Search Results (602)

The Shahejie Formation in Nanpu Sag is a crucial region for deep-layer hydrocarbon exploration in the Bohai Bay Basin. To address the impact of faults on sublacustrine fan formation and spatial distribution within the study area, this study integrated well logging, laboratory analysis, and 3D seismic data to systematically analyze sedimentary characteristics of sandbodies from the first member of the Shahejie Formation (Es₁) sublacustrine fans, clarifying their planar and cross-sectional distributions. Further research indicates that Gaoliu Fault activity during Es₁ deposition played a significant role in fan development through two mechanisms: (1) vertical displacement between hanging wall and footwall reshaped local paleogeomorphology; (2) tectonic stresses generated by fault movement affected slope stability, triggering gravitational mass transport processes that remobilized fan delta sediments into the central depression zone as sublacustrine fans through slumping and collapse mechanisms. Core observations reveal soft-sediment deformation features, including slump structures, flame structures, and shale rip-up clasts. Seismic profiles show lens-shaped geometries with thick centers thinning laterally, exhibiting lateral pinch-out terminations. Inverse fault-step architectures formed by underlying faults control sandbody distribution patterns, restricting primary deposition locations for sublacustrine fan development. The study demonstrates that sublacustrine fans in the study area are formed by gravity flow processes. A new model was established, illustrating the combined control of the Gaoliu Fault and reverse stepover faults on fan development. These findings provide valuable insights for gravity flow exploration and reservoir prediction in the Nanpu Sag, offering important implications for hydrocarbon exploration in similar lacustrine rift basins. Full article

Soil microbial communities are crucial for ecosystem services, soil fertility, and the resilience of agroecosystems. This study investigated how long-term (31 years) agronomic practices—tillage, NPK fertilization, and cropping system—along with measured environmental variables influence the microbial biomass and its community composition in Chernozem soil under corn cultivation. The polyfactorial field experiment included three tillage treatments ((moldboard (MT), ripped (RT), strip (ST)), two fertilization regimes (NPK (N: 160; P: 26; K: 74 kg/ha), and unfertilized control) and two cropping systems (corn monoculture and corn–wheat biculture). The soil samples (0–30 cm) were collected in June and September 2023. Microbial biomass and community structure were quantified using phospholipid fatty acid (PLFA) analysis, which allowed the estimation of total microbial biomass and community composition (arbuscular mycorrhizal (AM) fungi, fungi, Gram-negative (GN) and Gram-positive (GP) bacteria, actinomycetes). Our results showed that microbial biomass increased from June to September, rising by 270% in unfertilized plots and by 135% in NPK-fertilized plots, due to higher soil moisture. Reduced tillage, especially ST, promoted significantly higher microbial biomass, with biomass reaching 290% and 182% of that in MT plots in June and September, respectively. MT had a higher ratio of bacteria-to-fungi compared to RT and ST, indicating a greater sensitivity of fungi to disturbance. NPK fertilization lowered soil pH by about one unit (to 4.1–4.8) and reduced microbial biomass—by 2% in June and 48% in September—compared to the control, with the particular suppression of AM fungi. The cropping system had a smaller overall effect on microbial biomass. Full article

N6-methyladenosine (m6A) represents the most common and thoroughly investigated RNA modification and exerts essential functions in regulating gene expression through influencing the RNA stability, the translation efficiency, alternative splicing, and nuclear export processes. The rapid development of high-throughput sequencing approaches, including miCLIP and MeRIP-seq, has profoundly transformed epitranscriptomics research. These techniques facilitate the detailed transcriptome-wide profiling of m6A modifications, shedding light on their crucial roles in diverse biological pathways. This review comprehensively examines the identification, mechanisms of regulation, and functional consequences of m6A modifications. It emphasizes their critical roles in physiological contexts, encompassing immune function, neuronal development, and the differentiation of stem cells. Additionally, the review discusses the contributions of m6A dysregulation to pathological conditions, including cancer, neurodegenerative diseases, and disorders of metabolism. We also discuss the development and application of machine-learning algorithms for m6A site prediction, emphasizing the integration of sequence-based, structural, and evolutionary conservation features to enhance the predictive accuracy. Furthermore, the potential of applying the findings from m6A research in precision medicine and drug development is examined. By synthesizing the current knowledge and emerging trends, this review aims to provide a comprehensive understanding of m6A biology and its translational potential, offering new perspectives for future research and therapeutic innovation. Full article

