Far-field Super-resolution Chemical Microscopy

Far-field chemical microscopy providing molecular electronic or vibrational fingerprint information opens a new window for the study of three-dimensional biological, material, and chemical systems. Chemical microscopy provides a nondestructive way of chemical identification without exterior labels. However, the diffraction limit of optics hindered it from discovering more details under the resolution limit. Recent development of super-resolution techniques gives enlightenment to open this door behind far-field chemical microscopy. Here, we review recent advances that have pushed the boundary of far-field chemical microscopy in terms of spatial resolution. We further highlight applications in biomedical research, material characterization, environmental study, cultural heritage conservation, and integrated chip inspection.Comment: 34 pages, 8 figures,1 tabl

Probing Quasar Viewing Angle with the Variability Structure Function

Given the anisotropic emission from quasar accretion discs, their viewing angle affects estimates of the quasar luminosity, black-hole mass and Eddington ratio. Discs appear overluminous when viewed pole-on and underluminous when viewed at high inclination. In radio-quiet quasars, the viewing angle is usually unknown, although spectroscopic indicators have been proposed. Here, we use a recently discovered universality in the variability structure function (SF) of quasar light curves (LCs), where all quasars show the same SF when clocks run in units of orbital timescale. As an offset from the mean relation can be caused by incorrect orbital timescales and thus incorrect luminosities, we correlate these offsets with suggested inclination indicators. We derive SFs from NASA/ATLAS LCs spanning $\sim 6$ years of observation, using a sample of 183 luminous quasars with measured H$\beta$ lines as well as 753 quasars with CIV and MgII lines. Starting from the proposed orientation indicators, we expect quasars with narrower H$\beta$ lines and with more blueshifted CIV lines to be viewed more pole-on and thus appear overluminous. In contrast, our SF analysis finds that presumed pole-on discs appear underluminous, consistently for both line indicators. We discuss possible explanations for the behaviour of quasars with highly blueshifted CIV lines irrespective of inclination angle, including dusty outflows that might render the accretion disc underluminous and flatter disc temperature profiles with longer orbital timescales than in thin-disc models but reach no satisfying conclusion.Comment: 15 pages, 10 figures, Accepted for publication in MNRA

Multiple microRNAs regulate tacrolimus metabolism through CYP3A5

The CYP3A5 gene polymorphism accounts for the majority of inter-individual variability in tacmlimus pharmacokinetics. We found that the basal expression of CYP3A5 in donor grafts also played a significant role in tacrolimus metabolism under the same genetic conditions after pediatric liver transplantation. Thus, we hypothesized that some potential epigenetic factors could affect CYP3A5 expression and contributed to the variability. We used a high-throughput functional screening for miRNAs to identify miRNAs that had the most abundant expression in normal human liver and could regulate tacmlimus metabolism in HepaRG cells and HepLPCs. Four of these miRNAs (miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26-5p) were selected for testing. We found that these miRNAs inhibited tacmlimus metabolism that was dependent on CYP3A5. Putative miRNAs targeting key drug-metabolizing enzymes and transporters (DMETs) were selected using an in silico prediction algorithm. Luciferase reporter assays and functional studies showed that miR-26b-5p inhibited tacrolimus metabolism by directly regulating CYP3A5, while miR-29a-5p, miR-99a-5p, and miR-532-5p targeted HNF4a, NR1I3, and NR1I2, respectively, in turn regulating the downstream expression of CYP3A5; the corresponding target gene siRNAs markedly abolished the effects caused by miRNA inhibitors. Also, the expression of miR-29a-3p, miR-99a-5p, miR-532-5p, and miR-26b-5p in donor grafts were negatively correlated with tacmlimus C/D following pediatric liver transplantation. Taken together, our findings identify these miRNAs as novel regulators of tacrolimus metabolism

Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide

BACKGROUND: Accumulation of β-amyloid peptides is an important hallmark of Alzheimer\u27s disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line. RESULTS: NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer\u27s disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ(42) internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy. CONCLUSIONS: Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy

Bank Credit Strategy Model Based on AHP-Fuzzy Comprehensive Evaluation

Credit risk control and credit strategy formulation of medium and micro enterprises have always been important strategic issues faced by commercial banks. Banks usually make corporate loan policies based on the credit degree, the information of trading bills and the relationship of supply-demand chain of the enterprise. In this paper, we established the AHP-Fuzzy comprehensive evaluation model for quantifying enterprise credit risk. Based on the relevant data of 123 enterprises with credit records, the credit strategy is formulated according to the three indicators of enterprise strength, enterprise reputation and stability of supply-demand relationship. This paper also combines the credit reputation, credit risk and supply and demand stability rating in order to establish the bank credit strategic planning model to decide whether to lend or not and the lending order. The conclusion shows that, under the condition of constant total loan amount, the enterprises with the highest credit rating should be given priority. Then, combined with the change of customer turnover rate with interest rate, we take the bank's maximize expected income as objective to calculate the optimal loan interest rate of different customer groups

PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration