Search Results (38,458)

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article

Carassius auratus exhibits significant physiological and behavioral alterations under the combined stress of temperature and dissolved oxygen (DO) fluctuations, which are common challenges in aquaculture. In this investigation, we employed controlled thermal and DO gradients to characterize the multidimensional response profile of this species. The key findings revealed that thermal elevation profoundly influenced blood glucose and cortisol concentrations. Notably, exposure to hyperoxic conditions markedly attenuated stress responses relative to hypoxia at equivalent temperatures: cortisol levels were significantly suppressed (reductions of 60.11%, 118.06%, and 34.72%), while blood glucose levels exhibited concurrent increases (16.42%, 26.43%, and 26.34%). Distinctive behavioral patterns, including floating head behavior, surface swimming behavior, and rollover behavior, were identified as indicative behaviors of thermal–oxygen stress. Molecular analysis demonstrated the upregulated expression of stress-associated genes (HSP70, HSP90, HIF-1α, and Prdx3), which correlated temporally with elevated cortisol and glucose concentrations and the manifestation of stress behaviors. Furthermore, a muscle texture assessment indicated that increased DO availability mitigated the textural deterioration induced by heat stress. Collectively, this work establishes an authentic biomarker framework, providing crucial threshold parameters essential for the development of intelligent, real-time environmental monitoring and dynamic regulation systems to enhance climate-resilient aquaculture management. Full article

The widespread adoption of liquefied natural gas (LNG) as a marine fuel has driven the development of LNG bunkering operations in global ports. Major international hubs, such as Shenzhen Port, have implemented ship-to-ship (STS) bunkering practices. However, this process entails unique safety risks, particularly hazards associated with vapor cloud dispersion caused by bunkering hose releases. This study employs the Phast software developed by DNV to systematically simulate LNG release scenarios during STS operations, integrating real-world meteorological data and storage conditions. The dynamic effects of transfer flow rates, release heights, and release directions on vapor cloud dispersion are quantitatively analyzed under daytime and nighttime conditions. The results demonstrate that transfer flow rate significantly regulates dispersion range, with recommendations to limit the rate below 1500 m³/h and prioritize daytime operations to mitigate risks. Release heights exceeding 10 m significantly amplify dispersion effects, particularly at night (nighttime dispersion area at a height of 20 m is 3.5 times larger than during the daytime). Optimizing release direction effectively suppresses dispersion, with vertically downward releases exhibiting minimal impact. Horizontal releases require avoidance of downwind alignment, and daytime operations are prioritized to reduce lateral dispersion risks. Full article

Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequencing on skeletal muscle samples from 19 human patients with ER history, collected at a minimum of six months after the most recent ER event, and eight healthy controls to investigate the transcriptomic landscape of ER. To identify any alterations in biological processes between the case and control groups, functional pathway analyses were conducted. Results: Functional pathway enrichment analyses of differentially expressed genes revealed strong suppression of mitochondrial function. This suppression included the “aerobic electron transport chain” and “oxidative phosphorylation” pathways, indicating impaired energy production. Conversely, there was an upregulation of genes associated with adhesion and extracellular matrix-related pathways, indicating active restoration of muscle function in ER cases. Conclusions: The study demonstrated that muscle tissue exhibited signs of suppressed mitochondrial function and increased extracellular matrix development. Both of these facilitate muscle recovery within several months after an ER episode. Full article

Hydrogels, characterized by their high water content, tunable mechanical properties, and excellent biocompatibility, have emerged as a promising material platform for the preservation of cultural heritage. Their unique physicochemical features enable non-invasive and adaptable solutions for environmental regulation, structural stabilization, and antifungal protection. This review provides a comprehensive overview of recent progress in hydrogel-based strategies specifically developed for the conservation of cultural relics, with a particular focus on antifungal performance—an essential factor in preventing biodeterioration. Current hydrogel systems, composed of natural or synthetic polymer networks integrated with antifungal agents, demonstrate the ability to suppress fungal growth, regulate humidity, alleviate mechanical stress, and ensure minimal damage to artifacts during application. This review also highlights future research directions, such as the application prospects of novel materials, including stimuli-responsive hydrogels and self-dissolving hydrogels. As an early exploration of the use of hydrogels in antifungal protection and broader cultural heritage conservation, this work is expected to promote the wider application of this emerging technology, contributing to the effective preservation and long-term transmission of cultural heritage worldwide. Full article

