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Background: The precise mechanisms of hormone action responsible for the full course of events modulating folliculogenesis in crocodilian have not been determined, although histological features have been identified. Results: The Alligator sinensis ovarian morphological characteristics observed at 1, 15, 30, 60, 90, and 300 days post hatching(dph) revealed that the dynamic changes in germ cells varied in different meiotic and developmental stages, confirming that the processes of folliculogenesis were protracted and asynchronous. The presence of endogenous follicle-stimulating hormone(FSH) mRNA and protein expression within the cerebrum at 1 dph, in parallel with the increase in germ cells within the germ cell nests(Nest) from 1 dph to 15 dph, suggested that endocrine regulation of the pituitary-gonad axis is an early event in oogonia division. Furthermore, the endogenous expression of FSH showed a trend of negative feedback augmentation accompanied by the exhaustion of maternal yolk E2 observed at 15 dph. Such significant elevation of endogenous FSH levels was observed to be related to pivotal events in the transition from mitosis to meiosis, as reflected by the proportion of oogonia during premeiosis interphase, with endogenous FSH levels reaching a peak at the earliest time step of 1 dph. In addition, the simultaneous upregulation of premeiotic marker STRA8 mRNA expression and the increase in endogenous FSH further verified the above speculation. The strongly FSHr-positive label in the oocytes within Pre-previtellogenic follicles was synchronized with the significant elevation of ovarian cAMP detected at 300 dph, which suggested that diplotene arrest maintenance during early vitellogenesis might be FSH dependent. In addition, preferential selection in asynchronous meiotic initiation has been supposed to act on somatic supportive cells and not directly on germ cells via regulation of FSH that in turn affects downstream estrogen levels. This suggestion was verified by the reciprocal stimulating effect of FSH and E2 on the accelerated meiotic marker SYCP3 and by the inhibited cell apoptosis demonstrated in ovarian cell culture in vitro. Conclusion: The corresponding results contribute an expansion of the understanding of physiological processes and shed some light on the specific factors responsible for gonadotropin function in the early folliculogenesis of crocodilians. [ABSTRACT FROM AUTHOR]

Background: Newly diagnosed HIV-positive men who have sex with men (MSM) are an important subgroup in HIV intervention. How newly diagnosed HIV-positive MSM look at HIV/AIDS is consequential and is potentially associated with their risk behaviors and mental health problems. Illness representation has been used to define patients' beliefs and expectations on an illness, and the revised Illness Perception Questionnaire (IPQ-R) has been developed to measure illness representations. This study aims to examine the psychometric properties of the IPQ-R among newly diagnosed HIV-positive MSM and to investigate their views towards HIV/AIDS.Method: A total of 225 newly diagnosed HIV-positive MSM completed the Chinese version of IPQ-R. Both confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were applied to examine the factor structure of IPQ-R.Results: CFA showed a poor goodness of fit to the original factor structure of IPQ-R. EFA of the IPQ-R revealed 7 factors, including Emotional Response, Treatment Control, Timeline-acute/chronic, Illness Coherence, Consequence, Personal Control and Helplessness. Cronbach's alpha showed acceptable internal consistency for the derived factors, except the Personal Control (0.61) and Helplessness (0.55). Person correlation coefficients demonstrated that the derived factors of IPQ-R had significant associations with the outcome variables (depression and posttraumatic growth). The scores of the Emotional Response, Consequence, Treatment Control, Personal Control, Timeline-acute/chronic and Illness Coherence were above the midpoint, and the score of the Helplessness was below the midpoint.Conclusion: Both similarities and differences were found when the IPQ-R is applied to newly diagnosed HIV-positive MSM. The IPQ-R can be used with some refinements in future studies. Newly diagnosed HIV-positive MSM have a relatively high level of negative perceptions towards HIV/AIDS in both cognitive and emotional aspects. [ABSTRACT FROM AUTHOR]

