Search Results (21,278)

Hamamelis virginiana (witch hazel) is traditionally used in dermatology for its antibacterial and anti-inflammatory effects. However, the number of studies on its chemical composition and potentials in skin protection remains limited. This study aimed to investigate the qualitative and quantitative composition of polyphenolic compounds in the leaves and bark of the plant, as well as to explore their antioxidant, anti-inflammatory, and extracellular matrix (ECM)-protective activities in skin-relevant cell models. Human dermal fibroblasts and keratinocytes were exposed to oxidative and inflammatory stimuli and pretreated with leaf and bark extracts. ROS levels, antioxidant enzyme activity (SOD, GPx, CAT), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and inhibition of collagenase, hyaluronidase, and elastase were assessed. Both extracts strongly reduced ROS levels, enhanced SOD activity, and significantly decreased pro-inflammatory cytokines. Bark extract also exhibited potent inhibitory activity against collagenase and elastase. UPLC-DAD-MS analysis revealed that both plant parts contained high levels of tannins; however, the leaf extract showed a more diverse composition, including more complex tannin forms and a significant amount of flavonoids from the quercetin and kaempferol class. In conclusion, H. virginiana leaf and bark extracts demonstrate multifunctional antioxidant and anti-inflammatory properties, supporting their potential use in cosmeceuticals and dermatological formulations targeting skin aging and inflammation. Full article

The growing reliance on unconventional water sources requires effective strategies for forage production, particularly in semiarid regions. The objective of this study was to evaluate evapotranspiration, phytomass accumulation, and salt inputs to the soil in millet crops irrigated with wastewater under different soil water levels, both with and without organic fertilizer. We conducted the experiment in a protected environment using a randomized block design in a 4 × 2 + 1 (control) factorial scheme with three replicates. We applied four irrigation levels with wastewater (25, 50, 75, and 100% of available soil water) with or without organic fertilizer. The control treatment was watering with the public supply submitted to 100% of the available water from the soil without fertilization. Wastewater did not affect biomass without fertilization, but irrigation levels significantly influenced productivity under fertilization. Additionally, applying 50% of available soil water proved the most efficient system in terms of yield per unit of water consumed. Although irrigation improved productivity, water use efficiency in millet showed limited enhancement. The millet did not exhibit any symptoms of salt stress. Finally, we emphasize caution when using wastewater (graywater) for irrigation, as continuous application can lead to salt accumulation and subsequent soil salinization. Full article

Background/Objectives: Rice production faces threats from rising temperatures, demanding thermotolerant varieties. This study characterizes transcriptomic dynamics and identifies Hsp101-1 (heat shock protein 101-1)-associated gene regulatory modules in rice under reproductive-stage heat stress. Methods: Transcriptomics and WGCNA (weighted gene co-expression network analysis) were conducted in flag leaves and spikelets for wild-type (WT) and Hsp101-1-overexpressing (OE) lines under 40 °C stress at six time points (0–24 h) to reveal the change in gene expressions. Results: The number of DEGs (differentially expressed genes) revealed substantial pre-existing differences in WT and OE lines. Pre treatment, OE flag leaves showed 545 upregulated and 676 downregulated DEGs versus WT leaves. Post heat shock, the number of DEGs in flag leaves and spikelets was significantly reduced by 70–80%. KEGG enrichment of common DEGs across time points showed both WT and OE flag leaves enriched for ribosome biogenesis, ribosomes, and chaperones/folding catalysts. WGCNA identified that the MEdarkslateblue module correlated negatively with WT and positively with OE flag leaves. The MEturquoise module was suppressed at 1 h but activated by 8 h. Spikelet analysis identified the MElightpink4 module (negative correlation with WT, positive with OE) and a similarly dynamic MEturquoise module. Venn analysis identified 76 shared module genes, 71 of which were upregulated in the OE line, indicating that Hsp101-1 activates common protective targets. Hsp101-1’s expression in the WT line was low basally, significantly upregulated at 1–8 h post shock, and returned to low levels by 24 h. Conclusions: Hsp101-1 enhances thermotolerance by (1) constitutively pre-stabilizing transcriptomic networks and reducing transcriptional fluctuations under heat stress and (2) modularly coordinating tissue-specific responses, providing a climate resilience framework. Full article