Background/Objectives: Constitutive activation of the PI3K/AKT/mTOR signaling cascade underlies the aggressive phenotype of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA); however, a quantitative synthesis of in vitro data on pathway inhibition remains lacking. This systematic review and meta-analysis aimed to (i) aggregate standardized effects of pathway inhibitors on proliferation, apoptosis, migration/invasion, IL-6/IL-8 secretion, p-AKT, and LC3; (ii) assess heterogeneity and identify key moderators of variability, including stimulus type, cell source, and inhibitor class. Methods: PubMed, Europe PMC, and the Cochrane Library were searched up to 18 May 2025 (PROSPERO CRD420251058185). Twenty of 2684 screened records met eligibility. Two reviewers independently extracted data and assessed study quality with SciRAP. Standardized mean differences (Hedges g) were pooled using a Sidik–Jonkman random-effects model with Hartung–Knapp confidence intervals. Heterogeneity (τ², I²), 95% prediction intervals, and meta-regression by cell type were calculated; robustness was tested with REML-HK, leave-one-out, and Baujat diagnostics. Results: PI3K/AKT/mTOR inhibition markedly reduced proliferation (to –5.1 SD), IL-6 (–11.1 SD), and IL-8 (–6.5 SD) while increasing apoptosis (+2.7 SD). Fourteen of seventeen outcome clusters showed large effects (|g| ≥ 0.8), with low–moderate heterogeneity (I² ≤ 35% in 11 clusters). Prediction intervals crossed zero only in small k-groups; sensitivity analyses shifted pooled estimates by ≤0.05 SD. p-AKT and p-mTOR consistently reflected functional changes and emerged as reliable pharmacodynamic markers. Conclusions: Targeted blockade of PI3K/AKT/mTOR robustly suppresses the proliferative and inflammatory phenotype of RA-FLSs, reaffirming this axis as a therapeutic target. The stability of estimates across multiple analytic scenarios enhances confidence in these findings and highlights p-AKT and p-mTOR as translational response markers. The present synthesis provides a quantitative basis for personalized dual-PI3K/mTOR strategies and supports the adoption of standardized long-term preclinical protocols. Full article

The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H₂O₂, both suppressed oxidative damage to a comparable degree, as indicated by similar H₂O₂-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H₂O₂ concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H₂O₂-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress. Full article

In this study, we propose a bidirectional chemical sensor platform based on a reconfigurable ion-sensitive field-effect transistor (R-ISFET) architecture. The device incorporates Ni-silicide Schottky barrier source/drain (S/D) contacts, enabling ambipolar conduction and bidirectional turn-on behavior for both p-type and n-type configurations. Channel polarity is dynamically controlled via the program gate (PG), while the control gate (CG) suppresses leakage current, enhancing operational stability and energy efficiency. A dual-control-gate (DCG) structure enhances capacitive coupling, enabling sensitivity beyond the Nernst limit without external amplification. The extended-gate (EG) architecture physically separates the transistor and sensing regions, improving durability and long-term reliability. Electrical characteristics were evaluated through transfer and output curves, and carrier transport mechanisms were analyzed using band diagrams. Sensor performance—including sensitivity, hysteresis, and drift—was assessed under various pH conditions and external noise up to 5 V_pp (i.e., peak-to-peak voltage). The n-type configuration exhibited high mobility and fast response, while the p-type configuration demonstrated excellent noise immunity and low drift. Both modes showed consistent sensitivity trends, confirming the feasibility of complementary sensing. These results indicate that the proposed R-ISFET sensor enables selective mode switching for high sensitivity and robust operation, offering strong potential for next-generation biosensing and chemical detection. Full article

