Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-β in colorectal cells.

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-β mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-β, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-β, which may be the basis for the anti-cancer effect in colorectal cells

Invisible Users: Uncovering End-Users' Requirements for Explainable AI via Explanation Forms and Goals

Non-technical end-users are silent and invisible users of the state-of-the-art explainable artificial intelligence (XAI) technologies. Their demands and requirements for AI explainability are not incorporated into the design and evaluation of XAI techniques, which are developed to explain the rationales of AI decisions to end-users and assist their critical decisions. This makes XAI techniques ineffective or even harmful in high-stakes applications, such as healthcare, criminal justice, finance, and autonomous driving systems. To systematically understand end-users' requirements to support the technical development of XAI, we conducted the EUCA user study with 32 layperson participants in four AI-assisted critical tasks. The study identified comprehensive user requirements for feature-, example-, and rule-based XAI techniques (manifested by the end-user-friendly explanation forms) and XAI evaluation objectives (manifested by the explanation goals), which were shown to be helpful to directly inspire the proposal of new XAI algorithms and evaluation metrics. The EUCA study findings, the identified explanation forms and goals for technical specification, and the EUCA study dataset support the design and evaluation of end-user-centered XAI techniques for accessible, safe, and accountable AI.Comment: EUCA dataset, code, and appendix are at: https://weinajin.github.io/euca. An earlier longer version of the EUCA study (with EUCA prototyping framework) is at: arXiv:2102.02437. The followup paper applying the EUCA study findings is at: arXiv:2208.0873

Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter.

Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The β-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter

Colorectal cancer screening with fecal occult blood test: A 22-year cohort study.

The aim of the present study was to investigate the efficacy of colorectal cancer (CRC) screening with a three-tier fecal occult blood test (FOBT) in the Chinese population. The study was performed between 1987 and 2008 at the Beijing Military General Hospital, in a cohort of army service males and females aged >50 years. Between 1987 and 2005, a three-tier screening program, comprising guaiac-based FOBTs (gFOBTs), followed by immunochemical FOBTs for positive guaiac test samples and then colonoscopy for positive immunochemical test subjects, was performed annually. The cohort was followed up until 2008. The cohort included 5,104 subjects, of which, 3,863 subjects participated in screening (screening group) and 1,241 did not (non-screening group). The two groups did not differ in age, gender or other major risk factors for colon cancer. Overall, 36 CRCs occurred in the screening group and 21 in the non-screening group. Compared with the non-screening group, the relative risk for the incidence and mortality of CRC was 0.51 [95% confidence interval (CI), 0.30-0.87] and 0.36 (95% CI, 0.18-0.71), respectively, in the screening group. The general sensitivity of this three-tier FOBT was 80.6% (95% CI, 65.3-91.1). Thus, annual screening using the three-tier FOBT program may reduce the CRC incidence and mortality rate

Evolution of the strange-metal scattering in momentum space of electron-doped La2−xCexCuO4{\rm La}_{2-x}{\rm Ce}_x{\rm CuO}_4

The linear-in-temperature resistivity is one of the important mysteries in the strange metal state of high-temperature cuprate superconductors. To uncover this anomalous property, the energy-momentum-dependent imaginary part of the self-energy Im ${\rm \Sigma}(k, \omega)$ holds the key information. Here we perform systematic doping, momentum, and temperature-dependent angle-resolved photoemission spectroscopy measurements of electron-doped cuprate ${\rm La}_{2-x}{\rm Ce}_x{\rm CuO}_4$ and extract the evolution of the strange metal scattering in momentum space. At low doping levels and low temperatures, Im ${\rm\Sigma} \propto \omega$ dependence dominates the whole momentum space. For high doping levels and high temperatures, Im ${\rm\Sigma} \propto \omega^2$ shows up, starting from the antinodal region. By comparing with the hole-doped cuprates ${\rm La}_{2-x}{\rm Sr}_x{\rm CuO}_4$ and ${\rm Bi}_2{\rm Sr}_2{\rm CaCu}_2{\rm O}_8$, we find a dichotomy of the scattering rate exists along the nodal and antinodal direction, which is ubiquitous in the cuprate family. Our work provides new insight into the strange metal state in cuprates

Non-Markovian Transmission through Two Quantum Dots Connected by a Continuum

We consider a transport setup containing a double-dot connected by a continuum. Via an exact solution of the time-dependent Schr\"odinger equation, we demonstrate a highly non-Markovian quantum-coherence-mediated transport through this dot-continuum-dot (DCD) system, which is in contrast with the common premise since in typical case a quantum particle does not reenter the system of interest once it irreversibly decayed into a continuum (such as the spontaneous emission of a photon). We also find that this DCD system supports an unusual steady state with unequal source and drain currents, owing to electrons irreversibly entering the continuum and floating there