After heavy snowfall in the Uinta Basin, Utah, elevated surface ozone occurs if a cold-air pool persists and traps emissions from oil and gas industry operations. Sunlight and actinic flux from a high-albedo snowpack drive ozone buildup via photolysis. Snow coverage is paramount in initiating the cold pool and driving ozone generation. Its depth is critical for predicting ozone concentrations. The Basin’s location leeward of the Wasatch Mountains provides conditions for a precipitation shadow, where sinking air suppresses snowfall. We analyzed multiple years of ground-based snow depth measurements, surface ozone data, and meteorological observations; we found that ozone levels track with snow coverage, but diagnosing a shadow effect (and any impact on ozone levels) was difficult due to sparse, noisy data. The uncertainty in linking snowfall variation to ozone levels hinders forecast quality in, e.g., machine-learning training. We highlight the importance of a better understanding of regional variation when issuing outlooks to protect the local economy and health. A wider sampling of snow depth across the Basin would benefit operational forecasters and, likely, predictive skill. Full article

Background: Raising children with special needs presents unique emotional and practical challenges, often increasing parental loneliness and diminishing perceived social support, both of which can undermine family resilience. Although previous studies have explored these constructs separately, there is limited understanding of how loneliness and social support interact to influence family resilience. We examined the mediating role of loneliness and the moderating role of parent groups (parents with and without special needs children) in the association between social support and family resilience. Method: This cross-sectional study included 120 parents (60 parents of children with special needs, 60 parents of typically developing children), with children aged 3 to 18 years. Participants completed questionnaires measuring perceived social support, loneliness, and family resilience. Statistical analyses included t-tests, Pearson correlations, moderation, and mediation analyses using Hayes’ PROCESS macro. Results: Parents of children with special needs reported significantly lower levels of perceived social support and significantly higher levels of loneliness. However, no significant differences were found in family resilience. Across the sample, social support was positively associated with family resilience and negatively associated with loneliness. Moderation analysis revealed that the association between social support and family resilience was stronger among parents of typically developing children. Mediation analysis showed that loneliness fully mediated relations between social support and family resilience. Conclusions: These findings highlight loneliness as a critical psychological mechanism linking social support and family resilience. Although no significant group differences were found in family resilience, it is possible that unmeasured protective factors, such as coping strategies, may have buffered the negative impact of loneliness among parents of children with special needs. Interventions that focus on enhancing social support and addressing loneliness are vital for promoting resilience in parents, particularly those with special needs children. Full article

Objectives: Patients with rare diseases in China face extremely high medical expenses. The current coverage framework remains inadequate in terms of coverage depth and proactive risk control, underscoring an urgent need for institutional reform. Methods: This study employs a policy content analysis approach to review the current landscape of rare disease protection in China. Drawing on risk management theory and the health capital model, it constructs an analytical framework to examine potential institutional reforms through the lens of risk response pathways and the efficiency of health investment. Results: The findings reveal that basic medical insurance (BMI) provides limited financial protection for patients with rare diseases. Among China’s 31 provincial-level administrative centers, 24 have set general outpatient reimbursement ceilings under the urban and rural resident basic medical insurance (URRBMI) at 1000 RMB or less. In comparison, 24 cities have set outpatient reimbursement limits under the urban employee basic medical insurance (UEBMI) at 6000 RMB or less. The security system relies predominantly on the BMI, while supplementary mechanisms have failed to provide effective support or continuity in coverage. Current policies are generally reactive, with coverage typically triggered only after a confirmed diagnosis and often lacking early intervention or preventive strategies. Conclusions: China’s rare disease security system urgently requires structural improvements in coverage depth and proactive risk management. The proposed Dedicated Insurance Scheme for Rare Diseases (DISRD) presents a feasible and sustainable model for China’s multi-tiered system of securing rare diseases. It provides valuable institutional insights for other countries and regions seeking to build public health systems with proactive risk control capabilities. Full article

