dCAF-1-p180 activity suppresses gene silencing at heterochromatin and antagonizes Polycomb-mediated cell fate determination. Furthermore, heterozygous dCAF-1-p180 mutant flies display an increased sensitivity to γ-irradiation and a reduced efficiency in recombinational double strand break (DSB) repair. Our experiments also show that human hCAF-1-p150 can rescue the dCAF-1-p180 mutant flies, demonstrating a functional conservation of eukaryotic CAF-1 activities in vivo. Together, our results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo. [Copyright &y& Elsevier]

PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas, macrocephaly, and mental deficiencies. We have used PTEN +/− and PTEN +/+ mice to prepare subventricular zone (SVZ) precursor cells. Using DNA microarrays, we compared the expression profiles of PTEN +/+ and PTEN +/− cells and identified 91 differentially expressed genes in PTEN +/− precursor cells. Many of the PTEN-regulated genes are involved with signaling, cytoskeleton, extracellular matrix, metabolism, and transcription factors. Some of these changes are likely mediated by the transcription factor, HIF-1. We confirmed a subset of these changes by real-time PCR. In addition, we examined protein levels for two of the PTEN-up-regulated genes, vascular endothelial growth factor (VEGF) and doublecortin (DCX). PTEN haploinsufficiency increases immunostaining for VEGF for both cultured precursor cells and sections of the SVZ. PTEN haploinsufficiency shifted most of the DCX-positive cells from the SVZ to the olfactory bulb. These observations indicate that even a small decrease in PTEN levels results in substantial changes in gene expression and precursor cell function. [Copyright &y& Elsevier]

• BCMA is a suitable and promising target for CAR- T therapy. Anti-BCMA CAR-T cells could exhibit interferon-γ and cytotoxicity and eradicate tumor in vivo. • We developed a novel "safety switch" CAR-T to dampen CAR-T cells by using a commercially available drug as a safety mechanism in the event of an adverse reaction in patients. • This new development could make it possible to engineer a safer CAR-T and offer virtually unlimited potential for cancer therapy. Chimeric antigen receptor T cells (CAR-T) against B-cell maturation antigen (BCMA) has been used to treat multiple myeloma (MM). CAR-T cells co-expressing a truncated human EGFR (tEGFR) has been proposed for in vivo cell ablation. We designed and tested a novel anti-BCMA CAR. We transduced T cells with retroviral vectors encoding CAR and tEGFR. The anti-BCMA-CAR-transduced T cells were evaluated for the functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication of BCMA. Cetuximab was used for in vivo cell ablation. The CAR-T cells could specifically recognize BCMA, and anti-BCMA CAR-T cells could exhibit interferon-γ and cytotoxicity specifically produced by BCMA and eradicate tumor in vivo. Cetuximab could mediate antibody-dependent cellular cytotoxicity and in vivo elimination. We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular ablation. [ABSTRACT FROM AUTHOR]

• Compound 9d with memantine as a cap structure exhibits balanced anti-NMDAR and HDAC activity. • The structural activity relationship is explained in detail. • HDAC inhibitors of isohydroxamic showed a strong protective effect against hydrogen peroxide damage. Histone deacetylases (HDACs) have been indicated important roles in neurodegenerative disorders including Alzheimer's disease (AD). Herein, a series of novel compounds that contain a memantine moiety were designed to target HDACs and N -methyl- d -aspartate receptor (NMDAR) which are related to the treatment of AD. Biological characterization established that compound 9d exhibited a balanced inhibitory activity on NMDAR and HDACs. This compound is relatively selective to HDAC6 with IC 50 of 0.18 μM and also maintains comparable activity on NMDAR (K i = 0.59 μM) as memantine. Functionally, treatment with 9d increased the level of AcTubulin in MV4-11 cells and rescued PC-12 cells from H 2 O 2 -induced cytotoxicity with EC 50 of 0.94 μM. Studies in mice also demonstrated that compound 9d efficiently penetrates the blood brain barrier to reach the brain tissue. Collectively, the results strongly encourage further development of 9d as a potential therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

Abstract: We propose a new method to measure the viscosity of concentrated protein solutions in a high-throughput format. This method measures the apparent hydrodynamic radius of polystyrene beads with known sizes using a dynamic light scattering (DLS) system with a microplate reader. Glycerol solution viscosities obtained by the DLS method were in good agreement with those reported in the literature. Viscosity of the solutions of two monoclonal antibody molecules was acquired using both DLS and cone-and-plate techniques, and the results were comparable. The DLS method described here has the potential to be used in many aspects of protein characterization. [Copyright &y& Elsevier]

• Twenty-eight derivatives were designed, synthesized, and biologically evaluated. • Some compounds were found to potently inhibit both AChE and HDAC. • Compounds exhibited potential Cu2+ chelating properties, and HDAC isoform inhibition selectivity. • Compound A10 could serve as apromising candidate analogs as AD therapeutics. In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChE IC50 = 0.12 nM, BChE IC50 = 361.52 nM) but also potent inhibition on HDAC (IC 50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Aβ 1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics. [ABSTRACT FROM AUTHOR]

