Search Results (2,739)

The mechanism by which quorum sensing (QS) enhances stress resistance in enterohemorrhagic Escherichia coli (E. coli) O157:H7 remains unclear. We employed optimized exogenous QS signal N-acyl-homoserinelactones (AHL) (100 μM 3-oxo-C6-AHL, 2 h) in EHEC O157:H7 strain EDL933, which was validated with endogenous yenI-derived AHL, to investigate QS-mediated protection against acid stress. RNA-seq transcriptomics identified key upregulated genes (e.g., rmf). Functional validation using isogenic rmf knockout mutants generated via λ-Red demonstrated abolished stress resistance and pan-stress vulnerability. Mechanistic studies employing qRT-PCR and stress survival assays established Ribosomal Hibernation Factor (RMF) as a non-redundant executor in a SdiA–RMF–RpoS axis, which activates ribosomal dormancy and SOS response to enhance EHEC survival under diverse stresses. For the first time, we define ribosomal hibernation as the core adaptive strategy linking QS to pathogen resilience, providing crucial mechanistic insights for developing EHEC control measures against foodborne threats. Full article

Methylglyoxal (MGO) is a highly reactive a-dicarbonyl compound produced in foods and endogenously in humans and constitutes a predominant precursor of advanced glycation end products that contribute to the pathology of several diseases, including diabetes and neurodegenerative diseases. In this study, the efficiency of pyrogallol, gallic acid, ethyl, and propyl gallate in trapping MGO was investigated at pH 6.5 to 8.0. Pyrogallol was the most efficient MGO-trapping agent, followed by gallic acid, whereas the alkyl gallates were notably less efficient, particularly at slightly acidic and neutral pH. The increase of pH from slightly acidic to alkaline enhanced the MGO-trapping efficiency of all compounds, albeit to a different extent that correlated inversely to the pK_a of the most acidic -OH phenolic group, demonstrating the contribution of the deprotonated forms of the phenolic compounds in the enhanced reactivity towards MGO. The reaction products of pyrogallol, identified as the most efficient compound in MGO-trapping, were analyzed and characterized by liquid chromatography-mass spectrometry (LC-MS). Both mono-MGO and di-MGO conjugated adducts of pyrogallol were detected, with the mono-MGO adduct being dominant solely at acidic pH and the di-MGO pyrogallol adducts becoming prevalent at neutral and alkaline pH. Therefore, the pH was determined as a main factor that controls the reaction pathways of the phenolic compounds with MGO. Full article

Estrogens regulate many physiological processes in the human body, including the cardiovascular system. Importantly, Estradiol (E2) exerts its vascular protective actions, in part, by promoting endothelial repair via induction of endothelial cell (EC) proliferation, migration and angiogenesis. Recent evidence that microRNAs (miRNAs) play an important role in vascular health and disease as well as in regulating Estrogen actions in many cell types. We hypothesize that E2 may mediate its vascular protective actions via the regulation of miRNAs. Following initial screening, we found that E2 downregulates the levels of miR-193a-3p in ECs. Moreover, miR-193a-3p downregulation by miR-193a-3p-antimir mimicked the effects as E2 on EC growth, migration, and capillary formation. Restoring miR-193a-3p levels with mimics after E2 treatment abrogated the vasculogenic actions of E2, suggesting a key role of miR-193a-3p in E2-mediated EC-growth-promoting effects. We further investigated the cellular mechanisms involved and found that miR-193a-3p inhibits angiogenesis by blocking phosphoinositide-3-kinase (PI3K)/Akt-vascular endothelial growth factor (VEGF) and Activin receptor-like kinase 1 (ALK1)/SMAD1/5/8 signaling in ECs, both pathways that are important in E2-mediated vascular protection. Additionally, using reverse transcription polymerase chain reaction (RT-PCR), we demonstrate that E2 downregulates miR-193a-3p in ECs via Estrogen Receptor (ER)α, but not ERβ or G protein-coupled estrogen receptor (GPER). Moreover, these actions occur post-transcriptionally, as the expression of pri-miR-193a-3p was not affected. The anti-angiogenic actions of miR-193a-3p were also observed in in vivo Matrigel implant-based capillary formation studies in ovariectomized mice where E2 induced capillary formation, and these effects were abrogated in the presence of miR-193a-3p, but not in the control mimic. Assessment of miR-193a-3p levels in plasma collected from in vitro fertilization (IVF) subjects with low and high E2 levels showed significantly lower miR-193a-3p levels in responders during the high E2 period. Hence, our findings provide the first evidence that miR-193a-3p mimic inhibits angiogenesis whereas its antimir is angiogenic. Importantly, E2 mediates its regenerative actions on ECs/capillary formation by downregulating endogenous miR-193a-3p expression. Both miR-193a-3p mimic or antimir may represent important therapeutic molecules to prevent or to induce endothelial function in treating pathophysiologies associated with capillary growth. Full article

