Antagonistic Roles Research Articles

Competing instabilities reveal how to rationally design and control active crosslinked gels

How active stresses generated by molecular motors set the large-scale mechanics of the cell cytoskeleton remains poorly understood. Here, we combine experiments and theory to demonstrate how the emergent properties of a biomimetic active crosslinked gel depend on the properties of its microscopic constituents. We show that an extensile nematic elastomer exhibits two distinct activity-driven instabilities, spontaneously bending in-plane or buckling out-of-plane depending on its composition. Molecular motors play a dual antagonistic role, fluidizing or stiffening the gel depending on the ATP concentration. We demonstrate how active and elastic stresses are set by each component, providing estimates for the active gel theory parameters. Finally, activity and elasticity were manipulated in situ with light-activable motor proteins, controlling the direction of the instability optically. These results highlight how cytoskeletal stresses regulate the self-organization of living matter and set the foundations for the rational design and optogenetic control of active materials.

Transition to ripening in tomato requires hormone-controlled genetic reprogramming initiated in gel tissue.

Ripening is the last stage of the developmental program in fleshy fruits. During this phase, fruits become edible and acquire their unique sensory qualities and post-harvest potential. Although our knowledge of the mechanisms that regulate fruit ripening has improved considerably over the past decades, the processes that trigger the transition to ripening remain poorly deciphered. While transcriptomic profiling of tomato (Solanum lycopersicum L.) fruit ripening to date has mainly focused on the changes occurring in pericarp tissues between the Mature Green and Breaker stages, our study addresses the changes between the Early Mature Green and Late Mature Green stages in the gel and pericarp separately. The data showed that the shift from an inability to initiate ripening to the capacity to undergo full ripening requires extensive transcriptomic reprogramming that takes place first in the locular tissues before extending to the pericarp. Genome-wide transcriptomic profiling revealed the wide diversity of transcription factor (TF) families engaged in the global reprogramming of gene expression and identified those specifically regulated at the Mature Green stage in the gel but not in the pericarp, thereby providing potential targets toward deciphering the initial factors and events that trigger the transition to ripening. The study also uncovered an extensive reformed homeostasis for most plant hormones, highlighting the multihormonal control of ripening initiation. Our data unveil the antagonistic roles of ethylene and auxin during the onset of ripening and show that auxin treatment delays fruit ripening via impairing the expression of genes required for System-2 autocatalytic ethylene production that is essential for climacteric ripening. This study unveils the detailed features of the transcriptomic reprogramming associated with the transition to ripening of tomato fruit and shows that the first changes occur in the locular gel before extending to pericarp and that a reformed auxin homeostasis is essential for the ripening to proceed.

Molecular insight of p53/Sp1/MUC5AC axis in the tumorigenesis and progression of lung adenocarcinoma.

The aberrant expression of secretory mucin MUC5AC has been documented during the tumourigenesis and progression of various cancers. However, little is currently known on the function of MUC5AC in lung adenocarcinoma. The present study focused on the tumour-promoting role of MUC5AC and its regulatory mechanisms in lung adenocarcinoma. Firstly, MUC5AC expression was evaluated in NSCLC tissue microarrays by immunohistochemistry. Kaplan-Meier analysis were used to clarify the prognostic value of MUC5AC. Subsequently, small interfering RNA and small hairpin RNA were used to knockdown MUC5AC in lung ADC cell lines to elucidate its role in tumorigenesis and progression of lung adenocarcinoma via in vitro functional assays and xenograft mouse models. Finally, the regulatory mechanisms underlying p53/Sp1/MUC5AC axis were identified through dual-luciferase report. We found that MUC5AC was upregulated in lung ADC tissues and cell lines, especially in KRAS-mutant cases and correlated with poor prognosis. MUC5AC gene silencing resulted in reduced cell proliferation, invasion and migration. Furthermore, knockdown of MUC5AC led to reversion of the epithelial-mesenchymal transition. Additionally, downregulation of MUC5AC reduced tumourigenesis in mouse models. Finally, we found an antagonistic role between Sp1 and p53 in the regulation of MUC5AC gene expression. Our findings suggest that high MUC5AC expression promotes tumourigenesis and progression of lung ADC. Both p53 gene inactivation and Sp1 overexpression in lung ADC may enhance MUC5AC expression, especially in KRAS-mutated cases. Given the paucity of efficient drug-targeted approaches of KRAS-driven lung ADCs, therapies directed at downstream effectors such as MUC5AC could have huge prospects.

