Despite vertical stacking, the lateral scaling of 3D NAND Flash is critically important because otherwise >;16 stacking layers are needed to be cost competitive to 20nm 2D NAND. In this work, we ...propose a 3D vertical gate (VG) NAND using a self-aligned independently controlled double gate (IDG) string select transistor (SSL) decoding method. The IDG SSL provides excellent program inhibit and read selection without any penalty of cell size increase, making our 3D VG NAND cell as scalable as conventional 2D NAND. We present the world's first <; 50nm (37.5nm) half-pitch 3D NAND. The BL decoding and page operation methods are illustrated in detail. This highly pitch scalable VG with IDG SSL approach provides a very cost competitive 3D NAND.
Helicobacter pylori heat shock protein 60 (HpHsp60) was first identified as an adhesion molecule associated with
H. pylori infection. Here we have analyzed the structure of HpHsp60 via amino acid ...BLAST, circular dichroism, and electrophoresis and the results indicate that most recombinant HpHsp60 molecules exist as dimers or tetramers, which is quite different from
Escherichia coli Hsp60. Treatment of human monocytic cells THP-1 with HpHsp60 was found to up-regulate a panel of cytokines including IL-1α, IL-8, IL-10, IFN-γ, TNF-α, TGF-β, GRO, and RANTES. Carboxymethylated HpHsp60 molecules with a switched oligomeric status were able to further enhance NF-κB-mediated IL-8 and TNF-α secretion in THP-1 cells compared to unmodified HpHsp60 molecules. These results indicated that the oligomeric status of HpHsp60s might have an important role in regulating host inflammation and thus help facilitate
H. pylori persistent infection.
Primary cilia are antenna-like subcellular structures to act as signaling platforms to regulate many cellular processes and embryonic development. m
A RNA modification plays key roles in RNA ...metabolism and gene expression; however, the physiological function of m
A modification remains largely unknown. Here we find that the m
A demethylase ALKBH3 significantly inhibits ciliogenesis in mammalian cells by its demethylation activity. Mechanistically, ALKBH3 removes m
A sites on mRNA of Aurora A, a master suppressor of ciliogenesis. Depletion of ALKBH3 enhances Aurora A mRNA decay and inhibits its translation. Moreover, alkbh3 morphants exhibit ciliary defects, including curved body, pericardial edema, abnormal otoliths, and dilation in pronephric ducts in zebrafish embryos, which are significantly rescued by wild-type alkbh3, but not by its catalytically inactive mutant. The ciliary defects caused by ALKBH3 depletion in both vertebrate cells and embryos are also significantly reversed by ectopic expression of Aurora A mRNA. Together, our data indicate that ALKBH3-dependent m
A demethylation has a crucial role in the regulation of Aurora A mRNA, which is essential for ciliogenesis and cilia-associated developmental events in vertebrates.
The effects of age and gender on large-scale resting-state networks (RSNs) reflecting within- and between-network connectivity in the healthy brain remain unclear. This study investigated how age and ...gender influence the brain network roles and topological properties underlying the ageing process. Ten RSNs were constructed based on 998 participants from the REST-meta-MDD cohort. Multivariate linear regression analysis was used to examine the independent and interactive influences of age and gender on large-scale RSNs and their topological properties. A support vector regression model integrating whole-brain network features was used to predict brain age across the lifespan and cognitive decline in an Alzheimer’s disease spectrum (ADS) sample. Differential effects of age and gender on brain network roles were demonstrated across the lifespan. Specifically, cingulo-opercular, auditory, and visual (VIS) networks showed more incohesive features reflected by decreased intra-network connectivity with ageing. Further, females displayed distinctive brain network trajectory patterns in middle-early age, showing enhanced network connectivity within the fronto-parietal network (FPN) and salience network (SAN) and weakened network connectivity between the FPN-somatomotor, FPN-VIS, and SAN-VIS networks. Age — but not gender — induced widespread decrease in topological properties of brain networks. Importantly, these differential network features predicted brain age and cognitive impairment in the ADS sample. By showing that age and gender exert specific dispersion of dynamic network roles and trajectories across the lifespan, this study has expanded our understanding of age- and gender-related brain changes with ageing. Moreover, the findings may be useful for detecting early-stage dementia.
The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study ...aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn’t have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00–0.02; p<0.001), more significant V4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02–1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.
Three, new, fully synthetic glycosylated isomalyngamide A analogs 4–6 were prepared and evaluated for their anti-migratory activities in human breast cancer cells. The results of the study show that ...two glycosylated derivatives 4 and 5, containing mannose and galactose appendages, suppress metastatic events (e.g., migration, invasion and adhesion) in human breast adenocarcinoma MDA-MB-231 cells at “nontoxic” concentration levels. In contrast, derivative 6 that contains a lactose moiety, displays a less potent activity. The findings show that monosaccharide rather than disaccharide appendages to the isomalyngamide A backbone more greatly influence cell migration and invasive ability. Evidence has been gained for a mechanism for inhibition of metastatic activities in MDA-MB-231 cells by 4 and 5, involving inactivation of the expression of p-FAK and paxillin through the integrin-mediated antimetastatic pathway.
Display omitted Three glycosylated isomalyngamide A analogs 4–6 were prepared. Glycosides 4 and 5 suppress metastasis in MDA-MB-231 cells by inactivating the expression of p-FAK and paxillin through the integrin-mediated antimetastatic pathway.
•Three glycosylated isomalyngamide A analogs 4–6 were synthesized.•Glycosides 4 and 5 suppress metastatic events at “nontoxic” concentration levels.•These substances promote a decrease of p-FAK and paxillin expression.
Although several algorithms have been applied to treat patients with schizophrenia, their clinical use remains still limited, because most emphasize the prescription of antipsychotics. A new ...algorithm with a more holistic approach to treating patients with schizophrenia, to be used before applying traditional prescribing guidelines, was thus proposed by an expert team of Taiwanese psychiatrists. In this algorithm, several important treatment tasks/modalities are proposed, including long-acting injection antipsychotics, shared decision-making, a case management system, compulsory treatment by law, community rehabilitation programs, the patients' feeling about their health care professionals (patients' behaviors) and their attitude/knowledge of their conditions/ illness. This study proposes that evaluating the medication adherence of patients can be determined by two key domains, namely patients' behaviors and attitudes. Based on different levels of their behaviors (X-axis) and attitude/knowledge (Y-axis), it is possible to categorize patients with schizophrenia into six subgroups, for which various different interventions, including the use of antipsychotics, could be applied and integrated. Further research is needed to assess the applicability of this treatment algorithm in clinical settings.
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