Recent advances in medical research have improved survival outcomes for patients with life-threatening diseases. As a result, the existence of long-term survivors from these illnesses is becoming common. However, conventional models in survival analysis assume that all individuals remain at risk of death after the follow-up, disregarding the presence of a cured subpopulation. An important methodological advancement in this context is the use of defective distributions. In the defective models, the survival function converges to a constant value $p\in (0,1)$ as a function of the parameters. Among these models, the defective generalized Gompertz distribution (DGGD) has emerged as a flexible approach. In this work, we introduce a reparametrized version of the DGGD that incorporates the cure parameter and accommodates covariate effects to assess individual-level factors associated with long-term survival. A Bayesian model is presented, with parameter estimation via the Hamiltonian Monte Carlo algorithm. A simulation study demonstrates good asymptotic results of the estimation process under vague prior information. The proposed methodology is applied to a real-world dataset of patients with uterine cancer. Our results reveal statistically significant protective effects of surgical intervention, alongside elevated risk associated with age over 50 years, diagnosis at the metastatic stage, and treatment with chemotherapy. Full article

Background/Objectives: Bones are essential components of the human body, providing structural support, enabling mobility, storing minerals, and protecting internal organs. Bone fractures (BFs) are common injuries that result from excessive physical force and can lead to serious complications, including bleeding, infection, impaired oxygenation, and long-term disability. Early and accurate identification of fractures through radiographic imaging is critical for effective treatment and improved patient outcomes. However, manual evaluation of X-rays is often time-consuming and prone to diagnostic errors due to human limitations. To address this, artificial intelligence (AI), particularly deep learning (DL), has emerged as a powerful tool for enhancing diagnostic precision in medical imaging. Methods: This research introduces a novel convolutional neural network (CNN) model, the Multi-Level Feature Fusion Network (MLFNet), designed to capture and integrate both low-level and high-level image features. The model was evaluated using the Bone Fracture Multi-Region X-ray (BFMRX) dataset. Preprocessing steps included image normalization, resizing, and contrast enhancement to ensure stable convergence, reduce sensitivity to lighting variations in radiographic images, and maintain consistency. Ablation studies were conducted to assess architectural variations, confirming the model’s robustness and generalizability across data distributions. MLFNet’s high accuracy, interpretability, and efficiency make it a promising solution for clinical deployment. Results: MLFNet achieved an impressive accuracy of 99.60% as a standalone model and 98.81% when integrated into hybrid ensemble architectures with five leading pre-trained DL models. Conclusions: The proposed approach supports timely and precise fracture detection, optimizing the diagnostic process and reducing healthcare costs. This approach offers significant potential to aid clinicians in fields such as orthopedics and radiology, contributing to more equitable and effective patient care. Full article

Objectives: The objectives of this study are to investigate the therapeutic targets and mechanisms of proanthocyanidins in alleviating fluoride-induced liver injury through network pharmacology and animal experimental validation and to explore the medicinal value of grape seed proanthocyanidins. Methods: Potential targets of proanthocyanidins were predicted using databases such as PubChem, SwissTargetPrediction, and GeneCards, and disease-related targets of fluoride-induced liver injury were retrieved to identify common targets between proanthocyanidins and fluoride-induced liver injury. The STRING database was utilized to construct a protein–protein interaction network, and key targets were analyzed for network topology using Cytoscape software. GO and KEGG enrichment analyses were performed on core target genes to explore the potential molecular mechanisms by which proanthocyanidins alleviate fluoride-induced liver injury. The Genes-miRNA interaction network was generated using Networkanalyst, and the molecular docking results between active components and key targets were validated using the CB-Dock2 visualization tool. In the academic context, a rat model of chronic fluoride poisoning was successfully established by means of intragastric administration of sodium fluoride. The protein expression levels of p-mTOR, p-p70s6, p62, LC3-II, and PARP1 in rat liver tissues were detected via Western blot analysis. Results: Network pharmacological analysis successfully identified 96 key genes, through which proanthocyanidins mitigate fluoride-induced liver injury. KEGG enrichment analysis predicted that proanthocyanidins mainly exert their therapeutic effects through the mTOR signaling pathway. The molecular docking results further demonstrated strong binding affinities between proanthocyanidins and key targets, including mTOR and PARP1. The in vivo experimental results indicate that, compared with the control group, the protein expression levels of p-mTOR, p-p70s6k, and p62 in the liver tissues of rats exposed to sodium fluoride significantly increase. Conversely, the protein expression levels of LC3-II and PARP1 significantly decrease (p < 0.05). The outcome of liver intervention with proanthocyanidins is exactly the opposite. Conclusions: Proanthocyanidins can effectively alleviate fluoride-induced liver injury, potentially by regulating the mTOR signaling pathway, autophagy, and apoptosis mechanisms. This study provides valuable insights into the protective effects of proanthocyanidins against fluoride-induced hepatic damage and offers a theoretical basis for further research in this field. Full article