Background: China is facing an emerging epidemic of syphilis, and the cities in south China are most affected. Knowledge is a key factor in the prevention of syphilis infection, however, little is reported about how much people know about syphilis. This study was aimed at assessing peoples' awareness status in a city located in south China.Methods: Six populations were recruited for this study, including urban residents, factory workers, college students, pregnant women, female sex workers (FSWs), and men who have sex with men (MSM). A questionnaire designed by the National Center for Disease Control and Prevention was used to assess participants' awareness of syphilis knowledge. About 5% of participants were randomly selected to conduct a telephone survey for confirming the validity of fieldwork.Results: The study recruited 3470 participants, and 61.2% of participants were assigned to the awareness group. College students had the smallest percentage of awareness at 51.7% (371/718), followed by FSWs at 53.9% (200/371), factory workers at 56.0% (381/679), urban residents at 65.4% (435/665), pregnant women at 66.0% (451/683), and MSM at 81.1% (287/354). Multivariate logistic regression analysis showed that MSM and FSWs-but not factory workers and pregnant women-had more awareness of syphilis knowledge when comparing with urban residents; however, college students presented less awareness of syphilis knowledge than urban residents. Participants of younger age, of female gender, with lower education levels and without Shenzhen hukou possessed less awareness of syphilis knowledge than those of older age, of male gender, with higher education levels and with Shenzhen hukou respectively.Conclusions: The percentages of awareness on syphilis knowledge found in this study are far from the benchmark set in the national 10-year plan. Tailored interventions for different subgroups to increase syphilis awareness are urgently warranted. [ABSTRACT FROM AUTHOR]

Background: Core promoter controls transcription initiation. However, little is known for core promoter diversity in the human genome and its relationship with diseases. We hypothesized that as a functional important component in the genome, the core promoter in the human genome could be under evolutionary selection, as reflected by its highly diversification in order to adjust gene expression for better adaptation to the different environment. Results: Applying the "Exome-based Variant Detection in Core-promoters" method, we analyzed human core-promoter diversity by using the 2682 exome data sets of 25 worldwide human populations sequenced by the 1000 Genome Project. Collectively, we identified 31,996 variants in the core promoter region (− 100 to + 100) of 12,509 human genes (https://dbhcpd.fhs.um.edu.mo). Analyzing the rich variation data identified highly ethnic-specific patterns of core promoter variation between different ethnic populations, the genes with highly variable core promoters, the motifs affected by the variants, and their involved functional pathways. eQTL test revealed that 12% of core promoter variants can significantly alter gene expression level. Comparison with GWAS data we located 163 variants as the GWAS identified traits associated with multiple diseases, half of these variants can alter gene expression. Conclusion: Data from our study reals the highly diversified nature of core promoter in the human genome, and highlights that core promoter variation could play important roles not only in gene expression regulation but also in disease predisposition. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignances worldwide. Metastasis is responsible for the rapid recurrence and poor prognosis of CRC. However, the underlying molecular mechanism of CRC metastasis remains largely unclear. In this study we purposed to investigate the expression and biological functions of miR-490-3p in CRC metastasis, as well as to identify its downstream target genes and influenced pathway.Methods: The expression level of miR-490-3p in CRC cell lines, CRC adjacent normal tissues, non-metastasis and metastasis tissues were assessed by quantitative real-time PCR. Patient survivals were follow-up up to 7 years. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-490-3p mimics or inhibitors respectively. The molecular targets of miR-490-3p were computationally identified and experimentally verified by dual-luciferase reporter assay and western blot. Functional rescue was also conducted to confirm miR-490-3p inhibits CRC metastasis by targeting TGF-β signaling pathway.Results: miR-490-3p expression was persistently downregulated during CRC malignant progression, as well as in CRC cell lines. Artificially overexpression miR-490-3p in CRC cell lines inhibited cell migration and invasion abilities while knockdown miR-490-3p expression caused the reverse effects. TGFβR1 and MMP2/9 were the downstream targets of miR-490-3p in CRC. Inhibition of TGFβR1 could partially recover the tumor suppression effect of miR-490-3p.Conclusion: miR-490-3p is downregulated during CRC malignant progression. miR-490-3p represses CRC cell migration and invasion abilities, partially by targeting to the TGF-β signaling pathway. Taken together, miR-490-3p is acting as a tumor suppressor in CRC. [ABSTRACT FROM AUTHOR]

