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Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the terpenoid biosynthesis pathway, responsible for converting isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) into farnesyl pyrophosphate (FPP). In crustaceans, FPPS plays an important role in various physiological processes, particularly in synthesizing the crustacean-specific hormone methyl farnesoate (MF). This study analyzed the evolutionary differences in the physicochemical properties, subcellular localization, gene structure, and motif composition of FPPS in Neocaridina denticulata sinensis (named NdFPPS) compared to other species. The significant evolutionary divergence of FPPS was observed in crustaceans, likely linked to its role in MF synthesis. After the RNA interference (RNAi)-mediated knockdown of NdFPPS, transcriptomic analysis of gills revealed the significant enrichment of differentially expressed genes (DEGs) in pathways related to metabolism and immunity. Gene set enrichment analysis (GSEA) showed that most of these immune-related pathways were significantly suppressed, suggesting that NdFPPS may indirectly regulate the immune response by modulating metabolic levels. During the early stages of Vibrio parahaemolyticus infection, the expression of NdFPPS in the gills was significantly downregulated and subsequently returned to its original levels. Overall, our results provide new perspectives on the role of FPPS in immune regulation and enrich the functional information of FPPS. [ABSTRACT FROM AUTHOR]

With the progress of society and the improvement of agricultural scientific technology, the single focus on high yield for rice production has gradually shifted to high quality. Coordinated development of grain yield and rice quality has become a core issue for researchers, and the underlying mechanisms remain to be solved. Two varieties, Zhongzheyou1 (ZZY1) and Zhongzheyou8 (ZZY8), were used as study materials under field conditions. The yield of ZZY1 was higher than that of ZZY8, which was mainly characterized by a higher seed-setting rate and grain weight. The rice quality of ZZY8 was better than that of ZZY1, primarily due to lower chalkiness and a higher head rice rate. The total dry matter weight of ZZY1 was lower than that of ZZY8, but the proportion of panicle dry matter weight or nonstructural carbohydrate to the total in the former was higher than that of the latter. The maximum grain-filling rate, average grain-filling rate, and key enzyme activities of ZZY1 were significantly higher than those of ZZY8, while the active grain-filling period was shorter than that of ZZY8. Furthermore, the ATP/ATPase content and energy charge values in the grains of ZZY1 were higher than those of ZZY8 at the early grain-filling stage. Transcriptome analysis showed that carbohydrate and energy metabolism were the main ways affecting the yield and quality of the two varieties. The energy production of ZZY1 was insufficient to simultaneously supply the needs thus leading to the discordant formation in its grain yield and rice quality formation. [ABSTRACT FROM AUTHOR]

Fibroblasts, the principal cellular mediators of connective tissue remodeling, play a crucial role in the formation of physiological and pathological scars. Understanding the intricate interplay between fibroblasts and other cellular and molecular components is essential for elucidating the underlying mechanisms driving scar formation. Hypertrophic scars, keloids and atrophic scars arise from dysregulated wound healing processes characterized by persistent inflammation, aberrant collagen deposition, and impaired extracellular matrix remodeling. Fibroblasts play a central role in the pathogenesis of such pathological scars, driving aberrant extracellular matrix remodeling, subsequently contributing to the formation of raised or depressed fibrotic lesions. The investigation of complex interactions between fibroblasts and the microenvironment is crucial for developing targeted therapeutic interventions aimed at modulating fibroblast activity and improving clinical outcomes in patients with pathological scars. Further research into the molecular pathways governing fibroblast behavior and their heterogeneity holds promise for advancing scar management strategies. This narrative review was performed to shed light on the mechanisms behind scar formation, with a special focus on the role of fibroblasts in the formation of different types of scars, providing insights into the pathophysiology of these conditions. Through the analysis of current knowledge, this review seeks to identify the key cellular and molecular mechanisms involved in fibroblast activation, collagen synthesis, and extracellular matrix remodeling in hypertrophic scar, keloid, or atrophic scar formation. [ABSTRACT FROM AUTHOR]

Riboswitches are highly structured RNA regulators of gene expression. Although found in all three domains of life, they are particularly abundant and widespread in bacteria, including many human pathogens, thus making them an attractive target for antimicrobial development. Moreover, the functional versatility of riboswitches to recognize a myriad of ligands, including ions, amino acids, and diverse small-molecule metabolites, has enabled the generation of synthetic aptamers that have been used as molecular probes, sensors, and regulatory RNA devices. Generally speaking, a riboswitch consists of a ligand-sensing aptamer domain and an expression platform, whose genetic control is achieved through the formation of mutually exclusive secondary structures in a ligand-dependent manner. For most riboswitches, this involves formation of the aptamer's P1 helix and the regulation of its stability, whose competing structure turns gene expression ON/OFF at the level of transcription or translation. Structural knowledge of the conformational changes involving the P1 regulatory helix, therefore, is essential in understanding the structural basis for ligand-induced conformational switching. This review provides a summary of riboswitch cases for which ligand-free and ligand-bound structures have been determined. Comparative analyses of these structures illustrate the uniqueness of these riboswitches, not only in ligand sensing but also in the various structural mechanisms used to achieve the same end of regulating switch helix stability. In all cases, the ligand stabilizes the P1 helix primarily through coaxial stacking interactions that promote helical continuity. [ABSTRACT FROM AUTHOR]

