Search Results (462)

The transcription factor DMP1 is a positive regulator of the tumor suppressor ARF, which in turn controls cell-cycle progression and/or apoptosis through p53. Given the role of DMP1 in the ARF-p53 pathway, we investigated whether the p53 transcription factor might regulate DMP1 expression. We found that endogenous human (h)DMP1 mRNA levels were significantly decreased upon induction of the temperature-sensitive p53^Val135 in normal fibroblasts. Consistent with this observation, a p53 knockdown in MCF7 breast cancer cells resulted in increased hDMP1 mRNA and protein levels. At the molecular level, we found that p53 directly repressed the hDMP1 promoter activity by up to 90%. This repression was not mediated by p53 binding to the two putative p53-binding sites in the hDMP1 promoter. Instead, deletion analysis revealed a 300bp region containing an EGR1/SP1 binding site that is required for p53-dependent inhibition of hDMP1 promoter activity. Using Sp1-deficient SL2 insect cells, we confirmed that p53-mediated repression of hDMP1 is dependent on Sp1. Furthermore, chromatin immunoprecipitation demonstrated SP1 binding to the hDMP1 promoter. Together, our findings identify an Sp1-dependent, p53-mediated repression of DMP1. Full article

Compared to traditional marine productivity, marine new-quality productivity (MNQP) is composed of advanced productive forces driven by the deepening application of new technologies, is characterized by the rapid emergence of new industries, new business models, and new modes of operation, and is marked by a substantial increase in total factor productivity in the marine economy. It has, therefore, become a new engine and pathway for China’s development into a maritime power. The main research approaches and conclusions of this paper are as follows: ① Using a combined order relation analysis method–Entropy Weight Method (G1-EWM) weighting method that integrates subjective and objective factors, we measured the development level of China’s MNQP from 2006 to 2021 across two dimensions: “factor structure” and “quality and efficiency”. The findings indicate that China’s MNQP is developing robustly and still holds considerable potential for improvement. ② Utilizing Gaussian Kernel Density Estimation and Spatial Markov Chain analysis to examine the dynamic evolution of China’s MNQP, the study identifies breaking the low-end lock-in of MNQP as crucial for accelerating balanced development. Spatial imbalances in China’s MNQP may exist both at the national level and within the three major marine economic zones. ③ To further examine potential spatial imbalances, Dagum Gini decomposition was employed to assess regional disparities in China’s MNQP. The DER polarization index and EGR polarization index were used to analyze spatial polarization levels, revealing an intensifying spatial imbalance in China’s MNQP. ④ Finally, geographic detectors were employed to identify the factors influencing spatial imbalances in China’s MNQP. Results indicate that these imbalances result from the combined effects of multiple factors, with marine economic development emerging as the core determinant exerting a dominant influence. The core conclusions of this study provide theoretical support and practical evidence for advancing the enhancement of China’s MNQP, thereby contributing to the realization of the goal of building a maritime power. Full article

Hereditary polyneuropathies represent a genetically and clinically heterogeneous group of disorders affecting the peripheral nervous system, characterized by progressive motor, sensory, and autonomic impairment. Advances in molecular genetics have identified key causative genes, including PMP22, MPZ, MFN2, TTR, EGR2, and CX32 (GJB1), which are implicated in Charcot–Marie–Tooth disease, Dejerine–Sottas syndrome, and related neuropathies. These conditions display substantial allelic and locus heterogeneity. Pathogenetically, mechanisms involve impaired myelin maintenance, disrupted axonal transport, mitochondrial dysfunction, and aberrant Schwann cell biology. Despite these insights, therapeutic options remain limited, and there is a pressing need to translate genetic findings into effective interventions. This review aims to provide a comprehensive synthesis of current knowledge compiling all known mutations resulting in hereditary polyneuropathies. In addition, it underscores the molecular pathomechanisms of hereditary polyneuropathies and evaluates emerging therapeutic strategies, including adeno-associated virus mediated RNA interference, CRISPR-based gene editing, antisense oligonucleotide therapy, and small-molecule modulators of axonal degeneration. Furthermore, the integration of precision diagnostics, such as next-generation sequencing and functional genomic approaches, is discussed in the context of personalized disease management. Collectively, this review underscores the need for patient-centered approaches in advancing care for individuals with hereditary polyneuropathies. Full article