The FLT4 gene plays an important role in the onset and progression of obesity and is involved in the structure and function of lymphatic vessels. By inducing a mouse obesity model with a high-fat diet and knocking out the FLT4 gene, which is associated with lymphatic vessel growth in mice, FLT4+/− mice were found to be susceptible to high-fat diet-induced obesity, with significant accumulation of visceral fat. BODIPY™ FL C 16 imaging revealed dilated and branched mesenteric lymphatic vessels in FLT4+/− mice. Immunofluorescence staining showed that FLT4+/− exacerbated the morphological abnormalities of lymphatic vessels and submucosal lymphatic vessels in visceral adipose tissue of obese mice, accompanied by macrophage infiltration around lymphatic vessels. In addition, FLT4 knock down increased the proportion of M1-type macrophages in the adipose tissue of the epididymis, indicating significant chronic inflammation in FLT4+/− obese mice. These findings provide new evidence for the involvement of lymphatic vessel morphological abnormalities in the onset and progression of obesity and highlight the importance of further investigation of FLT4 to better understand the mechanism of HFD-induced obesity and to develop related treatments. • Wild-type hyper-fat mice were obese and developed mesenteric lymphangiectasia. • On a high-fat diet, FLT4+/− mice gained more weight and developed abnormal glucose tolerance than wild-type mice. • In obese FLT4+/− mice, fat accumulated in the mesentery, and lymphatic vessels increased in diameter and branching. • Obese FLT4+/- mice showed macrophage accumulation around mesenteric and epididymal adipose tissue lymphatic vessels. [ABSTRACT FROM AUTHOR]

Abstract Adipogenesis is one of the key processes during obesity development. Better understanding of this process could advance our knowledge on obesity and its treatment. Transcription factors (TFs) are master regulators during adipogenesis, however, a system-wide analysis of TFs dynamic proteome during adipogenesis is lacking. Here, we profiled 472 TFs and systematically elucidated their roles during the first 7 days of adipogenesis of human adipose-derived stem cells (hADSCs) on proteome scale. We identified two main and four sub-phases during adipogenesis. The commitment phase (0 h–8 h) mainly mediated stem cell proliferation, differentiation and chromatin remodeling, in which proteins of SWI/SNF family are the key centroid nodes. The determination phase (1D-7D) predominately regulated fat cell differentiation and response to lipid and oxygen, which could be associated with terminal differentiation of adipocyte and responsible for maturation. PPARγ, CREB1 and MYC are the centroid nodes of this phase. Remarkably, we identified and verified three TFs (BATF3, MAFF and MXD4) as novel regulators of adipogenesis, whose over-expression could inhibit adipogenesis of hADSCs in vitro. Overall, our study provided a valuable TFs resource to understand the complex process of adipogenesis. Highlights • Systematically depicted dynamic profiles of TFs during adipogenesis of hADSCs at proteome level. • Divided adipogenesis of hADSCs into two main and four sub-stages via dynamic proteome patterns of TFs. • Revealed featured biological responses during different stages of adipogenesis and figured out critical regulatory TFs. • Proposed three novel regulatory TFs (MAFF, BATF3 and MXD4), whose over-expression could inhibit adipogenesis of hADSCs. [ABSTRACT FROM AUTHOR]

• Screening candidate circpdlim5a from the Japanese flounder transcriptome. • Circpdlim5a has a stable structure and high RNase R tolerance. • Distributed in nucleus and cytoplasm and highly expressed in nucleus. • Circpdlim5a inhibits the expression of proliferation and differentiation genes. Circular RNAs (circRNAs) are non-coding RNAs with endogenous regulatory functions, including regulating skeletal muscle development. However, its role in the development of skeletal muscle in Japanese flounder (Paralichthys olivaceus) is not clear. Therefore we screened a candidate circpdlim5a, which is derived from the gene pdlim5a , from the skeletal muscle transcriptome of Japanese flounder. We characterized circpdlim5a, which was more stable compared to the linear RNA pdlim5a. Distributional characterization of circpdlim5a showed that circpdlim5a was predominantly distributed in the nucleus and was highly expressed in the skeletal muscle of adult Japanese flounder (24 months). When we further studied the circpdlim5a function, we found that it inhibited the expression of proliferation and differentiation genes according to the over-expression experiment of circpdlim5a in myoblasts. We concluded that circpdlim5a may inhibit the proliferation and differentiation of myoblasts and thereby inhibit skeletal muscle development in Japanese flounder. This experiment provides information for the study of circRNAs by identifying circpdlim5a and exploring its function, and offers clues for molecular breeding from an epigenetic perspective. [ABSTRACT FROM AUTHOR]

Apoptosis genes Egr2 , Fas and FasL are related to immune responses. However, the mechanism of these genes inducing apoptosis in fish are still not very clear. An acute hypoxia treatment (1.73 ± 0.06 mg/L) for 24 h was carried out on Japanese flounder (Paralichthys olivaceus). The increasingly dense apoptotic signals at 3 h, 6 h, 12 h by TUNEL in skeletal muscle indicated that hypoxia could quickly affect muscle growth and development. Furthermore, we concluded that the Egr2-FasL-Fas signal pathway, which was located at the upstream of apoptotic executor protein caspases, was related to the apoptosis by quantitative real-time PCR, protein concentration detection in ELISA and double gene in situ hybridization methods. The mechanism of the pathway was researched in transcription regulation and epigenetic modification by dual-luciferase reporter assay and bisulfite modified method, respectively. Egr2, as a transcription factor, could up-regulate the expression of FasL gene. And its binding site was mainly between −479 to −1 of FasL gene promoter. The 5th CpG dinucleotides (−514) methylation levels in FasL gene were significantly affected by hypoxia, and they were negatively correlated with its expressions. These suggested that the −514 site may be a very important site to regulate the FasL gene expression. Above results, we concluded that hypoxia activated the immune related signal pathway Egr2-FasL-Fas to induced skeletal muscle apoptosis to affect growth and development of Japanese flounder. The study revealed the mechanism of hypoxia induced apoptosis, which could provide a reference for fish immunity and aquaculture management. • Skeletal muscle cell immune response was activated by acute hypoxia stress. • The immunity was related to Egr2-FasL-Fas signal pathway to induce apoptosis. • Egr2 transcriptionally regulated the expression of FasL gene. • Hypoxia acts on the signal pathway by epigenetic modification. [ABSTRACT FROM AUTHOR]