In this work, energetic coordination compounds (ECCs) of transition metals (Fe, Ni, Cu, Zn) containing aliphatic amines as ligands were synthesized: ethylenediamine; 1,3-diaminopropane; tris(2-aminoethyl)amine; tris(3-aminopropyl)amine. The compounds were investigated in terms of ignition/explosion temperature, friction and impact sensitivity. For selected compounds, structural characterisation was presented (IR-ATR spectroscopy, Raman spectroscopy) and their morphology was determined (SEM, powder XRD). They were also investigated by differential scanning calorimetry (DSC). In order to assess the potential application of selected ECCs in detonators, underwater explosion tests were carried out, determining energetic performance. The results achieved for detonators containing ECCs were compared with those for reference detonators (containing pentaerythritol tetranitrate, PETN), indicating their potential use as a "green" alternative to nitric acid esters. [ABSTRACT FROM AUTHOR]

The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors. [ABSTRACT FROM AUTHOR]

China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb—the largest yet reported among bivalves—and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization. [ABSTRACT FROM AUTHOR]

Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000–2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis. [ABSTRACT FROM AUTHOR]

Skin injury always results in fibrotic, non-functional scars in adults. Although multiple factors are well-known contributors to scar formation, the precise underlying mechanisms remain elusive. This review aims to elucidate the intricacies of the wound healing process, summarize the known factors driving skin cells in wounds toward a scarring fate, and particularly to discuss the impact of fibroblast heterogeneity on scar formation. To the end, we explore potential therapeutic interventions used in the treatment of scarring wounds. [ABSTRACT FROM AUTHOR]

Dramatic shifts in global climate have intensified abiotic and biotic stress faced by plants. Plant microRNAs (miRNAs)—20–24 nucleotide non-coding RNA molecules—form a key regulatory system of plant gene expression; playing crucial roles in plant growth; development; and defense against abiotic and biotic stress. Moreover, they participate in cross-kingdom communication. This communication encompasses interactions with other plants, microorganisms, and insect species, collectively exerting a profound influence on the agronomic traits of crops. This article comprehensively reviews the biosynthesis of plant miRNAs and explores their impact on plant growth, development, and stress resistance through endogenous, non-transboundary mechanisms. Furthermore, this review delves into the cross-kingdom regulatory effects of plant miRNAs on plants, microorganisms, and pests. It proceeds to specifically discuss the design and modification strategies for artificial miRNAs (amiRNAs), as well as the protection and transport of miRNAs by exosome-like nanovesicles (ELNVs), expanding the potential applications of plant miRNAs in crop breeding. Finally, the current limitations associated with harnessing plant miRNAs are addressed, and the utilization of synthetic biology is proposed to facilitate the heterologous expression and large-scale production of miRNAs. This novel approach suggests a plant-based solution to address future biosafety concerns in agriculture. [ABSTRACT FROM AUTHOR]

Soluble epoxide hydrolase (sEH) is an important enzyme for metabolic and cardiovascular health. sEH converts FFA epoxides (EpFAs), many of which are regulators of various cellular processes, to biologically less active diols. In human studies, diol (sEH product) to EpFA (sEH substrate) ratios in plasma or serum have been used as indices of sEH activity. We previously showed these ratios profoundly decreased in rats during acute feeding, possibly reflecting decreases in tissue sEH activities. The present study was designed to test which tissue(s) these measurements in the blood represent and if factors other than sEH activity, such as renal excretion or dietary intake of EpFAs and diols, significantly alter plasma EpFAs, diols, and/or their ratios. The results show that postprandial changes in EpFAs and diols and their ratios in plasma were very similar to those observed in the liver but not in other tissues, suggesting that the liver is largely responsible for these changes in plasma levels. EpFAs and diols were excreted into the urine, but their levels were not significantly altered by feeding, suggesting that renal excretion of EpFAs and diols may not play a major role in postprandial changes in circulating EpFAs, diols, or their ratios. Diet intake had significant impacts on circulating EpFA and diol levels but not on diol-to-EpFA (D-to-E) ratios, suggesting that these ratios, reflecting sEH activities, may not be significantly affected by the availability of sEH substrates (i.e., EpFAs). In conclusion, changes in FFA D-to-E ratios in plasma may reflect those in the liver, which may in turn represent sEH activities in the liver, and they may not be significantly affected by renal excretion or the dietary intake of EpFAs and diols. [ABSTRACT FROM AUTHOR]

Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators. [ABSTRACT FROM AUTHOR]

Epigenetics is a rapidly developing science that has gained a lot of interest in recent years due to the correlation between characteristic epigenetic marks and cardiovascular diseases (CVDs). Epigenetic modifications contribute to a change in gene expression while maintaining the DNA sequence. The analysis of these modifications provides a thorough insight into the cardiovascular system from its development to its further functioning. Epigenetics is strongly influenced by environmental factors, including known cardiovascular risk factors such as smoking, obesity, and low physical activity. Similarly, conditions affecting the local microenvironment of cells, such as chronic inflammation, worsen the prognosis in cardiovascular diseases and additionally induce further epigenetic modifications leading to the consolidation of unfavorable cardiovascular changes. A deeper understanding of epigenetics may provide an answer to the continuing strong clinical impact of cardiovascular diseases by improving diagnostic capabilities, personalized medical approaches and the development of targeted therapeutic interventions. The aim of the study was to present selected epigenetic pathways, their significance in cardiovascular diseases, and their potential as a therapeutic target in specific medical conditions. [ABSTRACT FROM AUTHOR]

