Serum exosomal miR-200c is a potential diagnostic biomarker for breast cancer.

BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in breast cancer serum exosomes and its diagnostic value. METHODOLOGY: miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7,MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves. RESULTS: We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without breast cancer disease and could be used as an early diagnostic marker for breast cancer disease. CONCLUSION: Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.

miR-192 family in breast cancer: Regulatory mechanisms and diagnostic value.

There is a growing interest in the role of the miRNA family in human cancer. The miRNA-192 family is a group of conserved small RNAs, including miR-192, miR-194, and miR-215. Recent studies have shown that the incidence and mortality of breast cancer have been increasing epidemiologically year by year, and it is urgent to clarify the pathogenesis of breast cancer and seek new diagnostic and therapeutic methods. There is increasing evidence that miR-192 family members may be involved in the occurrence and development of breast cancer. This review describes the regulatory mechanism of the miRNA-192 family affecting the malignant behavior of breast cancer cells and evaluates the value of the miRNA-192 family as a diagnostic and prognostic biomarker for breast cancer. It is expected that summarizing and discussing the relationship between miRNA-192 family members and breast cancer, it will provide a new direction for the clinical diagnosis and treatment of breast cancer and basic medical research.

Deciphering the Allosteric Activation Mechanism of SIRT6 Using Molecular Dynamics Simulations.

As a member of the histone deacetylase protein family, the NAD+-dependent SIRT6 plays an important role in maintaining genomic stability and regulating cell metabolism. Interestingly, SIRT6 has been found to have a preference for hydrolyzing long-chain fatty acyls relative to deacetylation, and it can be activated by fatty acids. However, the mechanisms by which SIRT6 recognizes different substrates and can be activated by small molecular activators are still not well understood. In this study, we carried out extensive molecular dynamic simulations to shed light on these mechanisms. Our results revealed that the binding of the myristoylated substrate stabilizes the catalytically favorable conformation of NAD+, while the binding of the acetyl-lysine substrate leads to a loose binding of NAD+ in SIRT6. Based on these observations, we proposed a reasonable allosteric binding mode for myristic acid, which can enhance the catalytic activity of SIRT6 by stabilizing the binding of NAD+ with His131 as well as the acetylated substrate. Furthermore, our molecular dynamics simulations demonstrated that synthetic SIRT6 activators, such as UBCS039, MDL-801, and 12q, block the flipping of ribose in NAD+ and therefore can stabilize substrate-NAD+-His131 interactions in a manner similar to fatty acids. In summary, our newly proposed activation mechanism of SIRT6 highlights the importance of protein-substrate interactions, which would facilitate the rational design of new SIRT6 activators.

Efficient and selective removal of Pb2+ from aqueous solution by using an O- functionalized metal-organic framework.

Lead (Pb) is one of the most widespread and highly toxic heavy metals in the environment. The design and synthesis of adsorbent materials for the selective and efficient removal of Pb2+ from aqueous solution has received much attention. Herein, the ligand 4,4'-azoxydibenzoic acid with the O- group was elaborately selected to construct a novel Pr-based MOF for Pb2+ removal. The as-prepared MOF adsorbents with high stability exhibited ultra-high selectivity for Pb2+, even in the presence of various highly concentrated competitive ions (with the ratios from 1 : 5 to 1 : 50). Also, a high uptake capacity (560.26 mg g-1) can be achieved for the MOF material, due to the availability of sufficient adsorption sites. The strong electrostatic attraction and coordination interaction between the numerous active O- sites on MOF adsorbents and Pb2+ can account for the good adsorption performance for Pb2+, which was systematically verified by zeta potential, FT-IR and XPS studies.

Effects of physical exercise on attention deficit and other major symptoms in children with ADHD: A meta-analysis.

PURPOSE: To explore the effects of physical exercise intervention on the cardinal symptoms, motor skills and executive function among children with attention deficit hyperactivity disorder (ADHD). METHODS: Literature searches for randomized controlled trials (RCTs) were performed in PubMed, The Cochrane Library, Web of Science, Embase, CNKI, CBM, VIP and Wanfang databases from the time of database construction to March 28, 2021. Screening was conducted based on inclusion and exclusion criteria. The Cochrane bias risk assessment tools were used to evaluate methodological quality. Relevant data were analyzed with RevMan5.3.5 software, and Stata16.0 was used for publication bias tests. RESULTS: A total of 15 RCTs with 734 subjects were included. The meta-analysis showed that physical exercise can improve the attention of ADHD children (standardized mean difference [SMD] = -0.60, 95% confidence interval [CI] [-1.10, -0.11], p < 0.01), executive function (SMD = 1.22, 95% CI [0.61, 1.82], p < 0.01), and motor skills (SMD = 0.67, 95% CI [0.22, 1.12], p < 0.01). There were no significant effects on hyperactivity (SMD = 0.06, 95% CI [-0.26, 0.37], p = 0.72), depression (SMD = -0.72, 95% CI [-1.55, 0.11], p = 0.09), social problems (SMD = -0.27, 95% CI [-0.64, 0.09], p = 0.14), or aggressive behavior (SMD=-0.24, 95% CI [-0.69, -0.21], p = 0.30). Intervention duration and frequency might be the source of heterogeneity. CONCLUSION: Physical exercise can help alleviate the symptoms of ADHD in children. Specifically, it can improve attention, executive function, and motor skills.

Contrast optimization in broadband passive polarimetric imaging based on color camera.

Broadband polarimetric imaging consists of forming an image under spectrally wide illumination after having optimized the polarization state analyzer (PSA) to maximize the target/background discriminability. In previous works, the image sensor was monochrome, and only the intensity contrast was optimized. However, due to its spectrally varying response, the PSA not only changes the light's intensity, but also its color. This color information can serve as a further parameter to improve discrimination. In this paper, we employ a color camera in a broadband Stokes (passive) polarimetric imaging system and take into color difference's contribution to discrimination ability in optimizing the PSA setting. We show through experiments that a significant improvement of discrimination ability over monochrome imaging is obtained, especially when there are multiple objects in the scene.

Colorimetric discrimination for Stokes polarimetric imaging.

Traditional methods of discrimination for Stokes polarimetric imaging use grayscale images, in which the difference of the polarimetric properties is only reflected by the difference of grayscale. In this paper, we propose a method of colorimetric discrimination and classification for Stokes polarimetric imaging by the composed color polarimetric image, in which the objects with different polarization properties can appear in different colors. We show with real-world experiment that compared with the traditional method for the grayscale Stokes scalar image, the method proposed in this paper has a better performance for distinguishing objects with different polarization properties.

Underwater image recovery considering polarization effects of objects.

In underwater imaging scenarios, the scattering media could cause severe image degradation due to the backscatter veiling as well as signal attenuation. In this paper, we consider the polarization effect of the object, and propose a method of retrieving the objects radiance based on estimating the polarized-difference image of the target signal. We show with a real-world experiment that by taking into account the polarized-difference image of the target signal additionally, the quality of the underwater image can be effectively enhanced, which is particularly effective in the cases where both the object radiance and the backscatter contribute to the polarization, such as underwater detection of the artifact objects.