Water diversion has been widely utilized to enhance lake water quality and mitigate cyanobacterial blooms. However, previous studies have mainly focused on investigating the effects of water diversion on water quality or aquatic ecological health. Consequently, there is limited research investigating the combined impact of water diversion on the water quality and the ecological health of eutrophic lakes, and whether the WQI and phytoplankton assemblages demonstrate similar patterns following water diversion. In this study, the effects of water diversion on the ecosystem health of eutrophic lakes were comprehensively evaluated based on the WQI indices and phytoplankton assemblages during the NWDP-21 and WDP-22. The results showed that the annual mean of WQI increased from 52.02 to 54.36 after water diversion, which improved the water quality of the lake, especially NH 3 –N and TN decreased by 58.6% and 15.2%, respectively. The phytoplankton assemblages changed significantly before and after water diversion, and we observed that the total biomass of phytoplankton decreased by 12.3% and phytoplankton diversity indices (Shannon-Wiener diversity, Pielou evenness, and Simpson index) increased by 8.6%–8.9% after water diversion, with an improvement in the connectivity and stability of the phytoplankton. Notably, enhanced adaptations of rare sub-communities for resource use in water diversion environments, and water diversion inhibited the dispersal ability of dominant functional groups, and the effects of hydrological disturbances on the structure of phytoplankton assemblage favored the ecological health of eutrophic lakes. VPA analysis further reveals that water diversion alters the drivers of phytoplankton functional group biomass and phytoplankton diversity. The results of the PLS-PM analysis clarify that water diversion indirectly impacts the total phytoplankton biomass and phytoplankton diversity primarily by modifying light availability. Significant correlations are observed between the dominant functional groups biomass and diversity indices of WQI. The trends in changes observed in water quality indices and phytoplankton following water diversion align with the evaluation of water ecological health. This study provides valuable guidance for the ecological management of the diversion project in Yilong Lake and serves as a reference for similar projects in other lakes. [Display omitted] • Variations in WQI and phytoplankton assemblages integrated to evaluate the positive ecological effects of water diversions. • Rare sub-communities more stable after water diversion. • Hydrodynamic disturbances from water diversions inhibit the dispersal ability of many phytoplankton groups. • WQI was significantly correlated with major phytoplankton functional groups and phytoplankton diversity. • The increased availability of light after water diversion indirectly affects total phytoplankton biomass and diversity. [ABSTRACT FROM AUTHOR]

Vibrio anguillarum infection can activate NF-κB/TNFα pathway in the immune organs of fish. Fish muscle is also an important immune organ, but the research on its immune function is few. Our aim was to study regulating mechanism of NF-κB and TNFα gene expressions in the muscle of Japanese flounder (Paralichthys olivaceus) which was under Vibrio anguillarum infection (0, 24, 48, 72 and 96 h). The results showed that the expressions of NF-κB and TNFα increased significantly at 48 h, and there was a significant positive correlation between them. In situ hybridization confirmed the co-existence of NF-κB and TNFα genes in Japanese flounder muscle. Interestingly, the expression of the TNFα gene was regulated by the DNA methylation and its methylation level was negatively correlated with the expression. The lowest methylation level of TNFα occurred at 48 h under Vibrio anguillarum infection (P < 0.05). And more, when the fragment (−2122 ∼ −730) was deleted on TNFα gene promoter, double luciferase activity was the highest, indicating that fragment (−730–0) was the transcription factor binding region. The site (−78 ~ −69) on the fragment (−730–0) binding NF-κB was mutated, and double luciferase activity decreased significantly. The results confirmed that the site (−78 ~ −69) was indeed an important binding site for NF-κB. In addition, the activity of TNFα in the serum of Japanese flounder changed with the prolongation of vibrio anguillarum infection, and the concentration of other immune factors such as ALP, ALT, AST and LDH also changed in the muscle under vibrio anguillarum infection. They all showed a trend of first increasing and then decreasing. Above studies implied that Japanese flounder responded to Vibrio anguillarum infection at the immune level with the change of its methylation status and the activation of transcription factor. By studying the mechanism of immune pathways, understanding the response to immune stress is great significant to the research of fish breeding for disease resistance. • Immune stress of NF-κB/TNFα pathway immune gene caused by Vibrio anguillarum infection. • The change of epigenetic DNA methylation modification caused by Vibrio anguillarum infection. • The binding site of transcription factor NF-κB on TNFα promoter region was identified. • DNA methylation regulation and transcription factor worked together on immune regulation. [ABSTRACT FROM AUTHOR]

Highlights: [•] HOXA7 regulates MCF7 cell proliferation. [•] HOXA7 up-regulates ERα expression. [•] HOXA7 mediates estrogen-induced MCF7 cell proliferation. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a new family of high-order compact upwind difference schemes. Unknowns included in the proposed schemes are not only the values of the function but also those of its first and higher derivatives. Derivative terms in the schemes appear only on the upwind side of the stencil. One can calculate all the first derivatives exactly as one solves explicit schemes when the boundary conditions of the problem are non-periodic. When the proposed schemes are applied to periodic problems, only periodic bi-diagonal matrix inversions or periodic block-bi-diagonal matrix inversions are required. Resolution optimization is used to enhance the spectral representation of the first derivative, and this produces a scheme with the highest spectral accuracy among all known compact schemes. For non-periodic boundary conditions, boundary schemes constructed in virtue of the assistant scheme make the schemes not only possess stability for any selective length scale on every point in the computational domain but also satisfy the principle of optimal resolution. Also, an improved shock-capturing method is developed. Finally, both the effectiveness of the new hybrid method and the accuracy of the proposed schemes are verified by executing four benchmark test cases. [Copyright &y& Elsevier]

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy. [Display omitted] • Natural products are reliable and powerful sources for cancer drug discovery. • Baicalin and baicalein are two major flavones isolated from Scutellaria baicalensis Georgi. • Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells. • Baicalin and baicalein modulate tumor stromal cells and extracellular matrix in the tumor microenvironment. • Future research needs to reveal TID and improve the bioavailability for clinical applications of baicalin and baicalein. [ABSTRACT FROM AUTHOR]