The hard-shell mussel (Mytilus coruscus) is widespread in the temperate coastal areas of the northwest Pacific and holds a significant position in the shellfish aquaculture market in China. However, the natural resources of this species have been declining, and population genetic studies of M. coruscus are also lacking. In this study, we conducted whole-genome resequencing (WGR) of M. coruscus from eight different latitudes along the Chinese coast and identified a total of 25,859,986 single nucleotide polymorphism (SNP) markers. Our findings indicated that the genetic diversity of M. coruscus from the Zhoushan region was lower compared with populations from other regions. Furthermore, we observed that the evolutionary tree clustered into two primary branches, and the Zhangzhou (ZZ) population was in a separate branch. The ZZ population was partly isolated from populations in other regions, but the distribution of branches was not geographically homogeneous, and a nested pattern emerged, consistent with the population differentiation index (FST) results. To investigate the selection characteristics, we utilized the northern M. coruscus populations (Dalian and Qingdao) and the central populations (Zhoushan and Xiangshan) as reference populations and the southern ZZ population as the target population. Our selection scan analysis identified several genes associated with thermal responses, including Hsp70 and CYP450. These genes may play important roles in the adaptation of M. coruscus to different living environments. Overall, our study provides a comprehensive understanding of the genomic diversity of coastal M. coruscus in China and is a valuable resource for future studies on genetic breeding and the evolutionary adaptation of this species. [ABSTRACT FROM AUTHOR]

Peroxynitrite (ONOO−) is a crucial reactive oxygen species that plays a vital role in cellular signal transduction and homeostatic regulation. Determining and visualizing peroxynitrite accurately in biological systems is important for understanding its roles in physiological and pathological activity. Among the various detection methods, fluorescent probe-based spectroscopic detection offers real-time and minimally invasive detection, high sensitivity and selectivity, and easy structural and property modification. This review categorizes fluorescent probes by their fluorophore structures, highlighting their chemical structures, recognition mechanisms, and response behaviors in detail. We hope that this review could help trigger novel ideas for potential medical diagnostic applications of peroxynitrite-related molecular diseases. [ABSTRACT FROM AUTHOR]

Previous studies have found that Bifidobacterium infantis-mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN−45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF−1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV. [ABSTRACT FROM AUTHOR]

Mitochondria are essential for spermiogenesis. Prohibitins (PHBs; prohibitin 1, PHB1 or PHB, and prohibitin 2, PHB2) are evolutionarily conserved and ubiquitously expressed mitochondrial proteins that act as scaffolds in the inner mitochondrial membrane. In this study, we analyzed the molecular structure and dynamic expression characteristics of Ot-PHBs, observed the colocalization of Ot-PHB1 with mitochondria and polyubiquitin, and studied the effect of phb1 knockdown on mitochondrial DNA (mtDNA) content, reactive oxygen species (ROS) levels, and apoptosis-related gene expression in spermatids. Our aim was to explore the effect of Ot-PHBs on mitochondrial function during the spermiogenesis of Octopus tankahkeei (O. tankahkeei), an economically important species in China. The predicted Ot-PHB1/PHB2 proteins contained an N-terminal transmembrane, a stomatin/prohibitin/flotillin/HflK/C (SPFH) domain (also known as the prohibitin domain), and a C-terminal coiled-coil domain. Ot-phb1/phb2 mRNA were widely expressed in the different tissues, with elevated expression in the testis. Further, Ot-PHB1 and Ot-PHB2 were highly colocalized, suggesting that they may function primarily as an Ot-PHB compiex in O. tankahkeei. Ot-PHB1 proteins were mainly expressed and localized in mitochondria during spermiogenesis, implying that their function may be localized to the mitochondria. In addition, Ot-PHB1 was colocalized with polyubiquitin during spermiogenesis, suggesting that it may be a polyubiquitin substrate that regulates mitochondrial ubiquitination during spermiogenesis to ensure mitochondrial quality. To further investigate the effect of Ot-PHBs on mitochondrial function, we knocked down Ot-phb1 and observed a decrease in mtDNA content, along with increases in ROS levels and the expressions of mitochondria-induced apoptosis-related genes bax, bcl2, and caspase-3 mRNA. These findings indicate that PHBs might influence mitochondrial function by maintaining mtDNA content and stabilizing ROS levels; in addition, PHBs might affect spermatocyte survival by regulating mitochondria-induced apoptosis during spermiogenesis in O. tankahkeei. [ABSTRACT FROM AUTHOR]

Neuroinflammation is one of the postulated mechanisms for Pb neurotoxicity. However, the exact molecular mechanisms responsible for its pro-inflammatory effect are not fully elucidated. In this study, we examined the role of glial cells in neuroinflammation induced by Pb exposure. We investigated how microglia, a type of glial cell, responded to the changes caused by perinatal exposure to Pb by measuring the expression of Iba1 at the mRNA and protein levels. To assess the state of microglia, we analyzed the mRNA levels of specific markers associated with the cytotoxic M1 phenotype (Il1b, Il6, and Tnfa) and the cytoprotective M2 phenotype (Arg1, Chi3l1, Mrc1, Fcgr1a, Sphk1, and Tgfb1). Additionally, we measured the concentration of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). To assess the reactivity and functionality status of astrocytes, we analyzed the GFAP (mRNA expression and protein concentration) as well as glutamine synthase (GS) protein level and activity. Using an electron microscope, we assessed ultrastructural abnormalities in the examined brain structures (forebrain cortex, cerebellum, and hippocampus). In addition, we measured the mRNA levels of Cxcl1 and Cxcl2, and their receptor, Cxcr2. Our data showed that perinatal exposure to Pb at low doses affected both microglia and astrocyte cells' status (their mobilization, activation, function, and changes in gene expression profile) in a brain-structure-specific manner. The results suggest that both microglia and astrocytes represent a potential target for Pb neurotoxicity, thus being key mediators of neuroinflammation and further neuropathology evoked by Pb poisoning during perinatal brain development. [ABSTRACT FROM AUTHOR]