Direct Interaction of Coronavirus Nonstructural Protein 3 with Melanoma Differentiation-Associated Gene 5 Modulates Type I Interferon Response during Coronavirus Infection.

Coronavirus nonstructural protein 3 (nsp3) is a multi-functional protein, playing a critical role in viral replication and in regulating host antiviral innate immunity. In this study, we demonstrate that nsp3 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and avian coronavirus infectious bronchitis virus (IBV) directly interacts with melanoma differentiation-associated gene 5 (MDA5), rendering an inhibitory effect on the MDA5-mediated type I interferon (IFN) response. By the co-expression of MDA5 with wild-type and truncated nsp3 constructs, at least three interacting regions mapped to the papain-like protease (PLpro) domain and two other domains located at the N- and C-terminal regions were identified in SARS-CoV-2 nsp3. Furthermore, by introducing point mutations to the catalytic triad, the deubiquitylation activity of the PLpro domain from both SARS-CoV-2 and IBV nsp3 was shown to be responsible for the suppression of the MDA5-mediated type I IFN response. It was also demonstrated that both MDA5 and nsp3 were able to interact with ubiquitin and ubiquitinated proteins, contributing to the interaction between the two proteins. This study confirms the antagonistic role of nsp3 in the MDA5-mediated type I IFN signaling, highlighting the complex interaction between a multi-functional viral protein and the innate immune response.

Awareness of probiotics among dental practitioners of Puducherry-A cross-sectional questionnaire study.

The efficiency of probiotics in prevention and also treatment of oral infections including dental caries, periodontitis, halitosis is found to be appealing in the recent literature. Their antagonistic role in oral infections is mainly through formation of biofilm which needs documentation. Though the emergence and practice of oral probiotics is visualized for the past two decades, the consumption and knowledge level is found to be less among the community. Stronger source to spread scientific evidence to the community would be health professionals. The current study is aimed at assessing the level of awareness of probiotics among dental practitioners of Puducherry thereby aid and assist in the beneficial practice of the same in the community. The knowledge level was assessed through a cross sectional survey using closed ended questionnaire. Involves practicing dentists of Puducherry (n-173). A prevalidated questionnaire with 17 closed ended and one open ended question was employed as the research tool. The results revealed an acceptable knowledge in 77.4% and a greater level of knowledge in 20.8% of dentists. More number of studies are expected to fulfill the lacunae in the field of safety of usage and long term effects of probiotics. Responses of the current study which was focused on dental practitioners revealed that the knowledge level is well above the acceptable level. There is no profound difference in the awareness level noticed among BDS and MDS practitioners..

Jasmonic acid and salicylic acid modulate systemic reactive oxygen species signaling during stress responses.

Plants can send long-distance cell-to-cell signals from a single tissue subjected to stress to the entire plant. This ability is termed "systemic signaling" and is essential for plant acclimation to stress and/or defense against pathogens. Several signaling mechanisms are associated with systemic signaling, including the reactive oxygen species (ROS) wave, calcium wave, hydraulic wave, and electric signals. The ROS wave coordinates multiple physiological, molecular, and metabolic responses among different parts of the plant and is essential for systemic acquired acclimation (SAA) to stress. In addition, it is linked with several plant hormones, including jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA). However, how these plant hormones modulate the ROS wave and whether they are required for SAA is not clear. Here we report that SA and JA play antagonistic roles in modulating the ROS wave in Arabidopsis (Arabidopsis thaliana). While SA augments the ROS wave, JA suppresses it during responses to local wounding or high light (HL) stress treatments. We further show that ethylene and ABA are essential for regulation of the ROS wave during systemic responses to local wounding treatment. Interestingly, we found that the redox-response protein NONEXPRESSOR OF PATHOGENESIS RELATED PROTEIN 1 is required for systemic ROS accumulation in response to wounding or HL stress, as well as for SAA to HL stress. Taken together, our findings suggest that interplay between JA and SA might regulate systemic signaling and SAA during responses of plants to abiotic stress or wounding.