• We simultaneously introduce P doping and Se vacancies in NiSe 2 nanosheets. • The synergistic effects of P doping and Se vacancies promote HER activities. • DFT results demonstrate the lower Gibbs free energy of adsorbed H* in A-NiSe 2 |P. • A low voltage of 1.62 V is achieved at 10 mA cm−2 for overall water splitting. Element doping is a general and effective approach to modify the electrocatalytic performances, but the low intrinsic activity in each electroactive site still limits the further improvements. Herein, we provide an effective strategy by simultaneously introducing P doping and Se vacancies to enhance the intrinsic activities in NiSe 2 nanosheet arrays (A-NiSe 2 |P) through Ar plasma treatment. Owing to the increased active sites and enhanced electrical conductivity, the resulted A-NiSe 2 |P shows the enhanced hydrogen evolution performances. Theoretical calculations reveal that introduction of Se vacancies plays a significant role in lowering the adsorption free energy of H* in Ni, Se and P sites, leading to promoted intrinsic activities in A-NiSe 2 |P. Further, A-NiSe 2 |P as bifunctional electrocatalysts only needs 1.62 V to reach 10 mA cm−2 for overall water splitting. Our study and understanding of A-NiSe 2 |P may highlight the importance of element doping and vacancies in enhancing the catalytic activities in overall water splitting. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro , but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment. • The first report about protein kinase posttranslational function on occurrence PCOS. • CK2α-AR axis promotes AR and ovulation related genes excessive expression. • CK2α promotes KGN cell line proliferation and inhibits apoptosis. • CK2α-AR pathway may serve as a therapeutic target against PCOS. [ABSTRACT FROM AUTHOR]

Low levels of stresses cause eustress while high stressful situations result in distress. Female rainbow trout (Oncorhynchus mykiss) was reared under crowded conditions to mimic the stressful environment of intensive fishery production. Trout was stocked for 300 days with initial densities of 4.6 ± 0.02 (final: 31.1 ± 0.62), 6.6 ± 0.03 (final: 40.6 ± 0.77), and 8.6 ± 0.04 (final: 49.3 ± 1.09) kg/m3 as SD1, SD2 and SD3. We assessed molecular, cellular and organismal parameters to understand the flexibility of neuro-endocrine-immune network during stress. Trout with higher initial density (SD3) displayed the slightly activated hypothalamus-pituitary-interrenal (HPI) axis with positively increased antioxidant enzyme activities and anti-inflammatory cytokine transcriptions on day 60 or 120. These results indicated that low level of stress was capable of exerting eustress by activating neuro-endocrine-immune network with beneficial adaptation. Transition from eustress to distress was induced by the increased intensity and duration of crowding stress on day 240 and 300. The prolonged activation of HPI axis resulted in suppressed growth hormone-insulin-like growth factor (GH-IGF) axis, up-regulated cytokine transcriptions and severe reactive oxygen species stress. Stress means reset of neuro-endocrine-immune network with energy expenditure and redistribution. Digestive ability of trout with distress was also inhibited on day 240 and 300, indicating a decreased total energy supplement and energy distribution for functions are not necessary for surviving such as growth and reproduction. Consequently, we observed the dyshomeostasis of energy balance and neuro-endocrine-immune network of trout during long-term crowding conditions. Image 1 • Low levels of crowding stress provided eustress with positive HPI activation. • Eustress stimulate adaptive mechanisms in endocrine and immune network. • Long-term crowded conditions cause distress with negatively prolonged HPI activation. • Distress caused maladaptive mechanisms in endocrine and immune network. [ABSTRACT FROM AUTHOR]

• The methylation and expression of myomaker was assessed in Paralichthys olivaceus. • Myomaker expression increased throughout postnatal development. • Methylation was negatively correlated with myomaker expression. • Myomaker is likely a key myoblast fusion and muscle formation gene in P. olivaceus. Myomaker is a membrane protein that plays a crucial role in the fusion of myoblasts during muscle growth. DNA methylation, a significant factor, regulates gene expression. The aim of this study was to examine the methylation and mRNA expression patterns of the myomaker gene during 8 different postnatal developmental stages in the Japanese flounder (L: 7 days post hatch (dph); M1: 21 dph; M2: 28 dph; M3: 35 dph; J1: 90 dph; J2: 180 dph; A1: 24 months; A2: 36 months). Muscle tissue samples were taken from Japanese flounder at different postnatal development stages to measure the extent of DNA methylation and gene expression. Methylation level in the promoter and exon 1 of myomaker was measured using bisulfite sequencing, and the relative expression of myomaker during each developmental stage was measured by quantitative PCR. The relative expression levels of myomaker were up-regulated from stages L to M2, M3 to J2, and methylation of myomaker was negatively correlated with mRNA expression. Furthermore, the CpG site located at −26 bp in the promoter was the lowest methylated region in all developmental stages. These results offer a basis for understanding the mechanism by which myomaker regulates muscle formation during postnatal development. [ABSTRACT FROM AUTHOR]