CLEC16A is emerging as an important genetic risk factor for several autoimmune disorders and for Parkinson disease (PD), opening new avenues for translational research and therapeutic development. While the exact role of CLEC16A in health and disease is still being elucidated, the gene plays a critical role in the regulation of autophagy, mitophagy, endocytosis, intracellular trafficking, immune function, and in biological processes such as insulin secretion and others that are important to cellular homeostasis. As shown in both human and animal modeling studies, CLEC16A hypofunction predisposes to both autoinflammatory phenotype and neurodegeneration. While the two are clearly related, further functional studies are needed to fully understand the mechanisms involved for optimized therapeutic interventions. Based on recent data, mitophagy-inducing drugs may be warranted, and such therapy should be tested in clinical trials as these drugs would tackle the underlying pathogenic mechanism (s) and could treat or prevent symptoms of autoimmunity and neurodegeneration in individuals with CLEC16A risk variants. Accordingly, interventions directed at reversing the dysregulated mitophagy and the consequences of loss of function of CLEC16A without activating other detrimental cellular pathways could present an effective therapy. This review presents the emerging role of CLEC16A in health and disease and provides an update on the disease processes that are attributed to variants located in the CLEC16A gene, which are responsible for autoimmune disorders and neurodegeneration with emphasis on how this information is being translated into practical and effective applications in the clinic. [ABSTRACT FROM AUTHOR]

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent public health problem. Spike (S) protein mediates the fusion between the virus and the host cell membranes, consequently emerging as an important target of drug design. The lack of comparisons of in situ full-length S homotrimer structures in different states hinders understanding the structures and revealing the function, thereby limiting the discovery and development of therapeutic agents. Here, the steady-state structures of the in situ full-length S trimer in closed and open states (Sclosed and Sopen) were modeled with the constraints of density maps, associated with the analysis of the dynamic structural differences. Subsequently, we identified various regions with structure and property differences as potential binding pockets for ligands that promote the formation of inactive trimeric protein complexes. By using virtual screening strategy and a newly defined druggable cavity, five ligands were screened with potential bioactivities. Then molecular dynamic (MD) simulations were performed on apo protein structures and ligand bound complexes to reveal the conformational changes upon ligand binding. Our simulation results revealed that sulforaphane (SFN), which has the best binding affinity, could inhibit the conformational changes of S homotrimer that would occur during the viral membrane fusion. Our results could aid in the understanding of the regulation mechanism of S trimer aggregation and the structure-activity relationship, facilitating the development of potential antiviral agents. [ABSTRACT FROM AUTHOR]

In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a–d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response. [ABSTRACT FROM AUTHOR]

Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development and design of nanodevices with the ability to process time-related information could facilitate the development of molecular information processing systems. Here, we proposed a DNA finite-state machine that can dynamically respond to sequential stimuli signals. To build this state machine, a programmable allosteric strategy of DNAzyme was developed. This strategy performs the programmable control of DNAzyme conformation using a reconfigurable DNA hairpin. Based on this strategy, we first implemented a finite-state machine with two states. Through the modular design of the strategy, we further realized the finite-state machine with five states. The DNA finite-state machine endows molecular information systems with the ability of reversible logic control and order detection, which can be extended to more complex DNA computing and nanomachines to promote the development of dynamic nanotechnology. [ABSTRACT FROM AUTHOR]

MADS-box genes encode transcription factors that affect plant growth and development. Camellia chekiangoleosa is an oil tree species with ornamental value, but there have been few molecular biological studies on the developmental regulation of this species. To explore their possible role in C. chekiangoleosa and lay a foundation for subsequent research, 89 MADS-box genes were identified across the whole genome of C. chekiangoleosa for the first time. These genes were present on all the chromosomes and were found to have expanded by tandem duplication and fragment duplication. Based on the results of a phylogenetic analysis, the 89 MADS-box genes could be divided into either type I (38) or type II (51). Both the number and proportion of the type II genes were significantly greater than those of Camellia sinensis and Arabidopsis thaliana, indicating that C. chekiangoleosa type II genes experienced a higher duplication rate or a lower loss rate. The results of both a sequence alignment and a conserved motif analysis suggest that the type II genes are more conserved, meaning that they may have originated and differentiated earlier than the type I genes did. At the same time, the presence of extra-long amino acid sequences may be an important feature of C. chekiangoleosa. Gene structure analysis revealed the number of introns of MADS-box genes: twenty-one type I genes had no introns, and 13 type I genes contained only 1~2 introns. The type II genes have far more introns and longer introns than the type I genes do. Some MIKCC genes have super large introns (≥15 kb), which are rare in other species. The super large introns of these MIKCC genes may indicate richer gene expression. Moreover, the results of a qPCR expression analysis of the roots, flowers, leaves and seeds of C. chekiangoleosa showed that the MADS-box genes were expressed in all those tissues. Overall, compared with that of the type I genes, the expression of the type II genes was significantly higher. The CchMADS31 and CchMADS58 genes (type II) were highly expressed specifically in the flowers, which may in turn regulate the size of the flower meristem and petals. CchMADS55 was expressed specifically in the seeds, which might affect seed development. This study provides additional information for the functional characterization of the MADS-box gene family and lays an important foundation for in-depth study of related genes, such as those involved in the development of the reproductive organs of C. chekiangoleosa. [ABSTRACT FROM AUTHOR]

The Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), which is a vital member of the plant receptor-like kinase family, plays versatile roles in plant growth, development, and stress response. Although the primary screening of tomato CrRLK1Ls has been reported previously, our knowledge of these proteins is still scarce. Using the latest genomic data annotations, a genome-wide re-identification and analysis of the CrRLK1Ls in tomatoes were conducted. In this study, 24 CrRLK1L members were identified in tomatoes and researched further. Subsequent gene structures, protein domains, Western blot analyses, and subcellular localization analyses all confirmed the accuracy of the newly identified SlCrRLK1L members. Phylogenetic analyses showed that the identified SlCrRLK1L proteins had homologs in Arabidopsis. Evolutionary analysis indicated that two pairs of the SlCrRLK1L genes had predicted segmental duplication events. Expression profiling analyses demonstrated that the SlCrRLK1L genes were expressed in various tissues, and most of them were up- or down-regulated by bacteria and PAMP treatments. Together, these results will lay the foundation for elaborating the biological roles of SlCrRLK1Ls in tomato growth, development, and stress response. [ABSTRACT FROM AUTHOR]

Ornamental kale (Brassica oleracea L. var. acephala) is a popular decorative plant in late autumn and winter. However, only during low-temperature color-changed periods below rough 15 °C can the plant accumulate anthocyanins and exhibit a diverse array of foliar color patterns. In this study, we probed into the potential mechanism of inner leaf reddening in a red-leaf pure line of ornamental kale by physiological, metabolic, and transcriptomic analyses. Determination of anthocyanin contents in the uncolored new white leaves (S0), the light red leaves (S1) in the reddening period and the red leaves (S2) completing color change, and analysis of anthocyanin metabolites at stage S2, revealed that the coloring of red leaves was mainly attributed to the accumulation of cyanidins. We further used transcriptomic sequencing between the pairwise S0, S1, and S2 stages to identify 21 differentially expressed genes (DEGs) involved in anthocyanin biosynthesis, among which the expression level of 14 DEGs was positively correlated with anthocyanin accumulation, and 6 DEGs were negatively correlated with anthocyanin accumulation. A total of 89 co-expressed genes were screened out, from which three DEGs (BoCHI, Bo4CL3, and BoF3H) were identified as hub genes in co-expression DEGs network. BoDFR and BoCHI were the DEGs with the highest expressions at S2. Moreover, two co-expressed DEGs related to stress response (BoBBX17 and BoCOR47) also exhibited upregulated expressions and positive correlations with anthocyanin accumulation. A deep dive into the underlying regulatory network of anthocyanin accumulation comprising these six upregulated DEGs from S0 to S2 was performed via trend, correlation, and differentially co-expression analysis. This study uncovered the DEGs expression profiles associated with anthocyanin accumulation during ornamental kale inner leaf reddening, which provided a basis for further dissecting the molecular mechanisms of leaf color characteristic change in ornamental kale at low temperatures. [ABSTRACT FROM AUTHOR]

Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies or prion diseases, which are caused by an infectious isoform of the innocuous cellular prion protein (PrPC) known as PrPSc. DNA methylation, one of the most studied epigenetic mechanisms, is essential for the proper functioning of the central nervous system. Recent findings point to possible involvement of DNA methylation in the pathogenesis of prion diseases, but there is still a lack of knowledge about the behavior of this epigenetic mechanism in such neurodegenerative disorders. Here, we evaluated by immunohistochemistry the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in sheep and mouse brain tissues infected with scrapie. Expression analysis of different gene coding for epigenetic regulatory enzymes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, TET1, and TET2) was also carried out. A decrease in 5mC levels was observed in scrapie-affected sheep and mice compared to healthy animals, whereas 5hmC displayed opposite patterns between the two models, demonstrating a decrease in 5hmC in scrapie-infected sheep and an increase in preclinical mice. 5mC correlated with prion-related lesions in mice and sheep, but 5hmC was associated with prion lesions only in sheep. Differences in the expression changes of epigenetic regulatory genes were found between both disease models, being differentially expressed Dnmt3b, Hdac1, and Tet1 in mice and HDAC2 in sheep. Our results support the evidence that DNA methylation in both forms, 5mC and 5hmC, and its associated epigenetic enzymes, take part in the neurodegenerative course of prion diseases. [ABSTRACT FROM AUTHOR]

This study aimed to examine if methanolic extracts of Pulsatilla vulgaris Mill. can inhibit HeLa cell proliferation through the modulation of cancer-related signaling pathways. The cytotoxicity and chemical composition of P. vulgaris leaves and root extracts were also determined. Research showed that root extract of P. vulgaris inhibited 12 signaling pathways in a cervical cancer cell line and the most potent activation inhibition was observed for MYC, Notch, Wnt, E2F, Ets, Stat3, Smad, Hdghog, AP-1, and NF-κB, at a concentration of 40 µg/mL. The methanolic extracts of P. vulgaris enhanced apoptotic death and deregulated cellular proliferation, differentiation, and progression toward the neoplastic phenotype by altering key signaling molecules required for cell cycle progression. This is the first study to report the influence of P. vulgaris on cancer signaling pathways. Additionally, our detailed phytochemical analysis of the methanolic extracts of P. vulgaris gives a conclusion that compounds, which strongly suppressed the growth and proliferation of HeLa cancer cells were mainly triterpenoid saponins accompanied by phenolic acids. [ABSTRACT FROM AUTHOR]

