49 research outputs found
Genetics and Mechanisms Underlying Karyokinesis and Cytokinesis in Cardiomyocytes
No full textThe mammalian adult heart has limited ability to regenerate, partly because most cardiomyocytes (CMs) are polyploid. The frequency of potentially regenerative diploid CMs in the adult heart is determined by multiple polymorphic genes. By identifying these genes, it might be possible to clarify mechanisms that influence whether CMs entering the cell cycle can complete it or instead fail during karyokinesis or cytokinesis.
BALB/cJ and BALB/cByJ mice are highly related sister strains that diverge substantially in mononuclear CM frequency and CM ploidy. Our evidence suggests that the difference in CM ploidy is an autosomal trait, whereas the variation in mononuclear CM frequency is X-linked. Additionally, we identified a large deletion in the Cyth1 gene that arose uniquely in BALB/cByJ mice, creating a null allele. The deletion also results in ectopic transcription of the downstream gene Dnah17, although this transcript is unlikely to encode a protein. By evaluating the natural null allele from BALB/cByJ and an engineered knockout allele in the C57BL/6J background, we determined that absence of Cyth1 alone does not influence CM ploidy. The ready availability of BALB/cByJ mice may be helpful to other investigations of Cyth1 in other biological processes.
A genome-wide association study of the BXD mouse strains implicated a locus on Chr 3 that influences the percentage of mononuclear CMs. My analysis confirmed that Spg20, located within the locus, is more highly expressed in C57BL/6J compared to DBA/2J mice. A SNP in the 3’ untranslated sequence (rs30203612) in DBA/2J mice may underlie the differential expression. The Spg20 protein (Spartin) is known in other cell types to colocalize with the ESCRT III protein Ist1 at the midbody during the cytokinesis, where it regulates the microtubule-severing protein (Spastin). Immunostaining showed that Spartin is recruited to the midbody in primary neonatal CMs during cytokinesis. This work points to a potential molecular mechanism linking Spartin with the ESCRT complex in cytokinesis, influencing CM cell cycle completion.
In addition to genetic factors, we also found that the corncob bedding used in mouse cages affects CM phenotype. In summary, these research findings contribute to a better understanding of karyokinesis and cytokinesis in CMs, paving the way for heart regeneration
Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas
No full textThe Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles)? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics
Extraction of Mineralized Alteration Information Based on Remote Sensing in Western Tianshan, XinJiang
No full text
Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis
No full textAbstract Although there was no significant heterogeneity in the meta-publication, sensitivity analyses revealed significant heterogeneity. Overall, the prevalence was higher in women (N = 6, R = 4.6%, 95% CI 3.1%, 6.0%, and I2 = 99.8%) than in men (N = 6, R = 3.4%, 95% CI 2.0%, 4.7%, and I2 = 99.6the %); prevalence of type 2 diabetes (N = 9, R = 12.5%, 95% CI 7.7%, 17.3%, and I2 = 95.4%) was higher than type 1 diabetes (N = 7, R = 8.3%, 95% CI 6.4%, 10.2%, and I2 = 93.6%); the prevalence of DGP was slightly lower in DM patients aged over 60 years (N = 6, R = 5.5%, 95% CI 3.3%, 7.7%, and I2 = 99.9%) compared to patients under 60 years of age (N = 12, R = 15.8%, 95% CI 11 15.8%, 95% CI 11.4%, 20.2%, and I2 = 88.3%). In conclusion, our findings indicate that the combined estimated prevalence of gastroparesis in diabetic patients is 9.3%. However, the sensitivity of the results is high, the robustness is low, and there are significant bias factors. The subgroup analysis revealed that the prevalence of DM-DGP is associated with factors such as gender, diabetes staging, age, and study method
A Novel Rapeseed Mapping Framework Integrating Image Fusion, Automated Sample Generation, and Deep Learning in Southwest China
No full textRapeseed mapping is crucial for refined agricultural management and food security. However, existing remote sensing-based methods for rapeseed mapping in Southwest China are severely limited by insufficient training samples and persistent cloud cover. To address the above challenges, this study presents an automatic rapeseed mapping framework that integrates multi-source remote sensing data fusion, automated sample generation, and deep learning models. The framework was applied in Santai County, Sichuan Province, Southwest China, which has typical topographical and climatic characteristics. First, MODIS and Landsat data were used to fill the gaps in Sentinel-2 imagery, creating time-series images through the object-level processing version of the spatial and temporal adaptive reflectance fusion model (OL-STARFM). In addition, a novel spectral phenology approach was developed to automatically generate training samples, which were then input into the improved TS-ConvNeXt ECAPA-TDNN (NeXt-TDNN) deep learning model for accurate rapeseed mapping. The results demonstrated that the OL-STARFM approach was effective in rapeseed mapping. The proposed automated sample generation method proved effective in producing reliable rapeseed samples, achieving a low Dynamic Time Warping (DTW) distance (<0.81) when compared to field samples. The NeXt-TDNN model showed an overall accuracy (OA) of 90.12% and a mean Intersection over Union (mIoU) of 81.96% in Santai County, outperforming other models such as random forest, XGBoost, and UNet-LSTM. These results highlight the effectiveness of the proposed automatic rapeseed mapping framework in accurately identifying rapeseed. This framework offers a valuable reference for monitoring other crops in similar environments
Cellulose δ18O of Tree Rings Reflects Vapour Pressure Variations in the Ordos Plateau
