As an economically important fish,
Opsariichthys bidens
has obvious sexual dimorphism and strong reproductive capacity, but no epigenetics study can well explain its phenotypic variations. In recent ...years, many microRNAs involved in the regulation of reproductive development have been explored. In this study, the small RNA libraries of
O. bidens
on the testis and ovary were constructed and sequenced. A total of 295 known miRNAs were obtained and 100 novel miRNAs were predicted. By comparing testis and ovary libraries, 115 differentially expressed (DE) miRNAs were selected, of which 53 were up-regulated and 62 were down-regulated. A total of 64 GO items (padj < 0.01) and 206 KEGG pathways (padj < 0.01) were enriched in the target gene of miRNA. After that, the expression levels of nine DE miRNAs, including let-7a, miR-146b, miR-18c, miR-202-5p, miR-135c, miR-9-5p, miR-34c-3p, miR-460-5p and miR-338 were verified by qRT-PCR. Furthermore, bidirectional prediction of DE miRNAs and sex-related genes was carried out and the targeting correlation between miR-9-5p and
nanos1
was verified by Dual-Luciferase reporter assay. Our findings identified the differentially expressed miRNA and paved the way to new possibilities for the follow-up study on the mechanism of miRNA-mRNA interaction in the gonads of
O. bidens
.
As a small farmed fish, Opsariichthys bidens shows sex phenotypic difference between male and female individuals, but the molecular mechanism of gonadal development is still unclear. This study ...performed transcriptome sequencing on the adult testis and ovary of O. bidens to identify sex-related genes. A total of 50,321 unigenes were obtained from six libraries of gonadal tissues, with a total length of 69,070,743 bp and an average length of 1372 bp. Moreover, 29,889, 24,874, 14,564, 18,519, 27,195 and 22,558 unigenes were annotated in the non-redundant protein database, Swissprot, Kyoto Encyclopedia of Genes and Genomes (KEGG), eukaryotic orthologous group (KOG), evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Gene Ontology (GO) databases, respectively. By comparing testis and ovary libraries, 12,609 differentially expressed genes were identified, of which 5975 were up-regulated in the testis and 6634 were up-regulated in the ovary. Enrichment analysis of differentially expressed genes resulted in 3119 enriched GO items (padj<0.01) and 47 enriched KEGG pathways (padj<0.01). Subsequently, the expression levels of nine sex-related genes, including dazl, dnd, nanog, piwi, vasa, zp4, amh, cyp19a and dmrt1 were confirmed by qRT-PCR. Furthermore, molecular cloning and in situ hybridization demonstrated that both cyp19a and vasa were conserved in O. bidens. In addition, cyp19a was mainly expressed in early developmental stages of oocytes in the ovary but not in the testis. While vasa was present in both testis and ovary, and was highly expressed in the early stages of gametogenesis in gonads. These findings provide basic support for further research on the function of sex-related genes and the molecular mechanisms of sex determination in O. bidens.
•Transcriptome sequencing on the adult gonads of O. bidens was performed and analyzed.•Sex-related genes dazl, dnd, nanog, piwi, vasa, zp4, amh, cyp19a and dmrt1 were identified in O. bidens.•Cyp19a and vasa were specifically expressed in gonads among fish and their sub-cellular distributions were revealed in O. bidens.
An adjuvant is usually used to enhance the immune response induced by vaccines. The choice of adjuvant or immune enhancer determines the effectiveness of the immune response. Currently, aluminium ...(Alum, a generic term for salts of aluminium) is the only FDA-approved adjuvant. Alum predominantly induces the differentiation of Th2 cells and thus mediates an antibody immune response. Therefore, there is an urgent need for new adjuvants that enhance not only humoral but also cellular immune responses. In the present study, we demonstrates that PIKA (a stabilized dsRNA) as an adjuvant directly induces the activation and the proliferation of both B and NK cells in vitro. Injection of PIKA into mice results in the production of cytokines in vivo. In addition, the study demonstrates that PIKA promotes the maturation of bone marrow-derived dendritic cells (BMDCs) including up-regulation of the co-stimulatory molecules CD80, CD86 and CD40, and the induction of cytokines such as IL-12p70, IL-12p40 and IL-6. Importantly, after immunization of mice with HBsAg plus PIKA, the presence of PIKA enhances the titers of HBsAg-specific IgG and HBsAg-specific IFN-gamma production. These results demonstrate that PIKA as an adjuvant can promote both humoral and cellular immune responses. These might have an implication in applying PIKA as an adjuvant to be used in the design and development of both therapeutic and preventive vaccines, and used in the clinical study.
Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the ...function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.
In the era of fragmented global value chain enabled by digital networks, distributed manufacturing with effective global resource integration and optimisation has become important for multinational ...enterprises (MNEs) to organise. However, conventional theories and methods disregard the dynamic nature of integration optimisation triggered by knowledge accumulation and spillover during resource embeddedness in the local market and interaction amongst resources. This study establishes a novel embeddedness-interaction perspective, which refers to focusing on intra-network knowledge transfer and inter-network knowledge spillover frequently observed in the resource integration of global distributed manufacturing in MNEs. This study elaborates the mechanism of resource integration optimisation of distributed manufacturing with the presence of an embeddedness-interaction nexus. On this basis, a novel, dynamic resource integration optimisation model and a corresponding algorithm for global distributed manufacturing are constructed. In particular, we designate the minimisation of the weighted Euclidean distance between scores and expected value as the most essential objective of resource integration optimisation modelling and algorithm to highlight the effect of the embeddedness-interaction nexus on dynamic resource integration optimisation. We illustrate the value of the embeddedness-interaction perspective and verify the feasibility and validity of the model and algorithm by applying this optimisation method to a two-country, two-stage, six-resource case.
Freeze-thaw cycles (FTCs) change the soil physicochemical properties and biogeochemical cycles and possibly also change the spatial heterogeneity of soil total nitrogen (TN) in the watershed. In this ...study, 912 soil samples were collected at 0–5 cm, 5–10 cm and 10–20 cm soil depths in the autumn and the spring of next year after FTCs of 2016–2017 and 2017–2018 in a Mollisol watershed (1.86 km2) of northeast China. The field investigations combined with classical statistics and geographically weighted regression kriging (GWRK) were used to explore the spatiotemporal distribution of TN before and after FTCs. Terrain information (e.g., slope aspect) and land management (e.g., tillage method) was main covariates were used for GWRK. The results showed the following. (1) TN decreased by 3.7–5.7% after FTCs at 0–20 cm soil depths at the watershed scale, decreasing more than 60% of the total watershed area. (2) The spatial pattern of TN did not change in the field with slope aspects and tillage methods after FTCs, but it changed with slope steepness and land uses. (3) TN was mainly influenced by snowmelt erosion during FTCs. TN increased in parts of the top slope, at land use intersection, in gully banks and at the watershed outlet. (4) Simulation accuracy of GWRK was higher than ordinary kriging (OK) for predicted TN at 0–20 cm soil depths before and after FTCs. (5) Spatial distribution of soil TN after FTCs can be predicted (R2 = 0.521, p < 0.0001) and validated (R2 = 0.494, p < 0.0001) using the data before FTCs based on GWRK. Generally, to reduce N loss and increase farmland fertility after FTCs, conservational techniques, e.g., tillage and straw amendment, could be used, especially in the middle slope positions. Moreover, fertilization should be appropriately reduced in parts of the watershed after FTCs, especially on the top slope, land use intersection and watershed outlet.
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•Mean TN decreased 3.7–5.7% at watershed scale, and over 60% of area decreased after FTCs.•Snowmelt erosion was the key factor influencing on TN change during the FTCs.•GWRK has a higher accuracy than OK to estimate TN before and after FTCs.•Soil TN after FTCs can be coarsely predicted using the data before FTCs.•Fertilization on top slope, intersection of land use, watershed outlet in spring needs control.
Retinoic acid-related orphan receptor C (RORC) is a member of the nuclear orphan receptor family and performs critical regulatory functions in cell proliferation, metastasis, and chemoresistance in ...various types of malignant tumors. Here we showed that expression of RORC is lost in tumor tissues of bladder cancer patients. Enhanced expression of RORC suppressed cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis
and
. RORC bound the promoter region of programmed death ligand-1 (PD-L1) and negatively regulated PD-L1 expression. PD-L1 directly interacted with integrin β6 (ITGB6) and activated the ITGB6/FAK signaling pathway. RORC prevented the nuclear translocation of STAT3 via suppression of the PD-L1/ITGB6 signaling pathway, which further inhibited bladder cell proliferation and glucose metabolism and increased cisplatin-induced apoptosis. These findings reveal that RORC regulates bladder cancer cell proliferation, glucose metabolism, and chemoresistance by participating in the PD-L1/ITGB6/STAT3 signaling axis. Moreover, this new understanding of PD-L1 signaling may guide the selection of therapeutic targets to prevent tumor recurrence. SIGNIFICANCE: These findings suggest that RORC-mediated regulation of a PD-L1/ITGB6/FAK/STAT3 signaling axis in bladder cancer provides several potential therapeutic targets to prevent tumor progression.
Animal studies indicated that Bisphenol analogues (BPs) exhibited potential thyroid toxicity. However, little is known of the associations between maternal BPs exposure and offspring’s thyroid ...related hormones in humans. On the basis of Shanghai-Minhang Birth Cohort study, we analyzed BPs in maternal urine collected at the third trimester of pregnancy. Thyroid related hormones (THs), including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured in cord blood samples. We performed multiple linear regression and Bayesian kernel machine regression (BKMR) models to explore the single and joint effects of gestational BPs exposure on thyroid related hormones in cord blood among 258 mother-child pairs. Statistically significant inverse associations of categorized BPA with FT3 and TT4 concentrations were observed. We also found a significant association between the mixture of BPs in maternal urine and increased concentration of TT3 in cord blood and a marginally significant association between BPs mixture and increased FT3 concentrations. Further associations of BPA with lower TT4/FT4 and of Bisphenol AF (BPAF) with higher TT3/FT3 were also suggestive, by BKMR model, when other BPs were fixed at 25th percentiles. It was concluded that prenatal BPs exposure was associated with THs in cord blood. Exposure to BPA and BPAF might have large contributions to the effects on thyroid function than other bisphenols.
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•Maternal BPA exposure is associated with lower concentrations of TT4 and FT3.•BKMR models show that BPs mixture exposure is associated with increased TT3.•The effects of BPs on thyroid hormones differed according to newborn sex.
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