Hassanwang3512
Adolescents are characterized by a propensity for risky and impulsive behaviors, likely due to immature frontostriatal circuits. The medial orbitofrontal cortex (MO) is linked to risk and reward prediction during decision-making. Identifying age-dependent differences in MO activity and its inputs to downstream regions can elucidate the neural substrates that permit the transition from high-risk adolescent behaviors to increased risk assessment in adulthood. Action selection biased by information gathered by the MO is likely carried out by efferents into the nucleus accumbens (NAc), which guides reward-directed behaviors. Despite the large age dependency of risk-based decision-making, there is nothing known about adolescent MO activity. Here, we recorded action potentials of MO neurons from anesthetized adult and adolescent rats in vivo. On average, adolescent MO neurons fire faster and within narrower ranges than adults, and adolescents have more active MO neurons than adults. Using antidromic stimulation of axon terminals to identify MO neurons that project to NAc (MO→NAc), we found that adolescent MO→NAc neurons have a narrower range of firing frequencies than non-NAc-projecting MO neurons and adult MO→NAc neurons. These age-dependent differences in MO and MO→NAc populations may result from the fine-tuning of circuits between adolescence and adulthood that promote specific age-dependent behaviors.Circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) to play crucial roles in gene regulation and disease development. Computational approaches have attracted much attention to quickly predict highly potential RBP binding sites on circRNAs using the sequence or structure statistical binding knowledge. Deep learning is one of the popular learning models in this area but usually requires a lot of labeled training data. It would perform unsatisfactorily for the less characterized RBPs with a limited number of known target circRNAs. How to improve the prediction performance for such small-size labeled characterized RBPs is a challenging task for deep learning-based models. In this study, we propose an RBP-specific method iDeepC for predicting RBP binding sites on circRNAs from sequences. It adopts a Siamese neural network consisting of a lightweight attention module and a metric module. We have found that Siamese neural network effectively enhances the network capability of capturing mutual information between circRNAs with pairwise metric learning. To further deal with the small-sample size problem, we have performed the pretraining using available labeled data from other RBPs and also demonstrate the efficacy of this transfer-learning pipeline. We comprehensively evaluated iDeepC on the benchmark datasets of RBP-binding circRNAs, and the results suggest iDeepC achieving promising results on the poorly characterized RBPs. The source code is available at https//github.com/hehew321/iDeepC.
We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes.
We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antibodies were used to label rod and cone bipolar cells (BCs), horizontal cells (HCs), and retinal ganglion cells (RGCs), as well as synaptic components in control and glaucomatous eyes, to assess structural damage and cell loss. ERG recordings were made to assess outer retina function.
We found structural and functional damage of BCs, including significant cell loss and dendritic/axonal remodeling of HCs, following IOP elevation. The first significant loss of both BCs occurred at 4 to 5 weeks after microbead injection. However, early changes in the dendritic structure of RGCs were observed at 3 weeks, but significant changes in the rod BC axon terminal structure were not seen until 4 weeks. We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage.
Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.
Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.
Differentiated from adult stem cells (ASCs), transit-amplifying cells (TACs) play an important role in tissue homeostasis, development, and regeneration. This study aimed to characterize the gene expression profile of a candidate TAC population in limbal basal epithelial cells using single-cell RNA sequencing (scRNA-seq).
Single cells isolated from the basal corneal limbus were subjected to scRNA-seq using the 10x Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. BrdU proliferation assays, immunofluorescent staining, and real-time reverse transcription quantitative polymerase chain reaction were performed using multiple culture models of primary human limbal epithelial cells to characterize the TAC pool.
Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters. A unique cluster (3.21% of total cells) was identified as a TAC entity, based on its less differentiated progenitor status and enriched exclusive proli corneal homeostasis and diseases.
Many patients undergo percutaneous coronary intervention (PCI) multiple times before being referred for coronary artery bypass grafting (CABG), in which bypass grafts are often anastomosed to small distal targets with higher risk of graft failure. We aimed to assess whether multiple PCIs adversely affect the long-term outcomes of patients who undergo CABG subsequently.
A cohort of 368 patients with no history of PCI underwent initial isolated CABG between 2003 and 2013 (no PCI group). Ninety-seven patients who had undergone PCI 2 or more times preoperatively during the same period constituted the multiple PCI group. After propensity score matching, the group outcomes were compared.