Potential antagonistic relationship of fgf9 and rspo1 genes in WNT4 pathway to regulate the sex differentiation in Chinese giant salamander (Andrias davidianus).

Farmed chinese giant salamander (Andrias davidianus) was an important distinctive economically amphibian that exhibited male-biased sexual size dimorphism. Fgf9 and rspo1 genes antagonize each other in Wnt4 signal pathway to regulate mammalian gonadal differentiation has been demonstrated. However, their expression profile and function in A. davidianus are unclear. In this study, we firstly characterized fgf9 and rspo1 genes expression in developing gonad. Results showed that fgf9 expression level was higher in testes than in ovaries and increased from 1 to 6 years while rspo1 expression was higher in ovaries than in testes. In situ hybridization assay showed that both fgf9 and rspo1 genes expressed at 62 dpf in undifferentiated gonad, and fgf9 gene was mainly expressed in spermatogonia and sertoli cells in testis while strong positive signal of rspo1 was detected in granular cell in ovary. During sex-reversal, fgf9 expression was significantly higher in reversed testes and normal testes than in ovaries, and opposite expression pattern was detected for rspo1. When FH535 was used to inhibit Wnt/β-catenin pathway, expression of rspo1, wnt4 and β-catenin was down-regulated. Conversely, expression of fgf9, dmrt1, ftz-f1 and cyp17 were up-regulated. Furthermore, when rspo1 and fgf9 were knocked down using RNAi technology, respectively. We observed that female biased genes were down regulated in ovary primordial cells after rspo1 was knocked down, while the opposite expression profile was observed in testis primordial cells after fgf9 was knocked down. These results suggested that fgf9 and rspo1 played an antagonistic role to regulate sex differentiation in the process of the gonadal development and provided a foundation for further functional characterizations. The data also provided basic information for genome editing breeding to improve the Chinese giant salamander farming industry.

Diversity of bacterial community in Jerusalem artichoke (Helianthus tuberosus L.) during storage is associated with the genotype and carbohydrates.

Jerusalem artichoke (JA) is a fructan-accumulating crop that has gained popularity in recent years. The objective of the present study was to determine the dynamics of the JA-microbiome during storage. The microbial population on the surface of the JA tuber was determined by next-generation sequencing of 16S rRNA amplicons. Subsequently, the changes in carbohydrate and degree of polymerization of fructan in tubers during storage were measured. Among different genotypes of JA varieties, intergeneric differences were observed in the diversity and abundance of bacterial communities distributed on the surface of tubers. Additionally, bacterial diversity was significantly higher in storage-tolerant varieties relative to the storage-intolerant varieties. Redundancy analysis (RDA) and the correlation matrix indicated a relationship between changes in the carbohydrates and microbial community succession during tuber storage. The tuber decay rate correlated positively with the degree of polymerization of fructan. Moreover, Dysgonomonas and Acinetobacter in perishable varieties correlated significantly with the decay rate. Therefore, the bacteria associated with the decay rate may be involved in the degradation of the degree of polymerization of fructan. Furthermore, Serratia showed a significant positive correlation with inulin during storage but a negative correlation with the decay rate, suggesting its antagonistic role against pathogenic bacteria on the surface of JA tubers. However, the above correlation was not observed in the storage-tolerant varieties. Functional annotation analysis revealed that storage-tolerant JA varieties maintain tuber quality through enrichment of biocontrol bacteria, including Flavobacterium, Sphingobacterium, and Staphylococcus to resist pathogens. These results suggested that crop genotype and the structural composition of carbohydrates may result in differential selective enrichment effects of microbial communities on the surface of JA varieties. In this study, the relationship between microbial community succession and changes in tuber carbohydrates during JA storage was revealed for the first time through the combination of high-throughput sequencing, high-performance liquid chromatography (HPLC), and high-performance ion-exchange chromatography (HPIC). Overall, the findings of this study are expected to provide new insights into the dynamics of microbial-crop interactions during storage.

