BMSCs-derived exosomes inhibit macrophage/microglia pyroptosis by increasing autophagy through the miR-21a-5p/PELI1 axis in spinal cord injury.

Spinal cord injury (SCI) results in a diverse range of disabilities and lacks effective treatment options. In recent years, exosomes derived from bone mesenchymal stem cells (BMSCs) have emerged as a promising cell-free therapeutic approach for treating ischemic brain injury and other inflammatory conditions. Macrophage/microglial pyroptosis has been identified as a contributing factor to neuroinflammation following SCI. The therapeutic potential of BMSC-derived exosomes in macrophage/microglia pyroptosis-induced neuroinflammation, however, has to be determined. Our findings demonstrate that exosomes derived from BMSCs can enhance motor function recovery and mitigate neuroinflammation subsequent to SCI by upregulating the expression of autophagy-related proteins and inhibiting the activation of NLRP3 inflammasomes in macrophage/microglia. Moreover, miR-21a-5p is markedly increased in BMSCs-derived exosomes, and knocking down miR-21a-5p in BMSCs-derived exosomes eliminates the beneficial effects of administration; upregulation of miR-21a-5p in BMSCs-derived exosomes enhances the beneficial effects of administration. Mechanistically, miR-21a-5p positively regulates the autophagy of macrophage/microglia by reducing PELI1 expression, which in turn inhibits their pyroptosis. This research provides novel evidence that exosomes derived from BMSCs can effectively suppress macrophage/microglia pyroptosis through the miR-21a-5p/PELI1 axis-mediated autophagy pathway, ultimately facilitating functional restoration following SCI. In particular, our constructed miR-21a-5p overexpression exosomes greatly improved the efficacy of BMSCs-derived exosomes in treating spinal cord injury. These results establish a foundation for the prospective utilization of exosomes derived from BMSCs as a novel biological intervention for spinal cord injury.

Medical Image Fusion Based on Local Saliency Energy and Multi-scale Fractal Dimension.

BACKGROUND: At present, there are some problems in multimodal medical image fusion, such as texture detail loss, leading to edge contour blurring and image energy loss, leading to contrast reduction. OBJECTIVE: To solve these problems and obtain higher-quality fusion images, this study proposes an image fusion method based on local saliency energy and multi-scale fractal dimension. METHODS: First, by using a non-subsampled contourlet transform, the medical image was divided into 4 layers of high-pass subbands and 1 layer of low-pass subband. Second, in order to fuse the high-pass subbands of layers 2 to 4, the fusion rules based on a multi-scale morphological gradient and an activity measure were used as external stimuli in pulse coupled neural network. Third, a fusion rule based on the improved multi-scale fractal dimension and new local saliency energy was proposed, respectively, for the low-pass subband and the 1st closest to the low-pass subband. Layerhigh pass sub-bands were fused. Lastly, the fused image was created by performing the inverse non-subsampled contourlet transform on the fused sub-bands. RESULTS: On three multimodal medical image datasets, the proposed method was compared with 7 other fusion methods using 5 common objective evaluation metrics. CONCLUSION: Experiments showed that this method can protect the contrast and edge of fusion image well and has strong competitiveness in both subjective and objective evaluation.

Plant community diversity alters the response of ecosystem multifunctionality to multiple global change factors.

Biodiversity is considered important to the mitigation of global change impacts on ecosystem multifunctionality in terrestrial ecosystems. However, potential mechanisms through which biodiversity maintains ecosystem multifunctionality under global change remain unclear. We grew 132 plant communities with two levels of plant diversity, crossed with treatments based on 10 global change factors (nitrogen deposition, soil salinity, drought, plant invasion, simulated grazing, oil pollution, plastics pollution, antibiotics pollution, heavy metal pollution, and pesticide pollution). All global change factors negatively impacted ecosystem multifunctionality, but negative impacts were stronger in high compared with low diversity plant communities. We explored potential mechanisms for this unexpected result, finding that the inhibition of selection effects (i.e., selection for plant species associated with high ecosystem functioning) contributed to sensitivity of ecosystem multifunctionality to global change. Specifically, global change factors decreased the abundance of novel functional plants (i.e., legumes) in high but not low diversity plant communities. The negative impacts of global change on ecosystem multifunctionality were also mediated by increased relative abundance of fungal plant pathogens (identified from metabarcoding of soil samples) and their negative relationship with the abundance of novel functional plants. Taken together, our experiment highlights the importance of protecting high diversity plant communities and legumes, and managing fungal pathogens, to the maintenance of ecosystem multifunctionality in the face of complex global change.