There were no significant differences in the 10-year all-cause mortality and major adverse cardiac and cerebrovascular event rates in both groups. Although the left ventricular end-diastolic dimension in the multiple PCI group did not change markedly (from 48.0 ± 6.0 to 47.2 ± 7.9 mm; P = 0.25), it decreased significantly in the no PCI group (from 48.3 ± 6.1 to 44.9 ± 9.1 mm; P < 0.001). The left ventricular end-systolic dimension in the no PCI group decreased significantly (from 34.1 ± 8.7 to 31.4 ± 8.6 mm; P = 0.024), while it in the multiple PCI group did not (from 33.6 ± 8.3 to 32.7 ± 8.6 mm; P = 0.21).
For complex coronary artery disease, early surgical intervention could be considered with respect to postoperative left ventricular remodelling during the long-term follow-up.
For complex coronary artery disease, early surgical intervention could be considered with respect to postoperative left ventricular remodelling during the long-term follow-up.Drug abuse is a dramatic challenge for the whole society because of high relapse rate. Environmental cues are crucial for the preference memory of drug abuse. Extinction therapy has been developed to inhibit the motivational effect of drug cues to prevent the reinstatement of morphine abuse. However, extinction therapy alone only forms a new kind of unstable inhibitory memory. We found that morphine conditioned place preference (CPP) extinction training increased the association of nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the dorsal hippocampus (dHPC) significantly and blocking the morphine-induced nNOS-CAPON association using Tat-CAPON-12C during and after extinction training reversed morphine-induced hippocampal neuroplasticity defect and prevented the reinstatement and spontaneous recovery of morphine CPP. Moreover, in the hippocampal selective ERK2 knock-out or nNOS knockout mice, the effect of Tat-CAPON-12C on the reinstatement of morphine CPP and hippocampal neuroplasticity disappeared, suggesting ERK2 is necessary for the effects of Tat-CAPON-12C. Together, our findings suggest that nNOS-CAPON interaction in the dHPC may affect the consolidation of morphine CPP extinction and dissociating nNOS-CAPON prevents the reinstatement and spontaneous recovery of morphine CPP, possibly through ERK2-mediated neuroplasticity and extinction memory consolidation, offering a new target to prevent the reinstatement of drug abuse.Loss of B lymphocyte regeneration in the bone marrow (BM) is an immunological hallmark of advanced age, which impairs the replenishment of peripheral B-cell subsets and results in impaired humoral responses, thereby contributing to immune system dysfunction associated with aging. A better understanding of the mechanism behind this loss may suggest ways to restore immune competence and promote healthy aging. In the present work, we uncover an immune-endocrine regulatory circuit that mediates cross-talk between peripheral B-cells and progenitors in the BM, to balance B-lymphopoiesis in both human and mouse aging. We found that tumor necrosis factor alpha (TNFα), which is highly produced by peripheral B-cells in aging, stimulates the production of insulin-like growth factor-binding protein 1 (IGFBP-1), which binds and sequesters insulin-like growth factor 1 (IGF1) in the circulation, thereby restraining its activity in promoting B-lymphopoiesis in the BM. Upon B-cell depletion in aged humans and mice, circulatory TNFα decreases, resulting in increased IGF1 and reactivation of B-lymphopoiesis. Perturbation of this circuit by administration of IGF1 to old mice or anti-TNFa antibodies to human patients restored B-lymphopoiesis in the BM. Linsitinib Hence, we suggest that in both human and mouse aging, peripheral B-cells utilize the TNFα/IGFBP-1/IGF1 axis to repress B-lymphopoiesis.The novel coronavirus (COVID-19) pandemic has led to a surge in mental distress and fear-related disorders, including posttraumatic stress disorder (PTSD). Fear-related disorders are characterized by dysregulations in fear and the associated neural pathways. In the present study, we examined whether individual variations in the fear neural connectome can predict fear-related symptoms during the COVID-19 pandemic. Using machine learning algorithms and back-propagation artificial neural network (BP-ANN) deep learning algorithms, we demonstrated that the intrinsic neural connectome before the COVID-19 pandemic could predict who would develop high fear-related symptoms at the peak of the COVID-19 pandemic in China (Accuracy rate = 75.00%, Sensitivity rate = 65.83%, Specificity rate = 84.17%). More importantly, prediction models could accurately predict the level of fear-related symptoms during the COVID-19 pandemic by using the prepandemic connectome state, in which the functional connectivity of lvmPFC (left ventromedial prefrontal cortex)-rdlPFC (right dorsolateral), rdACC (right dorsal anterior cingulate cortex)-left insula, lAMY (left amygdala)-lHip (left hippocampus) and lAMY-lsgACC (left subgenual cingulate cortex) was contributed to the robust prediction.
