Search Results (74,202)

Marine ecosystems represent a largely untapped reservoir of bioactive compounds with significant pharmacological potential. This study aimed to evaluate the therapeutic properties of ethanol extracts from four marine species: Padina australis, Spatoglossum asperum, Holothuria (Halodeima) atra, and Hypnea valentiae. Phytochemical screening, along with a comprehensive series of in vitro, in vivo, and in silico assays, was performed to evaluate the extracts’ pharmacological activities, including antioxidant potential (2,2-diphenyl-1-picrylhydrazyl assay), anti-inflammatory effect (carrageenan-induced paw edema method), analgesic activity (acetic acid-induced writhing and tail immersion tests), and anti-arthritic efficacy (protein denaturation assay). The extracts were found to be rich in flavonoids, tannins, alkaloids, saponins, glycosides, and phenolic compounds, which may underlie the observed bioactivities. In the acetic acid–induced writhing test, Hypnea valentiae at 400 mg/kg exhibited the highest peripheral analgesic activity, producing 82.51% inhibition of writhing (p < 0.001). In the tail immersion assay, Padina australis at doses of 200 and 400 mg/kg showed significant central analgesic effects, as evidenced by increased latency time and percentage of maximum possible effect (MPE). In the carrageenan-induced paw edema model, several treatment groups, including Padina australis, Hypnea valentiae, Spatoglossum asperum, and Holothuria atra, at both tested doses showed marked suppression of inflammation, with some groups achieving complete inhibition (100%; p < 0.001) at 120 min. The ethanol extract of Holothuria atra exhibited the strongest antioxidant and anti-arthritic activities, with an IC₅₀ value of 88.39 µg/mL in the DPPH assay and 81.35% inhibition of protein denaturation. Additionally, the compounds derived from the four marine species exhibited significant binding affinity to the selected target receptors, thereby validating the experimental findings. The marine species studied possess multifaceted pharmacological properties, supporting their potential as natural sources for developing therapeutic agents supporting the blue economy. Further studies are recommended to isolate active compounds and elucidate underlying mechanisms to support future drug development efforts. Full article

The catalytic hydrogenation of carbon dioxide (CO₂) represents a transformative approach for reducing greenhouse gas emissions while producing sustainable fuels and chemicals, with ethanol being particularly promising due to its compatibility with existing energy infrastructure. Despite significant progress in converting CO₂ to C₁ products (e.g., methane, methanol), selective synthesis of C₂₊ compounds like ethanol remains challenging because of competing reaction pathways and byproduct formation. Recent advances in thermo-catalytic CO₂ hydrogenation have explored diverse catalyst systems including noble metals (Rh, Pd, Au, Ir, Pt) and non-noble metals (Co, Cu, Fe), supported on zeolites, metal oxides, perovskites, silica, metal–organic frameworks, and carbon-based materials. These studies reveal that catalytic performance hinges on the synergistic effects of multimetallic sites, tailored support properties and controlled reaction micro-environments to optimize CO₂ activation, controlled hydrogenation and C−C coupling. Mechanistic insights highlight the critical balance between CO₂ reduction steps and selective C−C bond formation, supported by thermodynamic analysis, advanced characterization techniques and theoretical calculations. However, challenges persist, such as low ethanol yields and undesired byproducts, necessitating innovative catalyst designs and optimized reactor configurations. Future efforts must integrate computational modeling, in situ/operando studies, and renewable hydrogen sources to advance scalable and economically viable processes. This review consolidates key findings, proposes potential reaction mechanisms, and outlines strategies for designing high-efficiency catalysts, ultimately providing reference for industrial application of CO₂-to-ethanol technologies. Full article