Chrysanthemum × morifolium (Ramat) Hemsl. (Hangbaiju), which has been widely consumed as a herbal tea for over 3000 years, is renowned for its biosafety and diverse bioactivities. This study investigates the impact of polyphenol-rich Hangbaiju extracts (HE) on high-fat diet-induced obesity in mice. HE contains phenolic acids and flavonoids with anti-obesity properties, such as apigenin, luteolin-7-glucoside, apigenin-7-O-glucoside, kaempferol 3-(6″-acetylglucoside), etc. To establish the obesity model, mice were randomly assigned into four groups (n = 8 per group) and administered with either HE or water for 42 days under high-fat or low-fat dietary conditions. Administration of low (LH) and high (HH) doses of HE both significantly suppressed body weight growth (by 16.28% and 16.24%, respectively) and adipose tissue enlargement in obese mice. HE significantly improved the serum lipid profiles, mainly manifested as decreased levels of triglycerides (28.19% in LH and 19.59% in HH) and increased levels of high-density lipoprotein cholesterol (44.34% in LH and 54.88% in HH), and further attenuated liver lipid deposition. Furthermore, HE significantly decreased the Firmicutes/Bacteroidetes ratio 0.23-fold (LH) and 0.12-fold (HH), indicating an improvement in the microecological balance of the gut. HE administration also elevated the relative abundance of beneficial bacteria (e.g., Allobaculum, norank_f__Muribaculaceae), while suppressing harmful pathogenic proliferation (e.g., Dubosiella, Romboutsia). In conclusion, HE ameliorates obesity and hyperlipidemia through modulating lipid metabolism and restoring the balance of intestinal microecology, thus being promising for obesity therapy. Full article

The barbel chub (Squaliobarbus curriculus) exhibits remarkable resistance to grass carp reovirus (GCRV), a devastating pathogen in aquaculture. To reveal the molecular basis of this resistance, we investigated complement factor D (DF)—a rate-limiting serine protease governing alternative complement pathway activation. Molecular cloning revealed that the barbel chub DF (ScDF) gene encodes a 1251-bp cDNA sequence translating into a 250-amino acid protein. Crucially, bioinformatic characterization identified a unique N-glycosylation site at Asn¹³⁹ in ScDF, representing a structural divergence absent in grass carp (Ctenopharyngodon idella) DF (CiDF). While retaining a conserved Tryp_SPc domain harboring the catalytic triad (His⁶¹, Asp¹⁰⁹, and Ser²⁰⁴) and substrate-binding residues (Asp¹⁹⁸, Ser²¹⁹, and Gly²²¹), sequence and phylogenetic analyses confirmed ScDF’s evolutionary conservation, displaying 94.4% amino acid identity with CiDF and clustering within the Cyprinidae. Expression profiling revealed constitutive ScDF dominance in the liver, and secondary prominence was observed in the heart. Upon GCRV challenge in S. curriculus kidney (SCK) cells, ScDF transcription surged to a 438-fold increase versus uninfected controls at 6 h post-infection (hpi; p < 0.001)—significantly preceding the 168-hpi response peak documented for CiDF in grass carp. Functional validation showed that ScDF overexpression suppressed key viral capsid genes (VP2, VP5, and VP7) and upregulated the interferon regulator IRF9. Moreover, recombinant ScDF protein incubation induced interferon pathway genes and complement C3 expression. Collectively, ScDF’s rapid early induction (peaking at 6 hpi) and multi-pathway coordination may contribute to barbel chub’s GCRV resistance. These findings may provide molecular insights into the barbel chub’s high GCRV resistance compared to grass carp and novel perspectives for anti-GCRV breeding strategies in fish. Full article

Herbivore-induced plant volatiles (HIPVs) are well known for their roles in herbivore deterrence and attraction of natural enemies, but their direct impact on insect reproduction remains largely unexplored. In this study, we provide novel evidence that two representative HIPVs, 2-heptanol and α-cedrene, exert opposing effects on the reproduction of Chilo suppressalis, a major rice pest. While both volatiles repelled adults, α-cedrene unexpectedly enhanced oviposition, whereas 2-heptanol significantly suppressed egg laying. To examine these effects, we conducted oviposition assays, preoviposition and longevity tests, combined with qPCR and transcriptome analyses to explore underlying molecular responses. Mechanistically, α-cedrene upregulated Kr-h1, a gene linked to juvenile hormone signaling and vitellogenesis, promoting reproductive investment. Transcriptomic profiling revealed divergent molecular responses: α-cedrene activated reproductive pathways, whereas 2-heptanol induced stress- and immune-related genes, suggesting a trade-off between stress defense and reproduction. These findings demonstrate that HIPVs can exert compound-specific reproductive effects beyond repellency. This work fills a key knowledge gap and highlights the potential of HIPVs as precision tools in pest management strategies that exploit behavioral and physiological vulnerabilities beyond repellency. Full article