Hypertension contributes to brain dysfunction through apoptosis, oxidative stress, reduced neuronal connectivity, and neurotransmitter imbalance. Exercise training is a non-pharmacological strategy known to modulate these molecular alterations. This study investigated the effects of high-intensity interval training (HIIT) on transcriptomic changes in the cerebral cortex of spontaneously hypertensive rats (SHR) fed a high-fat diet (HFD). Rats were assigned to either a HIIT intervention group (HIIT-HFD-SHR) or a sedentary control group (HFD-SHR). Cortical RNA was extracted, sequenced using the Illumina NovaSeq 6000 platform, and analyzed with DESeq2. Functional enrichment was conducted using Metascape. RNA-seq identified 1223 differentially expressed genes (DEGs) (adjusted p < 0.05), with 51 remaining significant under stringent criteria (adjusted p < 0.001, |log₂FC| > 0.5). Among these, eight key genes were closely associated with the regulation of apoptosis and autophagy, including seven downregulated (Egr1, Atf3, Tgm2, Lgals1, Nr4a1, Plekhf1, Nupr1) and one upregulated (Trim39). This transcriptomic analysis following HIIT also modulated circadian rhythm, long-term memory processes, and hypoxia response in the hypertensive brain. These findings indicate that HIIT decreases apoptosis and autophagy and improves circadian rhythm, long-term memory, and hypoxia in hypertensive rats’ brains. Full article

This research presents a cradle-to-grave Life Cycle Assessment (LCA) of a modern behind-the-ear hearing aid system, with the objective of assessing its environmental impacts and identifying areas for improvement and innovation. The assessment, developed in compliance with ISO 14040/14044, included the entire product system—including accessories, packaging, use phase, and end-of-life treatment—over a period of five years. The results provide an in-depth evaluation of its freshwater ecotoxicity, human carcinogenic toxicity, global warming, and fossil resource scarcity as key impact categories. Considerable environmental impacts were associated with certain components, manufacturing processes, and logistics. Strategies for improvement, including material replacement, increased component durability, packaging optimization, and sustainable sourcing of energy, were suggested. The investigation demonstrates how LCA can facilitate eco-design and sustainability in medical electronics. The findings of this work are derived from experimental modeling in an academic setting, which includes intrinsic uncertainties. The results emphasize the significance of using LCA as a strategic instrument to guide product development and to pinpoint opportunities for environmental improvement. Full article

The open reading frame 3 (ORF3) protein of the swine hepatitis E virus (SHEV) is a critical virulence factor implicated in viral infection, yet its precise mechanisms remain poorly understood. Circular RNAs (circRNAs) have emerged as key regulators of gene expression during viral infections by functioning as miRNA sponges. This study aimed to identify key circRNAs and construct a potential circRNA-miRNA-mRNA regulatory network associated with the viral infection pathway in HepG2 cells expressing genotype IV SHEV ORF3. Based on our previous high-throughput circRNA and transcriptome sequencing data from HepG2 cells with adenovirus-mediated ORF3 overexpression, we screened for differentially expressed circRNAs and mRNAs linked to viral infection pathways. Using bioinformatic tools, we predicted miRNAs targeted by these mRNAs and those that could bind to the circRNAs, ultimately constructing a competing endogenous RNA (ceRNA) network with Cytoscape. We identified 31 differentially expressed circRNAs and 7 mRNAs (HSPA8, HSPA1B, EGR2, CXCR4, SOCS3, NOTCH3, and ZNF527) related to viral infection. A potential ceRNA network comprising 32 circRNAs, 23 miRNAs, and the 7 mRNAs was constructed. Core circRNAs, including ciRNA203, circRNA14936, and circRNA5562, may act as miRNA sponges to regulate the expression of these mRNAs. This network suggests a novel mechanism by which SHEV ORF3 might modulate host cell functions to facilitate viral infection. Full article

Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost nothing is currently known about the function of EGR-01664 from E. granulosus. Methods: This study aimed to investigate the E. granulosus EGR-01664 gene (GenBank ID: 36337379), and the recombinant EGR-01664 protein was expressed successfully. Next, the transcription of the EGR-01664 gene across various developmental stages of E. granulosus was analyzed. Its spatial expression patterns in adult worms and protoscoleces were characterized using both quantitative PCR (qPCR) and immunofluorescence assays. Furthermore, the immunomodulatory effects of rEGR-01664 on cell proliferation, nitric oxide production, and cytokine secretion were examined by co-culturing the recombinant protein with canine PBMCs. Results: The rEGR-01664 could be recognized by sera from dogs infected with E. granulosus. Immunofluorescence assay (IFA) localization revealed the protein’s presence in the epidermis of protoscoleces, the adult epidermis, and some parenchymal tissues. qPCR revealed that EGR-01664 mRNA levels were significantly higher in protoscoleces compared to adults (p < 0.0001). At a concentration of 20 μg/mL, rEGR-01664 could significantly activate the transcription and expression of IL-10, TGF-β1, IL-17A, and Bax in canine PBMCs. However, with an increase in concentration, it inhibited the expression of IFN-γ, Bcl-2, GSDMD, IL-18, and IL-1β. These results suggest that the EGR-01664 gene plays a crucial role in the development, parasitism, and reproduction of E. granulosus. In vitro studies have shown that rEGR-01664 protein regulates the immune regulation function of canine PBMCs, suggesting its potential as a vaccine adjuvant or immunotherapy target. Conclusions: EGR-01664 may modulate canine PBMC functions to regulate host immune responses, thereby facilitating our understanding of how E. granulosus EGR-01664 contributes to the mechanism of parasitic immune evasion. Full article

Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary condition caused by the duplication of the PMP22 gene. Overexpression of peripheral myelin protein 22 in Schwann cells leads to myelin sheath defects and axonal loss. We have produced a cell model to facilitate studies of the molecular mechanisms involved in PMP22 accumulation and clearance. Our model is a stably transfected, clonal, immortalised human Schwann cell line with overexpressed levels of PMP22 fusion protein. A control-transfected cell line (vector lacking PMP22) was also produced. PMP22-transfected cells had reduced levels of mitosis, with the PMP22 fusion protein concentrated in punctate aggregates in the cytoplasm and expressed at the plasma membranes, which were often irregular and spindly. In contrast, control cells (control-transfected and parent cell lines) generally had smooth and regular plasma membrane morphology. Culturing in the presence of NRG1 and forskolin lead to upregulation of markers of myelination potential in the control cells. These markers were more variable in the cells stably transfected with PMP22, including decreased levels of transcripts of SOX10, JUN, S100B and NGFR, but increased levels of MPZ and EGR2 compared to controls. Using proximity-dependent biotin identification (BioID2), several hundred proteins were identified in the proximity of the overexpressed PMP22, of which 291 significant proteins were only detected in the proximity of PMP22 and not in that of control pull-downs. Among the most significantly enriched PMP22-interacting proteins were integrins alpha-2 (ITGA2) and alpha-7 (ITGA7), which play a role in myelination via their interactions with the extracellular matrix. The presence of ITGA2 in just the PMP22-transfected fraction was confirmed by western blot. Some of the proteins were associated with several enriched molecular pathways, including molecular transport and protein trafficking, and may represent potential therapeutic targets for CMT1A by promoting the degradation and enhanced trafficking of PMP22. Full article

The study of molecular mechanisms underlying late-life depression (LLD) is increasingly important in light of population aging. To date, LLD-related molecular brain changes remain poorly understood. Furthermore, environmental factors such as climate change and geography contribute to LDD risks. One overlooked factor might be deuterium—a stable hydrogen isotope—whose concentration in drinking water can vary geographically (~90–155 ppm) and alter the incidence of mood disorders. Conversely, potential effects of natural variations in deuterium content in drinking water on LLD symptoms and brain gene expression remain unknown. We conducted Illumina gene expression profiling in the hippocampi and prefrontal cortexes of 18-month-old C57BL/6J mice, a model of LLD-like behaviors, compared to 3-month-old controls. Separately, aged mice were allowed to consume deuterium-depleted (DDW, ~90 ppm) or control (~140 ppm) water for 21 days and were studied for LLD-like behaviors and Illumina gene expression of the brain. Naïve old mice displayed ≥2-fold significant changes of 35 genes. Housing on DDW increased their hedonic sensitivity and novelty exploration, reduced helplessness, improved memory, and significantly altered brain expression of Egr1, Per2, Homer1, Gadd45a, and Prdx4, among others. These genes revealed significant alterations in several GO-BP and KEGG pathways implicated in inflammation, cellular stress, synaptic plasticity, emotionality, and regeneration. Additionally, we found that incubation of primary neuronal cultures in DDW-containing buffer ameliorated Ca²⁺ influx and mitochondrial potential in a toxicity model, suggesting the involvement of mitochondrial mechanisms in the effects of decreased deuterium levels. Thus, aging induced profound brain molecular changes that may at least in part contribute to LLD pathophysiology. Reduced deuterium intake exerted modest but significant effects on LLD-related behaviors in aged mice, which can be attributed to, but not limited by ameliorated mitochondrial function and changes in brain gene expression. Full article

