Search

All-trans retinoic acid (ATRA) has been widely investigated for treatments of many cancers including prostate cancer. HOXB13, silenced in androgen receptor-negative (AR-) prostate cancer cells, plays a role in AR2 prostate cancer cell growth arrest. In this study we intended to elucidate the mechanisms that are involved in the proliferation inhibition of AR2 prostate cancer cells triggered by ATRA. We discovered that ATRA was able to induce the growth arrest and to increase HOXB13 expression in AR- prostate cancer cells. Both EZH2 and DNMT3b participated in the repression of HOXB13 expression through an epigenetic mechanism involving DNA and histone methylation modifications. Specifically, EZH2 recruited DNMT3b to HOXB13 promoter to form a repression complex. Moreover, ATRA could upregulate HOXB13 through decreasing EZH2 and DNMT3b expressions and reducing their interactions with the HOXB13 promoter. Concurrently, the methylation level of the HOXB13 promoter was reduced upon the treatment of ATRA. Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR- resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications. [ABSTRACT FROM AUTHOR]

The precision of star point location is significant to identify the star map and to acquire the aircraft attitude for star sensors. Under dynamic conditions, star images are not only corrupted by various noises, but also blurred due to the angular rate of the star sensor. According to different angular rates under dynamic conditions, a novel method is proposed in this article, which includes a denoising method based on adaptive wavelet threshold and a restoration method based on the large angular rate. The adaptive threshold is adopted for denoising the star image when the angular rate is in the dynamic range. Then, the mathematical model of motion blur is deduced so as to restore the blurred star map due to large angular rate. Simulation results validate the effectiveness of the proposed method, which is suitable for blurred star image processing and practical for attitude determination of satellites under dynamic conditions. [ABSTRACT FROM AUTHOR]

A facile encapsulation strategy was reported for preparing nanoparticles/ metal-organic framework hybrid thin films which exhibit both the active (catalytic, magnetic, and optical) properties derived from the NPs and the size-selectivity originating from the welldefined microporous structure of the MOF thin films. [ABSTRACT FROM AUTHOR]

Patients with Hutchinson-Gilford progeria syndrome (HGPS) present with a number of premature aging phenotypes, including DNA damage accumulation, and many of them die of cardiovascular complications. Although vascular pathologies have been reported, whether HGPS patients exhibit cardiac dysfunction and its underlying mechanism is unclear, rendering limited options for treating HGPS-related cardiomyopathy. In this study, we reported a cardiac atrophy phenotype in the LmnaG609G/G609G mice (hereafter, HGPS mice). Using a GFP-based reporter system, we demonstrated that the efficiency of nonhomologous end joining (NHEJ) declined by 50% in HGPS cardiomyocytes in vivo, due to the attenuated interaction between ?H2AX and Progerin, the causative factor of HGPS. As a result, genomic instability in cardiomyocytes led to an increase of CHK2 protein level, promoting the LKB1-AMPKa interaction and AMPKa phosphorylation, which further led to the activation of FOXO3A-mediated transcription of atrophy-related genes. Moreover, inhibiting AMPK enlarged cardiomyocyte sizes both in vitro and in vivo. Most importantly, our proof-of-concept study indicated that isoproterenol treatment significantly reduced AMPKa and FOXO3A phosphorylation in the heart, attenuated the atrophy phenotype, and extended the mean lifespan of HGPS mice by ~21%, implying that targeting cardiac atrophy may be an approach to HGPS treatment. [ABSTRACT FROM AUTHOR]

Background: Research on fetal congenital heart defect (CHD) mostly focuses on etiology and mechanisms. However, studies on maternal complications or pathophysiology are limited. Our objective was to determine whether vascular dysfunction exists in pregnant women carrying a fetus with congenital heart defects. Methods: We conducted a case-control study. 27 cases of pregnant women carrying a fetus with major CHD admitted to our hospital for delivery between April 2021 and August 2022 were selected. Every case was matched with about 2 pregnant complication-free controls without fetal abnormalities. The proangiogenic and anti-angiogenic factors and pregnancy outcomes were compared. Results: The proangiogenic factors include vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The anti-angiogenic factors involve soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng). No differences were found in maternal plasma concentrations of PlGF, VEGF, and sFlt-1 between case-control groups when analyzed at 36 weeks ≤ gestational age (GA) < 39 weeks and 39 weeks ≤ GA ≤ 41 weeks. The concentrations of sEng in maternal plasma in the fetal CHD group were significantly higher than those in the control group: 0.60 (0.77) vs. 0.32 (0.26) ng/ml at 36 weeks ≤ GA < 39 weeks, p = 0.001 and 0.75 (0.55) vs. 0.28 (0.27) ng/ml at 39 weeks ≤ GA ≤ 41 weeks, p < 0.001. Conclusion: Vascular dysfunction exists in pregnant women with fetal congenital heart defects, manifesting significantly elevated sEng concentration at delivery. [ABSTRACT FROM AUTHOR]

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy. [ABSTRACT FROM AUTHOR]

With high rates of food and nonrenewable fossil fuel consumption worldwide, we are facing great challenges in ensuring food and energy security to satisfy the world population. Intercropping, as an important and sustainable cropping practice in agroecosystems, has been widely practiced around the world. Many studies have shown that some plants can deliver high yields when intercropped with other plants. Here, we review the biological mechanisms in improving resource utilization efficiency and illustrate the practical application of intercropping in ensuring food and energy security through improving production. Identifying suitable energy plants for marginal land, land not suitable for food crops growth, is an effective strategy to acquire high production of bioenergy, thus removing competition between the use of land for food and energy. The effective application of intercropping provides a potential pathway for production of food crops and energy plants by improving resource use efficiency and resistance to environmental stress.

T cell immunoglobulin and mucin domain (Tim)-3 is a molecule expressed on terminally differentiated murine Th1 cells but not on Th2 cells. Identification of Galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3-Galectin-9 pathway as an important regulator of Th1 immunity, which results in apoptosis of Th1 cells. Here, we demonstrate that engagement of Tim-3 by mouse recombinant Galectin-9 remarkably suppresses allograft rejection and improves survival of allogeneic skin grafts. Furthermore, administration of recombinant Galectin-9 decreases Tim-3 positive cells in draining lymph node and selectively inhibits production of IFN-γ after skin transplantation. At last, even low dose of Galectin-9 (1 μg/ml) can obviously inhibit TCR crosslinking-induced primary T cell proliferation in vitro. These observations suggest that Tim-3- Galectin-9 pathway plays an important role in the termination of productive Th1 -immune response and could lead to developing novel therapies in transplant medicine. [ABSTRACT FROM AUTHOR]