Cancer remains a significant global health challenge, with China being particularly affected because of its large population. Regulated cell death (RCD) mechanisms, including autophagy, apoptosis, necroptosis, pyroptosis, and ferroptosis, play complex roles in cancer development and progression. This review explores the dual roles of autophagy and apoptosis in cancer, highlighting their tumor-suppressive and tumor-promoting functions. Autophagy can maintain genomic stability, induce apoptosis, and suppress protumor inflammation, but it may also support tumor cell survival and drug resistance. Apoptosis, while primarily tumor-suppressive, can paradoxically promote cancer progression in certain contexts. Other RCD mechanisms, such as necroptosis, pyroptosis, and ferroptosis, also exhibit dual roles in cancer, influencing tumor growth, metastasis, and immune responses. Understanding these mechanisms is crucial for developing targeted cancer therapies. This review provides insights into the intricate interplay between RCD mechanisms and cancer, emphasizing the need for context-dependent therapeutic strategies. Full article

Water scarcity and spatial variability in soil fertility are key constraints to stable grain production in the Huang-Huai-Hai Plain. However, the interaction mechanisms between regulated deficit irrigation and soil fertility influencing yield formation and water-nitrogen use efficiency in winter wheat remain unclear. In this study, a two-year field experiment (2022–2024) was conducted to investigate the effects of two irrigation regimes—regulated deficit irrigation during the heading to grain filling stage (D) and full irrigation (W)—under four soil fertility levels: F1 (N: P: K = 201.84: 97.65: 199.05 kg ha⁻¹), F2 (278.52: 135: 275.4 kg ha⁻¹), F3 (348.15: 168.75: 344.25 kg ha⁻¹), and CK (no fertilization). The results show that aboveground dry matter accumulation, total nitrogen content, pre-anthesis dry matter and nitrogen translocation, and post-anthesis accumulation significantly increased with fertility level (p < 0.05). Regulated deficit irrigation promoted the contribution of post-anthesis dry matter to grain yield under the CK and F1 treatments, but suppressed it under the F2 and F3 treatments. However, it consistently enhanced the contribution of post-anthesis nitrogen to grain yield (p < 0.05) across all fertility levels. Higher fertility levels prolonged the grain filling duration by 18.04% but reduced the mean grain filling rate by 15.05%, whereas regulated deficit irrigation shortened the grain filling duration by 3.28% and increased the mean grain filling rate by 12.83% (p < 0.05). Grain yield significantly increased with improved fertility level (p < 0.05), reaching a maximum of 9361.98 kg·ha⁻¹ under the F3 treatment. Regulated deficit irrigation increased yield under the CK and F1 treatments but reduced it under the F2 and F3 treatments. Additionally, water use efficiency exhibited a parabolic response to fertility level and was significantly enhanced by regulated deficit irrigation. Nitrogen partial factor productivity (NPFP) declined with increasing fertility level (p < 0.05); Regulated deficit irrigation improved NPFP under the F1 treatment but reduced it under the F2 and F3 treatments. The highest NPFP (41.63 kg·kg⁻¹) was achieved under the DF1 treatment, which was 54.81% higher than that under the F3 treatment. TOPSIS analysis showed that regulated deficit irrigation combined with the F1 fertility level provided the optimal balance among yield, WUE, and NPFP. Therefore, implementing regulated deficit irrigation during the heading–grain filling stage under moderate fertility (F1) is recommended as the most effective strategy for achieving high yield and efficient resource utilization in winter wheat production in this region. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

The force ripple of a permanent magnet synchronous linear motor (PMSLM) caused by multi-source disturbances in practical applications seriously restricts its high-precision motion control performance. The traditional single-mechanism model has difficulty fully characterizing the nonlinear disturbance factors, while the data-driven method has real-time limitations. Therefore, this paper proposes a hybrid modeling framework that integrates the physical mechanism and measured data and realizes the dynamic compensation of the force ripple by constructing a collaborative suppression algorithm. At the mechanistic level, based on electromagnetic field theory and the virtual displacement principle, an analytical model of the core disturbance terms such as the cogging effect and the end effect is established. At the data level, the acceleration sensor is used to collect the dynamic response signal in real time, and the data-driven ripple residual model is constructed by combining frequency domain analysis and parameter fitting. In order to verify the effectiveness of the algorithm, a hardware and software experimental platform including a multi-core processor, high-precision current loop controller, real-time data acquisition module, and motion control unit is built to realize the online calculation and closed-loop injection of the hybrid compensation current. Experiments show that the hybrid framework effectively compensates the unmodeled disturbance through the data model while maintaining the physical interpretability of the mechanistic model, which provides a new idea for motor performance optimization under complex working conditions. Full article