The abnormal growth of smooth muscle cells (SMCs) contributes to the vascular remodeling associated with coronary artery disease, a leading cause of death in women. Estradiol (E2) mediates cardiovascular protective actions, in part, by inhibiting the abnormal growth (proliferation and migration) of SMCs through various mechanism. Since microRNAs (miRNAs) play a major role in regulating cell growth and vascular remodeling, we hypothesize that miRNAs may mediate the protective actions of E2. Following preliminary leads from E2-regulated miRNAs, we found that platelet-derived growth factor (PDGF)-BB-induced miR-193a in SMCs is downregulated by E2 via estrogen receptor (ER)α, but not the ERβ or G-protein-coupled estrogen receptor (GPER). Importantly, miR-193a is actively involved in regulating SMC functions. The ectopic expression of miR-193a induced vascular SMC proliferation and migration, while its suppression with antimir abrogated PDGF-BB-induced growth, effects that were similar to E2. Importantly, the restoration of miR-193a abrogated the anti-mitogenic actions of E2 on PDGF-BB-induced growth, suggesting a key role of miR-193a in mediating the growth inhibitory actions of E2 in vascular SMCs. E2-abrogated PDGF-BB, but not miR-193a, induced SMC growth, suggesting that E2 blocks the PDGF-BB-induced miR-193a formation to mediate its anti-mitogenic actions. Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism. Furthermore, we found that miR-193a induces SMC growth by activating the phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway and promoting the G1 to S phase progression of the cell cycle, by inducing Cyclin D1, Cyclin Dependent Kinase 4 (CDK4), Cyclin E, and proliferating-cell-nuclear-antigen (PCNA) expression and Retinoblastoma-protein (RB) phosphorylation. Importantly, in mice, treatment with miR-193a antimir, but not its control, prevented cuff-induced vascular remodeling and significantly reducing the vessel-wall-to-lumen ratio in animal models. Taken together, our findings provide the first evidence that miR-193a promotes SMC proliferation and migration and may play a key role in PDGF-BB-induced vascular remodeling/occlusion. Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease. Full article

In this study, we investigated the effects of dietary supplementation with thermally modified attapulgite on the daily weight gain, serum biochemical indices, and serum metabolites of Simmental fattening cattle. A total of 30 healthy Simmental fattening beef calves of similar age (8 to 9 months old) and body weight (370 ± 10 kg) were randomly divided into two groups, each containing 15 animals. A control group was fed the basal diet, and a treatment group was fed the same basal diet with the addition of 4 g/kg of thermally modified attapulgite. After 75 days of formal experiment, the calves in the two groups were weighed, and blood samples were collected by tail vein blood sampling for determinations of the serum biochemical indices and serum metabolites using liquid chromatography–mass spectrometry (LC-MS) analysis. The results indicated that the addition of thermally modified attapulgite to the diet had no significant effects on the daily weight gain of fattening beef cattle. After feeding with modified attapulgite, the glutathione peroxidase and superoxide dismutase activities in the serum of the experimental group were 55.02% (257.26 U·mL⁻¹ to 165.95 U·mL⁻¹, p < 0.05) and 13.11% (18.98 U·mL⁻¹ to 16.78 U·mL⁻¹, p < 0.05) higher than that in the control group. Compared with the control group, the tumor necrosis factor-alpha content was reduced by 14.50% (31.27 pg·mL⁻¹ to 36.57 pg·mL⁻¹, p < 0.01), and the concentration of interleukin-6 and lipopolysaccharide decreased by 17.00% (34.33 pg·mL⁻¹ to 41.36 pg·mL⁻¹, p < 0.001) and 23.05% (51.34 EU·L⁻¹ to 66.72 EU·L⁻¹, p < 0.001) in the serum of the experimental group. Contrastingly, the thermally modified attapulgite had no significant effects on the levels of serum total protein, albumin, or globulin in Simmental fattening cattle (p > 0.05). Furthermore, the results of serum metabolomic analyses revealed that there were a total of 98 differential metabolites, which were mainly enriched with respect to glycerophospholipid metabolism, Th1 and Th2 cell differentiation, autophagy-other, retrograde endogenous cannabinoid signaling, and the NF-κB signaling pathway. Overall, thermally modified attapulgite was found to effectively increase the activity of antioxidant enzymes, reduce serum inflammatory mediators, may suppress oxidative damage, enhance immunity, and have a positive influence on the health of Simmental fattening beef calves. Full article