Background: The year 2025 witnessed paradigm-shifting advances in gynecologic oncology, with pivotal clinical trial results redefining therapeutic standards across cervical, ovarian, endometrial, and vulvar cancers. Objectives: This systematic review aimed to comprehensively identify, synthesize, and critically evaluate pivotal phase II and III randomized controlled trials and major studies presented at the major annual meetings, alongside significant peer-reviewed publications from 2025 that introduce innovative therapeutic strategies across gynecologic malignancies. Methods: Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, this review involved exhaustive searches of electronic databases (PubMed/MEDLINE, Embase), conference proceedings (ASCO 2025, ESMO 2025), and major oncology journals for records from January to December 2025. Inclusion criteria encompassed: (1) Phase II or III randomized controlled trials (RCTs) and (2) Non-randomized studies (including phase I and II trials), reporting on novel therapeutic approaches in gynecologic oncology. All studies were required to report primary survival endpoints (overall survival or progression-free survival) or key efficacy outcomes. Study selection, data extraction, and methodological quality assessment were performed independently by two reviewers, with disagreements resolved through consensus or third-party adjudication. Results: From 1842 records, 23 studies met inclusion criteria (17 phase-III RCTs and 6 non-phase III RCTs/early-phase studies), distributed as follows: cervical cancer (9 studies, 39%), ovarian cancer (9 studies, 39%), endometrial cancer (4 studies, 17.5%), and vulvar cancer (1 study, 4.5%). The major advances identified include: (1) In cervical cancer, the KEYNOTE-A18 trial established pembrolizumab combined with chemoradiotherapy as a new standard for high-risk locally advanced disease, while the PHENIX trial validated sentinel lymph node biopsy as a safe surgical de-escalation strategy. (2) In ovarian cancer, the ENGOT-ov65/KEYNOTE-B96 trial demonstrated the first statistically significant overall survival improvement with an immune checkpoint inhibitor in platinum-resistant recurrent disease, establishing pembrolizumab plus weekly paclitaxel as a new standard of care. Novel therapeutic mechanisms, including glucocorticoid receptor modulation (ROSELLA trial) and cadherin-6-targeted antibody-drug conjugates (REJOICE-Ovarian01), showed remarkable efficacy. (3) In endometrial cancer, updated analyses from NRG GY018 and RUBY trials solidified the role of first-line immuno-chemotherapy, with differential benefits according to mismatch repair status. (4) In vulvar cancer, a pivotal phase II study demonstrated meaningful clinical activity of anti-PD-1 therapy in advanced disease. (5) The extensive circulating tumor DNA analysis from the CALLA trial provided crucial insights into biomarker dynamics in cervical cancer. Conclusions: The convergence of high-impact data from 2025 established multiple new standards of care, emphasizing biomarker-driven approaches, immunotherapy integration across disease stages, and novel mechanisms to overcome resistance, while highlighting challenges in treatment sequencing and global access. Full article

During the high-intensity mining of shallow-buried thick coal seams, the formation of a water-conducting fracture zone within the overburden is a primary cause of damage to the groundwater system. To address the challenge of balancing efficiency and cost in traditional water-retaining mining methods, this study proposes and validates a trapezoidal strip filling mining technology based on the “span reduction effect”. By developing a mechanical model of a four-sided simply supported thin plate representing the key layer, the fundamental mechanism of the filling body was elucidated. This mechanism involves the active adjustment of the support boundary, which effectively reduces the force span of the key layer. Furthermore, leveraging the fourth-power relationship (w ∝ a⁴) between deflection and span, the bending deformation of the overburden rock is exponentially mitigated. This study employs a four-tiered integrated verification system comprising theoretical modeling, physical simulation, numerical simulation, and engineering field testing: First, theoretical calculations indicate that reducing the effective span of the key layer by 40% can decrease its maximum deflection by 87%. Second, large-scale physical similarity simulations predict that implementing this filling method can significantly control the height of the water-conducting fracture zone, reducing it from 94 m under the collapse method to 58 m, which corresponds to a 45.5% reduction in surface settlement. Third, FLAC^3D numerical simulations further elucidated the mechanical mechanism by which the backfill system transforms stress distribution from “coal pillar-dominated bearing capacity” to “synergistic bearing capacity of backfill and coal pillars”. Shear failure in the critical layer was suppressed, and the development height of the plastic zone was restricted to approximately 54 m, showing high consistency with physical simulation results. Finally, actual measurements of water injection through the inverted hole underground provide direct evidence: The heights of the water-conducting fracture zones in the filling working face and the collapse working face are 59 m and 93 m, respectively, reflecting a reduction of 36.6%. Based on the consistency between measured and simulated results, the numerical model employed in this study has been effectively validated. Research indicates that employing trapezoidal strip filling technology based on principal stress dynamics regulation can effectively promote a shift in the failure mode of the overlying critical layer from “fracture–conduction” to “bending–subsidence”. This mechanism provides a clear mechanical explanation and predictable design basis for the green mining of shallow coal seams. Full article