Clubroot disease is a soil-borne disease caused by Plasmodiophora brassicae. It occurs in cruciferous crops exclusively, and causes serious damage to the economic value of cruciferous crops worldwide. Although different measures have been taken to prevent the spread of clubroot disease, the most fundamental and effective way is to explore and use disease-resistance genes to breed resistant varieties. However, the resistance level of plant hosts is influenced both by environment and pathogen race. In this work, we described clubroot disease in terms of discovery and current distribution, life cycle, and race identification systems; in particular, we summarized recent progress on clubroot control methods and breeding practices for resistant cultivars. With the knowledge of these identified resistance loci and R genes, we discussed feasible strategies for disease-resistance breeding in the future. [ABSTRACT FROM AUTHOR]

Gelsemium elegans (G. elegans) is a Chinese medicinal plant with substantial economic and feeding values. There is a lack of detailed studies on the mitochondrial genome of G. elegans. In this study, the mitochondrial genome of G. elegans was sequenced and assembled, and its substructure was investigated. The mitochondrial genome of G. elegans is represented by two circular chromosomes of 406,009 bp in length with 33 annotated protein-coding genes, 15 tRNA genes, and three rRNA genes. We detected 145 pairs of repeats and found that four pairs of repeats could mediate the homologous recombination into one major conformation and five minor conformations, and the presence of conformations was verified by PCR amplification and Sanger sequencing. A total of 124 SSRs were identified in the G. elegans mitochondrial genome. The homologous segments between the chloroplast and mitochondrial genomes accounted for 5.85% of the mitochondrial genome. We also predicted 477 RNA potential editing sites and found that the nad4 gene was edited 38 times, which was the most frequent occurrence. Taken together, the mitochondrial genome of G. elegans was assembled and annotated. We gained a more comprehensive understanding on the genome of this medicinal plant, which is vital for its effective utilization and genetic improvement, especially for cytoplasmic male sterility breeding and evolution analysis in G. elegans. [ABSTRACT FROM AUTHOR]

The outbreak of white spot syndrome (WSS) is a looming challenge, due to dramatic losses to the crustacean aquaculture industry. However, at present, there are no prophylactic or therapeutic means to control this infectious viral disease. Here, we screened fifteen medicinal plants for their inhibitory activity on the white spot syndrome virus (WSSV), using red swamp crayfish (Procambarus clarkii) as a model species. The results showed that the crude extracts of Pinellia ternata (Thunb.) Breit. had the highest inhibitory effect (91.59%, 100 mg/kg) on WSSV proliferation, and its main component, beta-sitosterol, showed a much higher activity (95.79%, 50 mg/kg). Further, beta-sitosterol potently reduced (p < 0.01) viral loads and viral gene transcription levels in a concentration-dependent fashion, and significantly promoted the survival rate of WSSV-challenged crayfish (57.14%, 50 mg/kg). The co-incubation assay indicated that beta-sitosterol did not influence the infectivity of WSSV particles. Both pre- and post-treatment of beta-sitosterol exerted a significant inhibitory effect (p < 0.01) on the viral load in vivo. Mechanistically, beta-sitosterol not only interfered with the expression of viral genes (immediate early gene 1, ie1; DNA polymerase, DNApol) that are important in initiating WSSV transcription, but it also attenuated the hijacking of innate immune signaling pathways (Toll, IMD, and JAK/STAT pathways) by viral genes to block WSSV replication. Moreover, the expression of several antiviral immune, antioxidant, pro-inflammatory, and apoptosis-related genes changed significantly in beta-sitosterol-treated crayfish. Beta-sitosterol is a potent WSSV inhibitor and has the potential to be developed as an effective anti-WSSV agent against a WSS outbreak in crustacean aquaculture. [ABSTRACT FROM AUTHOR]

Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes. [ABSTRACT FROM AUTHOR]

Thermosensitive sterile lines are natural materials for exploring the effects of anther development on male fertility. To study the possible molecular mechanisms regulating protein activity during the induction of male sterility, proteomic and phosphoproteomic analyses with tandem mass tags (TMTs) were used to study the binucleate anther of the thermosensitive sterile wheat line YS3038. A total of 9072 proteins, including 5019 phosphoproteins, were identified. Enrichment analyses of differentially abundant proteins (DAPs) and phosphoproteins (DAPPs) in metabolic pathways showed that both were mainly related to energy metabolism. Soluble sugar and ATP content were significantly decreased, free fatty acid content was significantly increased, and ROS was abnormally accumulated in male sterile YS3038-A. In addition, 233 kinase–substrate pairs involved in potential phosphorylation control networks were predicted to regulate fertility. Candidate proteins were identified, and a quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to validate the TMT results. TaPDCD5 is likely to be involved in fertility conversion of YS3038 by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS). Our data provide new insights into the mechanism of TCMS, which has value for identifying potential candidate proteins associated with the formation or abortion of pollen and promotion of wheat heterosis utilization. [ABSTRACT FROM AUTHOR]

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs. [ABSTRACT FROM AUTHOR]

Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. It is more prevalent in males and has poorly understood pathogenic molecular mechanisms. Our primary objective was to characterize alterations in sex-specific microRNA (miRNA, miR) after periodontal bacterial infection. Using partial human mouth microbes (PAHMM) (Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model, we evaluated differential mandibular miRNA profiles by using high-throughput Nanostring nCounter® miRNA expression panels. All PAHMM mice showed bacterial colonization (100%) in the gingival surface, an increase in alveolar bone resorption (p < 0.0001), and the induction of a specific immunoglobin G antibody immune response (p < 0.001). Sex-specific differences in distal organ bacterial dissemination were observed in the heart (82% male vs. 28% female) and lungs (2% male vs. 68% female). Moreover, sex-specific differential expression (DE) of miRNA was identified in PAHMM mice. Out of 378 differentially expressed miRNAs, we identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of periodontitis. A strong relationship was found between male-specific miR-377 upregulation and bacterial dissemination to the heart. This study demonstrates sex-specific differences in bacterial dissemination and in miRNA differential expression. A novel PAHMM mouse and ETSPPI model that replicates human pathobiology can be used to identify miRNA biomarkers in periodontitis. [ABSTRACT FROM AUTHOR]

