IGFBP1a is a nutrient deficient response factor that can inhibit fish reproduction through the hypothalamus-pituitary-ovary axis†.

Reproduction is a high energy consuming process, so long-term malnutrition can significantly inhibit gonadal development. However, little is known about the molecular mechanism by which fasting inhibits reproduction. Our present study found that fasting could dramatically induce insulin-like growth factor binding protein 1 (IGFBP1) expression in the liver, hypothalamus, pituitary and ovaries of grass carp. In addition, IGFBP1a in the hypothalamus-pituitary-gonad axis could inhibit the development of gonads. These results indicated that fasting may participate in the regulation of fish gonadal development through the mediation of IGFBP1a. Further studies found that IGFBP1a could markedly inhibit gonadotropin-releasing hormone 3 expressions in hypothalamus cells. At the pituitary level, IGFBP1a could significantly reduce the gonadotropin hormones (LH and FSH) expression by blocking the action of pituitary insulin-like growth factor 1. Interestingly, IGFBP1a could also directly inhibit the expression of lhr, fshr, and sex steroid hormone synthase genes (cyp11a, cyp17a, and cyp19a1) in the ovary. These results indicated that IGFBP1a should be a nutrient deficient response factor that could inhibit fish reproduction through the hypothalamus-pituitary-ovary axis.

Neuropeptides and hormones in hypothalamus-pituitary axis of Chinese sturgeon (Acipenser sinensis).

The hypothalamus and pituitary serve as important neuroendocrine center, which is able to secrete a variety of neuropeptides and hormones to participate in the regulation of reproduction, growth, stress and feeding in fish. Chinese sturgeon is a basal vertebrate lineage fish with a special evolutionary status, but the information on its neuroendocrine system is relatively scarce. Using the transcriptome data on the hypothalamus-pituitary axis of Chinese sturgeon as reference, we found out 46 hypothalamus neuropeptide genes, which were involved in regulation of reproduction, growth, stress and feeding. The results of sequence alignment showed that the neuroendocrine system of Chinese sturgeon evolves slowly, which confirms that Chinese sturgeon is a species with a slow phenotypic evolution rate. In addition, we also isolated six pituitary hormones genes from Chinese sturgeon, including reproductive hormones: follicle-stimulating homone (FSH) and luteinizing hormone (LH), growth-related hormones: growth hormone (GH)/prolactin (PRL)/somatolactin (SL), and stress-related hormone gene: proopiomelanocortin (POMC). Similar to teleost, immunostaining localization analysis in Chinese sturgeon pituitary showed that LH and FSH were located in the pituitary proximal pars distalis, SL was located in the pituitary rostral pars distalis, and POMC was located in the pituitary pars intermedia and pituitary rostral pars distalis. This study will give a contribution to enrich our information on the neuroendocrine system in Chinese sturgeon.

Different pituitary action of NK3Ra and NK3Rb in grass carp.

In mammals, NK3R is the specific receptor for NKB, which played an important role in reproduction. Recently, two NK3R isoforms, namely NK3Ra and NK3Rb, have been identified in fish. However, little is known about the pituitary actions of the two NK3R isoforms in fish. In this study, both NK3Ra and NK3Rb were isolated from grass carp pituitary. Although their sequence similarity was only 61.6%, the two NK3R isoforms displayed similar ligand selectivity and binding affinity to TAC3 gene products (NKBa, NKBRPa and NKBRPb). In addition, both NK3Ra and NK3Rb displayed similar signaling pathways, including PKA, PKC, MAPK and Ca2+ cascades. Tissue distribution indicated that both NK3Ra and NK3Rb were highly detected in grass carp pituitary. Further study found that NK3Ra was mainly located in pituitary LHß cells, while NK3Rb was only detected in pituitary SLα cells. Furthermore, NK3Ra and NK3Rb activation could induce LHß and SLα promoter activity, respectively. These results suggested that the two NK3R isoforms displayed different pituitary actions in fish. Using grass carp pituitary cells as model, we found that PACAP could significantly reduce NK3Ra, but induce NK3Rb mRNA expression coupled with cAMP/PKA and PLC/PKC pathways. Interestingly, PACAP could also significantly inhibit LHß, but stimulate SLα mRNA expression in grass carp pituitary cells. Furthermore, NK3R antagonist could not only inhibit LHß mRNA expression, but also block PACAP-induced SLα mRNA expression in grass carp pituitary cells. These results suggested that NK3Ra and NK3Rb could mediate PACAP-reduced LHß and -induced SLα mRNA expression in grass carp pituitary, respectively.

