AS1411 binds to nucleolin via its parallel structure and disrupts the exos-miRNA-27a-mediated reciprocal activation loop between glioma and astrocytes.

The interaction between glioma cells and astrocytes promotes the proliferation of gliomas. Micro-RNAs (miRNAs) carried by astrocyte exosomes (exos) may be involved in this process, but the mechanism remains unclear. The oligonucleotide AS1411, which consists of 26 bases and has a G-quadruplex structure, is an aptamer that targets nucleolin. In this study, we demonstrate exosome-miRNA-27a-mediated cross-activation between astrocytes and glioblastoma and show that AS1411 reduces astrocytes' pro-glioma activity. The enhanced affinity of AS1411 toward nucleolin is attributed to its G-quadruplex structure. After binding to nucleolin, AS1411 inhibits the entry of the NF-κB pathway transcription factor P65 into the nucleus, then downregulates the expression of miRNA-27a in astrocytes surrounding gliomas. Then, AS1411 downregulates astrocyte exosome-miRNA-27a and upregulates the expression of INPP4B, the target gene of miRNA-27a in gliomas, thereby inhibiting the PI3K/AKT pathway and inhibiting glioma proliferation. These results were verified in mouse orthotopic glioma xenografts and human glioma samples. In conclusion, the parallel structure of AS1411 allows it to bind to nucleolin and disrupt the exosome-miRNA-27a-mediated reciprocal activation loop between glioma cells and astrocytes. Our results may help in the development of a novel approach to therapeutic modulation of the glioma microenvironment.

INPP4B inhibits glioma cell proliferation and immune escape via inhibition of the PI3K/AKT signaling pathway.

INPP4B (Inositol polyphosphate 4-phosphatase type II) has been regarded as a suppressor of several human tumors, but its biological function, expression, and clinical significance in glioma tissues and cell lines are unclear. Notably, whether INPP4B participates in immune escape of glioma deserves urgent attention. Here, we confirmed that INPP4B expression is often downregulated in low- and high-grade human glioma tissues, in tissues from an orthotopic mouse model of brain glioma and in glioma cells. We found that INPP4B overexpression restrained the proliferation, migration, apoptosis resistance, PD-L1 expression, and T cell suppression by glioma cells, whereas INPP4B silencing had the opposite effects. Moreover, we showed that INPP4B inhibited glioma cell proliferation, migration, and PD-L1 expression by downregulating PI3K/AKT signaling. Collectively, these data support that INPP4B may inhibit glioma progression, and particularly, glioma's immune escape. Thus, INPP4B may constitute a valuable target for glioma treatment.

Polarization recycling method for light-pipe-based optical engine.

In this paper, a polarization recycling method is proposed for a light-pipe-based liquid crystal on silicon (LCoS) pico-optical engine. The method is based on making use of the virtual light sources array forming at the light pipe's input surface. With traditional imaging optics, the virtual light sources array can be imaged to a plane after the light pipe, where the separated beams array can be obtained. By applying the polarization conversion system to the separated beams, the incoming unpolarized light can be converted to polarized light. The polarized light is then collected and transferred to the LCoS panel through the relay system. This new polarization recycling method can highly improve the light efficiency. A design example of a 0.29 in. (7.366 mm) color-filter LCoS pico-optical engine with 852×480 resolution is listed. High light efficiency of about 10.5 lm per LED Watt and high irradiance uniformity of about 95% has been achieved. The thickness of the optical engine is 8 mm.

Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A.

BACKGROUND: Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported. METHODS: Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. RESULTS: Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. CONCLUSIONS: Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

Wide viewing angle skewed effect of the point spread function in a wavefront coding system.

The point spread function (PSF) of a wavefront coding (WFC) system with a cubic phase mask is analyzed with a wide viewing angle based on physical optics for what is believed to be the first time. Two coordinate transformations are made to generate a pupil function, from which we obtain the encoded PSF of the WFC system with defocus parameters W(020) and object angles alpha and beta. The encoded PSFs are further side extended as the object angles get wider. When alphabeta<0, the included angle ? of encoded PSF will skew to an obtuse angle. When alphabeta=0, ? remains orthogonal; when alphabeta>0, ? will skew to an acute angle. Furthermore, the effect of skew and side extension is even symmetric about W(020). As a result, the wide viewing angle has a bad effect on the imaging quality of the WFC system.

Point spread function characteristics analysis of the wavefront coding system.

Most of the previous imaging characteristics analysis of the wavefront coding system has been carried out within the frequency domain. In this paper, the stationary phase method is employed to perform the analysis within the spatial domain. The approximate expression of point spread function (PSF) in the presence of defocus aberration is derived for the system with a cubic phase mask, which shows a good agreement with the Fast Fourier Transform (FFT) approach. Based on this, the PSF characteristics are analyzed in terms of the boundaries, oscillations and sensitivities to defocus, astigmatism and coma.

Ray aberrations analysis for phase plates illuminated by off-axis collimated beams.

Approximate expressions of the ray aberrations for off-axis collimated beams and free form phase plates with a small derivative magnitude are derived with the defocus aberration taken into account. The cubic phase plate, which is one of the most commonly used phase plates in wavefront coding imaging systems, is illustrated as an example. The approximate expressions for the upper and lower boundaries of ray map, and the spot size in the vicinity of the focal plane are derived. The sensitivity to the defocus aberration and the variation of the induced aberrations with respect to the field positions are analyzed with derived approximate expressions as well. Some characteristics unmentioned before are derived, showing a good agreement with the exact aberrations. Finally some useful guidelines are given for the design of imaging systems with phase plates.