Background: Phospholamban (PLN) is a key regulator of cardiac function connecting adrenergic signaling and calcium homeostasis. The R9C mutation of PLN is known to cause early onset dilated cardiomyopathy (DCM) and premature death, yet the detailed mechanisms underlie the pathologic remodeling process are not well defined in human cardiomyocytes. The aim of this study is to unravel the role of PLN R9C in DCM and identify potential therapeutic targets. Methods: PLN R9C knock-in (KI) and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated and comprehensively examined for their expression profile, contractile function, and cellular signaling under both baseline conditions and following functional challenges. Results: PLN R9C KI iPSC-CMs exhibited near-normal morphology and calcium handling, slightly increased contractility, and an attenuated response to ß-adrenergic activation compared to wild-type (WT) cells. However, treatment with a maturation medium (MM) has induced fundamentally different remodeling in the two groups: while it improved the structural integrity and functional performance of WT cells, the same treatment result in sarcomere disarrangement, calcium handling deficiency, and further disrupted adrenergic signaling in PLN R9C KI cells. To understand the mechanism, transcriptomic analysis showed the enrichment of protein homeostasis signaling pathways specifically in PLN R9C KI cells in response to the MM treatment and increased contractile demands. Further studies also indicated elevated ROS levels, interrupted autophagic flux, and increased pentamer PLN aggregation in functionally challenged KI cells. These results were further confirmed in patient-specific iPSC-CM models, suggesting that functional stresses exacerbate the deficiencies in PLN R9C cells through disrupting protein homeostasis. Indeed, treating stressed patient cells with autophagy-accelerating reagents, such as metformin and rapamycin, has restored autophagic flux, mitigated sarcomere disarrangement, and partially rescued ß-adrenergic signaling and cardiac function. Conclusions: PLN R9C leads to a mild increase of calcium recycling and contractility. Functional challenges further enhanced contractile and proteostasis stress, leading to autophagic overload, structural remodeling, and functional deficiencies in PLN R9C cardiomyocytes. Activation of autophagy signaling partially rescues these effects, revealing a potential therapeutic target for DCM patients with the PLN R9C mutation. Graphic abstracts: A graphic abstract is available for this article.
Computerized adaptive testing (CAT) is a widely embraced approach for delivering personalized educational assessments, tailoring each test to the real-time performance of individual examinees. Despite its potential advantages, CAT�s application in small-scale assessments has been limited due to the complexities associated with calibrating the item bank using sparse response data and small sample sizes. This study addresses these challenges by developing a two-step item bank calibration strategy that leverages the 1-bit matrix completion method in conjunction with two distinct incomplete pretesting designs. We introduce two novel 1-bit matrix completion-based imputation methods specifically designed to tackle the issues associated with item calibration in the presence of sparse response data and limited sample sizes. To demonstrate the effectiveness of these approaches, we conduct a comparative assessment against several established item parameter estimation methods capable of handling missing data. This evaluation is carried out through two sets of simulation studies, each featuring different pretesting designs, item bank structures, and sample sizes. Furthermore, we illustrate the practical application of the methods investigated, using empirical data collected from small-scale assessments.
Research on the microbiota associated with marine invertebrates is important for understanding host physiology and the relationship between the host and the environment. In this study, the microbiota of the green mussel Perna viridis was characterized at the tissue scale using 16S rRNA gene high-throughput sequencing and compared with the microbiota of the surrounding environment. Different mussel tissues were sampled, along with two environmental samples (the mussel's attachment substratum and seawater). The results showed that the phyla Proteobacteria, Bacteroidetes, and Spirochaetae were dominant in mussel tissues. The bacterial community composition at the family level varied among the tissues of P. viridis. Although the microbiota of P. viridis clearly differed from that of the surrounding seawater, the composition and diversity of the microbial community of the foot and outer shell surface were similar to those of the substratum, indicating their close relationship with the substratum. KEGG prediction analysis indicated that the bacteria harbored by P. viridis were enriched in the degradation of aromatic compounds, osmoregulation, and carbohydrate oxidation and fermentation, processes that may be important in P. viridis physiology. Our study provides new insights into the tissue-scale characteristics of mussel microbiomes and the intricate connection between mussels and their environment.