Wildlife trade targets colorful birds and threatens the aesthetic value of nature

A key component of nature's contribution to people is aesthetic value.1,2 Charismatic species rally public support and bolster conservation efforts.3,4 However, an insidious aspect to humanity's valuation of nature is that high value also drives wildlife trade,5,6 which can spearhead the demise of prized species.7-9 Here, we explore the antagonistic roles of aesthetic value in biodiversity conservation by using novel metrics of color to evaluate the aesthetics of the most speciose radiation of birds: passerines (i.e., the perching birds). We identify global color hotspots for passerines and highlight the breadth of color in the global bird trade. The tropics emerge as an epicentre of color, encompassing 91% and 65% of the world's most diverse and most uniquely colored passerine assemblages, respectively. We show that the pet trade, which currently affects 30% of passerines (1,408/5,266), traverses the avian phylogeny and targets clusters of related species that are uniquely colored. We identify an additional 478 species at risk of future trade based on their coloration and phylogenetic relationship to currently traded species-together totaling 1,886 species traded, a 34% increase. By modeling future extinctions based on species' current threat status, we predict localized losses of color diversity and uniqueness in many avian communities, undermining their aesthetic value and muting nature's color palette. Given the distribution of color and the association of unique colors with threat and trade, proactive regulation of the bird trade is crucial to conserving charismatic biodiversity, alongside recognition and celebration of color hotspots.

Ribonuclease H-like gene SMALL GRAIN2 regulates grain size in rice through brassinosteroid signaling pathway.

Grain size is a key agronomic trait that determines the yield in plants. Regulation of grain size by brassinosteroids (BRs) in rice has been widely reported. However, the relationship between the BR signaling pathway and grain size still requires further study. Here, we isolated a rice mutant, named small grain2 (sg2), which displayed smaller grain and a semi-dwarf phenotype. The decreased grain size was caused by repressed cell expansion in spikelet hulls of the sg2 mutant. Using map-based cloning combined with a MutMap approach, we cloned SG2, which encodes a plant-specific protein with a ribonuclease H-like domain. SG2 is a positive regulator downstream of GLYCOGEN SYNTHASE KINASE2 (GSK2) in response to BR signaling, and its mutation causes insensitivity to exogenous BR treatment. Genetical and biochemical analysis showed that GSK2 interacts with and phosphorylates SG2. We further found that BRs enhance the accumulation of SG2 in the nucleus, and subcellular distribution of SG2 is regulated by GSK2 kinase activity. In addition, Oryza sativa OVATE family protein 19 (OsOFP19), a negative regulator of grain shape, interacts with SG2 and plays an antagonistic role with SG2 in controlling gene expression and grain size. Our results indicated that SG2 is a new component of GSK2-related BR signaling response and regulates grain size by interacting with OsOFP19.

Antagonistic role of barley against bioaccumulation and oxidative stress of aflatoxin B1 in male rats

BackgroundThis study aims to evaluate the protective effect of barley against the bioaccumulation and oxidative stress of aflatoxin B1 (AFB1) in male rats. The lethality percentile doses (LDs: LD1 to LD99 at 24, 48, 72, and 96 h) were measured. To achieve these goals during subacute treatments, one hundred rats were divided into five groups, each with twenty rats. The groups I, II, III, IV, and V throughout 21 days were daily given drinking water, DMSO, 2.0 g of barley/kg, and 7.49 mg/kg of AFB1 alone or in combination with 2.0 g of barley/kg, respectively.ResultsThe results revealed that AFB1 was detected only in the liver, kidney, and serum of groups IV, in which the accumulated AFB1 exhibited a significant direct relationship with the experimental periods with a marked positive correlation coefficient. Additionally, the concentrations of AFB1 residue in the serum of rats given AFB1 alone exhibited a significant inverse relationship with the levels of GSH, activity of CAT, SOD, and GR, whereas the levels of MDA showed a significant positive relationship. In the serum of rats given AFB1 plus barley, all parameters were mostly recovered and didn’t correlate with either the experimental periods or AFB1 in the serum.ConclusionsThe present data concluded that barley accelerated the biotransformation of AFB1 to a hydrophilic metabolite that is easily eliminated outside the body, leading to the recovery of all studied parameters to normal levels.

