Enhancer of zeste homolog 2 (EZH2) is enzymatic catalytic subunit of polycomb repressive complex 2 (PRC2) that can alter downstream target genes expression by trimethylation of Lys-27 in histone 3 ...(H3K27me3). EZH2 could also regulate gene expression in ways besides H3K27me3. Functions of EZH2 in cells proliferation, apoptosis, and senescence have been identified. Its important roles in the pathophysiology of cancer are now widely concerned. Therefore, targeting EZH2 for cancer therapy is a hot research topic now and different types of EZH2 inhibitors have been developed. In this review, we summarize the structure and action modes of EZH2, focusing on up-to-date findings regarding the role of EZH2 in cancer initiation, progression, metastasis, metabolism, drug resistance, and immunity regulation. Furtherly, we highlight the advance of targeting EZH2 therapies in experiments and clinical studies.
The
maximum cardinality
and
maximum weight matching
problems can be solved in
Õ
(
m
√
n
) time, a bound that has resisted improvement despite decades of research. (Here
m
and
n
are the number of ...edges and vertices.) In this article, we demonstrate that this “
m
√
n
barrier” can be bypassed by approximation. For any
ε
> 0, we give an algorithm that computes a (1 −
ε
)-approximate maximum weight matching in
O
(
mε
−1
log
ε
−1
) time, that is, optimal
linear time
for any fixed
ε
. Our algorithm is dramatically simpler than the best exact maximum weight matching algorithms on general graphs and should be appealing in all applications that can tolerate a negligible relative error.
With the increasing demand for electricity, overheating has gradually become a common problem for power transformers. However, the imperfect traditional monitoring method fails to detect the whole ...transformer in real time, which affects the safe and economical operation of the transformer. This paper was the first research utilizing a distributed optical fiber sensing system inside a running 35 kV power transformer to realize the persistent temperature monitoring of the full region. The detection accuracy of the designed winding composite sensors was also proven feasible for actual monitoring by temperature-rise tests. The hotspots were persistently traced, fluctuating at 83 %~88 %, 84 %~89 %, and 85 %~90 % of the high voltage winding height for phase A, B, and C of the 35 KV three-phase transformer, respectively. Moreover, there are multiple typical models proposed by scientists to delineate the thermodynamic behaviors of power transformers, and the hottest-spot temperature (HST) could be visualized precisely through them. In the article, the construction of four models (IEC, Swift, Susa, and IEEE models) and their comparison with the HST data from the optical fiber sensor were presented, which provided a scientific basis for seeking superior thermodynamic models. According to the evaluation of the results, the Susa model was eventually selected, which could better describe the dynamic thermal behaviors of power transformers. (RMSE was 3.0776).
This study examines how the level of concreteness and abstraction of climate change imagery influences people’s responses via emotional valence, and how such effect is moderated by people’s visual ...literacy. Findings show that concrete images promote negative feelings, which subsequently reduce people’s perceived distance to climate change, and encourage concern and behavioral intention. Less visually literate people are more influenced by the visuals’ effect and are more motivated by concrete images. Our study integrates theoretical perspectives from construal level, emotional valence, and visual literacy, while also offering practical advice regarding how to effectively visualize climate change to engage a wide audience.
Food self-sufficiency in a large country with 1.4 billion people is very important for the Chinese government, especially in the context of COVID-19 and the Russian-Ukrainian conflict. The objective ...of this paper is to explore the spatial-temporal evolution and driving factors of non-grain production in thirteen major grain-producing provinces in China, which account for more than 75% of China's grain production, using 2011-2020 prefecture-level statistics. In the present study, the research methodology included GIS spatial analysis, hot spot analysis, and spatial Durbin model (SDM). The findings of this study are as follows: (1) The regions with a higher level of non-grain production were mainly concentrated in the central and western regions of Inner Mongolia, the middle and lower reaches of Yangtze River and Sichuan, while the regions with a low level of non-grain production were mainly distributed in the Northeast Plain. The regions with a higher proportion of grain production to the national total grain production were concentrated in the Northeast Plain, the North China Plain, and the Middle and Lower Yangtze River Plain of China. The hot spot regions with changes in non-grain production levels were mainly distributed in the Sichuan region and Alashan League City in Inner Mongolia, and the cold spot regions were mainly distributed in Hebei, Shandong, Henan, and other regions. (2) An analysis of the SDM indicated that the average air temperature among the natural environment factors, the ratio of the sum of gross secondary and tertiary industries to GDP, the ratio of gross primary industry to the GDP of economic development level, the urbanization rate of social development, and the difference in disposable income per capita between urban and rural residents of the urban-rural gap showed positive spatial spillover effects. The grain yield per unit of grain crop sown area of grain production resource endowment, the total population of social development, and the area sown to grain crops per capita of grain production resource endowment all showed negative spatial spillover effects. The research results of this paper can provide a reference for the country to carry out the governance of non-grain production and provide a reference for China's food security guarantee.
