Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities.

Interleukin-1 (IL-1) signaling is important for multiple potentially pathogenic processes in the central nervous system (CNS), but the cell-type-specific roles of IL-1 signaling are unclear. We used a genetic knockin reporter system in mice to track and reciprocally delete or express IL-1 receptor 1 (IL-1R1) in specific cell types, including endothelial cells, ventricular cells, peripheral myeloid cells, microglia, astrocytes, and neurons. We found that endothelial IL-1R1 was necessary and sufficient for mediating sickness behavior and drove leukocyte recruitment to the CNS and impaired neurogenesis, whereas ventricular IL-1R1 was critical for monocyte recruitment to the CNS. Although microglia did not express IL-1R1, IL-1 stimulation of endothelial cells led to the induction of IL-1 in microglia. Together, these findings describe the structure and functions of the brain's IL-1R1-expressing system and lay a foundation for the dissection and identification of IL-1R1 signaling pathways in the pathogenesis of CNS diseases.

Functional analysis of the ube3a response in Japanese flounder (Paralichthys olivaceus) to CSBV infection.

Ube3a is a member of the E3 ubiquitin ligase HECTc family, and its role has been established in neurodevelopmental disorders. However, studies on its role in Japanese flounder are scarce. Thus, in this study, the ube3a of Japanese flounder was cloned, and its role in conferring resistance against Chinook salmon bafnivirus (CSBV) was analyzed. Japanese flounder ube3a encoded a protein containing 834 amino acids. Interestingly, its homology with the Atlantic halibut was determined to be 94%. In addition, there were differential expressions of ube3a in different tissues of Japanese flounder, with the highest expression level observed in the fin, followed by the gills and skin (P ≤ 0.05). Subcellular localization analysis revealed that Ube3a is a cytoplasmic protein. We established an in vitro CSBV infection model using Japanese flounder gill cell line (FG). After ube3a overexpression, the viral load was significantly lower than that of the control group (P ≤ 0.05). Contrastingly, after incubation of FG cells with an E3 ubiquitin ligase inhibitor, the viral load was significantly higher than in the control group (P ≤ 0.01). Then, the expression levels of nf-κb, traf3, and tnf-α after incubation with an E3 ubiquitin ligase inhibitor were examined. The results demonstrated that ube3a may exerted a significant antiviral effect in Japanese flounder via the ubiquitination pathway.

Imaging Characteristics and Interpretation Strategy for Renal Hyperparathyroidism: A Retrospective 4-Dimensional Computed Tomography Study.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm. METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected. RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns. CONCLUSION: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Ochratoxin A detoxification potentials of basil, chan, and chia seeds.

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.

Prognostic implications of distinctive imaging characteristics in primary intracranial germ cell tumors: A retrospective analysis.

PURPOSE: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare brain tumors that encompass two subtypes: germinomas and non-germinomatous germ cell tumors (NGGCTs), NGGCTs have less favorable outcome and require multi-modality treatment. Biopsy is recommended for disease diagnosis, the specimen may not adequately reflect the entire tumor. This study aimed to assess distinct imaging characteristics to differentiate between GCT subgroups and to identify possible initial image and subgroup features that influence survival. METHOD: This retrospective study, conducted from January 2006 to March 2023, analyzed patient data and MRI findings of primary CNS GCTs. It evaluated tumor characteristics including cysts, seeding, multifocality, and hemorrhage. Tumor volumes and apparent diffusion coefficient (ADC) values of both tumoral and normal-appearing contralateral white matter were measured. These factors were correlated with overall and 5-year survival rates. RESULTS: This study included 51 participants with CGTs, comprising 19 germinoma and 32 NGGCTs cases. GCTs with hemorrhage had worse overall (P = 0.03) and 5-year (P = 0.01) survival rates. No survival difference between germinoma and non-hemorrhagic NGGCT. NGGCTs were more likely to bleed (P < 0.001) than germ cell tumor, especially those with choriocarcinoma or yolk sac tumor components (P = 0.001). The ADC ratios of germinomas were significantly lower than those of NGGCTs (P = 0.03 for whole tumor; P < 0.01 or solid part), The ADC ratios of choriocarcinoma were also lower than mixed tumor (P = 0.01; P = 0.02). CONCLUSION: Hemorrhage indicates worse prognosis. Intratumoral hemorrhage and ADC ratios differentiate germinoma from NGGCTs. Larger cohorts and advanced MR techniques are needed for future study.

Development of Rapid Detection Methods for Fusarium oysporum f. sp. melonis in Melon Seeds.