No full textIn arid and semi-arid regions, a better understanding of the effect of climate change mechanisms on environmental evolution can be used to guide regional ecological conservation and to improve water resource availability. Increased aridity in arid and semi-arid regions considerably affects the physiological functions of plants and the exchange of carbon and water with the environment. We collected Pinus tabuliformis Carr. samples from Ordos, Inner Mongolia, and measured their δ18O variations. Vapour pressure (VP) was the main factor dominating δ18O variations from July to August, indicating the regulatory role of plant leaf stomata. Based on the δ18O series in the Ordos region, we reconstructed VP variations for July–August (VPJA) for the past 205 years. Spatial analysis showed the reconstruction as spatially highly representative. VP variations in the Ordos region mainly reflected precipitation variations and did not show a significant correlation with temperature. Since the late 1950s, VP has been decreasing, which is related to the weakening of the Asian monsoon. The results of reconstruction decomposed using ensemble empirical mode decomposition showed that El Niño–Southern Oscillation may affect VP in the study area, and the effect of sea surface temperature on the central and eastern Pacific Ocean in the Ordos region may lead to an increase in the drought
In-situ synchrotron high energy X-ray diffraction study on the compressive creep behavior of an extruded Ti-45Al-8Nb-0.2C alloy
No full textWrought high Nb containing (high Nb-TiAl) alloys are potential materials for low pressure turbine blades in aero-engines. The performance and microstructure evolution under high temperature creep condition is of importance to the service stability of these materials. In this study, the internal strain and FWHM evolution of an extruded TNB-based high Nb-TiAl alloy during compressive creep are characterized by in-situ high energy X-ray diffraction (HEXRD) technique for the first time. The compressive creep test was conducted under a constant load of 300 MPa at 900 °C for 10 h in vacuum. The final creep strain is approximately 1.72 %. The microstructure and phase constitution after creep shows little difference from that before creep. Lattice strain analysis shows that γ phase is plastically deformed while the α2 phase deforms elastically due to the low creep strain. The lattice strain of α2 grains is dependent upon the deformation of surrounding γ grains. Creep induces dynamic recovery, exerting a softening effect. A high number of dislocations are visible in the γ lamellae while almost no dislocations exist within the lamellae. lamellae are partially decomposed and refined via the transformation
Attenuating lipid metabolism in atherosclerosis: The potential role of Anti-oxidative effects on low-density lipoprotein of herbal medicines
No full textAtherosclerosis (AS) is a multifactorial chronic disease with great harm to the health of human being, which is a basic pathogenesis of many cardiovascular diseases and ultimately threatens human life. Abnormal blood lipid level is one of the most common diagnostic indicators of AS in clinic, and lipid metabolism disorder is often observed in patients with AS. Cholesterol is an important lipid in the human body, which is of great significance for maintaining normal life activities. Generally, cholesterol is transported to peripheral tissues by low-density lipoprotein (LDL), and then transported to the liver by high-density lipoprotein (HDL) via its cholesterol reverse transport function, and finally discharged. Under oxidative stress condition, LDL is commonly oxidized to the form ox-LDL, which is ingested by macrophages in large quantities and further forms foam cells, disrupting the normal metabolic process of cholesterol. Importantly, the foam cells are involved in forming atherosclerotic plaques, whose rupture may lead to ischemic heart disease or stroke. Furthermore, ox-LDL could also promote the development of AS by damaging vascular endothelium, promoting the migration and proliferation of smooth muscle cells, and activating platelets. Therefore, inhibiting LDL oxidation may be an effective way to improve lipid metabolism and prevent AS. In recent years, increasing studies have shown that herbal medicines have great potentiality in inhibiting LDL oxidation and reducing ox-LDL induced foam cell formation. Accordingly, this paper summarized current research on the inhibitory effects of herbal medicines against LDL oxidation and foam cell formation, and made a brief description of the role of cholesterol and LDL in lipid metabolism disorder and AS pathogenesis. Importantly, it is suggested that herbal medicines could inhibit LDL oxidation and regulate cholesterol homeostasis via downregulation of CD36 and SR-A, whereas upregulation of ABCA1 and ABCG1
The role of GLI1 for 5-Fu resistance in colorectal cancer
No full textAbstract Colorectal cancer is a leading cause of cancer-related mortality worldwide, with Fluorouracil (5-FU)-based chemotherapy as the major treatment for advanced disease. Many patients with advanced colorectal cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for chemotherapy resistance will help design novel strategies to treat colorectal cancer. In this study, we established an acquired 5-FU resistant cell line, LoVo-R, from LoVo cells. Through exome sequencing, we discovered that elevated GLI1 signaling axis is a major genetic alteration in the 5-FU resistant cells. Hh signaling, a pathway essential for embryonic development, is an important regulator for residual cancer cells. We demonstrated that knockdown of GLI1 or GLI2 sensitized LoVo-R cells to 5-FU treatment, reduced cell invasiveness. The relevance of our studies to colorectal cancer patients is reflected by our discovery that high expression of GLI1 signaling molecules was associated with a high incidence of cancer relapse and a shorter survival in a larger cohort of colorectal cancer patients who underwent chemotherapy (containing 5-FU). Taken together, our data demonstrate the critical role of the GLI1 signaling axis for 5-FU resistance in colorectal cancer