Coronaviruses, particularly those classified as highly pathogenic species, pose a significant threat to global health. These viruses hijack host cellular membranes and proteins to facilitate their replication, primarily through the formation of replication organelles (ROs). However, the precise regulatory mechanisms underlying RO formation remain poorly understood. To elucidate these mechanisms, we conducted mass spectrometry analyses, identifying interactions between the host protein DnaJ homolog subfamily C member 11 (DNAJC11) and the SARS-CoV-2 nonstructural protein 3 (NSP3) protein. Notably, results showed that DNAJC11 depletion reduces SARS-CoV-2 infection, indicating possible positive regulatory involvement. But the ectopic expression of DNAJC11 did not lead to marked alterations in immune or inflammatory responses. DNAJC11 enhanced NSP3 expression stability through endogenous apoptosis pathways and facilitated its interaction with NSP4, thereby promoting the formation of double-membrane vesicles (DMVs). Knockdown of DNAJC11 reduced DMV number and size, accompanied by dysregulation of the endoplasmic reticulum and mitochondria. However, supplementation with DNAJC11 restored both DMV number and size. These findings provide novel insights into the role of DNAJC11 as a host factor that modulates DMV formation and supports SARS-CoV-2 replication by targeting the NSP3 protein. This study advances our understanding of the molecular interactions between host and viral components and highlights DNAJC11 as a potential target for antiviral interventions. Full article

Primary-level social risk prevention and control is a complex, systemic endeavor that requires close cooperation among various local government departments. Within this context, addressing bureaucratic segmentation and strengthening interdepartmental collaboration are critical issues in primary-level social risk governance. This study uses social network analysis and the exponential random graph model to examine the collaborative network structure and driving mechanisms among government departments engaged in risk prevention, with J City as a network study. The findings reveal that (1) while a collaborative governance framework exists, the network has low overall density, strong localized clustering, and a clear core-periphery structure, indicating the need for improved coordination and more refined collaborative mechanisms; (2) the formation of the risk prevention network is influenced by both endogenous structural factors and exogenous actor attributes. Endogenously, reciprocity and transitivity play significant roles in tie formation; exogenously, departments with similar resource mobilization capacities are more likely to collaborate, while those with strong communication, digital technology, and resource mobilization capabilities are more likely to initiate collaborations, and those with high communication capacity are more likely to accept collaborative offers. This study offers insights into the dynamics and formation mechanisms of departmental collaborative networks in primary-level social risk governance. Full article

As inevitable outcomes of the digital economy’s low-carbon development, green data centers play a crucial role in environmental impact and underlying mechanisms. This study focuses on green data center establishment as a representative practice, utilizing Chinese A-share listed companies and urban data from 2009 to 2023 to construct a multi-period difference-in-differences model. From a supply chain perspective, we investigate the impact of green data centers on corporate carbon emissions and their mechanisms. The results demonstrate that regional establishment of green data centers significantly promotes corporate carbon emission reduction, with conclusions remaining robust after a series of comprehensive robustness and endogeneity tests. This process primarily operates through two channels: green total factor energy efficiency and green attention. Green data center establishment significantly enhances green total factor energy efficiency and corporate green attention. The more developed the regional digital infrastructure and the higher the computing power development levels, the stronger the incentive effect on corporate carbon reduction. Heterogeneity analysis reveals that green data centers have more significant promoting effects on carbon emission reduction in state-owned enterprises and high-tech enterprises. This research contributes to a deeper understanding of the effects, mechanisms, and regional variations related to green data centers in facilitating corporate carbon emission reduction. Full article

