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Abstract Background Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic. Methods Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses. Results Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured. Conclusions We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.

Interferons (IFNs) play critical roles in the host defense against virus infection, and exhibit promising prospects for the prevention of viral diseases in aquaculture. Pufferfish is an important cultured fish in East Asia. However, the IFN genes haven’t been systematically analyzed in pufferfish until now. In this study, we identified three type I IFN genes (ToIFNd, ToIFNh and ToIFNc) and two type II IFN genes (ToIFNγ and ToIFNγrel) in obscure puffer, and compared their molecular characterizations and phylogenetic relationships. Then we revealed that the five IFN genes were constitutively expressed in all detected tissues with different tissue distribution patterns. Furthermore, the dynamic expression changes of the IFNs were analyzed after poly(I:C) stimulation, which implied that the IFNs played various roles in the antiviral responses of obscure puffer. Finally, we investigated the characteristic reactions and verified the key transcription factor binding sites of ToIFNd promoter, and analyzed the induction effects of ToIFNγ and ToIFNγrel. These results will be beneficial to understand the functional characteristics of IFNs in Takifugu.

Abstract Background Accompanied with rapid growth and high density aquaculture, gibel carp has been seriously threatened by Carassius auratus herpesvirus (CaHV) since 2012. In previous study, distinct CaHV resistances and immune responses were revealed in the diseased individuals of three gibel carp gynogenetic clones (A+, F and H). However, little is known about the gene expression changes in the survivors after CaHV challenge, particularly their differences of innate and adaptive immune system between susceptible clone and resistant clone. Results We firstly confirmed the CaHV carrier state in the survivors of three gibel carp clones after CaHV challenge by evaluating the abundances of five CaHV genes. The assay of viral loads indicated the resistant clone H possessed not only stronger resistance but also higher tolerance to CaHV. Then, 2818, 4047 and 3323 differentially expressed unigenes (DEUs) were screened from the head-kidney transcriptome profiles of survivors compared with controls from clone A+, F and H. GO and KEGG analysis suggested that a persistent immune response might sustain in resistant clone H and F, while susceptible clone A+ had a long-term impact on the circulatory system which was consistent with the major symptoms of bleeding caused by CaHV. Among the top 30 enriched pathways of specifically up-regulated DEUs in respective clones, 26, 7 and 15 pathways in clone H, F and A+ were associated with infections, diseases, or immune-related pathways respectively. In addition, 20 pathways in clone F belonged to “metabolism” or “biogenesis”, and 7 pathways involved in “circulatory system” were enriched in clone A+. Significantly, we revealed the differential expression changes of IFN system genes and immunoglobulin (Ig) genes among the survivors of three clones. Finally, myosins and Igs were identified as co-expression modules which were positively or negatively correlated to CaHV viral loads respectively. Conclusions Our results revealed the common and distinct gene expression changes in immune and circulatory system in the survivors of three gibel carp gynogenetic clones with different CaHV resistances. The current study represents a paradigm of differential innate and adaptive immune reactions in teleost, and will be beneficial to the disease-resistance breeding of gibel carp.

Chemokine receptor cxcr4 and its ligand cxcl12 have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated cxcr4 and cxcl12 genes from hexaploid gibel carp, Carassius gibelio, respectively. Cgcxcr4bs and Cgcxcl12as were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (CaHV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in CaHV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of CaHV in vivo. Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that CgCxcr4s and CgCxcl12s participate in to promote the antiviral response in vitro.

Existing systems for diagnosing heart diseases are time consuming, expensive, and error prone. Aiming at this, a detection algorithm for factors inducing heart diseases based on a particle swarm optimisation-support vector machine (PSO-SVM) optimised by association rules (ARs) was proposed. Firstly, AR was used to select features from a disease data set so as to train feature sets. Then, PSO-SVM was used to classify training and testing sets, and then the factors inducing heart diseases were analysed. Finally, the effectiveness and reliability of the proposed algorithm was verified by experiments on the UCI Cleveland data set with confidence as the index. The experimental results showed that females have less risk of having a heart attack than males. Irrespective of gender, once diagnosed with chest pain without symptoms and angina caused by exercise, people are more likely to suffer from heart disease. Moreover, compared with another two advanced classification algorithms, the proposed algorithm showed better classification performance and therefore can be used as a powerful tool to help doctors diagnose and treat heart diseases.