Cadmium (Cd) is an environmental toxicant that poses significant risks to food safety and public health through its bioaccumulation in the food chain. The liver is a primary target for chronic Cd toxicity, yet the system-level mechanisms, particularly in physiologically relevant swine models, remain incompletely understood. This study employed an integrated multi-omics approach to elucidate the mechanisms of Cd-exposed hepatotoxicity in weaned piglets. We combined histopathological examination, transmission electron microscopy, and transcriptome sequencing. Our results revealed severe hepatic damage, characterized by disorganized architecture, vacuolar degeneration, mitochondrial dysfunction, and autophagic activation. Network toxicology predicted 3727 potential targets of Cd-exposed liver injury, while transcriptomics identified 1092 differentially expressed genes (DEGs). Crucially, the convergent analysis of both datasets demonstrated that the PI3K-Akt signaling pathway was the central hub, pinpointing it as a pivotal mechanism in Cd-driven hepatotoxicity. Functional enrichment analyses further highlighted dysregulation in immune-inflammatory responses, lipid metabolism, and oxidative stress. Our findings provide a comprehensive systems-level perspective on chronic Cd hepatotoxicity in a translational swine model. We propose the PI3K-Akt pathway and other identified core targets (EGFR, histones, ribosomal proteins) as critical biomarkers for monitoring Cd contamination in swine production chains, offering valuable insights for environmental risk assessment and agricultural product safety. Full article

Abiotic stress of cold is one of the limitation factors that hinder the production of alfalfa (Medicago sativa). Although there are a large number of studies suggesting that non-coding RNAs (ncRNAs) play an important role in plant response to abiotic stress, the mechanism by which ncRNAs and competing endogenous RNAs (ceRNAs) influence the low-temperature tolerance of alfalfa remains understudied. In this study, we integrated whole-transcriptome RNA-seq and genome-wide association studies (GWASs) to identify cold stress-related metabolic pathways and candidate genes, differentially expressed (DE) mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Degradome sequencing was used to verify the ceRNA network under cold stress. A total of 46,936 DEmRNAs were identified. Ribosome (ko03010), amino sugar and nucleotide sugar metabolism (ko00520), ribosome biogenesis in eukaryotes (ko03008), circadian rhythm–plant (ko00270), and starch and sucrose metabolism (ko00500) were the top five KEGG terms with the highest p-value, enriching the most number of DEmRNAs. MS.gene53818 (MsUAM1) was considered to be the critical candidate gene for alfalfa response to cold stress by conjoint analysis of GWASs and DEmRNAs. A total of 223 DEmiRNAs, 1852 DElncRNAs, and 13 DEcircRNAs were identified under cold stress. Functional analysis indicates that they play important roles in GO terms such as leaf development (GO:0048366), DNA-binding transcription factor activity (GO:0003700), central vacuole (GO:0042807), response to auxin (GO:0009733), and water channel activity (GO:0015250), as well as in KEGG pathways such as plant hormone signal transduction, starch and sucrose metabolism, and flavone and flavonol biosynthesis (ko00944). A ceRNA network comprising 28 DElncRNAs, 8 DEcircRNAs, 11 DEmiRNAs, and 23 DEmRNA triplets was constructed. In this study, mRNAs and ncRNAs were identified that may be involved in alfalfa’s response to cold stress, and a ceRNA regulatory network related to cold stress was established, providing valuable genic resources for further research on the molecular mechanisms underlying alfalfa cold stress. Full article