Novel Pituitary Actions of TAC4 Gene Products in Teleost.

Tachykinin 4 (TAC4) is the latest member of the tachykinin family involved in several physiological functions in mammals. However, little information is available about TAC4 in teleost. In the present study, we firstly isolated TAC4 and six neurokinin receptors (NKRs) from grass carp brain and pituitary. Sequence analysis showed that grass carp TAC4 could encode two mature peptides (namely hemokinin 1 (HK1) and hemokinin 2 (HK2)), in which HK2 retained the typical FXGLM motif in C-terminal of tachyinin, while HK1 contained a mutant VFGLM motif. The ligand-receptor selectivity showed that HK2 could activate all 6 NKRs but with the highest activity for the neurokinin receptor 2 (NK2R). Interestingly, HK1 displayed a very weak activation for each NKR isoform. In grass carp pituitary cells, HK2 could induce prolactin (PRL), somatolactin α (SLα), urotensin 1 (UTS1), neuromedin-B 1 (NMB1), cocaine- and amphetamine-regulated transcript 2 (CART2) mRNA expression mediated by NK2R and neurokinin receptor 3 (NK3R) via activation cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3)/protein kinase C (PKC) and calcium2+ (Ca2+)/calmodulin (CaM)/calmodulin kinase-II (CaMK II) cascades. However, the corresponding stimulatory effects triggered by HK1 were found to be notably weaker. Furthermore, based on the structural base for HK1, our data suggested that a phenylalanine (F) to valine (V) substitution in the signature motif of HK1 might have contributed to its weak agonistic actions on NKRs and pituitary genes regulation.

Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0-1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database.

BACKGROUND: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0-1/M0 ILC. METHODS: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Aiming to minimize the selection bias of baseline characteristics, Propensity Score Matching (PSM) method was used. RESULTS: In a total of 12,334 patients with HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC, 1785 patients (14.5%) were allocated into adjuvant chemotherapy group and 10,549 (85.5%) into control group. Used PSM, the 1785 patients in adjuvant chemotherapy group matched to the 1785 patients in control group. By Kaplan-Meier survival analyses, we observed no beneficial effect of adjuvant chemotherapy on OS in both original samples (P = 0.639) and matched samples (P = 0.962), however, ineffective or even contrary results of adjuvant chemotherapy on BCSM both in original samples (P = 0.001) and in matched samples (P = 0.002). In both original and matched multivariate Cox models, we observed ineffectiveness of adjuvant chemotherapy on OS (hazard ratio (HR) for overall survival = 0.82, 95% confidence interval (CI) [0.62-1.09]; P = 0.172 and HR = 0.90, 95%CI [0.65-1.26]; P = 0.553, respectively), unexpectedly promoting effect of adjuvant chemotherapy on BCSM (HR = 2.33, 95%CI [1.47-3.67]; P = 0.001 and HR = 2.41, 95%CI [1.32-4.39]; P = 0.004, respectively). Standard surgery was beneficial to the survival of patients. Lymph node metastasis was detrimental to survival and radiotherapy brought survival benefit in original samples, but two issues had unobvious effect in matched samples. CONCLUSION: In this study, adjuvant chemotherapy did not improve survival for patients with HR-positive, HER2-negative pT1b-c/N0-1/M0 ILC.

MORC4 is a novel breast cancer oncogene regulated by miR-193b-3p.

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3' untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.

MiR-890 inhibits proliferation and invasion and induces apoptosis in triple-negative breast cancer cells by targeting CD147.