To observe the clinical characteristics of fungal and Brucella infections of the lumbar spine and explore the key points for their differential diagnosis. Methods: The clinical data of 12 patients with fungal infection (the fungal group) and 31 patients with Brucella infection (the Brucella group) of the lumbar spine confirmed by microbiological culture and antigen test were retrospectively analysed. The differences in the clinical characteristics and imaging manifestations were observed between the two groups. Results: The peripheral blood neutrophil ratio, erythrocyte sedimentation rate, serum total protein and serum globulin levels in the fungal group were higher compared with the Brucella group, while the peripheral blood lymphocyte count, lymphocyte ratio and albumin-globulin ratio were lower in the fungal group compared with the Brucella group (P < 0.05). As for imaging examinations, the proportion of bone destruction centred on the intervertebral disc with surrounding osteosclerosis on computed tomography (CT) imaging showed a statistical difference between the Brucella group and the fungal group (P < 0.05). Fungal infection patients showed more osteosclerosis-free areas around the bone destruction on magnetic resonance imaging (MRI) than Brucella infection patients. Conclusion: There are certain similarities in clinical manifestations between fungal and Brucella infections of the lumbar spine, but the haematological indices and image features of CT and MRI can effectively differentiate between them, providing guidance for the clinical differential diagnosis. [ABSTRACT FROM AUTHOR]

IntroductionUrinary incontinence (UI) significantly impairs women’s quality of life. Identifying its risk factors is essential for developing effective interventions. Sarcopenia, characterized by the accelerated loss of muscle mass and function, is an emerging concern often linked to obesity and abnormal metabolic status, exacerbating various adverse health outcomes. This population-based study aimed to explore the independent and joint associations of sarcopenia, obesity, and metabolic health with UI risk, as well as to evaluate the mediating role of metabolic indicators in these associationsMethodsA total of 3,557 women aged ≥20 years from the National Health and Nutrition Examination Survey were included. Sarcopenia was assessed using the appendicular lean mass index (ALMI), and obesity was defined by body mass index and waist circumference. Metabolic health was evaluated using revised criteria from the National Cholesterol Education Program-Adult Treatment Panel III. UI was identified through responses to the “Kidney Conditions-Urology” questionnaire and classified into stress UI (SUI), urgency UI (UUI), and mixed UI (MUI). Multivariable logistic regression and restricted cubic spline models were used to evaluate the associations and visualize the relationship between ALMI and UI. Mediation models were constructed to assess the mediating role of metabolic indicators.ResultsWe found that sarcopenia was significantly associated with an increased risk of MUI in the general population. Age-specific analysis revealed that sarcopenia is an independent risk factor for SUI in women aged ≥60, and for MUI in women aged 40–59 years. Sarcopenic obesity, particularly under central obesity criteria, further elevated the risk of UI. Notably, women with the metabolically unhealthy obese phenotype with sarcopenia were at the highest risk for both SUI and MUI. Metabolically unhealthy status, glycohemoglobin, vitamin D, and serum albumin levels were partial mediators of these associations.ConclusionOur findings elucidated the complex interactions between sarcopenia, obesity, and metabolic health, underscoring the critical need for integrated therapeutic strategies that address both metabolic health and targeted nutritional interventions, aiming to enhance muscular health and effectively manage and prevent UI.

Abstract Long-form collapsin response mediator protein-1 (LCRMP-1) belongs to the CRMP family which comprises brain-enriched proteins responsible for axon guidance. However, its role in spermatogenesis remains unclear. Here we find that LCRMP-1 is abundantly expressed in the testis. To characterize its physiological function, we generate LCRMP-1-deficient mice (Lcrmp-1 −/− ). These mice exhibit aberrant spermiation with apoptotic spermatids, oligospermia, and accumulation of immature testicular cells, contributing to reduced fertility. In the seminiferous epithelial cycle, LCRMP-1 expression pattern varies in a stage-dependent manner. LCRMP-1 is highly expressed in spermatids during spermatogenesis and especially localized to the spermiation machinery during spermiation. Mechanistically, LCRMP-1 deficiency causes disorganized F-actin due to unbalanced signaling of F-actin dynamics through upregulated PI3K-Akt-mTOR signaling. In conclusion, LCRMP-1 maintains spermatogenesis homeostasis by modulating cytoskeleton remodeling for spermatozoa release.

Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters. In CLP models, HLJ1 deletion reduces IFN-γ expression and sepsis mortality rate when mice are treated with antibiotics. HLJ1 deficiency also leads to reduced serum levels of IL-12 in LPS-treated mice, contributing to dampened production of IFN-γ in natural killer cells but not CD4+ or CD8+ T cells, and subsequently to improved survival rate. Adoptive transfer of HLJ1-deleted macrophages into LPS-treated mice results in reduced IL-12 and IFN-γ levels and protects the mice from IFN-γ-dependent mortality. In the context of molecular mechanisms, HLJ1 is an LPS-inducible protein in macrophages and converts misfolded IL-12p35 homodimers to monomers, which maintains bioactive IL-12p70 heterodimerization and secretion. This study suggests HLJ1 causes IFN-γ-dependent septic lethality by promoting IL-12 heterodimerization, and targeting HLJ1 has therapeutic potential in inflammatory diseases involving activated IL-12/IFN-γ axis.

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3′-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical “GCACGTTT” sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3′-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients.