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The results showed that TBP + β-actin could be the optimal combination of reference genes for fetal rat adrenals under physiological conditions, without obvious sex differences. In infancy and adolescence, the optimal combination of reference genes for adrenals had sex differences, and females were GAPDH + β-actin, while males were GAPDH + SDHA. In PCE model, the optimal combination of reference genes was consistent with physiological conditions. Using combination of reference genes to analyze target genes can improve the accuracy of the results. In summary, this study provided reliable combination of reference genes for RT-qPCR and experimental supports for researches on adrenal development.Dihydrotestosterone (DHT) is involved in the development of preantral follicles. However, the effect of DHT on the development of antral follicles has yet to be fully investigated. Herein, we used enzyme-linked immunosorbent assays, immunofluorescence assays, quantitative real time-polymerase chain reaction, immunohistochemical staining, and western blotting to investigate the effect of DHT on antral follicle development. First, we detected the concentration of DHT and the expression of the androgen receptor (AR) in different antral follicles. Second, multiple DHT concentration (10-10-10-7 M) were added to granulosa cells cultured in vitro to examine the influence of DHT on AR expression. Third, to study changes in the expression of oestrogen (E2) synthase and receptors during the development of antral follicles, we divided them according to their diameters into small (≤ 2 mm), medium (2-5 mm), and large (≥ 5 mm) groups. Fourth, we added DHT (10-8 M) and flutamide (Flu, 10-7 M) to granulosa cells to determine whether DHT regulates the expression of cytochrome P450 aromatase (CYP19A1) and the associated receptors through the AR pathway. Fifth, we tested the effect of DHT and Flu on the expression of apoptotic genes and proteins in granulosa cells. We found that AR was expressed in sheep antral follicle granulosa cells and was regulated by DHT. During antral follicle development, the concentration of E2 and the expression of CYP19A1 and E2 receptors significantly increased in granulosa cells. DHT influenced this increase, at least partially, through the AR. Moreover, DHT regulated the expression of apoptotic genes and proteins through the AR. Our study expands our knowledge on the regulatory mechanism of DHT in antral follicle development and guides further research on the androgen regulation of ovarian function.

Though cholesterol accumulation is an established hallmark of a tumor cell, the relationship between the two is still not clear. Previously, we identified 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Sterol Regulatory Element BindingTranscription Factor 2 (SREBF2), Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3), and Nuclear Receptor Subfamily 1 Group H Member 2 (NR1H2) as the key cholesterol homeostasis genes involved in colorectal cancer (CRC). In the present study, we aimed to identify microRNAs regulating these key genes in CRC.

miR-18a-5p, miR-144-3p, and miR-663b were selected as the miRNAs targeting NR1H2, HMGCR, and SREBF2, respectively, based on the bioinformatic prediction tools and literature review. Their expression was evaluated in the local and The Cancer Genome Atlas (TCGA) cohorts. Receiver Operating Characteristic Curves and Kaplan Meier analysis were performed to elucidate their diagnostic and prognostic potential. Pearson or Spearman's correlations were used to evaluate the relationship between miRNAs and their target genes. Protein-protein interaction networks and Gene Ontology analyses were performed to investigate the potential molecular mechanism of these miRNAs.

Deregulated expression of miR-18a-5p, miR-144-3p, and miR-663b was associated with various clinicopathological features. miR-18a-5p exhibited an inverse correlation with NR1H2. miR-18a-5p and miR-144-3p also had a significant direct correlation with miR-33a-5p, an important modulator of cholesterol homeostasis. These miRNAs also exhibited high centrality in the mirna-protein interaction network. miR-144-3p and miR-663b exhibited the potential to be used as diagnostic biomarkers.

miR-18a-5p and miR-144-3p exhibited the potential to modulate cholesterol homeostasis in CRC. miR-663b is an interesting candidate in CRC pathophysiology.

miR-18a-5p and miR-144-3p exhibited the potential to modulate cholesterol homeostasis in CRC. miR-663b is an interesting candidate in CRC pathophysiology.Progesterone is involved in dendritogenesis, synaptogenesis and maturation of cerebellar Purkinge cells, major sites of steroid synthesis in the brain. To study a possible time-relationship between myelination, neurosteroidogenesis and steroid receptors during development of the postnatal mouse cerebellum, we determined at postnatal days 5 (P5),18 (P18) and 35 (P35) the expression of myelin basic protein (MBP), components of the steroidogenic pathway, levels of endogenous steroids and progesterone's classical and non-classical receptors. In parallel with myelin increased expression during development, P18 and P35 mice showed higher levels of cerebellar progesterone and its reduced derivatives, higher expression of steroidogenic acute regulatory protein (StAR) mRNA, cholesterol side chain cleavage enzyme (P450scc) and 5α-reductase mRNA vs. P5 mice. Other steroids such as corticosterone and its reduced derivatives and 3β-androstanodiol (ADIOL) showed a peak increase at P18 compared to P5. Progesterone membrane receptors and binding proteins (PGRMC1, mPRα, mPRβ, mPRγ, and Sigma1 receptors) mRNAs levels increased during development while that of classical progesterone receptors (PR) remained invariable. PRKO mice showed similar MBP levels than wild type. Thus, these data suggests that progesterone and its neuroactive metabolites may play a role in postnatal cerebellar myelination.

During the coronavirus disease 2019 (COVID-19) pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 in this population.

Retrospective cohort study.

Maintenance dialysis patients in clinics of a midsize national dialysis provider that had at least 1 patient who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from February to June 2020.

Demographics, dialysis characteristics, residence in a congregated setting, comorbid conditions, measurements of frailty, and use of selected medications.

COVID-19, defined as having a positive SARS-CoV-2 test result, and all-cause mortality among those with COVID-19.

Logistic regression analyses conducted to identify clinical characteristics associated with COVID-19 and risk factors associated with mortality among patients fs, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.Sensory substitution refers to the concept of feeding information to the brain via an atypical sensory pathway. We here examined the degree to which participants (deaf and hard of hearing) can learn to identify sounds that are algorithmically translated into spatiotemporal patterns of vibration on the skin of the wrist. In a three-alternative forced choice task, participants could determine the identity of up to 95% and on average 70% of the stimuli simply by the spatial pattern of vibrations on the skin. Performance improved significantly over the course of 1 month. Younger participants tended to score better, possibly because of higher brain plasticity, more sensitive skin, or better skills at playing digital games. Similar results were obtained with pattern discrimination, in which a pattern representing the sound of one word was presented to the skin, followed by that of a second word. Participants answered whether the word was the same or different. With minimal difference pairs (distinguished by only one phoneme, such as "house" and "mouse"), the best performance was 83% (average of 62%), while with non-minimal pairs (such as "house" and "zip") the best performance was 100% (average of 70%). Collectively, these results demonstrate that participants are capable of using the channel of the skin to interpret auditory stimuli, opening the way for low-cost, wearable sensory substitution for the deaf and hard of hearing communities.Editorial on Non-negative matrix factorization as a tool to distinguish between synaptic vesicles in different functional states.Matrix metalloproteinase-9 (MMP-9) degrades collagen and other cellular matrix proteins. After acute ischemic stroke, increased MMP-9 levels are correlated with hemorrhage, lack of reperfusion and stroke severity. Nevertheless, definitive data that MMP-9 itself causes poor outcomes in ischemic stroke are limited. In a model of experimental ischemic stroke with reperfusion, we examined whether ischemia and recombinant tissue plasminogen activator (r-tPA) therapy affected MMP-9 expression, and we used specific inhibitors to test if MMP-9 affects brain injury and recovery. After stroke, MMP-9 expression increased significantly in the ischemic vs. non-ischemic hemisphere of the brain (p  less then  0.001). MMP-9 expression in the ischemic, but not the non-ischemic hemisphere, was further increased by r-tPA treatment (p  less then  0.001). To determine whether MMP-9 expression contributed to stroke outcomes after r-tPA treatment, we tested three different antibody MMP-9 inhibitors. When compared to treatment with r-tPA and saline, treatment with r-tPA and MMP-9 antibody inhibitors significantly reduced brain hemorrhage by 11.3 to 38.6-fold (p  less then  0.01), brain swelling by 2.8 to 4.3-fold (p  less then  0.001) and brain infarction by 2.5 to 3.9-fold (p  less then  0.0001). Similarly, when compared to treatment with r-tPA and saline, treatment with r-tPA and an MMP-9 antibody inhibitor significantly improved neurobehavioral outcomes (p  less then  0.001), decreased weight loss (p  less then  0.001) and prolonged survival (p  less then  0.01). In summary, both prolonged ischemia and r-tPA selectively enhanced MMP-9 expression in the ischemic hemisphere. When administered with r-tPA, specific MMP-9 inhibitors markedly reduced brain hemorrhage, swelling, infarction, disability and death, which suggests that blocking the deleterious effects of MMP-9 may improve outcomes after ischemic stroke.The neuroscience of music has recently attracted significant attention, but the effect of music style on the activation of auditory-motor regions has not been explored. The aim of the present study is to analyze the differences in brain activity during passive listening to non-vocal excerpts of four different music genres (classical, reggaeton, electronic and folk). A functional magnetic resonance imaging (fMRI) experiment was performed. Twenty-eight participants with no musical training were included in the study. XAV-939 They had to passively listen to music excerpts of the above genres during fMRI acquisition. Imaging analysis was performed at the whole-brain-level and in auditory-motor regions of interest (ROIs). Furthermore, the musical competence of each participant was measured and its relationship with brain activity in the studied ROIs was analyzed. The whole brain analysis showed higher brain activity during reggaeton listening than the other music genres in auditory-related areas. The ROI-analysis showed that reggaeton led to higher activity not only in auditory related areas, but also in some motor related areas, mainly when it was compared with classical music.