BACKGROUND: Triple-negative breast cancer (TNBC) is a type of breast cancer with a high degree of malignancy. Because of the remarkable biological characteristics of high invasion, metastasis and recurrence, TNBC is often accompanied by a poor prognosis. As a molecular characteristic of TNBC, high expression of CD147 has been confirmed by a large number of studies. However, the mechanism of CD147 expression regulation in TNBC remains elusive. In this study, we investigated the roles of miR-890 in inhibiting CD147. METHODS: Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect CD147 mRNA and miR-890 level, and western blotting was used to detect CD147 protein. Bioinformatics screening and 3'-Untranslated Region (3'-UTR) luciferase assays were used to analyze the microRNAs (miRNA) binding site. Cell proliferation, apoptosis and invasion were assessed by using CCK-8, flow cytometry and transwell assays. RESULTS: The upregulation of miR-890 inhibited cell proliferation and invasion, induced apoptosis in MDA-MB-231 and HCC-70 TNBC cells by negatively regulating its target gene, CD147, and the upregulation of CD147 rescued the inhibitory effects of miR-890. miR-890 targeted CD147 by binding to its 3'-UTR. Further results showed that the upregulation of miR-890 also inhibited the expression of MMPs, the downstream genes of CD147, and promoted the cleavage of Caspase-3. The CD147 recovery experiment was further confirmed by the activity changes in the downstream MMPs of CD147. In addition, it was confirmed that the effect of CD147 in promoting TNBC cell proliferation and invasion, inhibiting apoptosis was related to the change in caspase-3 activity. CONCLUSION: The downregulation of miR-890 is the potential cause of high CD147 expression in TNBC, which can promote the malignant transformation of TNBC.

Novel Pituitary Actions of Epidermal Growth Factor: Receptor Specificity and Signal Transduction for UTS1, EGR1, and MMP13 Regulation by EGF.

Epidermal growth factor (EGF) is a member of the EGF-like ligands family, which plays a vital role in cell proliferation, differentiation, and folliculogenesis through binding with EGF receptors, including ErbB1 (EGFR/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). In mammals, many functional roles of EGF have been reported in the ovaries and breasts. However, little is known about the functions of EGF in the pituitary, especially in teleost. In this study, using grass carp pituitary cells as the model, we try to examine the direct pituitary actions of EGF in teleost. Firstly, transcriptomic analysis showed that 599 different expressed genes (DEGs) between the control and EGF-treatment group were mainly involved in cell proliferation, cell migration, signal transduction, and transcriptional regulation. Then, we further confirmed that EGF could significantly induce UTS1, EGR1, and MMP13 mRNA expression in a time-and dose-dependent manner. The stimulatory actions of EGF on UTS1 and EGR1 mRNA expression were mediated by the MEK1/2/ERK1/2 and PI3K/AKT/mTOR pathways coupled with both ErbB1 and ErbB2 in grass carp pituitary cells. The receptor specificity and signal transductions for the corresponding responses on MMP13 mRNA expression were also similar, except that the ErbB2 and PI3K/AKT/mTOR pathway were not involved. As we know, MMP13 could release EGF from HB-EGF. Interestingly, our data also showed that the MMPs inhibitor BB94 could suppress EGF-induced UTS1 and EGR1 mRNA expression. These results, taken together, suggest that the stimulatory actions of EGF on UTS1 and EGR1 mRNA expression could be enhanced by EGF-induced MMP13 expression in the pituitary.