Construction of lncRNA-ceRNA Networks to Reveal the Potential Role of Lfng/Notch1 Signaling Pathway in Alzheimer's Disease.

Alzheimer's disease (AD) develops through a complex pathological process, in which many genes play a synergistic or antagonistic role. LncRNAs represent a kind of noncoding RNA, which can regulate gene expression at the epigenetic, transcriptional and posttranscriptional levels. Multiple lncRNAs have been found to have important regulatory functions in AD. Thus, their expression patterns, targets and functions should be explored as therapeutic targets. We used deep RNA-seq analysis to detect the dysregulated lncRNAs in the hippocampus of APP/PS1 mice. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to predict the biological roles and potential signaling pathways of dysregulated lncRNAs. Finally, we constructed lncRNA-miRNA-mRNA and lncRNA-mRNA co-expression networks to reveal the potential regulator roles in AD pathogenesis. Our findings revealed 110 significantly dysregulated lncRNAs. GO and KEGG annotations showed the dysregulated lncRNAs to be closely related to the functions of axon and protein digestion and absorption. The lncRNA-mRNA network showed that 19 lncRNAs regulated App, Prnp, Fgf10 and Il33, while 5 lncRNAs regulated Lfng via the lncRNA-miR-3102-3p-Lfng axis. Furthermore, we preliminarily demonstrated the important regulatory role of the Lfng/Notch1 signaling pathway through lncRNA-ceRNA networks in AD. We revealed the important regulatory roles of dysregulated lncRNAs in the etiopathogenesis of AD through lncRNA expression profiling. Our results showed that the mechanism involves the regulation of the Lfng/Notch1 signaling pathway.

32339 Expression of interleukin 36 receptor antagonist in a patient with generalized pustular psoriasis harboring the p.Pro82Leu variant in the IL36RN gene

Background: Mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)-36 receptor antagonist (IL-36Ra), which has antagonistic roles against IL-36. Li et al. performed sanger sequencing to identify IL36RN mutations in 62 Chinese GPP patients, and reported a new variant, c.245C>T (p.Pro82Leu) in a patient with GPP. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris and control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses.

Antioxidant, anticoagulant and thrombolytic properties of SIP-IV, a sulfated polysaccharide from Sepia esculenta ink, and its derivatives

Carboxymethylated, phosphorylated and sulfated derivatives of SIP-IV, a polysaccharide derived from Sepia esculenta ink, were prepared and their antioxidant, anticoagulant and thrombolytic properties were evaluated. Data showed that sulfation and phosphorylation modification improved antioxidant activity of SIP-IV, but carboxymethylation impaired the property. In vitro data showed that SIP-IV and its three modified derivatives could significantly prolong activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT), and also exhibited thrombolysis activity. In vivo, these polymers alleviated chemotherapy-induced blood hypercoagulation by reversing abnormal levels of coagulation factors II and X, and antithrombin III in plasma, resulting in prolonged bleeding time. Moreover, the polysaccharides play an antagonistic role against chemotherapy-mediated liver oxidative stress. Sulfate-modified polysaccharide (S-SIP-IV) has the best anticoagulant, thrombolytic and antioxidant effects.

Plant pathogens as introduced weed biological control agents: Could antagonistic fungi be important factors determining agent success or failure?