The intestinal mucosal barrier-comprising microbial, mechanical, chemical, and immunological barriers-is critical to protection against pathogens and maintenance of host health; however, it remains unclear whether it is affected by environmental contaminants. Therefore, the present study assessed whether exposure to ambient concentrations of nanopolystyrene (NP) and chrysene (CHR)-two ubiquitous environmental pollutants in the aquatic environment-affect the intestinal mucosal barrier in juvenile Siniperca chuatsi. After exposure for 21 days, S. chuatsi exhibited intestinal oxidative stress and imbalance of intestinal microbial homeostasis. NP and/or CHR exposure also disrupted the intestinal mechanical barrier, as evidenced by the altered intestinal epithelial cell morphology, disrupted structure of intercellular tight junctions, and decreased expression of tight junction proteins. Damage to the intestinal chemical barrier manifested as thinning of the mucus layer owing to the loss and damage of goblet cells. Furthermore, the intestinal immunological barrier was impaired as indicated by the loss of intestinal intraepithelial lymphocytes and increase in pro-inflammatory cytokines, chemokines, and immunoglobulins. These findings collectively suggest that the intestinal mucosal barrier was damaged. This study is, to the best of our knowledge, the first to report that exposure to NP and/or CHR at environmentally relevant concentrations disrupts the intestinal mucosal barrier in organisms and highlight the significance of nanoplastic/CHR pollution for intestinal health.
Environmental Pollutants , Environmental Pollutants/metabolism , Chrysenes/metabolism , Intestinal Mucosa/metabolism , Intestines
Nanopolystyrene (NP) and chrysene (CHR) are ubiquitous contaminants in the natural environment; however, research on their hepatotoxicity and associated adverse effects remains relatively inadequate. The present study aimed to investigate the hepatotoxic effects of NP and/or CHR at environmentally relevant concentrations, as well as the underlying molecular mechanisms, in juvenile Siniperca chuatsi (mandarin fish). After a 21-day exposure period, the livers of exposed S. chuatsi exhibited macrostructural and microstructural damage accompanied by oxidative stress. Importantly, our study provides the first evidence that NP exposure leads to the development of nonalcoholic fatty liver disease (NAFLD) and hepatitis in S. chuatsi. Similarly, CHR exposure has also been found, for the first time, to cause hepatic sinusoidal dilatation (HSD) and hepatitis. Exposure to the combination of NP and CHR alleviated the symptoms of NAFLD, HSD, and hepatitis. Furthermore, our comprehensive multi-omic analysis revealed that the pathogenesis of NP-induced NAFLD was mainly due to induction of the triglyceride synthesis pathway and inhibition of the very-low-density lipoprotein secretion process. CHR induced HSD primarily through a reduction in vasoprotective ability and smooth muscle contractility. Hepatitis was induced by activation of the JAK-STAT/NF-kappa B signaling pathways, which upregulated the expression of inflammation-specific genes. Collectively, results of this study offer novel insight into the multiple hepatotoxicity endpoints of NP and/or CHR exposure at environmentally relevant concentrations in organisms, and highlight the importance of nanoplastic/CHR pollution for liver health.
Chemical and Drug Induced Liver Injury , Hepatitis , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/chemically induced , Microplastics , Chrysenes , Fishes/genetics , Liver
Nanopolystyrene (NP) and diclofenac (DCF) are common environmental contaminants in the aquatic ecosystem; therefore, the present study aimed to investigate the hepatotoxicity of NP and/or DCF exposure on aquatic organisms and the underlying mechanisms. Juvenile Mylopharyngodon piceus were used as a model organism to study the effects of NP and/or DCF exposure at environmentally relevant concentrations for 21 days. Subchronic exposure to NP and/or DCF resulted in liver histological damage. In the NP group, the presence of large lipid droplets was observed, whereas the DCF group exhibited marked hepatic sinusoidal dilatation accompanied by inflammation. Additionally, this exposure induced liver oxidative stress, as evidenced by the changes in several physiological parameters, including catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), reactive oxygen species (ROS), and malondialdehyde (MDA). Integrated transcriptomic and metabolomic analysis was performed to further investigate the molecular mechanism underlying hepatotoxicity. Multi-omics analysis demonstrated, for the first time to our knowledge, that NP induced hepatic steatosis mainly through activating the glycerol-3-phosphate pathway and inhibiting VLDL assembly by targeting several key enzyme genes including GPAT, DGAT, ACSL, APOB, and MTTP. Furthermore, NP exposure disrupted arachidonic acid metabolism, which induced the release of inflammatory factors and inhibited the release of anti-inflammatory factors, ultimately causing liver inflammation in M. piceus. In contrast, DCF induced interleukin production and downregulated KLF2, causing hepatic sinusoidal dilatation with inflammation in juvenile M. piceus, which is consistent with the finding of JAK-STAT signaling pathway activation. In addition, the upregulated AMPK signaling pathway in the DCF group suggested perturbation of energy metabolism. Collectively, these findings provide novel insights into the molecular mechanism of the multiple hepatotoxicity endpoints of NP and/or DCF exposure in aquatic organisms.
Chemical and Drug Induced Liver Injury , Cypriniformes , Animals , Diclofenac/toxicity , Diclofenac/metabolism , Ecosystem , Multiomics , Oxidative Stress , Antioxidants/metabolism , Liver/metabolism , Cypriniformes/metabolism , Inflammation/metabolism
We identified that the genes heat shock transcription factor 5 (hsf5) and ring finger protein 43 (rnf43) happened fusion in Nile tilapia (Oreochromis niloticus), called hsf5-rnf43, and provided the characteristic and functional analysis of hsf5-rnf43 gene in fish for the first time. Analysis of spatiotemporal expression showed that hsf5-rnf43 was specifically expressed in the testis and located in primary spermatocytes of adult Nile tilapia and gradually increased during testis development from 5 to 180 days after hatching. We also found DNA methylation regulated sex-biased expression of hsf5-rnf43 in the early development of Nile tilapia, and was affected by high temperature during the thermosensitive period of Nile tilapia sex differentiation. Therefore, we first reported that the fusion gene hsf5-rnf43 was sex-biased expressed in the testis regulated by DNA methylation and affected by high temperature, which may be involved in the maintenance of testis function and sex differentiation of Nile tilapia.
BACKGROUND: As the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined. METHODS: The expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo. RESULTS: SBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors. CONCLUSION: SBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.
Selenium , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Animals , Humans , Mice , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Endothelial Cells , Receptors, Thyrotropin , Thioredoxins , Thyroglobulin , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Neoplasms/genetics , Selenium-Binding Proteins/metabolism
A novel and efficient tandem SN2 nucleophilic substitution/Dieckmann condensation reaction of α-iodomethyl phosphine oxide with methyl thiosalicylate derivatives has been developed by using NaOH as a base, which enables the expeditious synthesis of 2-phosphonyl-3-hydroxybenzo[b]thiophene derivatives in moderate to high yields under simple conditions. This research provides not only a convenient method for the functionalization of benzo[b]thiophenes at the 2-position and 3-position but also new organophosphorus molecules. Furthermore, several new phosphonyl-substituted benzo[b]thiophenes were obtained from the resultant 2-phosphonyl-3-hydroxybenzo[b]thiophenes.
Health risks caused by widespread environmental pollutants such as nanopolystyrene (NP) and chrysene (CHR) in aquatic ecosystems have aroused considerable concern. The present study established juvenile Mandarin fish (Siniperca chuatsi) models of NP and/or CHR exposure at ambient concentrations for 21 days to systematically investigate the underlying neurotoxicity mechanisms. The results showed that single and combined exposure to NP and CHR not only reduced the density of small neuronal cells in the grey matter layer of the optic tectum, but also induced brain oxidative stress according to physiological parameters including CAT, GSH-Px, SOD, T-AOC, and MDA. The co-exposure alleviated the histopathological damage, compared to NP and CHR single exposure group. These results indicate that NP and/or CHR causes neurotoxicity in S. chuatsi, in accordance with decreased acetylcholinesterase activity and altered expression of several marker genes of nervous system functions and development including c-fos, shha, elavl3, and mbpa. Transcriptomics analysis was performed to further investigate the potential molecular mechanisms of neurotoxicity. We propose that single NP and co-exposure induced oxidative stress activates MMP, which degrades tight junction proteins according to decreased expression of claudin, JAM, caveolin and TJP, ultimately damaging the integrity of the blood-brain barrier in S. chuatsi. Remarkably, the co-exposure exacerbated the blood-brain barrier disruption. More importantly, single NP and co-exposure induced neuronal apoptosis mainly activates the expression of apoptosis-related genes through the death receptor apoptosis pathway, while CHR acted through both death receptor apoptosis and endoplasmic reticulum apoptosis pathways. Additionally, subchronic CHR exposure caused neuroinflammation, supported by activation of TNF/NF-κB and JAK-STAT signaling pathways via targeting-related genes, while the co-exposure greatly alleviated the neuroinflammation. Collectively, our findings illuminate the underlying neurotoxicity molecular mechanisms of NP and/or CHR exposure on aquatic organisms.