Depression Induced by Total Mastectomy, Breast Conserving Surgery and Breast Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: To carry out a systematic review and meta-analysis of the literature to determine whether different type of surgery induces different depression occurrence in female breast cancer at mean time more than 1-year term postoperatively. METHODS: A systematic literature search of PubMed, Web of Science, EMBASE, OvidSP, EBSCO and PsycARTICLES was conducted. Observational clinical studies that compared the depression incidence in different surgery groups and presented empirical findings were selected. RESULTS: Sixteen studies met the inclusion criteria, including 5, 4, 2 and 5 studies compared depression between total mastectomy (TM) and breast conserving therapy (BCS), TM and breast reconstruction (BR), BCS and BR, or among all three groups (TM, BCS and BR), respectively. Only 1 of 5 studies, which subjected to multivariate analysis of depression in female breast cancer, reported a statistically significant effect of type of surgery on depression occurrence. Our meta-analysis showed no significant differences among the three types of surgery, with BCS patients versus TM patients (relative risk [RR] = 0.89, 95% confidence interval [CI] 0.78-1.01; P = 0.06), BR patients versus TM patients (RR = 0.87, 95% CI 0.71-1.06; P = 0.16) and BCS patients versus BR patients (RR = 1.10; 95% CI 0.89-1.35; P = 0.37), respectively. CONCLUSIONS: Our study showed that there were no statistically significant differences concerning the occurrence of depressive symptoms in breast cancer patients as a consequence of TM, BCS or BR at mean time more than 1-year term postoperatively.

Correction to: Depression Induced by Total Mastectomy, Breast Conserving Surgery and Breast Reconstruction: A Systematic Review and Meta-analysis.

The following grant funding information was omitted from the original article.

NK3R Mediates the EGF-Induced SLα Secretion and mRNA Expression in Grass Carp Pituitary.

Epidermal growth factor (EGF) is a potent regulator of cell function in many cell types. In mammals, the EGF/EGFR system played an important role in both pituitary physiology and pathology. However, it is not clear about the pituitary action of EGF in lower vertebrates. In this study, using grass carp as a model, we found that EGF could stimulate NK3R mRNA and protein expression through pituitary ErbB1 and ErbB2 coupled to MEK/ERK and PI3K/Akt/mTOR pathways. In addition, EGF could also induce pituitary somatolactin α (SLα) secretion and mRNA expression in a dose- and time-dependent manner in vivo and in vitro. The stimulatory actions of EGF on SLα mRNA expression were also mediated by PI3K/Akt/mTOR and MEK/ERK pathways coupled to ErbB1 and ErbB2 activation. Our previous study has reported that neurokinin B (NKB) could also induce SLα secretion and mRNA expression in carp pituitary cells. In the present study, interestingly, we found that EGF could significantly enhance NKB-induced SLα mRNA expression. Further studies found that NK3R antagonist SB222200 could block EGF-induced SLα mRNA expression, indicating an NK3R requirement. Furthermore, cAMP/PKA inhibitors and PLC/PKC inhibitors could both abolish EGF- and EGF+NKB-induced SLα mRNA expression, which further supported that EGF-induced SLα mRNA expression is NK3R dependent.

The Effectiveness of Radioactive Iodine Remnant Ablation for Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of radioactive iodine (RAI) remnant ablation for thyroid cancer-related outcomes of patients with papillary thyroid microcarcinoma (PTMC). METHODS: A systematic literature search of PubMed, EMBASE OvidSP, and EBSCO was conducted. Studies were selected that provided multivariable analysis of the effectiveness of RAI ablation or provided specific data of a 10 years history of thyroid cancer-related outcomes in patients that presented with PTMC. RESULTS: Nineteen studies met the inclusion criteria. A multivariable analysis of the effectiveness of RAI ablation for any recurrence or thyroid cancer-related mortality in patients with PTMC was performed in several studies, among which only one study reported a positive result. Furthermore, for PTMC patients treated by total or near-total thyroidectomy (TT/NT), with or without RAI ablative therapy, the meta-analysis suggested that RAI ablation did not decrease the 10 years history of any tumor recurrence (relative risk [RR] 0.96; 95% confidence interval [CI] 0.63-1.48; P = 0.87), locoregional recurrence (RR 1.15; 95% CI 0.75-1.76; P = 0.51), distant metastases (RR 0.32; 95% CI 0.08-1.32; P = 0.11) or thyroid cancer-related mortality (RR 0.76; 95% CI 0.22-2.63; P = 0.66). CONCLUSIONS: With regard to multivariable analyses, there was almost no positive treatment effect of RAI ablation noted for patients with PTMC. For PTMC patients already treated by TT/NT, incremental RAI ablation may not be beneficial at decreasing the 10 years recurrence of PTMC or incidence of thyroid cancer-related mortality.

Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio).

Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp (Cyprinus carpio) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro.