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral ...organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
During neonatal development, sensory cortices generate spontaneous activity patterns shaped by both sensory experience and intrinsic influences. How these patterns contribute to the assembly of ...neuronal circuits is not clearly understood. Using longitudinal in vivo calcium imaging in un-anesthetized mouse pups, we show that spatially segregated functional assemblies composed of interneurons and pyramidal cells are prominent in the somatosensory cortex by postnatal day (P) 7. Both reduction of GABA release and synaptic inputs onto pyramidal cells erode the emergence of functional topography, leading to increased network synchrony. This aberrant pattern effectively blocks interneuron apoptosis, causing increased survival of parvalbumin and somatostatin interneurons. Furthermore, the effect of GABA on apoptosis is mediated by inputs from medial ganglionic eminence (MGE)-derived but not caudal ganglionic eminence (CGE)-derived interneurons. These findings indicate that immature MGE interneurons are fundamental for shaping GABA-driven activity patterns that balance the number of interneurons integrating into maturing cortical networks.
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•GABA limits MGE-cIN participation in synchronous network events during development•Synaptic GABA regulates the emergence of interneuron-pyramidal cell assemblies•GABAergic restriction of pyramidal cell activity is required for MGE-cIN apoptosis•GABAAγ2-containing GABAA receptors are essential for interneuron apoptosis
Duan, Che, Chu et al. use genetic tools and in vivo imaging to show that cortical GABAergic signaling restricts functional assemblies and enables developmental apoptosis of MGE interneurons, balancing the number of interneurons integrating into maturing cortical networks.
The Role of Autophagy in Osteoarthritis Duan, Ran; Xie, Hui; Liu, Zheng-Zhao
Frontiers in cell and developmental biology,
11/2020, Letnik:
8
Journal Article
Recenzirano
Odprti dostop
Chondrocytes are the only cell type in normal cartilage. The pathological changes of osteoarthritis (OA) mostly revolve around the apoptosis and dysfunction of chondrocytes. Autophagy, as an ...intracellular degradation system that maintains the steady state of energy metabolism in cells, has been shown to restore the function of damaged chondrocytes, alleviating the occurrence and progression of OA. In this review, we explored the relationship between autophagy and OA and the key molecules of autophagy pathway that regulate the progression of OA, providing new ideas for OA treatment by targeting autophagy.
The developmental journey of cortical interneurons encounters several activity-dependent milestones. During the early postnatal period in developing mice, GABAergic neurons are transient preferential ...recipients of thalamic inputs and undergo activity-dependent migration arrest, wiring, and programmed cell-death. Despite their importance for the emergence of sensory experience and the role of activity in their integration into cortical networks, the collective dynamics of GABAergic neurons during that neonatal period remain unknown. Here, we study coordinated activity in GABAergic cells of the mouse barrel cortex using in vivo calcium imaging. We uncover a transient structure in GABAergic population dynamics that disappears in a sensory-dependent process. Its building blocks are anatomically clustered GABAergic assemblies mostly composed by prospective parvalbumin-expressing cells. These progressively widen their territories until forming a uniform perisomatic GABAergic network. Such transient patterning of GABAergic activity is a functional scaffold that links the cortex to the external world prior to active exploration.
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•In the developing barrel cortex, GABAergic neurons form functional assemblies•Prospective parvalbumin interneurons segregate into spatially clustered assemblies•Somatostatin interneurons display broadly correlated firing•GABA assemblies are regulated by sensory inputs
Using in vivo imaging in the barrel cortex, Modol et al. show that prospective parvalbumin interneurons form patches of correlated activity that merge during postnatal development. These assemblies are regulated by whisker inputs and altered by sensory deprivation.
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