Pentatricopeptide repeat (PPR) proteins are a large protein family in higher plants and play important roles during seed development. Most reported PPR proteins function in mitochondria. However, some PPR proteins localize to more than one organelle; functional characterization of these proteins remains limited in maize (Zea mays L.). Here, we cloned and analyzed the function of a P-subfamily PPR protein, PPR278. Loss-function of PPR278 led to a lower germination rate and other defects at the seedling stage, as well as smaller kernels compared to the wild type. PPR278 was expressed in all investigated tissues. Furthermore, we determined that PPR278 is involved in the splicing of two mitochondrial transcripts (nad2 intron 4 and nad5 introns 1 and 4), as well as RNA editing of C-to-U sites in 10 mitochondrial transcripts. PPR278 localized to the nucleus, implying that it may function as a transcriptional regulator during seed development. Our data indicate that PPR278 is involved in maize seed development via intron splicing and RNA editing in mitochondria and has potential regulatory roles in the nucleus. [ABSTRACT FROM AUTHOR]

Small brown planthopper (SBPH) and rice stripe virus (RSV) disease transmitted by SBPH cause serious damage to rice (Oryza sativa L.) in China. In the present study, we screened 312 rice accessions for resistance to SBPH. The indica variety, N22, is highly resistant to SBPH. One hundred and eighty two recombinant inbred lines (RILs) derived from a cross of N22 and the highly susceptible variety, USSR5, were used for quantitative trait locus (QTL) analysis of resistances to SBPH and RSV. In a modified seedbox screening test, three QTLs for SBPH resistance, qSBPH2, qSBPH3 and qSBPH7.1, were mapped on chromosomes 2, 3 and 7, a total explaining 35.1% of the phenotypic variance. qSBPH7.2 and qSBPH11.2, conferring antibiosis against SBPH, were detected on chromosomes 7 and 11 and accounted for 20.7% of the total phenotypic variance. In addition, qSBPH5 and qSBPH7.3, expressing antixenosis to SBPH, were detected on chromosomes 5 and 7, explaining 23.9% of the phenotypic variance. qSBPH7.1, qSBPH7.2 and qSBPH7.3, located in the same region between RM234 and RM429 on chromosome 7, using three different phenotyping methods indicate that the locus or region plays a major role in conferring resistance to SBPH in N22. Moreover, three QTLs, qSTV4, qSTV11.1 and qSTV11.2, for RSV resistance were detected on chromosomes 4 and 11. qSTV11.1 and qSTV11.2 are located in the same region between RM287 and RM209 on chromosome 11. Molecular markers spanning these QTLs should be useful in the development of varieties with resistance to SBPH and RSV. [ABSTRACT FROM AUTHOR]

Worldwide, metals have been distributed to excessive levels in the environment due to industrial and agricultural activities. Plants growing on soils contaminated with excess levels of metals experience a disturbance of the cellular redox balance, which leads to an augmentation of reactive oxygen species (ROS). Even though the increased ROS levels can cause cellular damage, controlled levels play an important role in modulating signaling networks that control physiological processes and stress responses. Plants control ROS levels using their antioxidative defense system both under non-stress conditions, as well as under stress conditions such as exposure to excess metals. Ascorbate (AsA) is a well-known and important component of the plant's antioxidative system. As primary antioxidant, it can reduce ROS directly and indirectly via ascorbate peroxidase in the ascorbate-glutathione cycle. Furthermore, AsA fulfills an essential role in physiological processes, some of which are disturbed by excess metals. In this review, known direct effects of excess metals on AsA biosynthesis and functioning will be discussed, as well as the possible interference of metals with the role of AsA in physiological and biochemical processes. [ABSTRACT FROM AUTHOR]

The potential energy curves (PECs) of the X2Π and A2Π electronic states of the SO+ ion are calculated using the complete active space self-consistent field method, which is followed by the internally contracted multireference configuration interaction (MRCI) approach for internuclear separations from 0.08 to 1.06 nm. The spin-orbit coupling effect on the spectroscopic parameters is included using the Breit-Pauli operator. To improve the quality of PECs and spin-orbit coupling constant (A0), core-valence correlation and scalar relativistic corrections are included. To obtain more reliable results, the PECs obtained by the MRCI calculations are corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). At the MRCI+Q/aug-cc-pV5Z+CV+DK level, the A0 values of the SO+(X2Π1/2, 3/2) and SO+(A2Π1/2, 3/2) are 362.13 and 58.16 cm-1 when the aug-cc-pCVTZ basis set is used to calculate the spin-orbit coupling splitting, and the A0 of the SO+(X2Π1/2, 3/2) and SO+(A2Π1/2, 3/2) are 344.36 and 52.90 cm-1 when the aug-cc-pVTZ basis set is used to calculate the spin-orbit coupling splitting. The conclusion is drawn that the core-valence correlations correction makes the A0 slightly larger. The spectroscopic results are obtained and compared with those reported in the literature. Excellent agreement exists between the present results and the measurements. The vibrational manifolds are calculated, and those of the first 30 vibrational states are reported for the J = 0 case. Comparison with the measurements shows that the present vibrational manifolds are both reliable and accurate [ABSTRACT FROM AUTHOR]