Association between cytochrome P450 2C9 gene polymorphisms and colorectal cancer susceptibility: evidence from 16 case-control studies.

Previous epidemiological studies have evaluated the association between common variations of cytochrome P450 (CYP)2C9 (430C>T and 1075A>C) and the risk of colorectal cancer (CRC) with conflicting results. To derive a more precise estimation of the relationship between these CYP2C9 polymorphisms and CRC, a meta-analysis was performed. PubMed, Embase, CNKI, and Web of Science databases were searched. A total of 16 studies including 9,463 cases and 11,416 controls were identified. Potential sources of heterogeneity including ethnicity, sample size of study, genotyping method, diagnostic criteria, and outcome were systematically assessed. Overall, the summary odds ratio of 430T variant for CRC was 0.92 (95% confidence interval (CI) 0.86-0.98; P = 0.012) and 1.39 (95% CI 1.07-1.81; P = 0.013) for colorectal adenomas (CRAs). As for CYP2C9 1075A>C polymorphism, no significant results were observed in overall and subgroup analysis. There was no evidence of publication bias. In conclusion, there is evidence to indicate a significant association between CYP2C9 430C>T polymorphism and CRC/CRA risk.

Neurokinin B and reproductive functions: "KNDy neuron" model in mammals and the emerging story in fish.

In mammals, neurokinin B (NKB), the gene product of the tachykinin family member TAC3, is known to be a key regulator for episodic release of luteinizing hormone (LH). Its regulatory actions are mediated by a subpopulation of kisspeptin neurons within the arcuate nucleus with co-expression of NKB and dynorphin A (commonly called the "KNDy neurons"). By forming an "autosynaptic feedback loop" within the hypothalamus, the KNDy neurons can modulate gonadotropin-releasing hormone (GnRH) pulsatility and subsequent LH release in the pituitary. NKB regulation of LH secretion has been recently demonstrated in zebrafish, suggesting that the reproductive functions of NKB may be conserved from fish to mammals. Interestingly, the TAC3 genes in fish not only encode the mature peptide of NKB but also a novel tachykinin-like peptide, namely NKB-related peptide (or neurokinin F). Recent studies in zebrafish also reveal that the neuroanatomy of TAC3/kisspeptin system within the fish brain is quite different from that of mammals. In this article, the current ideas of "KNDy neuron" model for GnRH regulation and steroid feedback, other reproductive functions of NKB including its local actions in the gonad and placenta, the revised model of tachykinin evolution from invertebrates to vertebrates, as well as the emerging story of the two TAC3 gene products in fish, NKB and NKB-related peptide, will be reviewed with stress on the areas with interesting questions for future investigations.

Corticotropin-Releasing Hormone: A Novel Stimulator of Somatolactin in Teleost Pituitary Cells.

Corticotropin-releasing hormone (CRH) is known for its crucial role in the stress response system, which could induce pituitary adrenocorticotropic hormone (ACTH) secretion to promote glucocorticoid release in the adrenal gland. However, little is known about other pituitary actions of CRH in teleosts. Somatolactin is a fish-specific hormone released from the neurointermediate lobe (NIL) of the posterior pituitary. A previous study has reported that ACTH was also located in the pituitary NIL region. Interestingly, our present study found that CRH could significantly induce two somatolactin isoforms' (SLα and SLß) secretion and synthesis in primary cultured grass carp pituitary cells. Pharmacological analysis further demonstrated that CRH-induced pituitary somatolactin expression was mediated by the AC/cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, transcriptomic analysis showed that both SLα and SLß should play an important role in the regulation of lipid metabolism in primary cultured hepatocytes. These results indicate that CRH is a novel stimulator of somatolactins in teleost pituitary cells, and somatolactins may participate in the stress response by regulating energy metabolism.

Sequences analysis and pituitary actions of tachykinins in Chinese sturgeon (Acipenser sinensis).

