The main aim of this paper is to explore the impact of financial development and globalization on consumption-based carbon emissions in Mexico while controlling growth, trade openness, and energy ...consumption. This impact has not been comprehensively explored for the case of Mexico using the newly developed dual adjustment approach. The fundamental innovation of the approach is that it offers an alternative to cointegration analysis, which reduces the implicit assumption of the singular adjustment in cointegration analysis. Furthermore, the study employs an autoregressive distributed lag approach to capture both the long-run and short-run association, while frequency domain causality tests are applied to capture causal linkages among the variables in the short run, medium run and long run. The empirical findings of this study reveal that: (a) globalization and financial development improve the quality of the environment; (b) energy consumption and economic growth deteriorate environmental quality; (c) trade openness exerts no significant impact on environmental quality. The findings from the frequency domain causality test reveal that financial development, energy usage, and economic growth can predict consumption-based carbon emissions at different frequencies, whereas trade openness and globalization can predict significant variations in consumption-based carbon emissions in the long and short term. Based on the empirical findings, the study suggests that the government of Mexico should be careful when formulating policies aimed at increasing growth, as they could be detrimental to the quality of the environment.
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•Exudates acted as endogenous carbon sources in micro-polluted CW.•Exudates and microorganisms varied significantly among plant species and seasons.•Denitrifier gene abundances were significantly ...affected by sucrose and glucose.•Microbial communities were significantly affected by sucrose and oxalic acid.
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In micro-polluted constructed wetland (CW), the low pollutant concentrations and the low COD/N ratios (chemical oxygen demand: total nitrogen in influent), make the biological treatment more difficult. It is expected that root exudates drive microbial-based transformations within plant rhizosphere. In this research, the roles of root exudates of three aquatic plants (Phragmites australis, Typha angustifolia and Cyperus alternifolius) in improving the growth of heterotrophic denitrifying bacteria were determined in a micro-polluted CW. In studied root rhizospheres, the total organic carbon (TOC) released from the plant roots varied significantly among plant species and seasons; the average TOC ranged from 0.1715 to 0.9221mgg−1rootDMd−1, which could fuel a denitrification rate of approximately 156–841kgNO3−-Nha−1year−1 if all were used by the denitrifying bacteria; the abundances of nirK- and nirS-encoding bacteria were significantly influenced by the concentration of sucrose and glucose (0.869≤r≤0.933, p<0.05), and microbial community richness and diversity had response to root exudates. The results revealed that root exudates can act as endogenous carbon sources for heterotrophic denitrifying bacteria and ultimately determine the microbe distribution patterns in micro-polluted CW.
Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates ...(NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
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•Single-cell transcriptomic roadmap of NHP ovarian aging•Molecular signatures revealed for NHP oocytes at stepwise developmental stages•Cell-type-specific inactivation of antioxidant genes in aged monkey and human ovaries
Single-cell transcriptomic analysis in ovaries of young and old cynomolgus monkeys identifies aging-associated and cell-type-specific dysregulation of antioxidative pathways.
Aging causes a functional decline in tissues throughout the body that may be delayed by caloric restriction (CR). However, the cellular profiles and signatures of aging, as well as those ameliorated ...by CR, remain unclear. Here, we built comprehensive single-cell and single-nucleus transcriptomic atlases across various rat tissues undergoing aging and CR. CR attenuated aging-related changes in cell type composition, gene expression, and core transcriptional regulatory networks. Immune cells were increased during aging, and CR favorably reversed the aging-disturbed immune ecosystem. Computational prediction revealed that the abnormal cell-cell communication patterns observed during aging, including the excessive proinflammatory ligand-receptor interplay, were reversed by CR. Our work provides multi-tissue single-cell transcriptional landscapes associated with aging and CR in a mammal, enhances our understanding of the robustness of CR as a geroprotective intervention, and uncovers how metabolic intervention can act upon the immune system to modify the process of aging.
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•A multitissue single-cell transcriptomic atlas for aging and CR in a mammal•CR alleviates aging-related accumulation of pro-inflammatory cells in various tissues•CR attenuates aging-associated cell-type-specific gene expression changes
Single-cell transcriptomic analysis in aging rats provides insights into the effects of caloric restriction on different tissue and cell types.
An inflammatory response is beneficial to the organism, while an excessive uncontrolled inflammatory response can lead to the nonspecific killing of tissue cells. Therefore, promoting the resolution ...of inflammation is an important mechanism for protecting an organism suffering from chronic inflammatory diseases. Resolvins are a series of endogenous lipid mediums and have the functions of inhibiting a leukocyte infiltration, increasing macrophagocyte phagocytosis, regulating cytokines, and alleviating inflammatory pain. By promoting the inflammation resolution, resolvins play an irreplaceable role throughout the pathological process of some joint inflammation, neuroinflammation, vascular inflammation, and tissue inflammation. Although a large number of experiments have been conducted to study different subtypes of resolvins in different directions, the differences in the action targets between the different subtypes are rarely compared. Hence, this paper reviews the generation of resolvins, the characteristics of resolvins, and the actions of resolvins under a chronic inflammatory response and clinical translation of resolvins for the treatment of chronic inflammatory diseases.
Triptolide (TP), a major extract of the herb
Hook F (TWHF), has been shown to exert potent pharmacological effects, especially an immunosuppressive effect in the treatment of rheumatoid arthritis ...(RA). However, its multiorgan toxicity prevents it from being widely used in clinical practice. Recently, several attempts are being performed to reduce TP toxicity. In this review, recent progress in the use of TP for RA, including its pharmacological effects and toxicity, is summarized. Meanwhile, strategies relying on chemical structural modifications, innovative delivery systems, and drug combinations to alleviate the disadvantages of TP are also reviewed. Furthermore, we also discuss the challenges and perspectives in their clinical translation.
Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs ...mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.
Background
Immunotherapy has shown promising results in bladder cancer therapy options.
Methods
Analysis of open-access data was conducted using the R software. Open-access data were obtained from ...The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and IMvigor210 databases. Immunofluorescence and co-culture systems were utilized to validate the effect of PTHLH on M2 macrophage polarization.
Results
Here, through the combined (TCGA, GSE128959, GSE13507, and GSE83586) and IMvigor210 cohorts, we comprehensively investigated the biological and immune microenvironment differences in patients with diverse immunotherapy responses. Meanwhile, we found that M2 macrophage could affect bladder cancer immunotherapy sensibility. Moreover, based on the machine learning algorithm (LASSO logistics regression), PTHLH, BHMT2, and NGFR were identified, which all have good prediction abilities for patient immunotherapy. Then, a logistics regression model was established based on PTHLH, BHMT2, and NGFR, and each patient was assigned a logistics score. Subsequently, we investigated the difference in patients with high low logistics scores, including biological enrichment, immune microenvironment, and genomic characteristics. Meanwhile, data from the Human Protein Atlas database indicated a higher protein level of PTHLH in bladder cancer tissue. Immunofluorescence indicated that the knockdown of PTHLH in bladder cancer cells can significantly inhibit the M2 polarization of co-culture M0 macrophages.
Conclusions
Our study investigated the difference between bladder cancer immunotherapy responders and non-responders. Meanwhile, the PTHLH was identified as a novel biomarker for bladder cancer immunotherapy.
Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical ...challenges. Here we design and synthesize a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX remains stable and inactive in the circulation. NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX is cleaved by cathepsin B and then the conjugated PTX is released for action. The NucA modification assists the selective accumulation of the conjugated PTX in ovarian tumor tissue rather than normal tissues, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for ...osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer-functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.
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