Parsimony analysis of endemicity (PAE) was used to identify areas of endemism (AOEs) for Chinese birds at the subregional level. Four AOEs were identified based on a distribution database of 105 endemic species and using 18 avifaunal subregions as the operating geographical units (OGUs). The four AOEs are the Qinghai-Zangnan Subregion, the Southwest Mountainous Subregion, the Hainan Subregion and the Taiwan Subregion. Cladistic analysis of subregions generally supports the division of China's avifauna into Palaearctic and Oriental realms. Two PAE area trees were produced from two different distribution datasets (year 1976 and 2007). The 1976 topology has four distinct subregional branches; however, the 2007 topology has three distinct branches. Moreover, three Palaearctic subregions in the 1976 tree clustered together with the Oriental subregions in the 2007 tree. Such topological differences may reflect changes in the distribution of bird species through circa three decades. [ABSTRACT FROM AUTHOR]

New organic dyes comprising carbazole, iminodibenzyl, or phenothiazine moieties, respectively, as the electron donors, and cyanoacetic acid or acrylic acid moieties as the electron acceptors/anchoring groups were synthesized and characterized. The influence of heteroatoms on carbazole, iminodibenzyl and phenothiazine donors, and cyano-substitution on the acid acceptor is evidenced by spectral, electrochemical, photovoltaic experiments, and density functional theory calculations. The phenothiazine dyes show solar-energy-to-electricity conversion efficiency (η) of 3.46-5.53%, whereas carbazole and iminodibenzyl dyes show η of 2.43% and 3.49%, respectively. [ABSTRACT FROM AUTHOR]

Methionine restriction reduces animal lipid deposition. However, the molecular mechanism underlying how the body reacts to the condition and regulates lipid metabolism remains unknown. In this study, a feeding trial was performed on rice field eel Monopterus albus with six isonitrogenous and isoenergetic feeds that included different levels of methionine (0, 2, 4, 6, 8, and 10 g/kg). Compared with M0 (0 g/kg), the crude lipid and crude protein of M. albus increased markedly in M8 (8 g/kg) (p < 0.05), serum (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and non-esterified free fatty acids), and hepatic contents (hepatic lipase, apolipoprotein-A, fatty acid synthetase, total cholesterol, triglyceride, and lipoprteinlipase). However, in the serum, very-low-density lipoprotein and hepatic contents (hormone-sensitive triglyceride lipase, Acetyl CoA carboxylase, carnitine palmitoyltransterase, and mirosomal triglygeride transfer protein) decreased markedly in M8 (p < 0.05). The contents of hepatic C18:2n-6, C22:6n-3, and n-3PUFA in the M8 group were significantly higher than those in M0 (p < 0.05), and the contents of lipid droplets in M8 were higher than those in M0. Compared with M0, the hepatic gcn2, eif2α, hsl, mttp, ldlrap, pparα, cpt1, and cpt2 were remarkably downregulated in M8, while srebf2, lpl, moat2, dgat2, hdlbp, srebf1, fas, fads2, me1, pfae, and icdh were markedly upregulated in M8. Moreover, hepatic SREBP1 and FAS protein expression were upregulated significantly in M8 (p < 0.01). In short, methionine restriction decreased the lipid deposition of M. albus, especially for hepatic lipid deposition, and mainly downregulated hepatic fatty acid metabolism. Besides, gcn2 could be activated under methionine restriction. [ABSTRACT FROM AUTHOR]

Mutations within the glucocorticoid receptor (GR) gene locus lead to glucocorticoid resistance which is characterized by several clinical symptoms such as adrenal gland hyperplasia and salt-sensitive hypertension, although the underlying mechanisms are still unknown. We studied GR haploinsufficient (GR+/−) Sprague Dawley rats which, on a standard diet, showed significantly increased plasma aldosterone and corticosterone levels and an adrenocortex hyperplasia accompanied by a normal systolic blood pressure. Following a high salt diet, these rats developed salt-sensitive hypertension and maintained elevated enzyme-soluble epoxide hydrolase (sEH) in adrenal glands, while sEH was significantly decreased in wild-type rats. Furthermore, GR+/− rats showed dysregulation of the equilibrated linoleic and arachidonic acid pathways, with a significant increase of less active metabolites such as 8,9-DiHETrE. In Sprague Dawley rats, GR haploinsufficiency induced steroid disturbances, which provoked hypertension only in combination with high salt intake, which was accompanied by disturbances in sEH and fatty acid metabolism. Our results suggest that sEH inhibition could be a potential target to treat hypertension in patients with GR haploinsufficiency. [ABSTRACT FROM AUTHOR]

In recent years, much progress has been made in elucidating the functional roles of plant glycine-rich RNA-binding proteins (GR-RBPs) during development and stress responses. Canonical GR-RBPs contain an RNA recognition motif (RRM) or a cold-shock domain (CSD) at the N-terminus and a glycine-rich domain at the C-terminus, which have been associated with several different RNA processes, such as alternative splicing, mRNA export and RNA editing. However, many aspects of GR-RBP function, the targeting of their RNAs, interacting proteins and the consequences of the RNA target process are not well understood. Here, we discuss recent findings in the field, newly defined roles for GR-RBPs and the actions of GR-RBPs on target RNA metabolism. [ABSTRACT FROM AUTHOR]