Acetylcholinesterase , Chrysenes , Animals , Ecosystem , Neuroinflammatory Diseases , Fishes , Receptors, Death Domain
Mandarin fish (Siniperca chuatsi) is a carnivorous freshwater fish and an economically important species. The digestive system (liver, stomach, intestine, pyloric caecum, esophagus, and gallbladder) is an important site for studying fish domestication. In our previous study, we found that mandarin fish undergoes adaptive changes in histological morphology and gene expression levels of the digestive system when subjected to artificial diet domestication. However, we are not clear which hub genes are highly associated with domestication. In this study, we performed WGCNA on the transcriptomes of 17 tissues and 9 developmental stages and combined differentially expressed genes analysis in the digestive system to identify the hub genes that may play important functions in the adaptation of mandarin fish to bait conversion. A total of 31,657 genes in 26 samples were classified into 23 color modules via WGCNA. The modules midnightblue, darkred, lightyellow, and darkgreen highly associated with the liver, stomach, esophagus, and gallbladder were extracted, respectively. Tan module was highly related to both intestine and pyloric caecum. The hub genes in liver were cp, vtgc, c1in, c9, lect2, and klkb1. The hub genes in stomach were ghrl, atp4a, gjb3, muc5ac, duox2, and chia2. The hub genes in esophagus were mybpc1, myl2, and tpm3. The hub genes in gallbladder were dyst, npy2r, slc13a1, and slc39a4. The hub genes in the intestine and pyloric caecum were slc15a1, cdhr5, btn3a1, anpep, slc34a2, cdhr2, and ace2. Through pathway analysis, modules highly related to the digestive system were mainly enriched in digestion and absorption, metabolism, and immune-related pathways. After domestication, the hub genes vtgc and lect2 were significantly upregulated in the liver. Chia2 was significantly downregulated in the stomach. Slc15a1, anpep, and slc34a2 were significantly upregulated in the intestine. This study identified the hub genes that may play an important role in the adaptation of the digestive system to artificial diet, which provided novel evidence and ideas for further research on the domestication of mandarin fish from molecular level.
Fishes , Perciformes , Animals , Fishes/genetics , Gene Expression Profiling , Transcriptome , Diet , Liver , Perciformes/genetics
Global warming threatens aquatic systems and organisms. Many studies have focused on the vulnerability and stress responses of aquaculture organisms to future thermal conditions. However, it may be of more practical significance to reveal their acclimation potential and mechanisms. In this study, the physiological, metabolic, and transcriptional responses to long-term temperature acclimation of northern and southern populations of Pacific abalone Haliotis discus hannai, a commercially important gastropod sensitive to environmental changes, were compared. This study conducted two common-garden experiments, including a thermostatic experiment in the lab and an aquaculture experiment on the farm. The abalone population cultured in warmer southern waters was tolerant of ongoing high temperatures, whereas the abalone population originally cultured in cooler northern waters exhibited vulnerability to high temperatures but could enhance its thermal tolerance through the process of natural selection in warmer southern waters. This difference was linked to divergence in the metabolic and transcriptional processes of the two populations. The tolerant population exhibited a greater capacity for carbohydrate and amino acid metabolism regulation and energy redistribution to cope with heat stress. This capacity may have been selected for, and accumulated, over many generations because the tolerant population originated from the intolerant population over two decades ago. This work provides insight into the vulnerability and acclimation potential of abalone to heat stress and discloses the molecular and metabolic traits underlying this phenomenon. Future research on the ability of abalone and other commercial shellfish species to acclimate to global warming should take this potential into account.
