Explore the vast range of titles available.

Micro-RNAs (miRNAs) are short non-coding single-stranded RNAs that modulate the expression of various target genes after transcription. The expression and distribution of kinds of miRNAs have been characterized in human placenta during different gestational stages. The identified miRNAs are recognized as key mediators in the regulation of placental development and in the maintenance of human pregnancy. Aberrant expression of miRNAs is associated with compromised pregnancies in humans, and dysregulation of those miRNAs contributes to the occurrence and development of related diseases during pregnancy, such as pre-eclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), recurrent miscarriage, preterm birth (PTB) and small-for-gestational-age (SGA). Thus, having a better understanding of the expression and functions of miRNAs in human placenta during pregnancy and thereby developing novel drugs targeting the miRNAs could be a potentially promising method in the prevention and treatment of relevant diseases in future. Here, we summarize the current knowledge of the expression pattern and function regulation of miRNAs in human placental development and related diseases.

Multi-UAV coverage planning in complex mountainous environments is often constrained by idealized energy modeling, the “wood barrel effect” of traditional global energy minimization paradigms, and a lack of dynamic fault tolerance. To address these limitations, this study proposes a survivability-oriented Min–Max optimization architecture driven by the novel Lévy–Flight Terrain-Following Constrained Planning Optimization (LF-TF-CPO) algorithm. Coupling a high-fidelity 3D topographical matrix with a nonlinear aerodynamic energy model, the framework prioritizes individual UAV safety. Monte Carlo simulations demonstrate that LF-TF-CPO compresses the average maximum individual energy consumption to 665.64 kJ, preserving an adequate operational margin below the 950 kJ physical redline to absorb unmodeled aerodynamic perturbations while ensuring a 31.30 min mission duration. Ablation studies verify the Min–Max objective mitigates localized overloads with a marginal 0.4% energy trade-off. Furthermore, an emergency recovery protocol validates dynamic resilience across simultaneous and cascading failures by consistently stabilizing post-failure peak loads within safe margins. Notably, statistical evaluations establish a robust empirical sweet spot (λ = 0.05), demonstrating the framework’s low sensitivity to parameter variations. By minimizing the need for manual retuning, this architecture serves as a promising simulation-validated planning framework for future rapid deployment in time-critical disaster responses.

When operating in complex and obstacle-dense environments, micro UAV swarms often face severe cooperative positioning failures due to transient non-line-of-sight (NLOS) interference and cascaded inertial sensor drift. To address this, this work proposes a fault-tolerant positioning framework integrating multi-agent deep reinforcement learning with cooperative extended Kalman filtering (MADRL-CEKF). The system incorporates a link-level dynamic soft isolation mechanism that dynamically adjusts observation covariance to effectively sever paths of cooperative error contagion. An adaptive Markov smoothing constraint is mathematically embedded to mitigate high-frequency control jitter typical of AI-driven policies. Crucially, the framework implements a resource-aware multi-objective reward architecture tailored for micro UAVs. Evaluated through high-fidelity simulations and offline physical datasets, the proposed framework achieves a 96.01% reduction in average tracking error (RMSE) under extreme multi-node cascaded failures, completely preventing system divergence. Furthermore, through autonomous multi-objective trade-offs, the system reduces processing delay by 44% (to 25.1 ms) and computational energy consumption by 41% with only a marginal accuracy compromise of 0.16 m, strictly keeping the execution time within the 50 ms real-time threshold. The MADRL-CEKF framework effectively bridges the gap between sophisticated AI decision-making and strict engineering constraints, providing a highly robust and resource-efficient navigation paradigm for swarm robotics.

Background Insufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown. Methods In the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining. Results MiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter of CDH1 gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT. Conclusions Together these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.

Ovarian cancer (OC) is the predominant gynecological cancer and is associated with severe morbidity and high mortality worldwide. Therefore, clarifying the molecular mechanisms underlying OC progression and exploring novel therapeutic targets are important. Here, using human OC samples, different OC cell lines, and xenograft nude mouse models in combination with multiple sequencings, we report that hnRPD, an RNA binding protein that modulates RNA stability, is highly expressed in OC tissues, and contributes to OC cell malignancy in human OC cells cultured in vitro and in OC cell-derived xenograft nude mouse models in vivo. Mechanistically, ectopically expressed GPR137 binds to hnRPD and enhances hnRPD protein stability, which reciprocally transactivates GPR137 through the transcription factor FLI1. On the other hand, elevated hnRPD upregulates RAB8A expression by interacting with RAB8A mRNA and promoting its stability, leading to activation of downstream cell signaling and thereby enhanced OC cell malignant behaviors including cell proliferation, cell invasion, cell migration, and colony formation ability as well as OC xenograft growth in nude mice. Moreover, cisplatin in combination with silencing of hnRPD expression, significantly induces apoptosis in cisplatin-resistant OC cells through regulation of OC cell metabolism. Therefore, our data provide evidence that hnRPD could represent an innovative prognostic indicator for OC and may be an attractive therapeutic target for improving clinical outcomes in OC treatment.

Due to the considerable variation in the range of rock content of the soil—rock mixture, when grouting experiments were conducted according to the existing grouting theory, it was found that a large number of pores not entirely filled by the slurry existed in the concretions of the medium to high rock content backfill area. Therefore, the existing slurry permeation grouting diffusion equation was optimized by adding the filling factor (γ). Based on the Bingham fluid rheological equation and the Newtonian fluid rheological equation, the optimized calculation equations for Bingham fluid and Newtonian fluid permeation diffusion considering the filling factor (γ) were derived. Furthermore, the indoor grouting experiment data are compared and analyzed with the calculation results of the original formula and the optimized formula. The results show that when ignoring the unfilled pores, the original formula calculating the diffusion radius will be small; the calculation results of the optimized formula considering the filling factor (γ) are closer to the actual experiment results. Moreover, based on the calculation results of the optimized formula, the order of influencing factors of the permeation diffusion radius is rock content > void ratio > water—cement ratio > grouting pressure.