Toll-like receptor (TLR) genes are the earliest reported pathogen recognition receptors (PRRs) and have been extensively studied. These genes play pivotal roles in the innate immune defense against pathogen invasion. In this study, a total of 16 tlr genes were identified and characterized in spotted sea bass (Lateolabrax maculatus). The tlr genes of spotted sea bass were classified into five subfamilies (tlr1 -subfamily, tlr3 -subfamily, tlr5 -subfamily, tlr7 -subfamily, and tlr11 -subfamily) according to the phylogenetic analysis, and their annotations were confirmed by a syntenic analysis. The protein domain analysis indicated that most tlr genes had the following three major TLR protein domains: a leucine-rich repeat (LRR) domain, a transmembrane region (TM) and a Toll/interleukin-1 receptor (TIR) domain. The tlr genes in spotted sea bass were distributed in 11 of 24 chromosomes. The mRNA expression levels of 16 tlr genes in response to Vibrio harveyi infection were quantified in the head kidney. Most genes were downregulated following V. harveyi infection, while only 5 tlr genes, including tlr1-1 , tlr1-2 , tlr2-2 , tlr5 , and tlr7 , were significantly upregulated. Collectively, these results help elucidate the crucial roles of tlr genes in the immune response of spotted sea bass and may supply valuable genomic resources for future studies investigating fish disease management. • 16 tlr genes were identified and characterized in spotted sea bass. • Phylogenetic and synteny analyses confirmed duplication and comprehensive types of tlr genes in spotted sea bass. • Intron-exon organization and predicted protein domain compositions of tlr genes were studied. • The mRNA expression levels of 16 tlr genes were quantified in the head kidney after V. harveyi challenge. [ABSTRACT FROM AUTHOR]

Apolipoproteins (Apos), which are the protein components of plasma lipoproteins, play important roles in lipid transport in vertebrates. It has been demonstrated that in teleosts, several Apos display antimicrobial activity and play crucial roles in innate immunity. Despite their importance, apo genes have not been systematically characterized in many aquaculture fish species. In our study, a complete set of 23 apo genes was identified and annotated from spotted sea bass (Lateolabrax maculatus). Phylogenetic and homology analyses provided evidence for their annotation and evolutionary relationships. To investigate their potential roles in the immune response, the expression patterns of 23 apo genes were determined in the liver and intestine by qRT-PCR after Vibrio harveyi infection. After infection, a total of 20 differentially expressed apo genes were observed, and their expression profiles varied among the genes and tissues. 5 apo genes (apoA1 , apoA4a.1 , apoC2, apoF and apoO) were dramatically induced or suppressed (log2 fold change >4, P < 0.05), suggesting their involvement in the immune response of spotted sea bass. Our study provides a valuable foundation for future studies aimed at uncovering the specific roles of each apo gene during bacterial infection in spotted sea bass and other teleost species. • A complete set of 23 apo genes was identified and annotated in spotted sea bass. • There exists tandem duplication and cluster events in the arrangement of apo genes. • The expressions of 5 apo genes were dramatically induced or suppressed after Vibrio harveyi infection. [ABSTRACT FROM AUTHOR]

The effects of raw attapulgite clay and thermally modified attapulgite clay on the growth status of submerged plant Vallisneria Spiralis (V. spiralis) and the microenvironment of sediment were first explored. The results demonstrated that the attapulgite could effectively promote the development of V. spiralis and improve plant stress resistance by enhancing the activity of antioxidant enzymes. The 10% addition of attapulgite clay increased the biomass of V. spiralis by 27%∼174%, and the promoted rate of raw attapulgite clay was 2∼5 times of modified attapulgite clay. The attapulgite increased redox potential in sediment (P < 0.05) and provided proper niches for organism propagation, further promoting the degradation of organic matter and nutrient metabolism in sediment. The value of Shannon, Chao, and Ace was 9.98, 4865.15, 5029.08 in the 10% modified attapulgite group, and 10.12, 4856.85, 4947.78 in the 20% raw attapulgite group, respectively, indicating that the attapulgite could increase the microbial diversity and abundance in sediment. Additionally, the nutrient elements, such as Ca, Na, S, Mg, K, Zn, and Mo, that dissolved from attapulgite may also promote the V. spiralis growth. This study provided an environment-friendly approach to facilitating submerged macrophyte restoration in the eutrophic lake ecosystem. [Display omitted] • Effects of attapulgite on V. spiralis growth and sediment microenvironment. • Attapulgite can improve the sediment microenvironment. • Attapulgite can effectively promote the growth of V. spiralis. • Sediment microenvironment was important to plant growth. • Elements dissolved from attapulgite may also promote the plant growth. [ABSTRACT FROM AUTHOR]

The input of agro-pollutants, such as microplastics and nanopesticides, on farmlands is widespread and may facilitate biological invasions in agroecosystems. Here, the effects of agro-pollutants that promote invasion of congener species is studied by examining the growth performance of native Sphagneticola calendulacea and its invasive congener, S. trilobata , when grown in a native only, invasive only and mixed community. Sphagneticola calendulacea naturally occurs in croplands in southern China, while S. trilobata was introduced to this region and has since naturalized, encroaching onto farmland. In our study, each plant community was subjected to the following treatments: control, microplastics only, nanopesticides only, and both microplastics and nanopesticides. The effects of the treatments on soils of each plant community were also examined. We found that aboveground, belowground, and photosynthetic traits of S. calendulacea were significantly inhibited by the combined microplastics and nanopesticides treatment in the native and mixed communities. The relative advantage index of S. trilobata was 69.90% and 74.73% higher under the microplastics only and nanopesticides only treatments respectively compared to S. calendulacea. Soil microbial biomass, enzyme activity, gas emission rates, and chemicals in each community were reduced when treated with both microplastics and nanopesticides. Yet, soil microbial biomass of carbon and nitrogen, CO 2 emission rates and nitrous oxide rates were significantly higher (56.08%, 58.33%, 36.84% and 49.95% respectively) in the invasive species community than in the native species community under microplastics and nanopesticides. Our results suggest that the addition of agro-pollutants to soils favors the more resistant S. trilobata and suppresses the less tolerant S. calendulacea. Soil properties from the native species community are also more impacted by agro-pollutants than substrates supporting the invasive species. Future studies should explore the effects of agro-pollutants by comparing other invasive and native species and considering human activities, industry, and the soil environment. • Plant performance of invasive and native species in response to agro-pollutants. • Invasive S. trilobata had higher competitive ability in response to agro-pollutants. • Increase in soil microbial biomass in the invasive community favoured S. trilobata. • Increase in soil gas emission may increase the invasion of S. trilobata in farmlands. [ABSTRACT FROM AUTHOR]