Gastropoda , Animals , Gastropoda/physiology , Shellfish , Heat-Shock Response , Temperature , Hot Temperature
After being exposed to environmental stimuli during early developmental stages, some organisms may gain or weaken physiological regulating abilities, which would have long-lasting effects on their performance. Environmental hypoxia events can have significant effects on marine organisms, but for breeding programs and other practical applications, it is important to further explore the long-term physiological effects of early hypoxia exposure in economically significant species. In this study, the Pacific abalone Haliotis discus hannai was exposed to moderate hypoxia (â¼4 mg/L) from zygote to trochophora, and the assessments of hypoxia tolerance were conducted on the grow-out stage. The results revealed that juvenile abalones exposed to hypoxia at the early development stages were more hypoxia-tolerant but with slower weight growth, a phenomenon called the trade-off between growth and survival. These phenotypic effects driven by the hypoxia exposure were explained by strong selection of genes involved in signal transduction, autophagy, apoptosis, and hormone regulation. Moreover, long non-coding RNA regulation plays an important role modulating carry-over effects by controlling DNA replication and repair, signal transduction, myocardial activity, and hormone regulation. This study revealed that the ability to create favorable phenotypic differentiation through genetic selection and/or epigenetic regulation is important for the survival and development of aquatic animals in the face of rapidly changing environmental conditions.
Epigenesis, Genetic , Gastropoda , Animals , Hypoxia/genetics , Hormones
Tea polysaccharides plays a role in lipid metabolism, antioxidant capacity and immunity of mammals. To investigate the functions of tea polysaccharides on fish, the common carp (Cyprinus carpio L.) was selected as the animal model in this study. In our study, the common carp (45±0.71g) were randomly divided into four groups and were fed fodder with 50% carbohydrate. The common carp were orally administrated with 0 mg/kg BW (control group), 200 mg/kg BW (low-dose group), 400 mg/kg BW (medium-dose group) and 800 mg/kg BW (high-dose group) tea polysaccharide for two week. At the end of experiment, the serum glucose, TG, MDA contents and antioxidase activities were measured by commercial kits. The serum immune factors levels were tested by ELISA. The genes expression levels related to antioxidant capacity, metabolism and immunity were measured by real-time PCR. The results showed that the glucose, TG and MDA contents in serum were significantly decreased by tea polysaccharides treatment. The serum activities of SOD were significantly increased by low-dose tea polysaccharides treatment. The serum activities of GPX were significantly increased by medium-dose tea polysaccharides treatment. The serum levels of IL-1ß and TNFα were significantly decreased in the tea polysaccharides treatment group. In the high-dose treatment group, the serum level of TGFß was significantly increased, and the serum level of IL-12 was markedly decreased. In the hepatopancreas, the expression of acc1, fas, srebp1c, lpl, gys and pparγ were significantly reduced, and the expression of pygl, cat, mnsod, ho-1 and gr were significantly up-regulated in the tea polysaccharides group. In the intestine, the expression of zo-1, occ and gip was significantly up-regulated in the high-dose treatment group. Moreover, the expression of glut2 and sglt1 were significantly down regulated. In the spleen, the expression of il-12, tnfα and il-6 were significantly decreased, and the expression of il-10 and tgfß was significantly increased by the tea polysaccharides. In the spleen cells, the tea polysaccharides could relieve the LPS-induced immune damage. In conclusion, tea polysaccharides can improve antioxidant capacity, lipid metabolism and immunity of common carp.
Carps , Animals , Antioxidants/pharmacology , Glucose , Interleukin-12 , Lipid Metabolism , Polysaccharides/pharmacology
We report the complete mitochondrial genome of Cuora mccordi. The complete genome is a closed circular molecule of 16,551 bp, with an overall base composition of 34.06% for A, 26.73% for T, 12.84% for G, and 26.37% for C. The A + T content is 60.79%. The full length consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region (D-loop). Phylogenetic analysis results showed that the mitogenome of Cuora mccordi was the closest to Cuora pani. The complete mitochondrial genome of Cuora mccordi (GenBank accession number: OM327796) can aid in understanding evolutionary relationships within Cuora.