The agricultural products trade network is essentially a complex adaptive system formed by nonlinear interactions between countries. Based on the complex system theory, this study reveals the dynamic self-organization law of the RCEP regional agricultural products trade network by using the panel data of RCEP agricultural products export trade from 2000 to 2023, combining social network analysis (SNA) and the temporal exponential random graph model (TERGM). The results show the following: (1) The RCEP agricultural products trade network presents a “core-edge” hierarchical structure, with China as the core hub to drive regional resource integration and ASEAN countries developing into secondary core nodes to deepen collaborative dependence. (2) The “China-ASEAN-Japan-Korea “riangle trade structure is formed under the RCEP framework, and the network has the characteristics of a “small world”. The leading mode of South–South trade promotes the regional economic order to shift from the traditional vertical division of labor to multiple coordination. (3) The evolution of trade network system is driven by multiple factors: endogenous reciprocity and network expansion are the core structural driving forces; synergistic optimization of supply and demand matching between economic and financial development to promote system upgrading; geographical proximity and cultural convergence effectively reduce transaction costs and enhance system connectivity, but geographical distance is still the key system constraint that restricts the integration of marginal countries. This study provides a systematic and scientific analytical framework for understanding the resilience mechanism and structural evolution of regional agricultural trade networks under global shocks. Full article

DNA is inherently unstable and is susceptible to damage from both endogenous sources (such as reactive oxygen species) and exogenous factors (including UV, ionizing radiation, and chemicals). The accumulation of DNA damage manifests as genetic mutations, chromosomal instability, and the stalling of DNA replication and transcription processes. Accumulated DNA damage influences apoptosis and cell cycle checkpoints, serving as one of the key triggers for the manifestation of the senescent phenotype. Both aging and cancer are associated with the accumulation of mutations in somatic cells. Disruption of cell cycle control and uncontrolled proliferation are fundamental characteristics of any cancer cell, with the majority of anticancer drugs acting as inhibitors of cyclin-dependent kinases, thereby inducing a transition of cells into a senescent state. Consequently, disturbances in the dynamics and regulation of inflammatory responses, oxidative stress, cell proliferation, DNA damage repair, and epigenetic anomalies, along with the influence of retroviruses and transposons, lead to the accumulation of senescent cells within the human body, characterized by blocked replication and cell cycle, as well as a distinct secretory phenotype. The age-related or disease-associated accumulation of these senescent cells significantly alters the physiology of tissues and the organism as a whole. Many secondary metabolites of higher plants exhibit senolytic and senomorphic activities, although most of them are not fully characterized. In this review, we will explore the principal signaling pathways in mammalian cells that govern the cell cycle and cellular senescence, with a particular emphasis on how their dynamics, expression, and regulation have been modified through the application of senotherapeutic compounds. The second section of the review will identify key target genes for the metabolic engineering, primarily aimed at enhancing the accumulation of plant secondary metabolites with potential therapeutic benefits. Lastly, we will discuss the rationale for utilizing liver cells as a model system to investigate the effects of senolytic compounds on human physiology and health, as well as how senotherapeutic substances can be leveraged to improve gene therapy approaches based on CRISPR/Cas9 and prime-editing technologies. Full article

The role of endophytic bacteria in the interaction between medicinal plants and microorganisms, secondary metabolite accumulation, plant nutrient changes, as well as their interactions with microbial communities, needs to be investigated in medicinal plants. In this study, 16S rRNA genes of endophytic bacterial communities in the root systems of three medicinal licorice species at different root depths (0–20, 20–40, and 40–60 cm) were sequenced using high-throughput sequencing technology, and their relationships with plant and soil factors were investigated. Our study indicated that the influence of Glycyrrhiza species on the structure of endophytic bacterial communities is significantly greater than that of root depth, and there are significant differences in the structure of endophytic bacterial communities at different sampling sites. At the phylum level, Proteobacteria and Actinobacteria are the dominant phylum. Functional gene prediction shows that functional genes related to metabolism dominate the endogenous bacterial community. Plant factors and soil physicochemical properties are important environmental drivers affecting the distribution of endophytic bacterial communities. This study will give new information on plant–soil–endophyte interactions and open up new possibilities for medicinal licorice development and use. Full article

It is increasingly recognized that the twin transitions of digitalization and green transformation are pivotal to achieving sustainable development. This study examines how digital trade affects corporate green total factor productivity (GTFP), using panel data from Chinese A-share listed firms and 287 prefecture-level cities in Mainland China from 2012 to 2022. The results demonstrate that digital trade exerts a significant positive impact on GTFP, primarily through improvements in technical efficiency, with heterogeneous effects across different stages of the corporate life cycle. Endogeneity concerns are carefully addressed through instrumental variable estimation and quasi-experimental designs, and robustness checks confirm the reliability of the findings. Mechanism analyses further reveal that digital trade enhances GTFP by stimulating green technological innovation and optimizing supply chain management. Importantly, threshold regression reveals non-linear effects. Both the level of digital trade and institutional factors, such as environmental regulation, intellectual property protection, and market integration, moderate the relationship between digital trade and GTFP in U-shaped, N-shaped, and other positive non-linear patterns. These insights enhance the understanding of how digitalization interacts with institutional contexts to drive sustainable productivity growth, providing practical implications for policymakers seeking to optimize digital trade strategies and complementary regulatory frameworks. Full article

