Ubiquitin Regulation: The Histone Modifying Enzyme\u27s Story

Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes

Tackle Epithelial-Mesenchymal Transition with Epigenetic Drugs in Cancer

Epithelial-mesenchymal Transition (EMT) is a de-differentiation process in which epithelial cells lose their epithelial properties to acquire mesenchymal features. EMT is essential for embryogenesis and wound healing but is aberrantly activated in pathological conditions like fibrosis and cancer. Tumor-associated EMT contributes to cancer cell initiation, invasion, metastasis, drug resistance and recurrence. This dynamic and reversible event is governed by EMT-transcription factors (EMT-TFs) with epigenetic complexes. In this review, we discuss recent advances regarding the mechanisms that modulate EMT in the context of epigenetic regulation, with emphasis on epigenetic drugs, such as DNA demethylating reagents, inhibitors of histone modifiers and non-coding RNA medication. Therapeutic contributions that improve epigenetic regulation of EMT will translate the clinical manifestation as treating cancer progression more efficiently

The Landscape of Histone Modification in Cancer Metastasis

Metastasis represents one of the most devastating aspects of cancer. Epithelial to mesenchymal transition (EMT) has been shown to play a critical role in tumorigenic metastasis. During metastatic progression, both genetic and epigenetic modifications endow cancer cells with properties that modulate the capacity for metastatic success. Histone modification is profoundly altered in cancer cells and contributes to cancer metastasis by controlling different metastatic phenotypes. Here, we first review histone modifications and discuss their roles in EMT and metastasis, with a particular focus on histone methylation and acetylation. Second, we review the major histone modification enzymes that control chromatin in cancer metastasis. Third, we discuss the transcriptional regulation concerted by these enzymes with EMT transcription factors at different molecular layers. Finally, we discuss pharmacologic manipulation of histone modification enzymes for metastasis treatment. A comprehensive understanding of histone modification in metastasis will not only provide new insights into our knowledge of cancer progression and metastasis, but also offer a novel approach for the development of innovative therapeutic strategies

Association Between Physical Activity and Prevalence/Mortality of Non-Alcoholic Fatty Liver Disease in Different Socioeconomic Settings

Objectives: We aimed to investigate the effect of physical activity (PA) on non-alcoholic fatty liver disease (NAFLD) prevalence and long-term survival, particularly in some specific population such as those with different socioeconomic status (SES).Methods: Multivariate regression and interaction analyses were conducted to deal with confounders and interacting factors.Results: Active PA was associated with lower prevalence of NAFLD in both cohorts. Individuals with active-PA had better long-term survival compared to those with inactive-PA in both cohorts, and the results were only statistically significant in NAFLD defined by US fatty liver index (USFLI). We found clear evidence that the beneficial role of PA was more obvious in individuals with better SES, and the statistical significances were presented in both two hepatic steatosis index (HSI)-NAFLD cohorts from the NHANES III and NHANES 1999–2014. Results were consistent in all sensitivity analyses.Conclusion: We demonstrated the importance of PA in decrease the prevalence and mortality of NAFLD, and highlights the need for improving SES simultaneously to increase the protective effect of PA

Staged characteristics analysis of a severe convection over the Dongting Lake area based on dual-polarization Doppler weather radar data

The multi-cell storm stage and squall line stage of a severe convective weather process over the Dongting Lake on 15 May 2021 in this study are analyzed mainly based on S-band dual-polarized doppler weather radar data. The study focuses on the analysis of the supercell storm I2 in the multi-cell storm stage. The results are as follows. (1) During the initial period of the I2, the strong echo area (the horizontal reflectivity factor, ZH > 55 dBz) and the differential reflectivity factor (ZDR) column (ZDR > 2.5 dB) extend to Wet Blub Zero (WBZ) level, corresponding to the areas with large specific differential phase (KDP) (> 1.7 °·km-1) and large correlation coefficient (CC) (0.9-0.99). It indicates that during this period, the precipitation phase is dominated by water condensate mingled with large raindrops, and these supercooled raindrops provide hail embryos for the later hail development. (2) During the hail colliding-growth period of the I2, ZH intensity and height increase rapidly, and vertically integrated liquid water content (VIL) shows an obvious leap increase. The strong-echo center (ZH > 60 dBz) extends to the level of above -10 ℃. In the corresponding regions, the ZDR drops below 0, the ZDR column (ZDR> 2.5 dB) extends to the level of -10 ℃, CC drops, and a "hole" appears in the KDP value area. These indicate that the precipitation during this period is dominated by solid particles and these solid particles are in an increasing period. (3) During the mature hailfall period of the I2, the bottom of the ZH intensity center (ZH > 60 dBz) drops below the WBZ level and the CC is locally as low as 0.8. There are ZDR negative areas and KDP voids in the corresponding area. These means that the dragging effect of the falling hail further weakens the strength of the updraft, which means that the hail is about to land. Then comes the squall line stage. (4) Unlike the multi-cell storm stage, the squall line stage has anomalously large KDP values and ZDR values greater than 1. (5) Before the occurrence of extreme gales of the squall line stage, the areas with strong echo greater than 55 dBz and velocity larger than 27 m·s-1 extend below 1 km, and the KDP in the strong echo area is obviously large, corresponding to the strong downdraft. Besides, the strong precipitation dragging effect caused by the melting of descending precipitation particles intensifies the generation of extreme gales

