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Abstract Obesity-induced β cell dysfunction contributes to the onset of type 2 diabetes. Nevertheless, elucidating epigenetic mechanisms underlying islet dysfunction at single cell level remains challenging. Here we profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets from lean or obese mice. Our study identifies distinct gene signatures and enhancer states correlating with β cell dysfunction trajectory. Intriguingly, while many metabolic stress-induced genes exhibit concordant changes in both H3K4me1 and H3K27ac at their enhancers, expression changes of specific subsets are solely attributable to either H3K4me1 or H3K27ac dynamics. Remarkably, a subset of H3K4me1+H3K27ac- primed enhancers prevalent in lean β cells and occupied by FoxA2 are largely absent after metabolic stress. Lastly, cell-cell communication analysis identified the nerve growth factor (NGF) as protective paracrine signaling for β cells through repressing ER stress. In summary, our findings define the heterogeneous enhancer responses to metabolic challenges in individual β cells.

The ultra-high pressure-assisted extraction (UHPE) of total phenols from Eucommia ulmoides leaves (TPEU) was optimized and its antioxidant activity on Eucommia ulmoides seed oil was studied. The effects of UHPE pressure, UHPE time, and ethanol concentration on the extraction yield of TPEU were examined by response surface methodology. In addition, TPEU was added to Eucommia ulmoides seed oil, and the effects of TPEU on the antioxidant activity (acid value, peroxide value) of Eucommia ulmoides seed oil during storage were studied. The optimal UHPE conditions were as follows: UHPE pressure, 406 MPa; UHPE time, 8.3 min; and ethanol concentration, 60.2%. Under these UHPE conditions, the yield of TPEU was 7.58%. TPEU had a good antioxidant effect when the TPEU content was 0.06%. The antioxidant effect of TPEU was lower than that of BHA. Both TPEU and BHA have a synergistic effect.

Objective: This study aimed to compare the effects of different sterilization on the quality of fermented jujube juice. Methods: The effects of cold plasma sterilization (CPS) and pulsed strong light sterilization (PLS) on the quality of jujube juice before and after fermentation were studied, with high pressure sterilization (SA) jujube juice as the control. Results: The contents of total sugar, reducing sugar and soluble solid in jujube juice before and after fermentation by CPS treatment were significantly higher than those of the other two sterilization methods, and the contents of total sugar, reducing sugar and soluble solid in jujube juice after fermentation were 1.7 mg/L, 1.64 mg/L and 12.4%, respectively. With SA treatment, the total phenol content of jujube juice before and after fermentation was the lowest, and the total phenol content of jujube juice after fermentation was only 2.19 mg/L. The color of jujube juice treated by PLS changed minimally before and after fermentation. The viable count of Lactobacillus plantarum in jujube juice treated by CPS, PLS and SA were more than 6.48 lg（CFU/mL） after 48 h fermentation by L. plantarum, and the viable count of L. plantarum in jujube juice was the highest 6.63 lg(CFU/mL) after PLS treatment. Conclusion: Non-thermal sterilization (especially PLS) has little effect on the quality of fermented jujube juice and could be applied in the processing of fermented jujube juice.

Recently, seismic inversion has made extensive use of supervised learning methods. The traditional deep learning inversion network can utilize the temporal correlation in the vertical direction. Still, it does not consider the spatial correlation in the horizontal direction of seismic data. Each seismic trace is inverted independently, which leads to noise and large geological variations in seismic data, thus leading to lateral discontinuity. Given this, the proposed method uses the spatial correlation of the seismic data in the horizontal direction. In the network training stage, several seismic traces centered on the well-side trace and the corresponding logging curve form a set of training sample pairs for training, to enhance the lateral continuity and anti-noise performance. Additionally, Attention U-Net is introduced in acoustic impedance inversion. Attention U-Net adds attention gate (AG) model to the skip connection between the encoding and decoding layers of the U-Net network, which can give different weights to different features, so the model can focus on the features related to the inversion task and avoid the influence of irrelevant data and noise during the inversion process. The performance of the proposed method is evaluated using the Marmousi2 model and the SEAM model and compared with other methods. The experimental results show that the proposed method has the advantages of high accuracy of acoustic impedance value inversion, good transverse continuity of inversion results, and strong anti-noise performance.