This study presents a discrete event simulation model to minimize operating costs in quarry mining processes by determining the optimal allocation of backhoes and dump trucks, which are the primary mining equipment. The modeling focuses on four principal vehicle types (24-ton dump truck, 2.0 m³ backhoe, 41-ton dump truck, 4.64 m³ backhoe) commonly deployed in quarry mining. The simulation replicates the sequential mining stages involving soil removal, rock ripping (weathered rock or weathered soil), and blasting operations. This methodology is applied to a case study of mining process planning under resource constraints, incorporating real-world quarry conditions in South Korea. Results demonstrate that optimizing the number of equipment units reduces construction costs and shortens the construction period by decreasing dump truck waiting times. When the number of backhoes is limited to 10 during operations, findings indicate an increase in costs and a gradual decline in net profit. Additionally, the interaction between the 24-ton and 41-ton dump trucks is shown to influence the optimal allocation strategy. The simulation-based optimization executes iterative experiments for each scenario, yielding statistically robust results within a 95% confidence interval, thereby supporting informed decision-making for managers. Full article

The accurate classification of cocoa pod ripeness is critical for optimizing harvest timing, improving post-harvest processing, and ensuring consistent quality in chocolate production. Traditional ripeness assessment methods are often subjective, labor-intensive, or destructive, highlighting the need for automated, non-invasive solutions. This study evaluates the performance of R-CNN-based deep learning models—Faster R-CNN and Mask R-CNN—for the detection and segmentation of cocoa pods across four ripening stages (0–2 months, 2–4 months, 4–6 months, and >6 months) using the RipSetCocoaCNCH12 dataset, which is publicly accessible, comprising 4116 labeled images collected under real-world field conditions, in the context of precision agriculture. Initial experiments using pretrained weights and standard configurations on a custom COCO-format dataset yielded promising baseline results. Faster R-CNN achieved a mean average precision (mAP) of 64.15%, while Mask R-CNN reached 60.81%, with the highest per-class precision in mature pods (C4) but weaker detection in early stages (C1). To improve model robustness, the dataset was subsequently augmented and balanced, followed by targeted hyperparameter optimization for both architectures. The refined models were then benchmarked against state-of-the-art YOLOv8 networks (YOLOv8x and YOLOv8l-seg). Results showed that YOLOv8x achieved the highest mAP of 86.36%, outperforming YOLOv8l-seg (83.85%), Mask R-CNN (73.20%), and Faster R-CNN (67.75%) in overall detection accuracy. However, the R-CNN models offered valuable instance-level segmentation insights, particularly in complex backgrounds. Furthermore, a qualitative evaluation using confidence heatmaps and error analysis revealed that R-CNN architectures occasionally missed small or partially occluded pods. These findings highlight the complementary strengths of region-based and real-time detectors in precision agriculture and emphasize the need for class-specific enhancements and interpretability tools in real-world deployments. Full article

The development of reversible animal models for the study of intestinal pathologies is essential to reduce the number of animals used in research and to better understand disease mechanisms. In this study, we present a reversible model of intestinal malabsorption through the administration of sublethal doses of ebulin-f, a ribosome-inactivating protein, and validate its usefulness by monitoring vitamin C absorption. The scientific community increasingly recognizes the importance of rationalizing experimental designs, optimizing treatment protocols, and minimizing the use of animals in research models. Thus, new methodologies are needed to minimize invasive sampling and to develop reversible animal models that recover physiologically post-study. Such models are essential for in vivo studies of human pathologies. Sublethal doses of ebulin-f (2.5 mg/kg) administered intraperitoneally to female Swiss CD1 mice (n = 6 per group) can cause reversible intestinal alterations in the small intestine, which offer the possibility of having a valuable reversible study model of malabsorption for the investigation of this syndrome. To verify whether nutrient absorption is altered, we used vitamin C as a traceable nutrient that can be quantified in the blood. Peripheral blood samples were collected through the retro-orbital area at 30, 80, 120, 180, and 1440 min post-administration, treated with DTT and MPA, and analyzed using a validated UV/Vis–HPLC method to indirectly determine vitamin C absorption by enterocytes. Pharmacokinetic analysis revealed significantly increased vitamin C absorption on days 1 and 3 post-treatment (AUC values of 3.65 × 10⁴ and 7.10 × 10⁴, respectively) compared to control (0.94 × 10⁴), with partial recovery by day 22 (3.27 × 10⁴). Blood concentration profiles indicate that intestinal damage peaks at day 3, followed by significant regeneration by day 22, establishing this as a viable reversible model for inflammatory bowel disease research. Full article

Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA N-glycosylases (also named ribosome-inactivating proteins, RIPs) are promising tools for cancer therapy because, by combining rRNA-glycosylase’s high cytotoxicity with carrier selectivity, they can specifically eliminate target neoplastic cells. In the last few years, 3D models have been extensively used in cancer research, particularly for target-specific drug screening. This study aimed to evaluate the possibility of utilizing ribosome-inactivating protein (RIP)-containing ITs to selectively target TfR1-, EGFR1- and Her2-expressing sarcoma adherent cells (ACs), spheroids (SSs) and organoids (ORs). To compare Its’ efficacy and ability to induce apoptosis, we performed dose–response viability and caspase 3/7 activation assays on rhabdomyosarcoma and osteosarcoma ACs, SSs and ORs treated with Tf-IT, αEGFR1-IT and αHer2-IT. Our results indicate that, compared to the corresponding unconjugated RIPs, all ITs showed increased cytotoxicity in sarcoma ACs. Despite the increased complexity characterizing 3D models, the higher IC₅₀ differences between ITs and unconjugated RIPs were obtained in ORs, which appeared more resistant to the nonspecific killing of the RIPs than either the ACs or SSs, thus augmenting the therapeutic window between unconjugated and conjugated RIPs. IT induced a more delayed apoptosis in 3D compared to 2D models. Our results provide essential outcomes for the potential use of these RIP-based ITs as a therapeutic strategy to treat sarcoma. Full article

Exercise is a well-recognized non-pharmacological strategy for preventing and managing metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD). While the benefits of exercise are thought to involve epigenetic mechanisms, the precise role of RNA m6A methylation remains unclear. This study investigates how treadmill exercise modulates RNA m6A methylation to prevent MASLD in a high-fat diet (HFD)-induced mouse model. Male C57BL/6 mice were fed either a standard diet (SD) or HFD for 12 weeks, with a subset of HFD-fed mice undergoing treadmill exercise (HFD + Ex). Liver pathology and biochemical markers were assessed. RNA sequencing (RNA-Seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to identify differentially expressed genes (DEGs) and m6A methylation changes. Key candidate gene Paqr7 was validated through siRNA-mediated knockdown in AML-12 cells to assess its role in lipid metabolism. Treadmill exercise alleviated MASLD-related pathology and biochemical abnormalities. RNA-Seq identified 984 DEGs in the HFD vs. SD comparison and 544 in the HFD + Ex vs. HFD comparison. Intersection analysis identified 155 genes upregulated in MASLD and downregulated following exercise. MeRIP-seq revealed 225 hypermethylated and 208 hypomethylated m6A peaks in HFD + Ex vs. HFD groups. Integrative analysis highlighted Adra2b, Lipa, and Paqr7 as key exercise-responsive genes. Silencing Paqr7 through siRNA-mediated knockdown reduced lipid accumulation and suppressed lipogenic gene expression, suggesting its role in exercise-mediated MASLD improvement. Treadmill exercise prevents MASLD by modulating RNA m6A methylation, with Paqr7 emerging as a potential regulator of lipid metabolism. These findings highlight epigenetic modulation as a key mechanism in exercise-induced liver protection. Full article

