Notes

Intergenerational Training along with 'Fabulous Stories'.
Axons of adult neurons in the mammalian central nervous system generally fail to regenerate by themselves, and few if any therapeutic options exist to reverse this situation. Due to a weak intrinsic potential for axon growth and the presence of strong extrinsic inhibitors, retinal ganglion cells (RGCs) cannot regenerate their axons spontaneously after optic nerve injury and eventually undergo apoptosis, resulting in permanent visual dysfunction. Regarding the extracellular environment, research to date has generally focused on glial cells and inflammatory cells, while few studies have discussed the potentially significant role of interneurons that make direct connections with RGCs as part of the complex retinal circuitry. In this study, we provide a novel angle to summarize these extracellular influences following optic nerve injury as "intercellular interactions" with RGCs and classify these interactions as synaptic and non-synaptic. By discussing current knowledge of non-synaptic (glial cells and inflammatory cells) and synaptic (mostly amacrine cells and bipolar cells) interactions, we hope to accentuate the previously neglected but significant effects of pre-synaptic interneurons and bring unique insights into future pursuit of optic nerve regeneration and visual function recovery.
Alzheimer's disease amyloid-beta peptides (Aβ) are generated via sequential cleavage of the amyloid precursor protein (APP) by β-secretase (Bace1) and γ-secretase. Though the precise subcellular location(s) of Bace1-mediated APP cleavage remains unresolved, current models suggest APP internalization into Bace1-containing endosomes is a critical step. However, direct evidence for this model is lacking, and previous reports that probed the APP/Bace1 interaction (using co-expressed APP and Bace1 differentially labeled with fluorescent protein tags) did not determine if APP fluorescence originated from full-length APP (fl-APP) molecules that had internalized from the cell surface pool.

We adapted the bungarotoxin-ligand (BTX) system to label surface APP and track internalized fluorescent APP/BTX puncta in rodent primary neurons co-expressing fluorescently-tagged Bace1. Subsequently, we employed imaging and biochemical-based approaches to measure N- and C-terminal APP epitope levels in primary neurons, N2a neutagged APP constructs, a large fraction of the APP fluorescence signal therefore likely arose from fluorescently-tagged β-C-terminal-fragment (β-CTF) or downstream proteolytic derivatives instead of fl-APP. Thus, care is needed in interpreting results where APP is detected only with a C-terminal tag in the presence of Bace1 co-expression, and previous findings may need to be reinterpreted if it is unclear whether fl-APP is present in normal physiological levels.Ischemic stroke is a cerebrovascular disease with high mortality and disability, which seriously affects the health and lives of people around the world. Effective treatment for ischemic stroke has been limited by its complex pathological mechanisms. Increasing evidence has indicated that mitochondrial dysfunction plays an essential role in the occurrence, development, and pathological processes of ischemic stroke. Therefore, strict control of the quality and quantity of mitochondria via mitochondrial fission and fusion as well as mitophagy is beneficial to the survival and normal function maintenance of neurons. Under certain circumstances, excessive mitophagy also could induce cell death. This review discusses the dynamic changes and double-edged roles of mitochondria and related signaling pathways of mitophagy in the pathophysiology of ischemic stroke. Furthermore, we focus on the possibility of modulating mitophagy as a potential therapy for the prevention and prognosis of ischemic stroke. Notably, we reviewed recent advances in the studies of natural compounds, which could modulate mitophagy and exhibit neuroprotective effects, and discussed their potential application in the treatment of ischemic stroke.Liver cancer is highly heterogeneous, and the tumor tissue harbors a variety of cell types. Liver tumor initiating cells (TICs) well contribute to tumor heterogeneity and account for tumor initiation and metastasis, but the molecular mechanisms of liver TIC self-renewal are elusive. Here, we identified a functional read-through rt-circRNA, termed rtcisE2F, that is highly expressed in liver cancer and liver TICs. rtcisE2F plays essential roles in the self-renewal and activities of liver TICs. rtcisE2F targets E2F6 and E2F3 mRNAs, attenuates mRNA turnover, and increases E2F6/E2F3 expression. Mechanistically, rtcisE2F functions as a scaffold of N-methyladenosine (m6A) reader IGF2BP2 and E2F6/E2F3 mRNA. rtcisE2F promotes the association of E2F6/E2F3 mRNAs with IGF2BP2, and inhibits their association with another m6A reader, YTHDF2. IGF2BP2 inhibits E2F6/E2F3 mRNA decay, whereas YTHDF2 promotes E2F6/E2F3 mRNA decay. By switching m6A readers, rtcisE2F enhances E2F6/E2F3 mRNA stability. E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation, and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis. In conclusion, the rtcisE2F-IGF2BP2/YTHDF2-E2F6/E2F3-Wnt/β-catenin axis drives liver TIC self-renewal and initiates liver tumorigenesis and metastasis, and may provide a strategy to eliminate liver TICs.Glioma is one type of primary intracranial carcinoma with a relatively poor prognosis. We investigated the level of SLC25A21-AS1 in gliomas and the association with survival and progression in patients with glioma. Specimens of gliomas from patients were assessed by quantitative real-time polymerase chain reaction analysis of the SLC25A21-AS1 level (117 specimens). For prognostic value assessment, χ2 test, Kaplan-Meier method with the log-rank test, and Multivariate survival analysis were performed. The direct targets for SLC25A21-AS1 were explored. The biological roles of SLC25A21-AS1 were investigated by manipulating the expression level of SLC25A21-AS1 in glioma cells. SLC25A21-AS1 was significantly downregulated in glioma specimens and cell lines compared to non-cancerous ones. Significant associations were found between SLC25A21-AS1 downregulation and WHO stage, IDH status, poor disease-free survival/overall survival. miR-221-3p/miR-222-3p were the target miRNAs for SLC25A21-AS1. Overexpression of SLC25A21-AS1 inhibited glioma cell growth, invasion, and migration while miR-221-3p/miR-222-3p-overexpressed groups could offset this effect. Downregulation of SLC25A21-AS1 in gliomas carries a universally poor prognosis. Overexpression of SLC25A21-AS1 inhibited glioma progression via miR-221-3p/miR-222-3p.Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR.
In recent years, the goal of universal coverage of the basic medical insurance schemes has been basically achieved in China, but the heavy economic burden of diseases is still the main cause of poverty in many households. Exploring catastrophic health expenditure (CHE) and its inequality are highly important for forward-looking policymaking. This study aims to compare the incidence, intensity and inequality of CHE between urban and rural households in China.