Purpose: This study investigated the prognostic value of the albumin-to-fibrinogen ratio (AFR) in patients with sepsis as a consequence of infection at various sites. Methods: A total of 300 patients with sepsis caused by various infection sites, who met the diagnostic criteria for sepsis hospitalized in the intensive care unit, were enrolled in this study. The observational endpoint was 28-day mortality. Cox proportional hazard regression analysis was performed to determine the potential prognostic factors for 28-day mortality in these septic patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate and compare the prognostic factors for 28-day mortality. Results: Of 300 participants, 147 died, corresponding to a 28-day mortality of 49% (147/300). Baseline Acute Physiology and Chronic Health Evaluation (APACHE II) score (hazard ratio (HR) 1.18 (95% confidence interval (CI) 1.07-1.30); P < 0.001), baseline lactic acid level (HR 1.27 (95% CI 1.08-1.50); P = 0.005), the presence of septic shock (HR 21.44 (95% CI 2.51-182.76); P = 0.005), and baseline AFR (HR 0.70 (95% CI 0.62-0.80); P < 0.001) were independent prognostic factors for 28-day mortality in patients with sepsis according to multivariate Cox analysis. Baseline AFR was an effective predictor of 28-day mortality, with an area under the ROC curve (AUC) of 0.700, and a specificity and sensitivity of 90.8% and 42.1%, respectively. A low baseline AFR level was associated with increased 28-day sepsis-related mortality. The quadruple index, which included the APACHE II score, lactic acid, septic shock, and AFR, showed a more accurate predictive value for septic patients than the APACHE II score, lactic acid, septic shock, and AFR alone, with an AUC of 0.922, and specificity and sensitivity of 86.9% and 83.6%, respectively. Moreover, the triple index, which included the APACHE II score, lactic acid, and septic shock, showed a significantly lower prognostic value for 28-day mortality compared with the ROC curve of the quadruple index and triple index, with an AUC of 0.877 and specificity and sensitivity of 77.8% and 82.3%, respectively. Conclusions: The results of this study demonstrate that AFR is an independent protective factor for predicting 28-day mortality in patients with sepsis due to various infection sites. AFR combined with the APACHE II score, lactic acid, and septic shock showed a higher prognostic value for sepsis prognosis.
Sepsis , Albumins , Communicable Diseases , Fibrinogen , Humans , Lactic Acid , Prognosis , ROC Curve , Retrospective Studies , Sepsis/diagnosis , Sepsis/mortality , Shock, Septic/etiology
Aquaculture is one of the world's fastest-growing and most traded food industries, but it is under the threat of climate-related risks represented by global warming, marine heatwave (MHW) events, ocean acidification, and deoxygenation. For the sustainable development of aquaculture, selective breeding may be a viable method to obtain aquatic economic species with greater tolerance to environmental stressors. In this study, we estimated the heritability of heat tolerance trait of Pacific abalone Haliotis discus hannai, performed genome-wide association studies (GWAS) analysis for heat tolerance to detect single nucleotide polymorphisms (SNPs) and candidate genes, and assessed the potential of genomic selection (GS) in the breeding of abalone industry. A total of 1120 individuals were phenotyped for their heat tolerance and genotyped with 64,788 quality-controlled SNPs. The heritability of heat tolerance was moderate (0.35-0.42) and the predictive accuracy estimated using BayesB (0.55 ± 0.05) was higher than that using GBLUP (0.40 ± 0.01). A total of 11 genome-wide significant SNPs and 2 suggestive SNPs were associated with heat tolerance of abalone, and 13 candidate genes were identified, including got2,znfx1,l(2)efl, and lrp5. Based on GWAS results, the prediction accuracy using the top 5K SNPs was higher than that using randomly selected SNPs and higher than that using all SNPs. These results suggest that GS is an efficient approach for improving the heat tolerance of abalone and pave the way for abalone selecting breeding programs in rapidly changing oceans.