Background Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. Methods Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. Results Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m 2 , and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19–1.72, P  < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07–1.40], P  = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92–0.98], P  = 0.011) and GLS (HR [95% CI], 1.04 [1.01–1.07], P  = 0.032). Conclusions EAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases. Trial registration URL: https://clinicaltrials.gov . Identifier: NCT00005121.

Glaucoma is the leading cause of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form globally and has been linked to mitochondrial dysfunction and energy deficiency. Plasma was used to investigate the energy metabolomic profiles of patients with POAG and controls, and to determine the metabolite flux within the core interconnected energy pathways. Targeted liquid chromatography-mass spectrometry (LC-MS) was used to analyze plasma energy metabolism in POAG patients and controls. Differential metabolite expression analysis, correlation analysis, and pathway flux analysis were then conducted to elucidate the metabolic alterations and the mechanisms underlying POAG. Our findings reveal elevated levels of D-Glucose-6-phosphate(G6P), 6-Phosphogluconic acid(6PGA), Adenosine diphosphate(ADP), Adenosine monophosphate(AMP), Adenosine triphosphate(ATP), Guanosine diphosphate(GDP), Inosine monophosphate(IMP), Phosphoenolpyruvic acid(PEP), Phosphorylethanolamine(pEtN), and uridine diphosphate N-acetylglucosamine(UDP-GlcNAc) in POAG patients. Conversely, POAG patients showed reduced ratios of ATP/ADP, Glycerol-3-phosphate(G3P)/ Dihydroxyacetone phosphate(DHAP), 1,3-Bisphosphoglyceric acid(BPG)/DHAP, PYR/PEP, Fumarate/Succinate, Arginine/ASA, and Citrulline/Ornithine. These findings collectively suggest disrupted flux in glycolysis, the TCA cycle, urea cycle, and tyrosine metabolism, offering new insights into POAG mechanisms and potential therapeutic strategies targeting energy metabolic pathways.

Introduction: The reduction of drag is a crucial concern within the shipping industry as it directly influences energy consumption. This study addresses this issue by proposing a novel approach inspired by the unique ridge structure found on killer whale skin. The objective is to develop a non-smooth surface drag reduction method that can effectively decrease drag and improve energy efficiency for ships. Methods: The study introduces a technique involving the creation of transverse bionic groove surfaces modeled after the killer whale skin’s ridge structure. These grooves are aligned perpendicular to the flow direction and are intended to modify the behavior of turbulent boundary layer flows that form around the ship’s hull. Numerical simulations are employed using the Shear Stress Transport k-ω model to analyze the effects of the proposed groove surface across a wide range of flow conditions. The research investigates the impact of various parameters, such as the width-to-depth ratio (λ/A), groove depth, and inlet velocity, on the drag reduction performance of the bionic groove surface. Results: The study reveals several key findings. Optimal shape parameters for the bionic groove surface are determined, enabling the most effective drag reduction. The numerical simulations demonstrate that the proposed groove surface yields notable drag reduction benefits within the velocity range of 2∼12 m/s. Specifically, the friction drag reduction ratio is measured at 26.91%, and the total drag reduction ratio at 9.63%. These reductions signify a substantial decrease in the forces opposing the ship’s movement through water, leading to enhanced energy efficiency. Discussion: Comparative analysis is conducted between the performance of the bionic groove surface and that of a smooth surface. This investigation involves the examination of velocity gradient, streamwise mean velocity, and turbulent intensity. The results indicate that the bionic groove structure effectively mitigates viscous stress and Reynolds stress, which in turn reduces friction drag. This reduction in drag is attributed to the alteration in flow behavior induced by the non-smooth surface. Conclusion: The study proposes a novel approach for drag reduction in the shipping industry by emulating the ridge structure of killer whale skin. The transverse bionic groove surface, aligned perpendicular to flow direction, demonstrates promising drag reduction outcomes across diverse flow conditions. Through systematic numerical simulations and analysis of key parameters, the research provides insights into the drag reduction mechanism and identifies optimal design parameters for the groove surface. The potential for significant energy savings and improved fuel efficiency in maritime transportation underscores the practical significance of this research.

Previously conducted studies have established that the soil–rock mixture in the Chongqing area has the characteristics of loose structure, poor stability, strong permeability, and so on. When building a tunnel in a soil–rock mixture stratum, it is necessary to reinforce the surface rock mass and surrounding rock by grouting to improve the safety of tunnel excavation. To study the diffusion mechanism of cement slurry (Bingham fluid) in soil–rock mixtures, based on the Bingham fluid flow equation and slurry diffusion model, the Bingham fluid fracture diffusion formula was derived, and field grouting tests and indoor model tests were carried out with soil–rock mixtures in the Chongqing area as the research object. The fracture grouting diffusion formula was verified and analyzed using the test data. The research results show that the theoretical calculation results of various working conditions are close to the actual test results (the error of indoor model test results is less than 3%, and the error of field test results is less than 5%). A Bingham fluid fracture diffusion formula has been developed that applies to various working conditions of fracture grouting of soil–rock mixtures and has a good prediction effect on the value of the fracture diffusion radius.