This study was based on a national representative household survey-the China Family Panel Studies (CFPS)-that was conducted from 2012 to 2018. Concentration index (CI) was employed to measure the inequality of CHE incidence and overshoot, while the decomposition method of the CI was used to estimate the main influencing factors affecting inequality of CHE incidence.

From 2012 to 2018, the CHE incidence of urban households increased from 11.01 to 11.88%, while the CHE incidence of rural households decreased from 18.42 to 18.31%. During the same perio CHE incidence and overshoot could be found in both two groups. The problem of poverty due to illness was more severe among low-income groups in rural areas than in urban areas. The relevant policy interventions should further focus on encouraging the development of supplementary medical insurance and increasing the reimbursement rate for hospitalization expenses in the medical assistance system.TG18 recommends bailout surgery (BOS) for difficult laparoscopic cholecystectomy. However, there is not a clear criterion on the decision process on whether to continue laparoscopic BOS or open BOS, and optimal procedure for treatment for the remnant cystic bile duct also awaits discussion. We comparted with open BOS and laparoscopic BOS, and compared with suture close and clipping or ligating of remnant cystic duct. We have accrued 57 patients underwent BOS during study period. Seventeen cases underwent laparoscopic BOS, and 38 cases underwent open BOS. There were 22 patients were accrued in suture closing and 35 patients were accrued in clipping or ligating. Open BOS experienced high levels of CRP, WBC, NLR, and CAR, and was associated with significantly longer hospitalization, operating time, and amount of bleeding. Suture close was higher in patients with preoperative endoscopic lithotripsy (EL). BOS can be sufficiently performed under laparoscopy. Patients underwent preoperative EL tended to be higher necessity to suture close of cystic duct.Accurate electromagnetic modeling of the head of a subject is of main interest in the fields of source reconstruction and brain stimulation. 1-Methylnicotinamide manufacturer Those processes rely heavily on the quality of the model and, even though the geometry of the tissues can be extracted from magnetic resonance images (MRI) or computed tomography (CT), their physical properties such as the electrical conductivity are difficult to measure with non intrusive techniques. In this paper, we propose a tool to assess the uncertainty in the model parameters, the tissue conductivity, as well as compute a parametric forward models for electroencephalography (EEG) and transcranial direct current stimulation (tDCS) current distribution.
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