Ubiquitin-proteasome system-mediated ubiquitination modification patterns and characterization of tumor microenvironment infiltration, stemness and cellular senescence in low-grade glioma.

The Ubiquitin-proteasome system (UPS) performs a crucial role in immune activation and tumorigenesis. Nevertheless, the comprehensive role of the ubiquitin-proteasome system in the low-grade glioma (LGG) tumor microenvironment (TME) remains unknown. Ubiquitination modification patterns in LGG patients and corresponding characteristics of tumor immune traits, CSC stemness, and cellular senescence were evaluated via a comprehensive analysis of 20 ubiquitination modification regulators. For quantification of the ubiquitination modification status of individual patients, the UM-score was constructed and associated with TME characteristics, clinical features, cancer stem cell stemness, cellular senescence, prognosis, and immunotherapy efficacy. We identified that alterations in multiple ubiquitination regulators are linked to patient survival and the shaping of the tumor microenvironment. We found two different styles of ubiquitination modification in patients with low-grade glioma (immune-inflamed differentiation and immune-exclude dedifferentiation), characterized by high and low UM-score, and the two regulatory patterns of ubiquitination modification on immunity, stemness feature, and cellular senescence. We demonstrate that the UM-score could forecast the subtype of LGG, the immunologic infiltration traits, the biological process, the stemness feature, and the cellular senescence trait. Notably, the UM-score was related to immunotherapeutic efficacy, implying that modifying ubiquitination modification patterns by targeting ubiquitination modification regulators or ubiquitination modification pattern signature genes to reverse unfavorable TME properties will provide new insights into cancer immunotherapy. This research indicated that the ubiquitin-proteasome system is crucial in the formation of TME complexity and multiformity. The UM-score can determine ubiquitination modification status in individual patients, bringing about more personalized and effective immunotherapeutic tactics.

Tocilizumab attenuates acute lung injury in rats with sepsis by regulating S100A12/NLRP3.

OBJECTIVE: To investigate the mechanism of Tocilizumab (TCZ) in attenuating acute lung injury in rats with sepsis by regulating the S100A12/NLRP3 axis. METHODS: A rat model of sepsis was constructed using cecal ligation and puncture (CLP). Rats were treated with TCZ, and their lung tissue was collected. H&E staining was used to detect pathologic damage to lung tissue, and lung wet/dry (W/D) weight ratio was measured to assess pulmonary edema. Lipid oxidation assay and superoxide dismutase (SOD) activity assay kits were used to measure malondialdehyde (MDA) and SOD levels. Primary rat pulmonary microvascular endothelial cells (MPVECs) were treated with lipopolysaccharide (LPS) to construct a rat model of sepsis, which was then treated with TCZ. The mRNA and protein expressions of S100A12/NLRP3 were detected by qRT-PCR and western blot, respectively. S100A12 knockdown and overexpression plasmids, and NLRP3 knockdown plasmids were constructed and transfected into sepsis cells to intervene in the levels of S100A12/NLRP3. The apoptosis rate was detected by apoptosis assay. The levels of IL-6, TNF-α, and IL-10 in cells and tissues were analyzed by ELISA. RESULTS: Compared to the Sham group, the CLP group had increased W/D weight ratio of lung tissue, IL-6, TNF-α, and MDA levels, lowered IL-10 and SOD levels, and more severe tissue damage (all P<0.05). After TCZ treatment, the above indicators were improved. The expressions of S100A12/NLRP3 cells were increased in LPS-induced MPVECs, but decreased after TCZ treatment. LPS induced apoptosis, but TCZ reduced the apoptosis, weakened the secretion levels of IL-6 and TNF-α, and enhanced IL-10 secretion levels. Transfection to cause the overexpression of S100A12 or NLRP3 plasmid partially counteracted the effect of TCZ. Knockdown of S100A12 was transfected on the basis of overexpression of NLRP3, which weakened the countervailing effect of overexpressed NLRP3 on TCZ. CONCLUSION: TCZ has a therapeutic effect on lung injury in rats with sepsis by reducing the expressions of S100A12/NLRP3.