The impact of the annual solar eclipse, starting on 21st June 2020, attributable to surface ozone concentration (O3) has been investigated in this study. To estimate the influence of the solar eclipse on O3 better, the variations of one reaction precursor of ozone production [nitrogen dioxide (NO2)], coupled with the meteorological factors (including Total Solar Irradiance (TSI), Temperature (T), and Relative Humidity (RH)), were analyzed in Yunnan Province, China. The results show observed O3 decreases from the beginning of the eclipse, reaching its minimum value when the eclipse left Yunnan province. During the period of the solar eclipse, the O3 decrease lasted for 20 h with a reduction of more than 40%. The reduction of TSI lasted for 5 h with a maximum at -90%. Simultaneously, the temperature decreased but the relative humidity increased during the reduction in solar radiation. O3 exhibits a significantly positive correlation with temperature and a negative correlation with relative humidity. However, NO2 did not show a clear response with changes lasting for 4 h. O3 and NO2 show a negative correlation. The influence of CO on O3 is minor except for Kunming. Thus, O3 in seriously polluted cities is more sensitive to NO2 and CO during the eclipse, such as in Kunming.

The possibility of accomplishing sustainable objectives is largely connected to the management and flourishing of an organizational system which keeps human capital engaged and committed. Our study investigated the association of inspirational leadership and innovative communication with employee engagement and commitment under the lens of leader member exchange theory. Specifically, we emphasized the mediating role of mutual trust in connection to social sustainability facets. A survey of data from employees in the manufacturing sector of Yunnan, China was utilized to test the hypothesized model. The study findings reported a significant association and came to the conclusion that a leader’s inspirational behavior coupled with innovative communication is a significant predictor of engagement and commitment in socially sustainable organizations. Moreover, mutual trust significantly mediated the relationship of innovative communication and inspirational leadership with employee engagement and commitment reaching the social perspective of sustainability. The current study added to the literature of sustainable organization by pointing out the social dimensions of sustainability.

β cell dysfunction and failure are driving forces of type 2 diabetes mellitus (T2DM) pathogenesis. Investigating the underlying mechanisms of β cell dysfunction may provide novel targets for the development of next generation therapy for T2DM. Epigenetics is the study of gene expression changes that do not involve DNA sequence changes, including DNA methylation, histone modification, and non-coding RNAs. Specific epigenetic signatures at all levels, including DNA methylation, chromatin accessibility, histone modification, and non-coding RNA, define β cell identity during embryonic development, postnatal maturation, and maintain β cell function at homeostatic states. During progression of T2DM, overnutrition, inflammation, and other types of stress collaboratively disrupt the homeostatic epigenetic signatures in β cells. Dysregulated epigenetic signatures, and the associating transcriptional outputs, lead to the dysfunction and eventual loss of β cells. In this review, we will summarize recent discoveries of the establishment and disruption of β cell-specific epigenetic signatures, and discuss the potential implication in therapeutic development.

Summary: PGC1α is a pleiotropic co-factor that affects angiogenesis, mitochondrial biogenesis, and oxidative muscle remodeling via its association with multiple transcription factors, including the master oxidative nuclear receptor ERRγ. To decipher their epistatic relationship, we explored ERRγ gain of function in muscle-specific PGC1α/β double-knockout (PKO) mice. ERRγ-driven transcriptional reprogramming largely rescues muscle damage and improves muscle function in PKO mice, inducing mitochondrial biogenesis, antioxidant defense, angiogenesis, and a glycolytic-to-oxidative fiber-type transformation independent of PGC1α/β. Furthermore, in combination with voluntary exercise, ERRγ gain of function largely restores mitochondrial energetic deficits in PKO muscle, resulting in a 5-fold increase in running performance. Thus, while PGC1s can interact with multiple transcription factors, these findings implicate ERRs as the major molecular target through which PGC1α/β regulates both innate and adaptive energy metabolism. : Fan et al. demonstrate that ERRγ improves mitochondrial energy metabolism in PGC1α/β-deficient muscle through its direct activation of target genes. Such ERRγ-induced effects are further boosted in combination with exercise training, suggesting ERRs are the major transcriptional modulator through which PGC1α/β regulates both innate and adaptive energy metabolism. Keywords: ERR, estrogen related receptor, PGC1, mitochondria, muscle, exercise, vasculature, fatty acid oxidation, glycolysis, muscle damage

Resveratrol in Polygonum cuspidatum is a β-glycoside, which can be hydrolyzed to resveratrol by β-glucosidase. it is an efficient production process to degrade polydatin from Polygonum cuspidatum extract by immobilized β-glucosidase. It is of great significance to explore suitable immobilization conditions to improve the catalytic efficiency and reusability of β-glucosidase for polydatin degradation and cost reduction. In this paper, the recombinant Escherichia coli bgl2238, which was screened and constructed from corn soil of Heilongjiang Province in the early laboratory, was immobilized by chitosan adsorption and glutaraldehyde crosslinking. The preparation conditions and immobilization process of bgl2238 were determined by single factor method: the optimal crosslinking time was 1 h, the optimal crosslinking temperature was 20 °C, the recovery rate of enzyme activity of bgl2238 was 87 %, and the enzyme activity was 859.65 mU/g. The optimum temperature of the immobilized bgl2238 is 50 °C, which is 6 °C higher than that of the free bgl2238, and the temperature stability and pH stability are improved. After six consecutive hydrolysis of Polygonum cuspidatum, the degradation rate of polydatin is still over 70 %, which proves that the immobilized bgl2238 has good reusability. This will be helpful to evaluate the application prospect of β - glucosidase immobilized in this system and determine the best conditions for its production.