Abstract High circulating androgen in women with polycystic ovary syndrome (PCOS) may increase the risk of cardiovascular disease in offspring. The aim of the present study is to investigate whether maternal androgen excess in the rat PCOS model would lead to cardiac hypertrophy in offspring. Maternal testosterone propionate (maternal-TP)–treated adult female offspring displayed cardiac hypertrophy associated with local high cardiac dihydrotestosterone (DHT). The molecular markers of cardiac hypertrophy along with androgen receptor (AR) and PKCδ, were increased in the Maternal-TP group. Treatment of primary neonatal rat ventricular cardiomyocytes (NRCMs) and H9c2 cells with DHT significantly increased cell size and upregulated PKCδ expression, which could be attenuated by AR antagonist. Treatment with phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly increased cell size and upregulated myh7 level. Rottlerin, that may inhibit PKCδ, significantly reduced the hypertrophic effect of DHT and PMA on NRCMs and H9c2 cells. Chromatin immunoprecipitation revealed that AR could bind to Pkcδ promoter. Our results indicate that prenatal exposure to testosterone may induce cardiac hypertrophy in adult female rats through enhanced Pkcδ expression in cardiac myocytes. Highlights • Maternal-TP–treated adult female offspring displayed cardiac hypertrophy associated with local high cardiac DHT level. • Androgen regulates PKCδ transcription in cardiomyocytes hypertrophy. • PKCδ may regulate cardiomyocyte growth in vitro. [ABSTRACT FROM AUTHOR]

To study the expression of four estrogen receptor genes ( erα1, erα2, erβ1, erβ2 ) of female rainbow trout ( Oncorhynchus mykiss ) during first ovarian development, trouts were sampled from different ovarian stages. Serum E 2 (estradiol) was measured by ELISA and estrogen receptors mRNA expression were examined by qRT-PCR. Our results showed a close association between increased erα1 and vitellogenin mRNA expression during ovarian maturation and increased erα2 mRNA expression in mature ovarian stages. Correlation analysis revealed that a negative relationship between serum E 2 and ovarian erβ1 (or hepatic erβ2 ), but ovarian erβ2 mRNA expression was relatively unchanged during first ovarian development. Trout were also reared in different densities as stocking density 1, 2 and 3 (SD1, 4.6–31.1 kg/m 3 ; SD2, 6.6–40.6 kg/m 3 ; SD3, 8.6–49.3 kg/m 3 ) to elucidate effects of high density on estrogen receptor expression. Histology observation showed ovarian development of trout in higher densities were retard with a relatively early stage and fewer vitellogenin accumulation. Trout in high densities showed significantly decreased serum E 2 , erα mRNA expression and increasing trends of erβ mRNA expression. A noticeable increase of ovarian erβ2 mRNA expression was seen in trout when density is approaching to 50 kg/m 3 . In conclusion, we may hypothesize that increased erβ mRNA expression triggered by high density result in decreased erα mRNA expression and vitellogenesis. As a result, ovarian development in higher densities was retard. [ABSTRACT FROM AUTHOR]

Three serum amyloid A (SAA) genes were identified from the common carp ( Cyprinus carpio ) by PCR and RT-PCR. Considering both direction and sequence similarity with mammal's orthologs, they were named CcSAA3a, CcSAA3b and CcSAA1 . CcSAA3b and CcSAA1 are adjacent on contig LHQP01017858, suggesting that the prototype of or the simplest SAA multigene family have occurred in common carp. A phylogenetic analysis of the SAAs indicated that the fish SAAs were closer to those of invertebrates and Ornithorhynchus anatinus , a primitive mammal, than to mammalian SAAs. Quantitative real-time RT-PCR results displayed different expression profiles of three CcSAAs . The CcSAA3a was detected in all tested tissues, and was most abundant in the muscle; CcSAA3b was predominately expressed in the intestine and liver, and CcSAA1 in the skin. The expression level of CcSAA3a was higher than that of CcSAA3b and CcSAA1 in most tissues. Stimulation with Aeromonas hydrophila dramatically induced the expression of the three CcSAAs in all examined tissues, especially in the liver. Like Epinephelus coioides SAA, all of three rCcSAA fusion proteins could bind to both Gram-negative bacteria ( A. hydrophila and E. coli ) and Gram-positive bacterium ( S. aureus ), playing a role in the identification of bacteria. However, only rCcSAA3a showed significantly anti- A. hydrophila and anti- E. coli in vitro antibacterial activity assays. These results suggested that the three CcSAAs were in functional differentiation and play significant roles in the innate immunity of common carp. [ABSTRACT FROM AUTHOR]

Inflammatory mediators and adhesion molecules have been implicated in a variety of diseases including atherosclerosis. As both the mediator-releasing and targeted cells, vascular endothelial cells play key role in pathological processes. NF-κB signaling regulates a cluster of inflammatory factors in LPS-activated vascular endothelial cells but the underlying mechanisms remain largely unknown. Here, we investigated the epigenetic regulation of LPS upon the expression of inflammatory mediators and adhesion molecules. We found that LPS treatment promoted jmjd3 expression, enhanced Jmjd3 nuclear accumulation in human vascular endothelial cells. In addition, LPS enhanced the demethylation of H3K27me3, a specific substrate of Jmjd3. LPS treatment recruited Jmjd3 and NF-κB to the promoter region of target genes, suggesting Jmjd3 synergizes with NF-κB to activate the expression of target genes. We further found that Jmjd3 attenuated the methylation status in promoter region of target genes, culminating in target gene expression. Our findings unveil epigenetic regulations of LPS upon NF-κB pathway and identify Jmjd3 as a critical modulator of NF-κB pathway and potential therapeutic target for NF-κB related diseases including atherosclerosis. [ABSTRACT FROM AUTHOR]