Growth of grasses and forbs, nutrient concentration, and microbial activity in soil treated with microbeads.

Microplastics have emerged as an important threat to terrestrial ecosystems. To date, little research has been conducted on investigating the effects of microplastics on ecosystem functions and multifunctionality. In this study, we conducted the pot experiments containing five plant communities consisting of Phragmites australis, Cynanchum chinense, Setaria viridis, Glycine soja, Artemisia capillaris, Suaeda glauca, and Limonium sinense and added polyethylene (PE) and polystyrene (PS) microbeads to the soil (contained a mixture of 1.5 kg loam and 3 kg sand) at two concentrations of 0.15 g/kg (lower concentration, hereinafter referred to as PE-L and PS-L) and 0.5 g/kg (higher concentration, hereinafter referred to as PE-H and PS-H) to explore the effects of microplastics on total plant biomass, microbial activity, nutrient supply, and multifunctionality. The results showed that PS-L significantly decreased the total plant biomass (p = 0.034), primarily by inhibiting the growth of the roots. ß-glucosaminidase decreased with PS-L, PS-H, and PE-L (p < 0.001) while the phosphatase was noticeably augmented (p < 0.001). The observation suggests that the microplastics diminished the nitrogen requirements and increased the phosphorus requirements of the microbes. The decrease in ß-glucosaminidase diminished ammonium content (p < 0.001). Moreover, PS-L, PS-H, and PE-H reduced the soil total nitrogen content (p < 0.001), and only PS-H considerably reduced the soil total phosphorus content (p < 0.001), affecting the ratio of N/P markedly (p = 0.024). Of interest, the impacts of microplastics on total plant biomass, ß-glucosaminidase, phosphatase, and ammonium content did not become larger at the higher concentration, and it is observable that microplastics conspicuously depressed the ecosystem multifunctionality, as microplastics depreciated single functions such as total plant biomass, ß-glucosaminidase, and nutrient supply. In perspective, measures to counteract this new pollutant and eliminate its impact on ecosystem functions and multifunctionality are necessary.

Trait value and phenotypic integration contribute to the response of exotic Rhus typhina to heterogeneous nitrogen deposition: A comparison with native Rhus chinensis.

The temporal heterogeneity of nitrogen availability in soils is increasing due to agricultural deposition. We here compared the effects of gradually increasing nitrogen deposition rate and its increasing temporal heterogeneity patterns on the functional traits of seedlings of exotic species Rhus typhina and the native species Rhus chinensis. Nitrogen deposition rates of 0, 8, 20 g N m-2 year-1 and constant, single-peak, and double-peak nitrogen were added to simulate deposition rate and temporal heterogeneity. After 60 days of treatment, R. typhina seedlings had several advantageous growth trait values, such as higher total biomass production, but lower phenotypic plasticity than R. chinensis seedlings. R. typhina seedlings also had higher phenotypic integration, measured as the correlation among functional traits. The increased nitrogen deposition rate affected several traits of the two species differently. Thus, while R. chinensis seedlings allocated more biomass to leaves and less to roots with increasing N deposition, R. typhina seedlings had stable biomass allocation among all N treatments. Chlorophyll content, leaf phosphorus concentration, and water use efficiency increased, but the maximum net photosynthetic rate decreased, with N availability in R. chinensis, but not in R. typhina. Temporal heterogeneity had no significant effect on the total biomass of R. typhina and R. chinensis seedlings. Overall, the performance of R. typhina is better than that of R. chinensis seedlings under different nitrogen deposition treatments, which is due to the significantly advantageous trait values and greater phenotypic integration of R. typhina seedlings, whereas R. chinensis seedlings have higher phenotypic plasticity.

Long noncoding RNAs Colorectal Neoplasia Differentially Expressed and taurine-upregulated gene 1 are downregulated in sepsis and positively regulate each other to suppress the apoptosis of cardiomyocytes.