This paper addresses the core conflict between long-range communication and ultra-low power requirements in sensing nodes for Wireless Sensor Networks (WSNs) by proposing a wake-up receiver (WuRx) design featuring nanowatt-level power consumption and high sensitivity. Conventional architectures are plagued by low energy efficiency, poor demodulation reliability, and insufficient clock synchronization accuracy, which hinders their practical application in real-world scenarios like WSNs. The proposed design employs an event-triggered mechanism, where a continuously operating, low-power WuRx monitors the channel and activates the main system only after validating a legitimate command, thereby significantly reducing standby power. At the system design level, a key innovation is direct conjugate matching between the antenna and a multi-stage rectifier, replacing the traditional 50 Ohm interface, which substantially improves energy transmission efficiency. Furthermore, a mean-detection demodulation circuit is introduced to dynamically generate an adaptive reference level, effectively overcoming the challenge of discriminating shallow modulation caused by signal saturation in the near-field region. At the baseband processing level, a configurable fault-tolerant correlator logic and a data-edge-triggered clock synchronization circuit are designed, combined with oversampling techniques to suppress clock drift and enhance the reliability of long data packet reception. Fabricated in a TSMC 0.18 µm CMOS process, the receiver features an ultra-low power consumption of 305 nW at 0.5 V and a high sensitivity of −47 dBm, enabling a communication range of up to 400 m in the 920–925 MHz band. Through synergistic innovation at both the circuit and system levels, this research provides a high-efficiency, high-reliability wake-up solution for long-range WSN nodes, effectively promoting the large-scale application of WSN technology in practical deployments. Full article

Control of process-related impurities is of critical importance for developing an efficient and suitable synthetic process of an active pharmaceutical ingredient. In the study of a key intermediate of silodosin (KIS), two process-related impurities including the benzaldehyde impurity (BAI) and indole impurity (IDI) were prepared and fully characterized to determine their downstream fate. Under optimized conditions, BAI was formed in a yield of ~48% by treating KIS with 10% hydrogen peroxide at 60 °C. Interestingly, BAI would not be expected to be the major product under the apparent Baeyer–Villiger oxidative condition. Furthermore, by adding 20 mM FeCl₃ into the above 10% hydrogen peroxide solution, IDI became the major product in a yield of ~43% under this Fenton reaction-like condition. The probable formation mechanism of IDI was discussed and validated in the context of certain structurally similar substrates. Full article

Waste battery powder (WBP) can effectively enhance the service performance of virgin asphalt with sol–gel structures; however, its toughening mechanism for sol–gel virgin asphalt still lacks rigorous mechanical characterization. Therefore, the objective of this study is to investigate the toughening of WBP-modified asphalt based on the mechanical parameter of cracking area. First, a 12% content of WBP was incorporated into the sol–gel 70# virgin asphalt to prepare WBP-modified asphalt and its fatigue performance was evaluated through linear amplitude, non-damage, and damage time sweep tests. Then, energy–mechanics balance equations were used to establish a cracking area model. Furthermore, the asphalt cracking area was employed to quantify its induced damage and determine the representative rate for the cracking damage process (k_cd). Finally, the activation energy for cracking damage (E_acd) was used to quantify the difficulty of the cracking damage process. The scanning electron microscope test was employed to examine the microstructure of WBP-modified asphalt and the E_acd and microscopic morphology of WBP-modified asphalt were analyzed to reveal the toughening effect of WBP on virgin asphalt. The results showed that WBP-modified asphalt exhibits three nonlinear cracking stages, with a lower cracking rate than virgin asphalt. Its cracking damage generally increases over time, and the damage evolution parameter β serves as k_cd. The micro-grooves and wrinkles of WBP improve bonding to asphalt, increasing the E_acd of sol–gel 70# virgin asphalt from 10.6 to 23.88 kJ·mol⁻¹, thus achieving toughening. In summary, the fatigue damage process of WBP-modified asphalt can be characterized by the kinetic parameters β and E_acd. Full article