Distant hybridization is key to trait innovation and speciation, with Cyprinidae hybrid phylogeny helping to clarify diversification mechanisms. Yet, a major gap persists in Cyprinidae studies: the stabilization mechanisms of interspecific distant hybrid lineages. To address this, we systematically analyzed the molecular phylogeny of seven Cyprinidae distant hybrid lineages and their parental species, using an integrative genetic framework encompassing four mitochondrial genes (Cytb, COI, 16S rRNA, D-loop) and five nuclear genes (EGR2b, IRBP2, RAG1, RAG2, RH2). Homologous sequences of 41 representative Cyprinidae species (85 samples) were retrieved from GenBank to supplement the dataset. Phylogenies were reconstructed from concatenated sequences, complemented by haplotype networks. Intra-/interspecific divergence was quantified using two mitochondrial genes (COI, Cytb) and two nuclear (RAG1, RH2). The results showed that these hybrid lineages exhibited variation patterns analogous to other Cyprinidae species. Both ML and BI trees reconstructed exhibited congruent topologies with high support (bootstrap/BPP > 80%), resolving genus/species-level relationships. While most hybrids clustered intermediately between their parental species, they typically displayed maternal affinity. A notable exception was the 2nNCRC (a homodiploid hybrid from Cyprinus carpio ♀ × Megalobrama amblycephala ♂), which displayed convergent evolution toward Carassius auratus. COI-based K2P genetic distance analysis revealed 2nNCRC had a much closer relationship with C. auratus (0.0119) than with its parents (0.1249 to C. carpio, 0.1552 to M. amblycephala). These nine genes elucidate the genetic relationships between Cyprinid hybrid lineages and progenitors, serving as pivotal molecular markers for parentage tracing and genetic dissection of distant hybridization mechanisms. The integrated mitochondrial–nuclear marker system in this study advances understanding of cytonuclear coadaptation and the stabilization of interspecific distant hybrid lineages in Cyprinidae. Specifically, it provides a precise tool for parentage tracing, Cyprinid germplasm conservation, and targeted regulation of hybrid breeding—laying a foundation for exploring hybrid speciation and developing elite aquaculture germplasms. Full article

Tight gas reservoirs are characterized by low porosity, low permeability, and strong heterogeneity. CO₂ flooding, as an important approach for enhancing gas recovery while achieving carbon sequestration, is often restricted by gas channeling. Based on the sandstone reservoir parameters of the Shihezi Formation in the Ordos Basin, a two-dimensional fracture–matrix coupled numerical model was developed to systematically investigate the effects of fracture number, fracture inclination, fracture width, injection pressure, and permeability contrast on gas breakthrough time and sweep efficiency. A second-order regression model was further established using response surface methodology (RSM). The results show that a moderate fracture density can extend breakthrough time and improve sweep efficiency, while permeability contrast is the fundamental factor controlling gas channeling risk. When the contrast increases from 0.7 to 9.9, the breakthrough efficiency decreases from 88.5% to 68.9%. The response surface analysis reveals significant nonlinear interactions, including the coupled effects of fracture number with fracture width, injection pressure, and inclination angle. Under the optimized conditions, the breakthrough time can be extended to 46,984 h, with a corresponding sweep efficiency of 87.7%. These findings provide a quantitative evaluation method and engineering optimization guidance for controlling CO₂ channeling in tight gas reservoirs. Full article

Improving the efficiency of spark-ignited (SI) engines while simultaneously reducing emissions remains a critical challenge in meeting global energy demands and increasingly stringent environmental regulations. Lean burn combustion is a proven strategy for increasing efficiency in SI engines. However, the air dilution level is limited by the mixture’s ignition ability and poor combustion efficiency and stability. A promising method to extend the dilution limit and ensure stable combustion is the implementation of an active pre-chamber combustion system. The pre-chamber spark-ignited (PCSI) engine facilitates stable and rapid combustion of very lean mixtures in the main chamber by utilizing high ignition energy from multiple flame jets penetrating from the pre-chamber (PC) to the main chamber (MC). Together with the increase in efficiency by dilution of the mixture, nitrogen oxide (NO_X) emissions are lowered. However, at peak efficiencies, the NO_X emissions are still too high and require aftertreatment. The use of exhaust gas recirculation (EGR) as a dilutant might enable simple aftertreatment by using a three-way catalyst. This study experimentally investigates the use of EGR as a dilution method in a PCSI engine fueled by methane and analyzes the benefits and drawbacks compared to the use of air as a dilution method. The experimental results are categorized into three sets: measurements at wide open throttle (WOT) conditions, at a constant engine load of indicated mean effective pressure (IMEP) of 5 bar, and at IMEP = 7 bar, all at a fixed engine speed of 1600 rpm. The experimental results were further enhanced with numerical 1D/0D simulations to obtain parameters such as the residual combustion products and excess air ratio in the pre-chamber, which could not be directly measured during the experimental testing. The findings indicate that air dilution achieves higher indicated efficiency than EGR, at all operating conditions. However, EGR shows an increasing trend in indicated efficiency with the increase in EGR rates but is limited due to misfires. In both dilution approaches, at peak efficiencies, aftertreatment is required for exhaust gases because they are above the legal limit, but a significant decrease in NO_X emissions can be observed. Full article