Melon (Cucumis melo L.) is a global commercial crop that is sensitive to seed-borne wilt infections caused by Fusarium oxysporum f. sp. melonis (Fom). To address the challenge of detecting Fom contamination, we designed a probe-based real-time PCR method, TDCP2, in combination with rapid or column-based DNA extraction protocols to develop reliable molecular detection methods. Utilizing TDCP2, the detection rate reached 100% for both artificially Fom-inoculated (0.25-25%) and pod-inoculated melon seeds in conjunction with DNA samples from either the rapid or column-based extraction protocol. We performed analyses of precision, recall, and F1 scores, achieving a maximum F1 score of 1 with TDCP2, which highlights the robustness of the method. Additionally, intraday and interday assays were performed, which revealed the high reproducibility and stability of column-based DNA extraction protocols combined with TDCP2. These metrics confirm the reliability of our developed protocols, setting a foundation for future enhancements in seed pathology diagnostics and potentially broadening their applicability across various Fom infection levels. In the future, we hope that these methods will reduce food loss by improving the control and management of melon diseases.

Characterization and function of Japanese flounder (Paralichthys olivaceus) slc2a6 in response to lymphocystis disease virus infection.

Slc2a6 is a member of the slc2 family (solute carrier 2 family) and previous reports have indicated its involvement in the inflammatory response. Slc2a6 is regulated by the NF-ĸB signaling pathway. This study investigated the differential expression of slc2a6 in the early embryonic development of Japanese flounder, revealing that the early gastrula stage had the highest level of slc2a6 expression. Moreover, slc2a6 expression was increased in vitro after stimulation by lymphocystis disease virus (LCDV), and in vivo experiments also showed significantly elevated levels in the spleen and muscle tissues following LCDV stimulation. Subcellular localization revealed that Slc2a6 was expressed in both the nucleus and cytoplasm of cells. The pcDNA3.1-slc2a6 overexpression plasmid was successfully constructed; the si-slc2a6 interfering strand was screened and samples were collected. The expression of NF-ĸB signaling pathway-related genes il-1ß, il-6, nf-ĸb, and tnf-α was evaluated in overexpressed, silenced, and LCDV-stimulated samples. The results showed that slc2a6 is involved in viral regulation in Japanese flounder by regulating innate immune responses.

Cr(OH)3nanosheets@ZIF67 electrocatalysts prepared by electrodeposition method for efficient oxygen evolution reaction.

In this paper, a Cr(OH)3NSs@ZIF67 (NSs = nanosheets) electrocatalyst is prepared on foam Ni via a simple and rapid electrochemical deposition method. Excellent electrocatalytic activity of Cr(OH)3NSs@ZIF67 is demonstrated. It can use the overpotential of 281 mV and 390 mV respectively to drive 10 mA cm-2and 50 mA cm-2. It is observed that the Cr(OH)3NSs@ZIF67 electrode has the highest initial current density at 1.57 V compared with the other two monomer electrodes and shows excellent stability at the end of 60 000 s. It has the largest electrochemical activity specific surface and lowest charge-transfer resistance, and M-O bonds (M = Co, Cr) and shifting of binding energy peaks at the interface lead to more active sites and more efficient electron transfer for oxygen evolution reaction. This work highlights the construction of highly efficient composite electrocatalysts composted of low-dimensional non-precious transition metal compounds and metalorganic frameworks, promoting the development of low-cost non-noble metal composites in energy chemistry.

Molecular identification and function characterization of four alternative splice variants of trim25 in Japanese flounder (Paralichthys olivaceus).

Trim25 is a member of Tripartite Motif (TRIM) family. Previous studies report that trim25 modulates antiviral activity by activating RIG-I. In this study we explored the four alternative splicing (AS) variants X1-X4 of Japanese flounder trim25. The sequences of the AS variants were highly conserved. Expression levels of trim25 X1-X4 were increased after 12 h of poly I:C treatment in vitro. In vivo expression of X2-X4 in liver, kidney (except X2) and blood was significantly up-regulated in early stages of poly I:C treatment. Subcellular localization analysis showed that Trim25 X1-X4 were distributed in different cellular organelles. The recombinant vector pcDNA3.1-Trim25 X1-X4 were successfully overexpressed in Flounder cells and the samples were collected. Expression patterns of RIG-I pathway genes dhx58, traf6, traf2, nfkbia and il-8 were explored in vitro and in vivo after poly I:C treatment, as well as overexpressed samples. The findings of this study imply that AS variants of trim25 confer antiviral activity in Japanese flounder by modulating innate immune response.