Advance on risk assessment methods of multiple chemicals combined exposure and its enlightenment to the construction of relevant systems in China

People in the real world are exposed to multiple chemicals via multiple routes and co-exposure to multiple agents may induce joint effects, which draws extensive attention from the international community. Regulations of many countries oblige risk assessors to conduct cumulative risk assessments based on their own guidelines, findings of which provide the basis for scientific decision-making. By analyzing the method and frameworks of international risk assessment models of multiple chemicals, this paper explores the establishment of a risk assessment framework of multiple chemicals combined exposure to in food in China

Tracking sustainability: co-evolution of economic and ecological activities in the industrialization of the United Kingdom and China

The co-evolution of economic and ecological activities represents one of the fundamental challenges in the realm of sustainable development. This study on the word trends in mainstream newspapers from the UK and China reveals that both early-industrialised countries and latecomers follow three modes of economic and ecological co-evolution. First, both economic and ecological words demonstrate an S-shaped growth trajectory, and the mode underscores the importance of information propagation, whilst also highlighting the crucial role of self-organisation in the accept society. Second, the co-occurrence of these two type words exhibits a Z-shaped relationship: for two-thirds of the observed period, they display synergistic interactions, while the remaining time shows trade-offs. Lastly, the words related to ecological degradation follow M-shaped trajectories in parallel with economic growth, suggesting periodic disruptions and reconstructions in their interrelationships. Our findings contribute to a more nuanced understanding of the co-evolutionary mechanisms that govern collective behaviours in human society

Association between γ-glutamyl transferase and metabolic syndrome: A cross-sectional study of an adult population in Beijing

The relationship between liver enzymes and clustered components of metabolic syndrome (MetS) is explored and the predictive power of γ-glutamyl transferase (GGT) for the diagnosis of MetS in an adult population in Beijing is investigated. A total of 10,553 adults aged 20-65 years who underwent health examinations at Beijing Tongren Hospital in 2012 were enrolled in the study. Multivariate logistic regression analysis is conducted to determine the associations between the levels of various liver enzymes and clustered components of MetS. A receiver operating characteristic analysis is used to determine the optimal cut-off value of GGT for the diagnosis of MetS. A high level of GGT is found to be positively associated with clustered components of MetS in both men and women after adjusting for age, body mass index (BMI), history of alcoholic fatty liver, and the presence of taking anti-hypertensive, anti-dyslipidemic, and anti-diabetic drugs. Among all components of MetS, GGT is more predictive of triglyceride, and BMI. The area-under-the-curve values of GGT for discriminating MetS from normal metabolic status in men and women are 0.73 and 0.80, respectively. The optimal cut-off value of GGT for men is 31.50 U/L, demonstrating a sensitivity of 74.00% and specificity of 62.00%. For women, it is 19.50 U/L (sensitivity 76.00% and specificity 70.00%). GGT is therefore recommended as a useful diagnostic marker for MetS, because the test is inexpensive, highly sensitive, and frequently encountered in clinical practice

Nanocontact Disorder in Nanoelectronics for Modulation of Light and Gas Sensitivities

To fabricate reliable nanoelectronics, whether by top-down or bottom-up processes, it is necessary to study the electrical properties of nanocontacts. The effect of nanocontact disorder on device properties has been discussed but not quantitatively studied. Here, by carefully analyzing the temperature dependence of device electrical characteristics and by inspecting them with a microscope, we investigated the Schottky contact and Mott\u27s variable-range-hopping resistances connected in parallel in the nanocontact. To interpret these parallel resistances, we proposed a model of Ti/TiOx in the interface between the metal electrodes and nanowires. The hopping resistance as well as the nanocontact disorder dominated the total device resistance for high-resistance devices, especially at low temperatures. Furthermore, we introduced nanocontact disorder to modulate the light and gas responsivities of the device; unexpectedly, it multiplied the sensitivities compared with the intrinsic sensitivity of the nanowires. Our results improve the collective understanding of electrical contacts to low-dimensional semiconductor devices and will aid performance optimization in future nanoelectronics