Common carp ( Cyprinus carpio ) is a widespread freshwater fish and economically important species in China and other East Asian countries. Recent studies suggest that insulin can alter the expression of immune genes and, thus, can be regarded as an immunomodulatory hormone. To understand the mechanism of the immune response to insulin, we performed a comparative RNA-seq transcriptome analysis using livers from common carp injected with insulin (5 μg/g bodyweight) or saline as a control. After filtering the low-quality reads and removing the adaptors, the clean raw reads were assembled into 60,421 unigenes with mean length of 746.81 bp. Furthermore, 37,107 unigenes were annotated based on homology after blast search in public databases. Differentially expressed genes were identified using the fragments per kb per million fragments method and EdgeR software. In total, 782 differentially expressed genes were found. Thereinto, 444 and 338 genes were upregulated and downregulated, respectively, in the insulin-injected group. A Gene Ontology analysis indicated that these genes were concentrated in glucose metabolism, hormone secretion, andimmune system processes. Moreover, 153 enriched KEGG pathways were associated with the differentially expressed genes, including the Toll-like receptor (TLR) and nuclear factor kappa beta (NF-κB) signaling pathways. Signal transducer and activator of transcription 1 (10.56-fold), TLR3 (0.089-fold), activator protein-1 (0.007-fold), tumor necrosis factor-α (0.139-fold), and macrophage inflammatory protein-1β (0.038-fold) expression were significantly changed after the insulin injection. This study characterized the profile of genes expression response to insulin in common carp liver for the first time and provided new insight into understanding the molecular mechanism of insulin as an immunomodulatory hormone. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the hypothalamus-pituitary-gonad (HPG) axis of female rainbow trout ( Oncorhynchus mykiss ) during early ovarian development and under high rearing density. Trouts were sampled from 240 (ovarian stage II) to 540 (ovarian stage IV) days following hatching (DFH) as control group (Ctrl, 4.6–31.1 kg/m 3 ) to determine HPG axis during early ovarian development. Trouts from the same batch of fertilized eggs were reared in two higher densities during 240–540 DFH as stocking density 1 and 2 (SD1, 6.6–40.6 kg/m 3 ; SD2, 8.6–49.3 kg/m 3 ) to elucidate effects of high density on reproductive parameters. Dopamine, E 2 (estradiol), 17α,20β-P (17α,20β-dihydroxy4-pregnen-3-one) and P4 (progesterone) were evaluated by radioimmunoassay or ELISA. mRNA expression of hypothalamic gnrh-1, -2 (gonadotropin-releasing hormone-1, -2), pituitary gonadotropins ( fsh/lh , follicle-stimulating hormone/luteinizing hormone) and their cognate receptors ( fshr/lhr ) in ovaries were examined by qRT-PCR. Our findings demonstrated mRNA expression of hypothalamic sgnrh-1 , pituitary fsh and ovarian fshr increased in early ovarian development (360 DFH). Serum 17α,20β-P and pituitary lh mRNA expression first increased when trouts were in ovarian stage III (420 DFH). Ovaries were at different stages when reared in different densities. Long-term high density treatment (over 31.7 kg/m 3 ) resulted in decreased hypothalamic sgnrh-1 , pituitary fsh , ovarian fshr , serum E 2 , and increased hypothalamus gnrh-2 and serum dopamine during vitellogenin synthesis, suggesting HPG of rainbow trout might be retarded under dense rearing condition. [ABSTRACT FROM AUTHOR]

While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP. The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated. The fitted curves for ICP incidence were similar to the temporal trends of PM 2.5 , PM 10 , SO 2 , CO and NO 2 but not that of O 3. The risk of ICP was significantly elevated following a 10-μg/m3 increase in PM 2.5 (aOR [adjusted odds ratio] = 1.057, 95% CI [confidence interval]: 1.017–1.099) and PM 10 (aOR = 1.043, 95% CI: 1.013–1.074) and a 1-h decrease in sunshine duration (aOR = 1.039, 95% CI: 1.011–1.068) during the 3 months before conception. In the second trimester, a 1-μg/m3 increase in the concentration of SO 2 was associated with an increased risk of ICP (aOR = 1.011, 95% CI: 1.001–1.021). Increased concentrations of PM 2.5 and PM 10 had interactive effects with reduced sunshine duration during the 3 months before conception on increasing the risk of ICP. Exposure to PM 2.5 and PM 10 during the 3 months before conception and exposure to SO 2 in the second trimester were associated with an increased ICP risk. Reduced sunshine duration had an interactive effect with increased concentrations of PM 2.5 and PM 10 during the 3 months before conception on the occurrence of ICP. [Display omitted] • This is the first study to explore the effects of air pollutants on ICP. • Three months preconception is a sensitive exposure window for PM on ICP. • PM 2.5 and PM 10 interact with less sunshine duration to increase the risk of ICP. • Increased concentrations of SO 2 in the 2nd trimester aggregate the risk of ICP. [ABSTRACT FROM AUTHOR]