Unveiling the Mechanism of Urine Source Separation-Derived Pretreatment on Enhancing Short-Chain Fatty Acid Yields from Anaerobic Fermentation of Waste Activated Sludge.

A novel strategy employing urine wastewater derived from source separation technology, to pretreat waste activated sludge (WAS) for promoting yields of short-chain fatty acids (SCFAs), has been proposed in this study. It was found experimentally that SCFA production could ascend up to 305.4 mg COD/g VSS (volatile suspended solids) with a urine volumetric proportion of 1:2 to the whole reaction system, being 8.8 times that produced in the control. Exploration of the mechanism indicated that WAS disintegration was significantly enhanced due to the synergistic effect of urea and free ammonia (FA). Degradation rates of model organic substrates and measurements of critical enzymatic activities demonstrated that hydrolysis and acidogenesis were inhibited under high urine content (urine proportion of 1:2), while not significantly affected under low urine content (i.e., 1:4), which might be attributed to metal ions existing in urine wastes alleviating the inhibition induced by FA. In contrast, methanogenesis was negatively suppressed by any urine concentration owing to its higher sensitivity to the environmental variations. Shift of microbial population further elucidated the abundance of hydrolytic and acidogenic microbes were enriched in the fermenters with urine addition. The findings provide a new thought for recovering resources from wastes, potentially reducing the pressure of sewage and sludge treatment in wastewater treatment plants.

Localization Approach for Underwater Sensors in the Magnetic Silencing Facility Based on Magnetic Field Gradients.

Localization of the underwater magnetic sensor arrays plays a pivotal role in the magnetic silencing facility. A localization approach is proposed for underwater sensors based on the optimization of magnetic field gradients in the inverse problem of localization. In the localization system, a solenoid coil carrying direct current serves as the magnetic source. By measuring the magnetic field generated by the magnetic source in different positions, an objective function is established. The position vector of the sensor is determined by a novel multi-swarm particle swarm optimization with dynamic learning strategy. Without the optimization of the magnetic source's positions, the sensors' positions, especially in the z-axis direction, struggle to meet the requested localization. A strategy is proposed to optimize the positions of the magnetic source based on magnetic field gradients in the three directions of x, y and z axes. Compared with the former method, the model experiments show that the proposed method could achieve a 10 cm location error for the position type 2 sensor and meet the request of localization.

Performance and mechanism of sodium percarbonate (SPC) enhancing short-chain fatty acids production from anaerobic waste activated sludge fermentation.

A novel pretreatment technique (i.e., using Sodium percarbonate, SPC) to improve the short-chain fatty acids (SCFA) production waste activated sludge (WAS) was proposed in this study. Results indicated that the maximum SCFA production of 1605.7 mg COD/L and acetic acid of 52.9% were attained at 0.2 g SPC/g TSS, being 8.4 and 2.8 times of the control (191.3 mg COD/L and 19%), respectively. Meanwhile, the optimal time for SCFA accumulation was decreased from 6d (control) to 4d (0.2 g/g TSS). Mechanism explorations unraveled that SPC largely accelerated WAS solubilization and enhanced the bioavailability of organics released from WAS. It improved enzymatic activities related to hydrolysis and acidogenesis, while suppressed the Coenzyme F420 responsible for SCFA consumption. Illumina MiSeq sequencing analysis showed that SPC substantially enhanced the relative abundances of hydrolytic and/or acid-forming microbes. Furthermore, CO3- and O2- were the key factors to production enhancement in SPC-involved sludge fermentation.

Associations between perceived overqualification, transformational leadership and burnout in nurses from intensive care units: A multicentre survey.

AIMS: To explore whether perceived overqualification increases the risk of burnout and whether transformational leadership negatively moderates this relationship. BACKGROUND: Perceived overqualification might contribute to burnout and lead to poor experience of transformational leadership, and transformational leadership might be associated with burnout. However, these relationships have not yet been confirmed. METHODS: A multicentre cross-sectional study. A total of 321 nurses from intensive care units were recruited from six tertiary hospitals. Scale of Perceived OverQualification, Transformational Leadership Questionnaire and emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey were employed to collect the data. Hierarchical multiple regression and bootstrap resampling were applied to analyse the data. RESULTS: Burnout was positively associated with perceived overqualification and negatively associated with transformational leadership (each p < 0.05). Transformational leadership significantly mediated the relationship between perceived overqualification and burnout (b = -0.6389, 95% confidence interval: -0.8706, -0.4072). CONCLUSION: Our findings indicated that perceived overqualification and transformational leadership directly or indirectly affect burnout among nurses from intensive care units. IMPLICATIONS FOR NURSING MANAGERS: Personal and organizational-oriented interventions utilizing nurses' overall qualifications and implementing transformational leadership should be employed by nurse managers to alleviate burnout and promote the work performance of nurses from intensive care units.

Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis.

Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4+ T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4+Th17 cells but increased numbers of CD4+CD8+FoxP3+ regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4+CCR9+ T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4+CCR9+ T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103+CD11b+ DCs were decreased and that the ability of these cells to upregulate CD4+ T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103+CD11b+ DC dysfunction contributes to the gut immune imbalance observed in NASH.

Early spot sign is associated with functional outcomes in primary intracerebral hemorrhage survivors.

BACKGROUND: The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and 30-day mortality in intracerebral hemorrhage (ICH). However, whether the spot sign predicts worse functional outcomes among ICH survivors remains unclear. This study investigated the frequency of the spot sign and its association with functional outcomes and length of hospital stay among ICH survivors. METHODS: This was a retrospective analysis of consecutive patients with primary ICH who received CTA within 24 h from presentation to admission to the emergency department of a single medical center between January 2007 and December 2017. Patients who died before discharge and those referred from other hospitals were excluded. CTAs with motion artifacts were excluded from the analysis. The presence of a spot sign was examined by an experienced neuroradiologist. Functional outcomes were determined based on the modified Rankin Scale (mRS) score and Barthel Index (BI). Severe dependency in activities of daily living (ADL) was defined as BI of ≤60 and severe disability as an mRS score of ≥4. Odds ratio (OR) and multiple linear regression were used as measures of association. RESULTS: In total, 66 patients met the inclusion criteria, of whom 9 (13.64%) were positive for a spot sign. No significant differences were observed in baseline characteristics between patients with and without a spot sign. Patients with a spot sign tended to be severely dependent in ADL at discharge (66.67% vs 41.07%; OR = 2.87; p = 0.15) and were more likely to require ICH-related surgery (66.67% vs 24.56%; OR = 6.14; p = 0.01). In multiple linear regression, patients with a higher spot sign score had a significantly longer hospital stay (coefficient = 9.57; 95% CI = 2.11-17.03; p = 0.013). CONCLUSIONS: The presence of a spot sign is a common finding and is associated with longer hospital stay and possibly worse functional outcomes in ICH survivors.

Association of surgical margins with local recurrence in patients undergoing breast-conserving surgery after neoadjuvant chemotherapy.

BACKGROUND: The aim of the current study was to report a single-institution experience using breast-conserving surgery after neoadjuvant chemotherapy (NACT), focusing on the association between microscopic resection margin status and locoregional recurrence (LRR). METHODS: Our institutional prospectively maintained database was reviewed to identify patients who were treated with NACT between January 2008 and April 2018. RESULTS: Among the main partial mastectomy specimens available for analysis (n = 161), 28 had margins < 1 mm, 21 had margin width of 1-2 mm and the remaining 112 had margins > 2 mm. LRR occurred in 16 patients (9.9%) and distant metastases were detected in 27 (16.8%) patients. There was no significant difference in the LRR between the > 2 mm margin group with a 60-month cumulative survival of 85.2% compared with 76.2% for the ≤2 mm group (P = 0.335) in the Kaplan-Meier analysis. When we stratified patients by margin widths of ≥1 mm or <  1 mm, there was no LRR-free survival benefit observed for the ≥1 mm pathologic excision margin group in the univariate analysis (hazard ratio = 0.443; 95% confidence interval = 0.142-1.383; P = 0.161) with a 60-month cumulative LRR-free survival of 84.9% compared with 69.5% for the < 1 mm margin cohort (P = 0.150). CONCLUSIONS: In the absence of multiple scattered microscopic tumour foci, a negative margin of no ink on tumour maybe sufficient for stage I-III invasive breast cancer treated with NACT and breast-conserving surgery.

Corticosterone Production during Repeated Social Defeat Causes Monocyte Mobilization from the Bone Marrow, Glucocorticoid Resistance, and Neurovascular Adhesion Molecule Expression.

Repeated social defeat (RSD) stress promotes the release of bone marrow-derived monocytes into circulation that are recruited to the brain, where they augment neuroinflammation and cause prolonged anxiety-like behavior. Physiological stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal gland (HPA) axis, and both of these systems play a role in the physiological, immunological, and behavioral responses to stress. The purpose of this study was to delineate the role of HPA activation and corticosterone production in the immunological responses to stress in male C57BL/6 mice. Here, surgical (adrenalectomy) and pharmacological (metyrapone) interventions were used to abrogate corticosterone signaling during stress. We report that both adrenalectomy and metyrapone attenuated the stress-induced release of monocytes into circulation. Neither intervention altered the production of monocytes during stress, but both interventions enhanced retention of these cells in the bone marrow. Consistent with this observation, adrenalectomy and metyrapone also prevented the stress-induced reduction of a key retention factor, CXCL12, in the bone marrow. Corticosterone depletion with metyrapone also abrogated the stress-induced glucocorticoid resistance of myeloid cells. In the brain, these corticosterone-associated interventions attenuated stress-induced microglial remodeling, neurovascular expression of the adhesion molecule intercellular cell adhesion molecule-1, prevented monocyte accumulation and neuroinflammatory signaling. Overall, these results indicate that HPA activation and corticosterone production during repeated social defeat stress are critical for monocyte release into circulation, glucocorticoid resistance of myeloid cells, and enhanced neurovascular cell adhesion molecule expression.SIGNIFICANCE STATEMENT Recent studies of stress have identified the presence of monocytes that show an exaggerated inflammatory response to immune challenge and are resistant to the suppressive effects of glucocorticoids. Increased presence of these proinflammatory monocytes has been implicated in neuropsychiatric symptoms and the development of chronic cardiovascular, autoimmune, and metabolic disorders. In the current study, we show novel evidence that corticosterone produced during stress enhances the release of proinflammatory monocytes from the bone marrow into circulation, augments their recruitment to the brain and the induction of a neuroinflammatory profile. Overproduction of corticosterone during stress is also the direct cause of glucocorticoid resistance, a key phenotype in individuals exposed to chronic stress. Inhibiting excess corticosterone production attenuates these inflammatory responses to stress.

Controlled dimerization of insulin-like growth factor-1 and insulin receptors reveals shared and distinct activities of holo and hybrid receptors.

Breast cancer development and progression are influenced by insulin-like growth factor receptor 1 (IGF1R) and insulin receptor (InsR) signaling, which drive cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and InsR form IGF1R/InsR hybrid receptors (HybRs) consisting of one molecule of IGF1R and one molecule of InsR. The specific signaling and functions of HybR are largely unknown, as HybR is activated by both IGF1 and insulin, and no cellular system expresses HybR in the absence of holo-IGF1R or holo-InsR. Here we studied the role of HybR by constructing inducible chimeric receptors and compared HybR signaling with that of holo-IGF1R and holo-InsR. We cloned chemically inducible chimeric IGF1R and InsR constructs consisting of the extracellular domains of the p75 nerve growth factor receptor fused to the intracellular ß subunit of IGF1R or InsR and a dimerization domain. Dimerization with the drugs AP20187 or AP21967 allowed specific and independent activation of holo-IGF1R, holo-InsR, or HybR, resulting in activation of the PI3K pathway. Holo-IGF1R and HybR both promoted cell proliferation and glucose uptake, whereas holo-InsR only promoted glucose uptake, and only holo-IGF1R showed anti-apoptotic effects. We also found that the three receptors differentially regulated gene expression: holo-IGF1R and HybR up-regulated EGR3; holo-InsR specifically down-regulated JUN and BCL2L1; holo-InsR down-regulated but HybR up-regulated HK2; and HybR specifically up-regulated FHL2, ITGA6, and PCK2. Our findings suggest that, when expressed and activated in mammary epithelial cells, HybR acts in a manner similar to IGF1R and support further investigation of the role of HybR in breast cancer.

microRNA-mRNA analysis in pituitary and hypothalamus of sterile Japanese flounder.

Double haploidy is an advantageous situation for genetic mapping and genome sequencing studies. In the present study, the hypothalamus and pituitary gland from sterile and fertile double-haploid (DH) Japanese flounders (aged 5 years) were used as experimental materials for studying the expression of genes in individuals with reproductive disorders, using high-throughput sequencing technology. The results revealed abnormal levels of some hormones in sterile DHs during the breeding season. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the significantly different microRNAs and messenger RNAs were related to metabolism, signal transduction, and melanogenesis; those related to steroid hormone synthesis and secretion related pathways were not detected. Our results suggest that the key to sterility in DHs was the arrested ovary development. However, the reason for arrested ovary development was mainly related to the lower levels of expression of genes involved in steroid biosynthesis in gonads, and was not related to the pituitary. For maintaining homeostasis, the hypothalamus and pituitary would have large differences in several processes, including signal transduction, metabolism, and immune response. The present study provides primary data for further studies on sterility in fish, and even in other animals.