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Abstract Background A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA). Methods In order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. We then constructed protein–protein interaction networks to find 10 top ranked hub genes among differentially expressed mRNAs. Second, in order to explore the effectiveness of BMSCs and ADSCs on neural tissue-derived ECM materials for repairing PNI, sixty-eight rats were randomized into four groups: ANA group, ANA+BMSC group, ANA+ADSC group, and AUTO group. In the ANA+BMSC and ANA+ADSC groups, ADSCs/BMSCs were equally injected along the long axis of the 10-mm ANA. Then, we performed histological and functional assessments up to 12 weeks postoperatively. Results The results of flow cytometry and RT-PCR showed that ANA combined with BMSCs exhibited more significant immunomodulatory effects, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1β and tumor necrosis factor-alpha (TNF-α) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). ANA combined with ADSCs exhibited more pronounced features of pro-myelination and angiogenesis, as evidenced by the up-regulation of myelin-associated protein gene (MBP and MPZ) and angiogenesis-related factors (TGF-β, VEGF). Moreover, differentially expressed genes from whole transcriptome sequencing results further indicated that ANA loaded with BMSCs exhibited notable immunomodulatory effects and ANA loaded with ADSCs was more associated with angiogenesis, axonal growth, and myelin formation. Notably, ANA infused with BMSCs or ADSCs enhanced peripheral nerve regeneration and motor function recovery with no statistically significant differences. Conclusions This study revealed that both ANA combined with BMSCs and ADSCs enhance peripheral nerve regeneration and motor function recovery, but their biological characteristics (mainly including immunomodulatory effects, pro-vascular regenerative effects, and pro-myelin regenerative effects) and underlying molecular mechanisms in the process of repairing PNI in vivo are different, providing new insights into MSC therapy for peripheral nerve injury and its clinical translation.

Acanthopanax senticosus (Rupr. et Maxim.) Harms is a perennial shrub of the Acanthopanax genus in the Araliaceae family and has a high medicinal value. The application of zinc fertilizer can improve the yield and quality of medicinal materials. However, there are limited reports on approaches to increase the content of medicinal components in A. senticosus, hindering the improvement of its medicinal quality. In this study, A. senticosus was treated with 0.1% (LZn) and 0.4% (HZn) zinc sprayed on the leaf surface. The effects of zinc treatment on the medicinal components in the roots of A. senticosus were analyzed by comprehensive metabolomics and transcriptomics analyses. A total of 316 metabolites were detected, with a prevailing occurrence of terpenoids and phenylpropanoids. We identified metabolites related to the medicinal components that were upregulated after Zn treatment, including 43 terpenoids, 19 phenylpropanoids, eight phenols, and three flavonoids. Combining differential gene expression and K-means analysis, we found 95, 65, and 25 upregulated genes related to phenylpropanoid biosynthesis, terpenoid biosynthesis, and flavonoid biosynthesis, respectively. Under different concentrations of Zn treatment, the upregulated metabolite biosynthesis-related genes and differentially expressed transcription factors varied. Pearson correlation network analysis revealed significant correlations among terpenoids, phenylpropanoids, flavonoids biosynthetic genes, and several transcription factors (ERFs, WRKYs, bHLHs, NACs, and MYBs). This study lays the foundation for understanding the metabolic processes in response to varying levels of zinc foliar spray and provides a theoretical basis for enhancing the efficiency of zinc fertilizer utilization in A. senticosus.

To explore the effects of pulsed electric field treatment on the germination of Scutellaria baicalensis seeds and the growth of seedlings, this study used the response surface methodology to design the working parameters of the pulsed electric field and treated and cultured Scutellaria baicalensis seeds. The results showed that the pulsed electric field treatment was beneficial for the germination of Scutellaria baicalensis seeds, improving the metabolic activity and stress resistance of seedlings. When the pulsed electric field treatment’s parameters were 0.5 kV·cm−1, 120 μs, and 99 pulses, the germination potential of seeds was significantly increased by 29.25% and the germination index significantly increased by 20.65%, compared to the control. From 5th to 15th day, the activities of SOD, POD, and α-amylase in the seedlings, and the contents of Pro, soluble sugars, and soluble proteins were significantly increased, compared to the control. This study provides a theoretical basis for improving the germination and seedling growth of medicinal herbs such as Scutellaria baicalensis and their practical application in production.