Cutaneous melanoma is one of the most aggressive skin cancers. Over the years, multiple studies have focused on identifying novel treatment strategies, with increasing attention directed toward immune-modulating mechanisms within the tumor microenvironment. Among these, ATP-binding cassette transporters and stem-associated pathways have been shown to influence drug response and immune escape. ABCB5 is a gene with multiple isoforms that significantly influences the immune response. In melanoma, the ABCB5α isoform is predominantly expressed, particularly in tumor stem-like cells where it promotes chemoresistance through active drug efflux. ABCB5 has also been linked to the regulation of PI3K/Akt, BCL-2, and miR-145-associated pathways. Moreover, ABCB5-positive cells contribute to the formation of an immunosuppressive microenvironment by secreting cytokines (IL-6, IL-8, TGF-β) and expressing immune checkpoint ligands, such as PD-L1, thereby favoring tumor progression and a poor prognosis. This review integrates current data on the molecular and microenvironmental mechanisms underlying melanoma progression and therapy resistance, and positions ABCB5 within the broader landscape of melanoma resistance mechanisms, emphasizing both its potential and its current limitations as a biomarker and therapeutic target. Full article

The increasing crisis of antimicrobial resistance requires innovative therapeutic strategies that can overcome the limitations of conventional antibiotics. Based on our previous finding that AP10 (a derivative of AP29) possesses antimicrobial activity but lacks thermal stability, we rationally redesigned ten new AP10 analogues to enhance functional robustness while maintaining efficacy. Among these, AP10RW is identified as the optimal candidate due to its exceptional broad-spectrum activity against both drug-sensitive and multidrug-resistant (MDR) bacterial pathogens. Structural analysis reveals that AP10RW adopts an environmentally responsive conformation, transitioning from random coil to amphiphilic α-helix in membrane-mimicking environments, while demonstrating remarkable stability under challenges including serum exposure, varying pH, high salt concentrations, and thermal stress. Mechanistic studies indicate that AP10RW exerts its effects through multiple bactericidal mechanisms involving initial high-affinity binding to bacterial characteristic molecules (LTA, LPS and PGN), followed by rapid membrane depolarization, ultrastructural damage and the induction of lethal oxidative stress. Notably, this potent antimicrobial efficacy is coupled with exceptional biosafety, demonstrating little hemolysis and negligible cytotoxicity against mammalian cells. This systematic optimization represents a significant advancement in antimicrobial peptide engineering. We have successfully transformed a thermally unstable peptide into a robust therapeutic candidate and positioned AP10RW as a promising clinical candidate for addressing the growing threat of multidrug-resistant infections. Full article

Fish is highly prone to spoilage due to a combination of intrinsic biochemical processes and microbial proliferation, which together drive rapid quality deterioration during post-harvest handling and storage. These processes are further accelerated by factors such as elevated temperatures, mechanical damage, and suboptimal handling. In Mediterranean aquaculture, ice slurry is the standard harvesting method. This study aimed to characterize the initial post-harvest enzymatic activity of key proteolytic enzymes, calpain, collagenase, cathepsin B (CTSB), and cathepsin L (CTSL), in the white muscle of three commercially important species (Sparus aurata, Dicentrarchus labrax, and Pagrus major) harvested under standard practices across three seawater harvest temperatures (low, medium, and high). Muscle samples were collected over a 13-day chilled storage period post-harvest, and enzymatic activity was assessed using standardized fluorometric assays. Our findings establish the basal post-mortem proteolytic profiles for each species and reveal marked species-specific differences in enzyme activity patterns. Calpain and collagenase exhibited early and parallel activation, while CTSB and CTSL showed a coordinated increase during storage. Harvest temperature emerged as a critical factor, with the highest enzymatic activities consistently observed during the moderate temperature period. These results underscore the importance of species-specific physiology and seasonal conditions in shaping post-harvest filet degradation, offering a basis for refining harvest strategies to enhance quality management in Mediterranean aquaculture. Full article