Long noncoding RNAs (lncRNAs) Colorectal Neoplasia Differentially Expressed (CRNDE) and taurine-upregulated gene 1 (TUG1) play similar roles in sepsis, indicating the existence of the crosstalk between them. Sepsis is a major cause of injuries in heart, which are related to high mortality rates. This study was therefore carried out to analyze the potential crosstalk between CRNDE and TUG1 in sepsis, with a focus on sepsis-induced cell apoptosis in heart. Expression of CRNDE and TUG1 was analyzed with RT-qPCR. Correlations between them were analyzed by Pearson's correlation coefficient. CRNDE and TUG1 were overexpressed in cardiomyocytes to determine the relationship between them. The roles of CRNDE and TUG1 in regulating the apoptosis of cardiomyocytes were explored by cell apoptosis assay. We found that both CRNDE and TUG1 were downregulated in sepsis. In cardiomyocytes, LPS treatment resulted in the downregulation of CRNDE and TUG1. Overexpression of CRNDE and TUG1 in cardiomyocytes increased the expression levels of each other. Under lipopolysaccharide (LPS) treatment, decreased apoptosis rates of cardiomyocytes were observed after CRNDE and TUG1 overexpression. CRNDE and TUG1 co-overexpression showed a stronger effect. In conclusion, CRNDE and TUG1 are downregulated in sepsis and they positively regulate each other to suppress the apoptosis of cardiomyocytes.

Increased soil moisture aggravated the competitive effects of the invasive tree Rhus typhina on the native tree Cotinus coggygria.

BACKGROUND: Invasive exotic species have caused significant problems, and the effects of extreme precipitation and drought, which might occur more frequently under the global climate change scenarios, on interspecific relationship between invasive and native species remain unclear. RESULTS: We conducted a greenhouse experiment with three soil water levels (30-40%, 50-60%, and 70-80% of field capacity) and two cultivation treatments (monoculture pots, one seedling of either species and mixture pots, one seedling of each species) to investigate soil water content effects on the relationship between invasive Rhus typhina and native Cotinus coggygria. Rhus typhina had lower height but bigger crown area than C. coggygria in the monoculture treatment. Rhus typhina had higher height, bigger crown area and total biomass than C. coggygria in the mixture treatment. Drought decreased the growth parameters, total chlorophyll concentration, and leaf biomass, but did not change gas exchange and other biomass parameters in R. typhina. The growth parameters, leaf area index, biomass parameters, total chlorophyll concentration, and net photosynthetic rate of C. coggygria decreased under drought conditions. The log response ratio (lnRR), calculated as ln (total biomass of a target plant grown in monoculture/total biomass of a target plant grown in mixed culture), of R. typhina was lower than that of C. coggygria. The lnRR of R. typhina and C. coggygria decreased and increased with increase in soil water content, respectively. CONCLUSIONS: Rhus typhina has greater capacity to relatively stable growth to the drought condition than C. coggygria and has strong competition advantages in the mixture with C. coggygria, especially in the drought condition. Our study will help understand the causes of invasiveness and wide distribution of R. typhina under various moisture conditions and predict its expansion under climate change scenarios.

Nitrogen deposition does not affect the impact of shade on Quercus acutissima seedlings.

Light and atmospheric nitrogen (N) deposition are among the important environmental factors influencing plant growth and forest regeneration. We used Quercus acutissima, a dominant broadleaf tree species native to the deciduous forests of Northern China, to study the combined effects of light exposure and N addition on leaf physiology and individual plant growth. In the greenhouse, we exposed Quercus acutissima seedlings to one of two light conditions (8% and 80% of full irradiation) and one of three N treatments (0, 6, and 12 g N m-2 y-1). After 87 d, we observed that nitrogen deposition had no significant effects on the seedlings regardless of light exposure. In addition, shade significantly reduced plant height, basal diameter, leaf number, total biomass, gas exchange capacity, and carbohydrate content. In contrast, however, shade significantly increased the amount of photosynthetic pigment, above-ground biomass allocation, and specific leaf area. There was also a hierarchical plasticity among the different seedling characteristics. Compared to traits of growth, biomass, biomass allocation and leaf morphology, the leaf physiology, including photosynthetic pigment, gas exchange, carbohydrate, and PUNE, is more sensitive to light conditions. Among the biomass allocation parameters, the leaf and root mass ratios had a relatively low phenotypic plasticity. The seedlings had high foliar physiological plasticity under various light conditions. Nevertheless, we recommend high irradiance to maintain vigorous seedling growth and, in turn, promote the restoration and reconstruction of vegetation.