Background: China is facing an emerging epidemic of syphilis, and the cities in south China are most affected. Knowledge is a key factor in the prevention of syphilis infection, however, little is reported about how much people know about syphilis. This study was aimed at assessing peoples' awareness status in a city located in south China., Methods: Six populations were recruited for this study, including urban residents, factory workers, college students, pregnant women, female sex workers (FSWs), and men who have sex with men (MSM). A questionnaire designed by the National Center for Disease Control and Prevention was used to assess participants' awareness of syphilis knowledge. About 5% of participants were randomly selected to conduct a telephone survey for confirming the validity of fieldwork., Results: The study recruited 3470 participants, and 61.2% of participants were assigned to the awareness group. College students had the smallest percentage of awareness at 51.7% (371/718), followed by FSWs at 53.9% (200/371), factory workers at 56.0% (381/679), urban residents at 65.4% (435/665), pregnant women at 66.0% (451/683), and MSM at 81.1% (287/354). Multivariate logistic regression analysis showed that MSM and FSWs-but not factory workers and pregnant women-had more awareness of syphilis knowledge when comparing with urban residents; however, college students presented less awareness of syphilis knowledge than urban residents. Participants of younger age, of female gender, with lower education levels and without Shenzhen hukou possessed less awareness of syphilis knowledge than those of older age, of male gender, with higher education levels and with Shenzhen hukou respectively., Conclusions: The percentages of awareness on syphilis knowledge found in this study are far from the benchmark set in the national 10-year plan. Tailored interventions for different subgroups to increase syphilis awareness are urgently warranted.

Background: Cellular senescence is linked to aging and tumorigenesis. The senescence of mesenchymal stem cells (MSCs) may influence the tumor growth, metastasis, and angiogenesis by secreting a variety of cytokines and growth factors., Results: The conditioned media of adipose derived MSCs (AD-MSCs) stimulated the proliferation of human LoVo colorectal-cancer cells, and the replicative senescent MSCs had the more obvious effects in comparison to that of premature AD-MSCs. Analysis of the factors secreted in the MSCs culture media determined that senescent MSCs expressed and secreted high levels of galectin-3. Galectin-3 expression correlated with the stimulatory effect of senescent AD-MSCs on LoVo cells proliferation, as knockdown of galectin-3 in senescent AD-MSCs significantly reversed the effect of MSCs-mediated growth stimulation of LoVo cells. Furthermore, the simultaneous addition of recombinant galectin-3 to the co-culture systems partially restored the tumor-promoting effect of the senescent AD-MSCs. Analysis of the mechanisms of senescent MSCs and galectin-3 on LoVo cells signal transduction determined that senescent MSCs and exogenous galectin-3 promoted cell growth by activating the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase [ERK]1/2) pathway., Conclusions: Senescent MSCs may alter the tissue microenvironment and affect nearby malignant cells via cytokine secretion, and galectin-3 is an important mediator of senescent AD-MSC-mediated stimulation of colon cancer cell growth. Therefore, thorough assessment of AD-MSCs prior to their implementation in clinical practice is warranted.

Background: An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens., Results: A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus., Conclusions: Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates.

Background: Influenza A virus can infect a wide variety of animal species including humans, pigs, birds and other species. Viral ribonucleoprotein (vRNP) was involved in genome replication, transcription and host adaptation. Currently, firefly luciferase (Fluc) reporter system was used in vRNP functional assay. However, its limitation for the testing by virus infection resulted in an increased need for rapid, sensitive, and biosafe techniques. Here, an influenza A virus UTR-driven gene reporter for vRNP assay based on secreted Gaussia luciferase (Gluc) activity was evaluated., Results: By measuring Gluc levels in supernatants, reporter gene activity could be detected and quantitated after either reconstitution of influenza A virus polymerase complex or viral infection of 293T and A549 cells, respectively. As compared with Fluc reporter, Gluc-based reporter was heat-tolerant (65°C for 30 min) and produced 50-fold higher bioluminescent activity at 24 h posttransfection. Signals generated by Gluc reporter gene could be detected as early as 6 h post-infection and accumulated with time. Testing by viral infection, stronger signals were detected by Gluc reporter at a MOI of 0.001 than that of 1 and the effects of PB2-627K/E or amantadine on influenza vRNP activity were elucidated more effectively by the Gluc reporter system., Conclusions: This approach provided a rapid, sensitive, and biosafe assay of influenza vRNP function, particularly for the highly pathogenic avian influenza viruses.