Mycoparasitic interactions are common in nature, form part of the microbiota of plants, and are considered significant contributors to fungus-fungus antagonism. Mycoparasites kill plant pathogens, protect the plant from abiotic and biotic stressors, and reduce disease incidence and severity at the plant population level. Their exploitation as biocontrol agents in agriculture is well documented. However, mycoparasites may potentially affect classical fungal biocontrol agents of invasive weed species. Classical biological control, or biocontrol, of invasive weeds involves the intentional introduction of exotic, usually co-evolved plant pathogens and insects, for permanent establishment and long-term control of the target plant. Agent establishment, effectiveness, and safety are the critical elements for a successful weed biocontrol programme. Establishment and effectiveness of agents on the invasive plant often vary throughout the invaded range with about two-thirds of weed biocontrol agents failing to suppress their target weed. There are many documented reasons why weed biocontrol agents do not establish or are ineffective when they do, and the presence and accumulation of natural enemies in the invaded range is one of them. Endophyte-enriched, invasive weeds and those forming mutualistic associations with indigenous, native endophytes could explain the lack of consistency of some classical biological control introductions. However, another variable could be factored into the mix: mycoparasitism, where one fungus parasitises another, the natural enemies of the plant's natural enemies. In this review article, we introduce the concept of invasive weed biocontrol and the history of using plant pathogens as biocontrol agents. We discuss the success and failure of fungal agent programmes and delve into the patterns of success or failure, with a focus on the potential antagonistic role of endophytes and mycoparasites.

Endogenous calcium mediates seedling growth and fluoride stress tolerance in four bean genotypes

Fluoride (F) pollution is a global environmental problem representing a severe risk for food and vegetables grown in contaminated soils. Phaseolus vulgaris L. is widely cultivated in arid and semi-arid regions and in F contaminated areas of the world. For that reason, F tolerance during germination and seedling growth was evaluated for four bean genotypes: Borlotto nano (commercial variety) and three African genotypes (Lyamungu 85, Lyamungu 90 and Jesca). Seeds were grown in sand enriched with NaF or KF at three different levels (0, 80 and 200 mg kg-1). NaCl was used as a benchmark to determine the potential effect of different Na levels in plant. Total F content and mineral accumulation (Na, K and Ca) in roots and shoots were measured. The translocation factor, growth ratio, F tolerance index were evaluated to estimate plant-salt response. Germination rate decreased with increased F level. Borlotto was more F sensitive (0% germination with 200 mg kg-1of KF and NaF) than the African genotypes. Under the highest F concentration (200 mg kg-1), F preferentially accumulated in shoots (Jesca 75.7 mg kg-1, Lyamungu 85 100.1 mg kg-1 and Lyamungu 90 115.4 mg kg-1). Ca content in roots was negatively correlated to F absorption, suggesting its antagonistic role to F mobility. Based on these parameters, Jesca and Lyamungu 85 were the most tolerant species, recording a low F uptake and a high Ca content in the root. This study highlighted the central role of Ca, as a key secondary messenger in regulating the plant growth and development under F stress. Highlights - F stress negatively affected bean germination and seedling growth - F mainly accumulated in the shoots of bean varieties - Ca concentration in the roots played a crucial role in mitigating F accumulation

A Review on Metabolic Paradoxes and their Impact on Metabolism.

The current review paper portrays the important link of different nutrients like trace elements, proteins, fatty acids, vitamins, and amino acids with the immune system as well as information related to metabolic paradoxes. Optimum working of the metabolic system is essential because it gives various types of supplements to the human body and aid in chemical pathways. Here related data have been retrieved from two databases i.e., PubMed and Google scholar to grasp detailed knowledge about micronutrients and nutrients as well as their association in the metabolic system. Like protein play important role in the normal development of different immune components, amino acids including alanine, Arginine, and glutamic acid properly control the movement of neutrophils, macrophages, and cytokines. While fatty acids act as an anti-inflammatory agent because they possess the ability to inhibit the expression of the MHC class. Apart from these, many essential molecules like uric acid, proteins, calcium, lanolin are also obtained as end products after catabolic and anabolic reactions, and it was found that the uric acid paradox has a cancer inhibitory role. Additionally, TGF and IL-6 paradoxes have a role in the development of tumors, the onset of diabetes, and low-grade inflammatory disorders respectively. However, the entire functioning of metabolic processes depends upon daily diet because humans get the important nutrient from the diet which further vital role in the immune system. Moreover, it was also observed that calcium paradox is related to heart disorders because high calcium accumulation leads to cardiac disorders. Thus, the complete knowledge about these essential components as well as metabolic paradoxes is very important due to their antagonistic role to plan better and improved therapeutic strategies for various diseases.