Tachykinins belong to a large, evolutionarily conserved family of brain/gut peptides that are involved in a variety of physiological functions in mammals, such as reproductive regulation. However, little information was available about tachykinins in ancient fish lineage. In the present study, we firstly identified three tachykinin genes (named tac1, tac3 and tac4) and three neurokinin receptors (named nk1r, nk2r and nk3r) from Chinese sturgeon brain and pituitary. Sequence analysis showed that tac1 encoded substance P (SP) and neurokinin A (NKA), tac3 encoded neurokinin B (NKB) and NKB-related peptide (NKBRP), and tac4 encoded hemokin 1 (HK-1) and hemokin 2 (HK-2), respectively. The luciferase reporter assay results showed that NK1R preferentially selected asSP, NK2R preferentially selected asNKA, and NK3R preferentially selected asNKB. Tissue expression analysis showed that the three tac genes were highly detected in the telencephalon and hypothalamus, whereas nkr genes were widely expressed in peripheral tissues. Spatio-temporal expression analysis showed that all three tac genes were highly expressed in unknown sex individuals. Intraperitoneal injection experiments showed that both asSP and asNKB could stimulate luteinizing hormone (LH) release in Chinese sturgeon serum. At the transcriptional level, asSP and asNKB could significantly reduce pituitary follicle-stimulating hormone beta (fshß) mRNA expression, but induce pituitary growth hormone (gh) mRNA expression. In addition, estradiol (E2) could stimulate tac3 mRNA expression in hypothalamus. Taken together, this study provided information on the tachykinin family in Chinese sturgeon and demonstrates that asNKB and asSP could be involved in reproductive and growth regulation in pituitary.

The function of glucose metabolism in embryonic diapause of annual killifish.

Annual killifish could survive as diapaused embryos buried in soil during dry seasons. When the embryos in diapause III were incubated in water, the larvae could be hatched quickly. However, the mechanism of diapause and hatching of annual killifish was ambiguous. In the present study, Nothobranchius guentheri were used as the model to clarify the physiological mechanism of diapause and hatching of annual killifish. The results indicated that incubation with water could significantly enhance the heart rate and blood circulation of embryos. To clarify the molecular mechanism, the transcriptomic analysis was used to compare the embryos in diapause I, diapause III, and hatching period. The results showed that DNA replication-related genes, cell division cycle 45 and proliferating cell nuclear antigen were more highly expressed in diapause I compared to diapause III. In addition, the transcript levels of glucagon, glucokinase and phosphofructokinase were more abundantly detected in hatching period compared to diapause III, but insulin receptor and insulin-like growth factor-binding protein were lower. These results indicated glucose metabolism might play an important role in diapause and hatching of killifish. To further confirm this result, several reagents involved in glucose metabolism were used to incubate embryos in diapause III. The results displayed that glucose and glucagon could both shorten the hatching time of embryos. In contrast, 2-deoxy-d-glucose, metformin, and insulin could prolong the hatching time and reduce the hatching rate. The results further confirmed that glucose metabolism played an important role in the diapause and hatching of annual killifish.

Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis.

Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.

Sexual dimorphism in Odontobutis sinensis brain-pituitary-gonad axis and liver highlighted by histological and transcriptomic approach.

In this study, sexual dimorphism in Chinese dark sleeper (Odontobutis sinensis) brain-pituitary-gonad axis and liver was highlighted by histological and transcriptomic approach. The results showed that there were two significant differences between males and females. Firstly, males grew larger and faster than females. Transcriptomic analysis and qPCR validation indicated that two key growth genes, insulin-like growth factor (igf) and 25-hydroxyvitamin D-1 alpha hydroxylase (cyp27b), were more highly detected in male liver than that in female liver. Secondly, histological analysis displayed that the liver in males showed an obvious ivory fatty phenomenon with more fat vacuoles and lipid droplet aggregation compared to that in females. Transcriptomic analysis indicated that the transcript level of vitellogenin (vtg) in male liver were significantly lower than that in female liver. After 17ß-estradiol (E2) treatment of primary cultured hepatocytes, the vtg mRNA expression was induced significantly, while dihydrotestosterone (DHT) treatment had little effect on it. Generally, this study will provide some ideas for further exploring the mechanism of sexual dimorphism in Odontobutis sinensis.