In the present work, thermal exposure was performed on the 7B50-T7451 aluminium alloy friction stir welding (FSW) joints at different temperatures (150 °C, 175 °C and 220 °C) for 200 h. The results show that the microstructure and mechanical properties of as-welded joints along the thickness direction of the plate are heterogeneous. The hardness and strength of FSW joints decrease while the elongation continuously increases with increasing thermal exposure temperature. Compared with the base material, the joints present much higher hardening capacity which is further increased with increasing temperature. The precipitates in the heat-affected zone (HAZ) exhibit continuous coarsening and the precipitate distribution becomes broader as the temperature rises. The transformation from η′ phase to η phase is obvious at 220 °C. The weld nugget zone (WNZ) re-precipitates a large number of nano-scale η particles subjected to 200 h thermal exposure at 150 °C and re-precipitated η phase in WNZ of the double-sided joint has reached micron-sized at 175 °C and 220 °C. When exposed at different temperatures, all FSW joints show typical ductile fracture features. Fracture positions at different thermal exposure temperatures are inconsistent and this variation is closely related to different microstructural characteristics.

“Re-visits and drug renewal” is difficult for chronic disease patients during COVID-19 and will continue in the post-pandemic era. To overcome this dilemma, the scenario of chronic disease diagnosis and treatment systems was set, and an evolutionary game model participated by four stakeholder groups including physical medical institutions, medical service platforms, intelligent medical device providers, and chronic disease patients, was established. Ten possible evolutionary stabilization strategies (ESSs) with their mandatory conditions were found based on Lyapunov's first method. Taking cardiovascular and cerebrovascular diseases, the top 1 prevalent chronic disease, as a specific case context, and resorting to the MATLAB simulation, it is confirmed that several dual ESSs and four unique ESS circumstances exist, respectively, and the evolution direction is determined by initial conditions, while the evolution speed is determined by the values of the conditions based on the quantitative relations of benefits, costs, etc. Accordingly, four governance mechanisms were proposed. By their adjustment, the conditions along with their values can be interfered, and then the chronic disease diagnosis and treatment systems can be guided toward the desired direction, that is, toward the direction of countermeasure against the pandemic, government guidance, global trends of medical industry development, social welfare, and lifestyle innovation. The dilemma of “Re-visits and drug renewal” actually reflects the uneven distribution problem of qualified medical resources and the poor impact resistance capability of social medical service systems under mass public emergency. Human lifestyle even the way of working all over the world will get a spiral upgrade after experiencing COVID-19, such as consumption, and meeting, while medical habits react not so rapidly, especially for mid or aged chronic disease patients. We believe that telemedicine empowered by intelligent medical devices can benefit them and will be a global trend, governments and the four key stakeholders should act according to the governance mechanisms suggested here simultaneously toward novel social medical ecosystems for the post-pandemic era.

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.

The failure of strata with different strength under coal pillar in close distance coal seams has its particularity. Theoretical analysis, numerical simulation, and similar test were used to obtain the failure mechanism of the soft and hard stratification of floor strata under the boundary of wide coal pillar and make out the influence of the strata failure on roadway layout. It shows that the failure of the soft and hard stratification is not synchronous and with different failure forms. The deformation and plastic failure of the soft strata occurs at first; then the fracture of the main bearing hard stratum occurs. Based on the main bearing stratum unbalanced forces acted by upper and lower strata, the initial fracture position and broken blocks span were calculated by bending fracture mechanics model of ultimate span beam. The coal pillar side of the roadway under coal pillar forms “column-beam-column” superimposed structure. The roadway layout under coal pillar and under coal pillar boundary with close distance has large influence on the plastic extension of the “column-beam-column” superimposed structure and the broken of main bearing stratum. The influence of roadway arrangement in floor strata outside coal pillar is smaller than those under coal pillar. It is difficult to control the deformation of roadway surrounding rock if the roadway locates beneath the broken blocks of the main bearing stratum.

Acer L. species are well known as ornamental trees due to their colourful leaves in autumn season. Acer pictum subsp. mono (Maxim.) H. Ohashi (APM) and Acer tataricum subsp. ginnala (Maximowicz) Wesmael (ATG) form leaves with completely different colours in autumn, yellow and red, respectively. In response to this phenomenon, we investigated the metabolic regulation of APM and ATG in different seasons by combining metabolomics, ionomics, the antioxidant system and pigment content. The results showed that the process of senescence and discolouration exists in leaves of different Acer species, and the regulatory strategy shows species specificity. Compared with green leaves, the accumulation of primary metabolites in autumn leaves of APM was extensively depleted, chlorophyll content was decreased, and antioxidant enzymes and C6C3C6 type phenolic compounds synergistically enhanced the antioxidant capacity of plants to cope with senescence. Carotenoid content was raised, which together with phenolic compounds (chlorogenic acid, rutin) provides the leaves with a yellow colour. The response of chlorophyll and the antioxidant system in autumn leaves of ATG is consistent with that of APM, while sugar content increases. The increased anthocyanin content in autumn leaves of ATG explains the transition of leaves from green to the red colour, which may be accompanied by the combined effect of elements (Fe, Zn, Mn) and isoflavones. This study provides a reference for the study of colouration mechanism and seasonal adaptation in Acer L. species.

