Dissecting the roles and clinical potential of YY1 in the tumor microenvironment

Yin-Yang 1 (YY1) is a member of the GLI-Kruppel family of zinc finger proteins and plays a vital dual biological role in cancer as an oncogene or a tumor suppressor during tumorigenesis and tumor progression. The tumor microenvironment (TME) is identified as the “soil” of tumor that has a critical role in both tumor growth and metastasis. Many studies have found that YY1 is closely related to the remodeling and regulation of the TME. Herein, we reviewed the expression pattern of YY1 in tumors and summarized the function and mechanism of YY1 in regulating tumor angiogenesis, immune and metabolism. In addition, we discussed the potential value of YY1 in tumor diagnosis and treatment and provided a novel molecular strategy for the clinical diagnosis and treatment of tumors

A mutual information theory-based approach for assessing uncertainties in deterministic multi-category precipitation forecasts

The very nature of weather forecasts and verifications and the way they are used make it impossible for one single or absolute standard of evaluation. However, little research has been conducted on verifying deterministic multi-category forecasts, which is based on the attribute of uncertainty. The authors propose a new approach using two mutual information theory-based scores for assessing the comprehensive uncertainty of all categories and the uncertainty for a certain category in deterministic multi-category precipitation forecasts, respectively. Specifically, the comprehensive uncertainty is defined as the average reduction in uncertainty about the observations resulting from the use of a predictive model to provide all categories forecasts; the uncertainty of a certain category is defined as the reduction in uncertainty about the observations resulting from the use of a predictive model to provide a certain category forecast. By applying the proposed approach and traditional verification methods, the four precipitation forecasting products from the China Meteorological Administration (CMA), European Centre for Medium-Range Weather Forecasts (ECMWF), National Centers for Environmental Prediction (NCEP) and United Kingdom Meteorological Office (UKMO) were verified in the Dahuofang Reservoir Drainage Basin, China. The results indicate that: (1) the proposed approach can better capture the changing patterns of uncertainties with lead times and distinguish the forecasting performance among different forecast products; (2) the proposed approach is resistant to the extreme bias; (3) the proposed approach needs a careful choice of bin width; and (4) the bias analysis is necessary before verifying the uncertainties in precipitation forecasts

Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo

We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFκB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFα), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD

Large Constant-Sign Solutions of Discrete Dirichlet Boundary Value Problems with p-Mean Curvature Operator

In this paper, we consider the existence of infinitely many large constant-sign solutions for a discrete Dirichlet boundary value problem involving p -mean curvature operator. The methods are based on the critical point theory and truncation techniques. Our results are obtained by requiring appropriate oscillating behaviors of the non-linear term at infinity, without any symmetry assumptions

Existence of Solutions for the Discrete Dirichlet Problem Involving p-Mean Curvature Operator

This work is to discuss the Dirichlet boundary value problem of the difference equation with p -mean curvature operator. Under some determinate growth conditions on the nonlinear term, the existence of one solution or two nontrivial solutions is obtained via variational methods and some analysis techniques. Examples are also given to illustrate our theorems in the last section

Phase-Shifted Eccentric Core Fiber Bragg Grating Fabricated by Electric Arc Discharge for Directional Bending Measurement

A phase-shifted eccentric core fiber Bragg grating (PS-ECFBG) fabricated by electric arc discharge (EAD) is presented and demonstrated. It is composed of a fraction of eccentric core fiber fusion spliced in between two pieces of commercial single mode fibers, where a PS-FBG was written. The EAD in this work could flexibly change the amount of phase-shift by changing the discharge number or discharge duration. Because of the offset location of the eccentric core and the ultra-narrow resonant peak of the PS-ECFBG, it has a higher accuracy for measuring the directional bend. The elongation and compression of the eccentric core keep the magnitude of phase shift still unchanged during the bending process. The bending sensitivities of the PS-ECFBG at two opposite most sensitive directions are 57.4 pm/m−1 and −51.5 pm/m−1, respectively. Besides, the PS-ECFBG has the potential to be a tunable narrow bandpass filter, which has a wider bi-directional adjustable range because of the bending responses. The strain and temperature sensitivities of the PS-ECFBG are experimentally measured as well, which are 0.70 pm/με and 8.85 pm/°C, respectively

QTL mapping for seed density per silique in Brassica napus

Abstract Seed density per silique (SDPS) and valid silique length (VSL) are two important yield-influencing traits in rapeseed. SDPS has a direct or indirect effect on rapeseed yield through its effect on seed per silique. In this study, a quantitative trait locus (QTL) for SDPS was detected on chromosome A09 using the QTL-seq approach and confirmed via linkage analysis in the mapping population obtained from 4263 × 3001 cross. Furthermore, one major QTL for SDPS (qSD.A9-1) was mapped to a 401.8 kb genomic interval between SSR markers Nys9A190 and Nys9A531. In the same genomic region, a QTL (qSL.A9) linked to VSL was also detected. The phenotypic variation of qSD.A9-1 and qSL.A9 was 53.1% and 47.6%, respectively. Results of the additive and dominant effects demonstrated that the expression of genes controlling SDPS and VSL were derived from a different parent in this population. Subsequently, we identified 56 genes that included 45 specific genes with exonic (splicing) variants. Further analysis identified specific genes containing mutations that may be related to seed density as well as silique length. These genes could be used for further studies to understand the details of these traits of rapeseed