As a type II ribosome-inactivating protein (RIP-II) toxin, Ricin has garnered widespread recognition due to its inherent qualities as an easily prepared and highly stable substance, posing serious implications as a potential chemical and biological terrorist threat. For the detection of ricin, traditional immunoassay technologies, including methods like peptide cleavage combined with liquid chromatography mass spectrometry (LC-MS) or the more commonly used enzyme-linked immunosorbent assay (ELISA), have offered reliable results. However, these techniques are unfortunately limited by the requirement of a complex sample pretreatment process, which can be time-consuming and labor-intensive. In an effort to overcome these limitations, a highly sensitive and selective method was introduced via metal element labeling combined with inductively coupled plasma mass spectrometry (ICP-MS) in this research. The method centered on designing and synthesizing a europium-labeled compound (DOTA-NHS-Eu) that specifically targets the amino groups (-NH₂) on ricin. The compound, coupled with the application of specific magnetic beads, achieved the specific enrichment and subsequent quantitative detection of ricin by ICP-MS, which is based on the amount of europium element present. The established method demonstrated high specificity for ricin recognition, with a signal response to bovine serum protein that was found to be less than 10% of that for ricin. Furthermore, the calibration curve created for the method (y = 81.543x + 674.02 (R² > 0.99)) for quantifying ricin in a concentration range of 1.0–100 μg/mL demonstrated good linearity. The method was further evidenced by the limit of detection and quantitation results of 0.1 and 1.89 μg/mL, respectively. Collectively, these findings suggested that the research has offered a highly sensitive and selective method for ricin detection, which was not only easy to operate but also provided efficient results. The scheme showed great potential for the verification of chemical weapons and the destruction of toxic chemicals, therefore representing a significant advancement in the field of biomolecular detection and analysis. Full article

This study examines the cytotoxicity of two silver nanoparticle formulations—AgNPs conjugated with chlorhexidine (AgNPs-CHL) and AgNPs conjugated with polyethylene glycol and metronidazole (AgNPs-PEG-MET)—as examples of the surface functionalization of silver nanoparticles with drugs via sulfur–silver bonds and nitrogen–silver interactions. We previously reported the synthesis of these NPs and their efficiency in periodontitis treatment. Here, we analyze the relationships between the cytotoxic mechanisms of AgNPs and their surface chemistry. UV–Vis spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX) were used for physicochemical studies of the conjugates in two environments: aqueous solutions and commonly used cell culture media. Cytotoxicity was assessed in human fetal osteoblasts (hFOB 1.19) and human gingival fibroblasts (HGF-1) through BrdU and LDH assays, ROS detection, cell cycle analysis, apoptosis assays, and protein expression studies. AgNPs-CHL showed aggregation and increased hydrodynamic diameters in the culture medium, while AgNPs-PEG-MET remained stable. Both exhibited concentration-dependent cytotoxicity: AgNPs-CHL at 0.4–10 μg/mL and AgNPs-PEG-MET at 0.75–10 μg/mL. AgNPs-CHL, in which silver surface functionalization was realized via nitrogen–silver interactions, induced significant ROS generation, LDH release, and necroptosis, marked by increased RIP1, RIP3, and MLKL proteins. In the case of AgNPs-PEG-MET, where sulfur–silver bonds combined the drug via a PEG linker, they triggered apoptosis, as evidenced by elevated caspase-2 levels and flow cytometry. These findings highlight that the type of surface functionalization of silver nanoparticles significantly influences their physicochemical behavior and biological effects. Understanding these mechanisms is crucial in designing safer, more effective nanoparticle-based therapies for periodontal and other inflammatory conditions. Full article