Verteporfin mitigates sepsis-induced liver injury by blocking macrophage-derived inflammation

Purpose: To study the role of yes-associated protein (YAP) inhibition by verteporfin (VTF) in LPSinduced acute liver injury (ALI) after sepsis.Methods: In vitro, VTF was used to treat LPS-stimulated RAW 267.4 cells. In vivo, LPS was injected to induce sepsis in mice, followed by treatment with VTF. The inflammatory mediators were determined using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence spectroscopy (IF) and immunohistochemical staining (IHC), and the levels of YAP, P53 and ERK were measured by qRT-PCR, WB and IHC. Moreover, liver histology and liver function were examined using HE staining and ELISA respectively.Results: The results showed that VTF reduced YAP expression and inhibited LPS-induced cell activation and inflammatory cytokine production such as IL-6 and IL-1β, by attenuating the expressions of p53 and ERK pathway in macrophages. The levels of AST, AIL and TBiL remarkably decreased in ALI mice after VTF treatment (p < 0.05). Moreover, it was observed that inflammatory mediators, including inducible nitric oxide synthase (iNOS), IL-6 and IL-1β, decreased significantly in VTF treated mice (P < 0.05).Conclusion: VTF plays an antagonistic role in LPS-induced inflammatory response after ALI. Therefore, VTF is a potential medicinal agent for preventing infectious acute liver injury.

Ethylene and polyamines form a negative feedback loop to regulate peach fruit ripening via the transcription factor PpeERF113 by regulating the expression of PpePAO1

Ethylene and polyamines (PAs) have antagonistic roles during fruit ripening. PAs affect both ethylene biosynthetic and signal transduction pathways, but the regulatory effects of ethylene on PA metabolism during fruit ripening have remained largely unknown. Here, we found that ethylene enhanced PA catabolism by regulating expression of a peach PA oxidase gene, PpePAO1. Knocking out PpePAO1 delayed peach fruit ripening, whereas PpePAO1 overexpression promoted tomato fruit ripening. Both in vitro and in vivo assays demonstrated that an ethylene response factor (ERF), PpeERF113, activated PpePAO1 by direct binding to the promoter. PA levels were significantly increased and ripening was delayed in PpeERF113 knockdown peach fruit. Correspondingly, PA levels were significantly decreased when PpeERF113 was overexpressed in peach. PpeERF113 was also found to be upregulated in PpePAO1 knockdowns, indicating that PA catabolism has a regulatory function in ethylene signal transduction. Together, our results suggest that ethylene accelerates peach fruit ripening in part by promoting PA catabolism through PpeERF113-mediated regulation of PpePAO1 expression. To our knowledge, this is the first report related to the regulatory mechanism of ethylene in PA catabolism during fruit ripening. This study contributes new understanding of the crosstalk between ethylene and PAs during fruit ripening.

PRD-Class Homeobox Genes in Bovine Early Embryos: Function, Evolution, and Overlapping Roles.

Eutherian Totipotent Cell Homeobox (ETCHbox) genes are mammalian-specific PRD-class homeobox genes with conserved expression in the preimplantation embryo but fast-evolving and highly divergent sequences. Here, we exploit an ectopic expression approach to examine the role of bovine ETCHbox genes and show that ARGFX and LEUTX homeodomain proteins upregulate genes normally expressed in the blastocyst; the identities of the regulated genes suggest that, in vivo, the ETCHbox genes play a role in coordinating the physical formation of the blastocyst structure. Both genes also downregulate genes expressed earlier during development and genes associated with an undifferentiated cell state, possibly via the JAK/STAT pathway. We find evidence that bovine ARGFX and LEUTX have overlapping functions, in contrast to their antagonistic roles in humans. Finally, we characterize a mutant bovine ARGFX allele which eliminates the homeodomain and show that homozygous mutants are viable. These data support the hypothesis of functional overlap between ETCHbox genes within a species, roles for ETCHbox genes in blastocyst formation and the change of their functions over evolutionary time.