Estimating the adsorption data and understanding the adsorption behavior and mechanism of organic pollutants on nanoplastics are crucial for assessing their ecological risks. Herein, in silico techniques, i.e., grand canonical Monte Carlo simulations, density functional theory computations, and quantitative structure activity relationship (QSAR) modeling, were integrated to examine the adsorption of 39 representative aliphatic and aromatic compounds and nine emerging pollutants (brominated flame retardants and phosphorus flame retardants) onto 12 different nanoplastics under atmospheric conditions. Three QSAR models were constructed to predict the adsorption equilibrium constant (logK) for polyethylene, polyoxymethylene, and polyvinyl alcohol nanoplastics individually, along with 12 QSAR models for separately estimating adsorption capacities (C_m) on different nanoplastics. Furthermore, a novel multi-dimensional prediction model was developed, enabling simultaneous, high-throughput prediction of adsorption capacities across multiple nanoplastics and pollutants with a single input. These results revealed that van der Waals and electrostatic interactions serve as the primary driving forces for the adsorption. The novel multi-dimensional prediction model facilitates rapid and comprehensive assessment of pollutant–nanoplastic interactions with one-click, and paves the way for improved risk evaluations and advancing predictive environmental research. Full article

Exposure to lead is associated with microglial dysfunction and the development of neuroinflammation. This contributes to accelerated neurodegeneration. Even low doses of this element modulate inflammatory responses and might contribute to central nervous system dysfunction. Extracts from the mushroom Hericium erinaceus (HE) possess well-documented neurotropic properties; however, its potential neuroprotective mechanisms under conditions of environmental neurotoxicity remain poorly defined. In this study, we investigated the effects of HE on inflammatory signaling in a microglia-oriented in vitro model using THP-1-derived macrophages exposed to low levels of lead (3.5 µg/dL). In our study, Pb exposure did not increase tumor necrosis factor (TNF) alpha levels but reduced monocyte chemoattractant protein-1 (MCP-1) secretion and altered cyclooxygenase (COX) expression, indicating immune response modulation rather than inflammatory activation. Under combined Pb and HE exposure, a marked shift in cyclooxygenase expression toward COX-2 at both the gene and protein levels was observed, accompanied by increased PGE₂ production; these effects were dose-dependent. The inflammatory signaling was modulated rather than amplified. Also, TNF alpha levels were elevated after combined treatment, whereas gene expression responses were dose-dependent. MCP-1 secretion was fine-tuned toward control values, consistent with macrophage morphological changes, while IL-6 levels were increased. Overall, these findings indicate that Hericium erinaceus exerts immunomodulatory effects in microglia-like cells under low-level lead exposure, supporting its neuroprotective potential through modulation of neuroinflammatory signaling. Full article

This review describes the immunosuppressive effect of secreted phosphoprotein 1 (SPP1)+ tumor-associated macrophages (TAMs) in coordinating the tumor microenvironment (TME) as a functionally unique myeloid cell subgroup. SPP1+ TAMs transcend the traditional M1/M2 paradigm and represent a group of cells that are widely found in various cancer types. SPP1+ TAMs have the characteristics of high expression of SPP1 and promoting immune escape, matrix remodeling and metastasis. We clarify the dual developmental source of SPP1+ TAMs, and introduce the activation process of SPP1+ TAMs through recruitment, polarization and epigenetic locking. After SPP1+ TAMs are activated, they are strategically enriched in the tumor core and tumor marginal area to play their functions. Functionally, SPP1+ TAMs mainly promote the progression of tumors through three mechanisms: (1) Interacting with cancer-associated fibroblasts (CAFs): constructing an immunoexcluded fibrotic niche; (2) Multiple regulation of immune cells; (3) Promoting tumor metastasis and the construction of pre-metastatic niche (PMN). Overall, this review aims to provide a comprehensive overview of the mechanisms mediated by SPP1+ TAMs in the TME, and emphasize their unique role in cancer progression. At the same time, the treatment strategies targeting them are further explored, highlighting their potential as precise therapeutic targets for tumor treatment. Full article