There has been a long debate about the neural mechanism of event-related potentials (ERPs). Previously, no evidence or method was apparent to validate the two competing models, the evoked model and the oscillation model. One argument is whether the pre-stimulus brain oscillation could influence the following ERP. This study carried out an innovative visual oddball task experiment to investigate the dynamic process of visual evoked potentials. A period of stable oscillations of specified dominant frequencies and initial phases, i.e. the steady-state baseline, would be induced before responses to transient stimuli of different contrasts, which could overcome the artifact problem caused by the ‘sorting’ method. The result first revealed a ‘three-period-transition’ for the generation of visual evoked potentials by an objective decomposition. The ERP almost retained the preceding oscillation during the first period, provided an unstable negative potential in the second period, and generated the N1 component in the third period. The cross term analysis showed that the evoked model couldn't be the whole explanation for the ERP generation. Furthermore, the component analysis revealed that the N1 latency was sensitive to the initial phase under the low stimulus contrast (supporting the oscillation model) but not under the high stimulus contrast (supporting the evoked model). It demonstrated that the external stimulus contrast is a significant factor deciding the explicit model for ERPs. Our method and preliminary results may help reconcile the previous, seemly contradictory findings on the ERP mechanism. [ABSTRACT FROM AUTHOR]

Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM 2.5 , PM 10, SO 2 , CO, NO 2 , and O 3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. The risk for developing PPD symptoms was significant following a 10 μg/m3 increase in PM 10 (aOR = 1.47, 95%CI:1.36–1.59), NO 2 (aOR = 1.63, 95%CI:1.44–1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99–2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO 2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03–1.18). Consistent effects were also observed in DLMs, except for PM 2.5 and O 3 , which showed no significant sensitive windows throughout pregnancy period. Exposure to PM 10 , CO, NO 2 , and SO 2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public. [Display omitted] • Exposure to PM10, NO2 and CO in pregnancy increased risk of developing depression at 6 weeks postpartum. •The second trimester of pregnancy was the most susceptible period for developing PPD when exposed to SO2. •Prenatal exposure to multiple ambient air pollutants may contribute to development of PPD. [ABSTRACT FROM AUTHOR]

Upf1, Upf2, and Upf3 are the principal regulators of nonsense-mediated mRNA decay (NMD), a cytoplasmic surveillance pathway that accelerates the degradation of mRNAs undergoing premature translation termination. These three proteins interact with each other, the ribosome, the translation termination machinery, and multiple mRNA decay factors, but the precise mechanism allowing the selective detection and degradation of nonsense-containing transcripts remains elusive. Here, we have determined the crystal structure of the N-terminal mIF4G domain from Saccharomyces cerevisiae Upf2 and identified a highly conserved region in this domain that is essential for NMD and independent of Upf2's binding sites for Upf1 and Upf3. Mutations within this conserved region not only inactivate NMD but also disrupt Upf2 binding to specific proteins, including Dbp6, a DEAD-box helicase. Although current models indicate that Upf2 functions principally as an activator of Upf1 and a bridge between Upf1 and Upf3, our data suggest that it may also serve as a platform for the association of additional factors that play roles in premature translation termination and NMD. [ABSTRACT FROM AUTHOR]

Abstract: The gene encoding HSP70 was isolated from Korean rockfish Sebastes schlegeli by homologous cloning and rapid amplification of cDNA ends (RACE). The full-length of HSP70 cDNA was composed of 2259 bp and encoded a polypeptide of 639 amino acids. BLAST analysis showed that HSP70 of S. schlegeli shared high identities with those of the Lates calcarifer, Oreochromis niloticus, Seriola quinqueradiata HSP70s (88–89%). Our current study also revealed that HSP70 of Korean rockfish was expressed in many tissues by RT-PCR under unstressed condition. Quantitative real-time PCR showed that the expression patterns of Korean rockfish HSP70 were developmental stage-dependency. The expression of HSP70 was measured by quantitative real-time PCR after different oxygen treatments. The results showed that expression of HSP70 increased significantly after exposure to hypoxia for 30 min in gill and ovary, and then decreased for 60 min, and the level in spleen and liver gradually increased and reached the highest at 60 min. In addition, in gill, spleen and liver, the HSP70 mRNA level reached the maximum in hypoxia group after one hour different oxygen concentration stress. Increased amounts of serum thyroxine (T4), and triiodothyronine (T3) were also found during 30 min hypoxia treatment and 60 min normoxia group in our study. All of the results provide information to further study the mechanism of physiology and immune function under stress conditions of ovoviviparous teleosts. [Copyright &y& Elsevier]

The effects of clay mineral bentonite on the growth process of submerged macrophyte V. spiralis and sediment microenvironment were investigated in the study for the first time, aiming to determine whether it is suitable for application in the field of ecological restoration. The growth index, and physiological and biochemical index of V. spiralis in the experiments were measured once a month, and the changes of rhizosphere microorganisms and physicochemical properties of sediments were also studied at the same time. The results demonstrated that bentonite can effectively promote the growth of V. spiralis. The treatment groups of RB1/1 and MB1/5 (the mass ratios of bentonite to sediment were 1/1 and 1/5, respectively.) showed the best V. spiralis growth promotion rates which were 18.78%, and 11.79%, respectively. The highest microbial diversity and abundance existed in group of RB10 (the mass ratio of sediment to bentonite was 10/1), in which the OTUs, Shannon, Chao and Ace were 1521.0, 5.20, 1712.26, and 1686.31, respectively. Bentonite was conducive to the propagation of rhizosphere microorganisms, and further changed the physical and chemical properties of the sediment microenvironment. The nutrient elements dissolved from bentonite may be one of the main reasons that promoted the growth of V. spirali s. The purpose of this result is to prove that bentonite can be further applied as sediment improver and growing media in ecological restoration projects in eutrophic shallow lakes. [Display omitted] • Effects of bentonite on growth process of V. spiralis and sediment microenvironment. • Bentonite can effectively promote the growth of V. spiralis. • Bentonite was conducive to the propagation of rhizosphere microorganisms. • Bentonite changed physical and chemical properties of the sediment microenvironment. • Nutrient dissolved from bentonite may be a reason promoted growth of V. spiralis. Bentonite can effectively promote the growth of V. spiralis. Bentonite was conducive to the propagation of rhizosphere microorganisms, and further changed the physical and chemical properties of the sediment microenvironment. [ABSTRACT FROM AUTHOR]