Kazakh mares have drawn significant attention for their outstanding lactation traits. Lactation, a complex physiological activity, is modulated by multiple factors. This study utilized high-throughput sequencing to conduct whole-transcriptome sequencing analysis on the mammary gland tissue of eight Kazakh mares, of which four were pregnant and four were non-pregnant, to systematically reveal the molecular regulatory mechanisms. The results showed differential expression in 2136 mRNAs, 180 lncRNAs, 104 miRNAs, and 1162 circRNAs. Gene ontology functional annotation indicates that these differentially expressed genes are involved in multiple key biological processes, such as the cellular process (BP), metabolic process, and biological regulation. Kyoto Encyclopedia of Genes and Genomes analysis suggests that the differentially expressed genes are significantly enriched in essential pathways such as cytokine–cytokine receptor interaction, the chemokine signaling pathway, and the PI3K-Akt signaling pathway. Additionally, this study constructed a competing endogenous RNA (ceRNA) regulatory network based on the differentially expressed genes (|log₂FC| > 1, FDR < 0.05), offering a novel perspective for revealing the functional regulation of the mammary gland. This study compared genomic differences in mammary gland tissue of pregnant and non-pregnant Kazakh mares and identified candidate genes that are closely related to lactation regulation. It found that various genes, such as PIK3CG, IL7R, and SOD2, play central regulatory roles in activating mammary gland functions. These findings provide theoretical support for explaining the molecular mechanisms underlying the mammary gland development of Kazakh mares. Full article

The ratooning capacity of sugarcane cultivars represents a crucial agronomic trait that significantly influences the sustainability of crop yields. This study elucidates the physiological and molecular mechanisms underlying the sugarcane ratooning ability observed in ratoon-competent GuiTang 29 (GT29) and ratoon-deficient Badila cultivars following stem excision. Through integrated hormonal profiling and transcriptome analysis, we identified significant differences in hormone levels and gene expression patterns. The quantification of 15 endogenous hormones via HPLC revealed marked reductions in zeatin (ZA) and zeatin riboside (ZR) in both cultivars. Additionally, GT29 exhibited notable reductions in gibberellins (GA3 and GA5) and strigolactone (5-DS) post-stem-excision, while Badila displayed stable or distinct hormonal changes. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that hormone signal transduction, MAPK signaling pathways, phenylpropanoid biosynthesis, flavonoid biosynthesis, and other metabolic pathways were significantly enriched in both GT29 and Badila, with a particularly higher enrichment of plant hormone signal transduction in GT29. Furthermore, several differentially expressed genes (DEGs) had different expression patterns between GT29 and Badila, including the cytokinin receptor B-ARR and transcription factor A-ARR, gibberellin pathway components GID1 and DELLA, and AUX/IAA and SAUR in the auxin pathway. The real-time quantitative PCR (qRT-PCR) validation of 12 DEGs corroborated the RNA-seq data, further supporting the reliability of the transcriptomic analysis. This study delineates a clear molecular framework distinguishing ratoon competence, offers novel insights into the molecular basis of perennial regeneration and provides reliable candidate genes for functional marker development in sugarcane breeding. Full article

While airlines can directly quantify carbon emissions based on flight-specific fuel burn data, such data, along with data on other gaseous emissions that do not scale linearly with fuel consumption, are often unavailable to external stakeholders, necessitating the reliance on estimation models. Emissions are thus approximated from known quantities, with most usually from the fuel burned and distance travelled. Emission approximators developed for the aviation industry thus involve some degree of approximation and assumptions, as well as different exogenous and endogenous factors. As a result, such solutions differ primarily due to the significant methodological variations they incorporate. This paper assesses carbon emission approximators developed to valorize emissions generated by flight operations. It reveals the significance and sources of the misestimation of emissions by focusing on the ICAO Carbon Emission Calculator (ICEC), ICAO CORSIA CO₂ Estimation and Reporting Tool (CERT) and EUROCONTROL’ Advanced Emission Model (AEM) and Small Emitters Tool (SET). Thereby, the main research findings indicate considerable estimation uncertainty among the reviewed solutions, ranging from 1.77% to 27.95% on average compared to the baseline, which translates to statistical confidence levels ranging from 15% to 77.50% on average with respect to a 95% confidence threshold. Full article