BACKGROUND: Transcriptome sequencing is an effective tool to reveal the essential genes and pathways underlying countless biotic and abiotic stress adaptation mechanisms. Although severely challenged by diverse environmental conditions, the Pacific abalone Haliotis discus hannai remains a high-value aquaculture mollusk and a Chinese predominantly cultured abalone species. Salinity is one of such environmental factors whose fluctuation could significantly affect the abalone's cellular and molecular immune responses and result in high mortality and reduced growth rate during prolonged exposure. Meanwhile, hybrids have shown superiority in tolerating diverse environmental stresses over their purebred counterparts and have gained admiration in the Chinese abalone aquaculture industry. The objective of this study was to investigate the molecular and cellular mechanisms of low salinity adaptation in abalone. Therefore, this study used transcriptome analysis of the gill tissues and flow cytometric analysis of hemolymph of H. discus hannai (DD) and interspecific hybrid H. discus hannai â x H. fulgens â (DF) during low salinity exposure. Also, the survival and growth rate of the species under various salinities were assessed. RESULTS: The transcriptome data revealed that the differentially expressed genes (DEGs) were significantly enriched on the fluid shear stress and atherosclerosis (FSS) pathway. Meanwhile, the expression profiles of some essential genes involved in this pathway suggest that abalone significantly up-regulated calmodulin-4 (CaM-4) and heat-shock protein90 (HSP90), and significantly down-regulated tumor necrosis factor (TNF), bone morphogenetic protein-4 (BMP-4), and nuclear factor kappa B (NF-kB). Also, the hybrid DF showed significantly higher and sustained expression of CaM and HSP90, significantly higher phagocytosis, significantly lower hemocyte mortality, and significantly higher survival at low salinity, suggesting a more active molecular and hemocyte-mediated immune response and a more efficient capacity to tolerate low salinity than DD. CONCLUSIONS: Our study argues that the abalone CaM gene might be necessary to maintain ion equilibrium while HSP90 can offset the adverse changes caused by low salinity, thereby preventing damage to gill epithelial cells (ECs). The data reveal a potential molecular mechanism by which abalone responds to low salinity and confirms that hybridization could be a method for breeding more stress-resilient aquatic species.
Atherosclerosis , Gastropoda , Animals , Gastropoda/genetics , Gene Expression Profiling , Salinity , Salt Stress/genetics , Transcriptome
Feed efficiency (FE) is critical to the economic and environmental benefits of aquaculture. Both the intestines and intestinal microbiota play a key role in energy acquisition and influence FE. In the current research, intestinal microbiota, metabolome, and key digestive enzyme activities were compared between abalones with high [Residual feed intake (RFI) = -0.029] and low FE (RFI = 0.022). The FE of group A were significantly higher than these of group B. There were significant differences in intestinal microbiota structures between high- and low-FE groups, while higher microbiota diversity was observed in the high-FE group. Differences in FE were also strongly correlated to variations in intestinal digestive enzyme activity that may be caused by Pseudoalteromonas and Cobetia. In addition, Saprospira, Rhodanobacteraceae, Llumatobacteraceae, and Gaiellales may potentially be utilized as biomarkers to distinguish high- from low-FE abalones. Significantly different microorganisms (uncultured beta proteobacterium, BD1_7_clade, and Lautropia) were found to be highly correlated to significantly different metabolites [DL-methionine sulfoxide Arg-Gln, L-pyroglutamic acid, dopamine, tyramine, phosphatidyl cholines (PC) (16:0/16:0), and indoleacetic acid] in the high- and low-FE groups, and intestinal trypsin activity also significantly differed between the two groups. We propose that interactions occur among intestinal microbiota, intestinal metabolites, and enzyme activity, which improve abalone FE by enhancing amino acid metabolism, immune response, and signal transduction pathways. The present study not only elucidates mechanisms of variations in abalone FE, but it also provides important basic knowledge for improving abalone FE by modulating intestinal microbiota.
GIP plays an important regulatory role in glucose and lipid metabolism. As the specific receptor, GIPR is involved in this physiological process. To assess the roles of GIPR in teleost, the GIPR gene was cloned from grass carp. The ORF of cloned GIPR gene was 1560 bp, encoding 519 amino acids. The grass carp GIPR was the G-protein-coupled receptor which contains seven predicted transmembrane domains. In addition, two predicted glycosylation sites were contained in the grass carp GIPR. The grass carp GIPR expression is in multiple tissues and is highly expressed in the kidney, brain regions, and visceral fat tissue. In the OGTT experiment, the GIPR expression is markedly decreased in the kidney, visceral fat, and brain by treatment with glucose for 1 and 3 h. In the fast and refeeding experiment, the GIPR expression in the kidney and visceral fat tissue was significantly induced in the fast groups. In addition, the GIPR expression levels were markedly decreased in the refeeding groups. In the present study, the visceral fat accumulation of grass carp was induced by overfed. The GIPR expression was significantly decreased in the brain, kidney, and visceral fat tissue of overfed grass carp. In primary hepatocytes, the GIPR expression was promoted by treatment with oleic acid and insulin. The GIPR mRNA levels were significantly reduced by treatment with glucose and glucagon in the grass carp primary hepatocytes. To our knowledge, this is the first time the biological role of GIPR is unveiled in teleost.