Rip currents at featureless beaches (i.e., beaches lacking sandbars or channels) are often hydrodynamically controlled, exhibiting intermittent and unpredictable behaviors that pose significant risks to recreational beach users. This study assessed occurrences of rip currents under a range of idealized morphology configurations and hydrodynamic wave forcing parameters using a wave-resolving Boussinesq-type model. Numerical experiments revealed that rip currents with durations on the time scale of 10 min are generated in the forms of vortex pairs, intensified eddies, mega-rips, and eddies shedding from longshore currents. In general, the key conditions that promote rip current formation at featureless beaches include shoreline curvature, headlands, moderately mild beach slopes (e.g., 0.02–0.03), normal or near-normal wave incidence, and large wave heights. Most importantly, this study highlights inherent uncertainties in rip current occurrences, particularly under conditions usually perceived as low risk: low wave heights, short wave periods, oblique wave incidence, and straight shorelines. These conditions can lead to transient rip currents and pose an unexpected hazard that coastal communities should be aware of. Full article

Extreme rainfall events pose a growing threat to slab track subgrades by triggering mud pumping through fines migration and structural voids. This study introduces two innovations to enhance climate resilience in high-speed railway infrastructure: (i) the Rain Intensity Ponding (RIP) method, which links regional rainfall statistics with axle-pass thresholds to predict mud pumping potential; (ii) an optimized drainage retrofit using permeable shoulders and blind ditches. Physical model tests reveal that mud pumping occurs only when structural gaps, ponding, and cyclic loading coincide. The RIP method correctly identified a 71% exceedance in the critical ponding duration (52 min) on a representative high-speed line in Eastern China, explaining recurrent failures. Parametric analyses show that the proposed drainage retrofit—using shoulder fill with ka > 23 mm/s and blind ditches with kg > 23 mm/s—reduces ponding time by up to 90% under 1-year recurrence storms. This study establishes a physics-based, region-specific strategy for mud pumping mitigation, offering guidance for climate-adaptive slab track design and operation. Full article

Second-order Linear Active Disturbance Rejection Controller (SLADRC) is a powerful control technique. Ongoing research is focused on simplifying tuning procedures, extending applicability to handle more complex systems, and ensuring efficient real-time implementation. In this proposed work, four different tuning approaches, using the Atomic Orbital Search (AOS) optimization algorithm concerning the number of tuning parameters, are presented. The performance of each tuning method for stabilizing the rotary inverted pendulum in the upright position and tracking trajectory is analyzed and validated through simulation and experimentation. The results indicate that the reduced number of SLADRC controller parameters tuned using AOS optimization provides superior performance compared to the controller with more tuning parameters for the nonlinear rotary inverted pendulum. From the analysis method, II tuning, $b_0, {\omega }_c, \mathrm{a}\mathrm{n}\mathrm{d} k$ provide the optimum results of settling time ($T_s$), 1.5 s, and maximum angle deviation of $\theta \left(3.8°\right), \alpha (3°)$. Full article

Butein (3,4,2′,4′-tetrahydroxycalone) is a chalcone derivative and plant polyphenol extracted from Rhus verniciflua Stokes. Butein has an open C-ring structure and a variety of biological activities. Molecular mechanisms by which butein could affect cell viability, ROS levels, mitochondrial function, apoptosis, and necrosis in prostate cancer cells were investigated using 2D monolayer and 3D sphere culture systems. Cytotoxicity and cell cycle monitoring showed that butein treatment decreased cell viability and increased peaks of sub-G₀/G₁ and G₂/M phases analyzed by flow cytometry. These changes were observed with a concurrent induction of DNA damage, apoptosis, and necrosis. Although 3D spheres treated with butein showed decreased cell viability, they were slightly more resistant than cells in 2D cultures. This phenomenon was accompanied by an increase in mediators of apoptosis and necrosis. Monitoring changes of apoptosis-related proteins via Western blot showed that butein decreased caspase-3, PARP, and Bcl-2, but increased Bax. Meanwhile, butein increased levels of p-receptor interacting serine/threonine–protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like kinase (p-MLKL) known to be mediators of necrosis. Overall, our data suggest that butein can induce apoptosis and necrosis of prostate cancer cells by regulating pro- and anti-apoptotic proteins via ROS. Thus, butein might be a potential agent for treating prostate cancer. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article