The module partition is the key step and foundation of module design. Firstly,the fuzzy similitude matrix between the parts is constructed according to the analysis of the functional correlation,geometric correlation,physics correlation among parts. Secondly,the partitioned modules are evaluated by high cohesion and low coupling. Finally,the products is classified by using the simulated annealing and genetic algorithm（ SAGA）,which is proved to be an efficient and rational way for module partition through the reducer instance.

Neural progenitor cells (NPCs) are multipotent cells that can self-renew and differentiate into neurons and glial cells. However, mechanisms that control their fate decisions are poorly understood. Here, we show that Smek1, a regulatory subunit of the serine/threonine protein phosphatase PP4, promotes neuronal differentiation and suppresses the proliferative capacity of NPCs. We identify the cell polarity protein Par3, a negative regulator of neuronal differentiation, as a Smek1 substrate and demonstrate that Smek1 suppresses its activity. We also show that Smek1, which is predominantly nuclear in NPCs, is excluded from the nucleus during mitosis, allowing it to interact with cortical/cytoplasmic Par3 and mediate its dephosphorylation by the catalytic subunit PP4c. These results identify the PP4/Smek1 complex as a key regulator of neurogenesis.

For problems that it was difficult to maintain, communication distance and reliability were constrained of traditional monitoring system of fully mechanized excavation face with communication method of laying dedicated cable channels based and wireless communication supplemented, monitoring system of fully mechanized excavation face based on power line carrier was proposed. The system uses existing coal power cables to communicate, without laying dedicated communication cables, which greatly reduces system cost and decreases problems of communication interruption due to link failure, realizes stable and reliable monitoring of fully mechanized excavation face.

Model organisms are instrumental substitutes for human studies to expedite basic, translational, and clinical research. Despite their indispensable role in mechanistic investigation and drug development, molecular congruence of animal models to humans has long been questioned and debated. Little effort has been made for an objective quantification and mechanistic exploration of a model organisms resemblance to humans in terms of molecular response under disease or drug treatment. We hereby propose a framework, namely Congruence Analysis for Model Organisms (CAMO), for transcriptomic response analysis by developing threshold-free differential expression analysis, quantitative concordance/discordance scores incorporating data variabilities, pathway-centric downstream investigation, knowledge retrieval by text mining, and topological gene module detection for hypothesis generation. Instead of a genome-wide vague and dichotomous answer of poorly or greatly mimicking humans, CAMO assists researchers to numerically quantify congruence, to dissect true cross-species differences from unwanted biological or cohort variabilities, and to visually identify molecular mechanisms and pathway subnetworks that are best or least mimicked by model organisms, which altogether provides foundations for hypothesis generation and subsequent translational decisions.

Glutamine synthetase (GS) catalyzes de novo synthesis of glutamine that facilitates cancer cell growth. In the liver, GS functions next to the urea cycle to remove ammonia waste. As a dysregulated urea cycle is implicated in cancer development, the impact of GS's ammonia clearance function has not been explored in cancer. Here, we show that oncogenic activation of β-catenin (encoded by CTNNB1) led to a decreased urea cycle and elevated ammonia waste burden. While β-catenin induced the expression of GS, which is thought to be cancer promoting, surprisingly, genetic ablation of hepatic GS accelerated the onset of liver tumors in several mouse models that involved β-catenin activation. Mechanistically, GS ablation exacerbated hyperammonemia and facilitated the production of glutamate-derived nonessential amino acids, which subsequently stimulated mechanistic target of rapamycin complex 1 (mTORC1). Pharmacological and genetic inhibition of mTORC1 and glutamic transaminases suppressed tumorigenesis facilitated by GS ablation. While patients with hepatocellular carcinoma, especially those with CTNNB1 mutations, have an overall defective urea cycle and increased expression of GS, there exists a subset of patients with low GS expression that is associated with mTORC1 hyperactivation. Therefore, GS-mediated ammonia clearance serves as a tumor-suppressing mechanism in livers that harbor β-catenin activation mutations and a compromised urea cycle.