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts.Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF.Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a global epidemic afflicting 20–30% in the general population. The animal model of NAFLD available at the present are less clinically relevant. In this study. We aimed to establish a NAFLD model of rhesus monkeys and develop an ultrasonographic steatosis score (USS) system to grade hepatic steatosis in this model. Methods We performed hepatic ultrasonography and blood biochemical tests on 86 rhesus monkeys with and without metabolic syndrome (MetS), among which 45 animals were further assessed by histopathological analysis. Results The liver histological features of rhesus monkeys NAFLD were resemble to those of NAFLD patients. There was a close correlation between the histological steatosis grade and the USS (Spearman’s coefficient, 0.705, p

Hyperinsulinemia can precede the development of insulin resistance. Here the authors identify a PKD2 mutation that leads to hyperinsulinemia and insulin resistance in Rhesus monkey and show that PKD2 deficiency promotes beta cell insulin secretion by activating L-type Ca2+ channels.

In order to satisfy the further improvement of new communication equipment, filling the ridge grooves on side walls with fillers is the effective method to improve the quality of double-ridged rectangular bent tube in H-typed rotary draw bending. However, how to choose appropriate material filling in ridge grooves to reduce deformation more effectively is a critical issue. Therefore based on the reliable FE models of H-typed rotary draw bending and twice-springback of double-ridged rectangular tube with fillers with different material parameters, a selection criterion of the material of filler to minimize the cross-sectional deformation of bent tube was studied. The selection criterion is that only the height size accuracy of filler should be made sure to be consistent with that of the ridge groove. The strength coefficient K of filler should be considered firstly, and the larger K can reduce the deformation more effectively. The yield strength σ _s and hardening exponent n can be considered secondly, and filler with higher σ _s or smaller n can be selected as far as possible. Elastic modulus E may not be taken into account. The reliability of this selection criterion is verified by using 65Mn spring steel filler.

Moso bamboo has large potential to alleviate global warming through carbon sequestration. Since soil respiration (Rs) is a major source of CO2 emissions, we analyzed the dynamics of soil respiration (Rs) and its relation to environmental factors in a Moso bamboo (Phllostachys heterocycla cv. pubescens) forest to identify the relative importance of biotic and abiotic drivers of respiration. Annual average Rs was 44.07 t CO2 ha−1 a−1. Rs correlated significantly with soil temperature (P

Age is a fundamental social dimension and a youthful appearance is of importance for many individuals, perhaps because it is a relevant predictor of aspects of health, facial attractiveness and general well-being. We recently showed that facial contrast—the color and luminance difference between facial features and the surrounding skin—is age-related and a cue to age perception of Caucasian women. Specifically, aspects of facial contrast decrease with age in Caucasian women, and Caucasian female faces with higher contrast look younger (Porcheron et al., 2013). Here we investigated faces of other ethnic groups and raters of other cultures to see whether facial contrast is a cross-cultural youth-related attribute. Using large sets of full face color photographs of Chinese, Latin American and black South African women aged 20–80, we measured the luminance and color contrast between the facial features (the eyes, the lips, and the brows) and the surrounding skin. Most aspects of facial contrast that were previously found to decrease with age in Caucasian women were also found to decrease with age in the other ethnic groups. Though the overall pattern of changes with age was common to all women, there were also some differences between the groups. In a separate study, individual faces of the 4 ethnic groups were perceived younger by French and Chinese participants when the aspects of facial contrast that vary with age in the majority of faces were artificially increased, but older when they were artificially decreased. Altogether these findings indicate that facial contrast is a cross-cultural cue to youthfulness. Because cosmetics were shown to enhance facial contrast, this work provides some support for the notion that a universal function of cosmetics is to make female faces look younger.

In proliferating cells, where most Polycomb repressive complex 2 (PRC2) studies have been performed, gene repression is associated with PRC2 trimethylation of H3K27 (H3K27me3). However, it is uncertain whether PRC2 writing of H3K27me3 is mechanistically required for gene silencing. Here, we studied PRC2 function in postnatal mouse cardiomyocytes, where the paucity of cell division obviates bulk H3K27me3 rewriting after each cell cycle. EED (embryonic ectoderm development) inactivation in the postnatal heart (EedCKO) caused lethal dilated cardiomyopathy. Surprisingly, gene upregulation in EedCKO was not coupled with loss of H3K27me3. Rather, the activating histone mark H3K27ac increased. EED interacted with histone deacetylases (HDACs) and enhanced their catalytic activity. HDAC overexpression normalized EedCKO heart function and expression of derepressed genes. Our results uncovered a non-canonical, H3K27me3-independent EED repressive mechanism that is essential for normal heart function. Our results further illustrate that organ dysfunction due to epigenetic dysregulation can be corrected by epigenetic rewiring.