This study presents a comparative investigation of combustion and emission characteristics in a two-stroke MAN 5S35ME-B9.5 marine diesel engine equipped with a Controllable Pitch Propeller and an Exhaust Gas Recirculation system. Experimental data were obtained from both factory shop tests conducted under the IMO NOx Technical Code 2008 E2 cycle and sea trials performed onboard the T/S Baek-Kyung. Engine performance was evaluated under Tier II-FB, ecoEGR, and Tier III modes, focusing on specific fuel oil consumption, peak cylinder pressure, exhaust gas temperature, and regulated emissions. Results indicate that Tier III achieved the greatest NOx abatement, reducing emissions by up to 76.4% (1464 to 346 ppm), but with penalties of 16.8% higher SFOC and 45.2% higher CO₂ concentration. EcoEGR provided a more favorable compromise, reducing NOx by 52.3% while limiting SFOC increases to ≤15.4% and CO₂ increases to ≤30.9%. Strong correlations were observed between NOx, Pmax, and exhaust gas temperature, reaffirming fundamental trade-offs, while O₂ and CO correlations showed greater variability under sea operation. Despite operational scatter, sea trial results reproduced the key patterns observed in shop tests, confirming robustness across conditions. Overall, this correlation-based analysis provides quantified evidence of performance–emission trade-offs and offers a practical foundation for optimizing CPP-equipped two-stroke engines under varying EGR strategies. Full article

Diesel engines power much of the heavy-duty equipment used in underground mines, where exhaust emissions pose acute environmental and occupational health challenges. However, predicting the amount of air required to dilute these emissions is difficult because exhaust mass flow and pollutant concentrations vary nonlinearly with multiple operating parameters. We apply deep learning to predict the total exhaust mass flow and carbon monoxide (CO) concentration of a six-cylinder gas–diesel (dual-fuel) turbocharged KAMAZ 910.12-450 engine under controlled operating conditions. We trained artificial neural networks on the preprocessed experimental dataset to capture nonlinear relationships between engine inputs and exhaust responses. Model interpretation with Shapley additive explanations (SHAP) identifies torque, speed, and boost pressure as dominant drivers of exhaust mass flow, and catalyst pressure, EGR rate, and boost pressure as primary contributors to CO concentration. In addition, symbolic regression yields an interpretable analytical expression for exhaust mass flow, facilitating interpretation and potential integration into control. The results indicate that deep learning enables accurate and interpretable prediction of key exhaust parameters in dual-fuel engines, supporting emission assessment and mitigation strategies relevant to underground mining operations. These findings support future integration with ventilation models and real-time monitoring frameworks. Full article

This study aimed to compare blood samples from Yili horses with outstanding and average performance in 5000 m races through transcriptome sequencing, identify key differentially expressed genes, lncRNAs, and circRNAs, as well as related enriched pathways, and elucidate their regulatory networks. This study used six healthy four-year-old Yili stallions as subjects, divided into an excellent group (E group, n = 3) and an ordinary group (O group, n = 3) based on their 5000-m race performance. Blood RNA-Seq technology was used to analyze differentially expressed mRNAs, lncRNAs, and circRNAs. A total of 2298 mRNAs, 264 lncRNAs, and 215 circRNAs were identified as differentially expressed. Key genes such as EGR1, FOSB, MRPL1, LOC100049811, SIRPB2, and CYTB regulate athletic performance. These genes and their associated RNAs synergistically participate in energy metabolism, protein homeostasis, and muscle remodeling processes, revealing the molecular mechanisms influencing athletic performance and providing important references for identifying candidate genes associated with equine athletic performance. Full article