Coastal marine ecosystems are facing serious ecological risks from metals pollution, threatening biodiversity and human health. The main objective of this study is to evaluate the spatial distributions and ecological risks of dissolved cadmium (Cd), lead (Pb), and copper (Cu) in the Shandong Peninsula coastal areas, China. Two sampling campaigns were conducted at 21 sites in early spring 2025 to measure the concentrations of the three trace metals in the study area using an electrochemical detection system. The results revealed higher metals concentrations in nearshore areas (e.g., port entrances, aquaculture zones, and estuaries). Specifically, the Cd, Pb, and Cu concentrations in the study area ranged from 0 to 0.079 µg L⁻¹, 0.30 to 0.84 µg L⁻¹, and 2.19 to 4.79 µg L⁻¹, with average concentrations of 0.033, 0.55, and 3.18 µg L⁻¹, respectively. The contamination factors (C_f) of the three metals were below 1, indicating low pollution levels and thus meeting China’s Class I seawater quality standard. However, the ecological risk assessment, employing complementary methods, revealed varying interpretations: the risk quotient (RQ), based on species sensitivity distribution and predicted no-effect concentrations (PNECs), indicated low risks associated with Cd and Pb (RQ < 0.1) but a high risk for Cu (RQ > 1) at all sites, attributable to the exceedance of Cu’s protective threshold (0.46 µg L⁻¹), despite its low C_f. These findings highlight the need for continuous monitoring of Cu due to its high ecological impacts. In contrast, the Hakanson potential ecological risk index (ERI), which incorporates toxicity coefficients, suggested overall low risks (ERI < 150) for the combined metals; however, Cd contributed approximately 70% to the ERI due to its high toxicity coefficient, warranting attention despite the low individual Erⁱ values for Cd across the study area. This study provides valuable recent data on metals pollution dynamics in the Shandong Peninsula coastal areas, offering a scientific basis for developing marine pollution control policies and sustainable marine resource management. Full article

Background/Objectives: The continued evolution and cross-species transmission of clade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses underscores the need for broadly protective vaccines in swine, a key intermediary host. This study aimed to evaluate systemic and mucosal immune responses elicited by adenoviral-vectored (Ad) vaccines encoding a centralized consensus hemagglutinin antigen (H5CC) in mice and swine. Methods: We constructed H5CC-based vaccines that were delivered using replication-defective (Ad5 and Ad6) and replication-competent (Ad28 and Ad48) human adenoviral vectors. Using a serotype-switched prime-boost strategy, vaccines were delivered intramuscularly (IM) or intranasally (IN) in mice and swine. We determined humoral, mucosal, and cell-mediated immune responses by hemagglutination inhibition (HI), microneutralization assay (MNA), ELISA, and IFN-γ ELISpot. Protective efficacy was evaluated by lethal H5N1 challenge in mice. Results: All vaccine strategies and routes induced significant levels of anti-H5 immunity. Ad5/Ad6 IM immunization elicited strong systemic IgG and MNA titers and robust T cell responses. IN delivery with Ad5/Ad6 induced superior mucosal IgA levels in lungs and nasal secretion. In swine, Ad5/Ad6 IM conferred the highest MNA titer and T cell responses, while the IN route enhanced mucosal IgA. The Ad28/Ad48 vaccines induced immunity in a similar pattern as compared to the Ad5/Ad6 strategy, but to a slightly lesser degree, in general. The commercial H1/H3 swine influenza vaccine failed to elicit cross-protective immunity. All H5CC vaccinated mice survived lethal H5N1 challenge without weight loss. Conclusions: Adenoviral-vectored H5CC vaccines elicit broad, cross-clade immunity with route-dependent immune profiles. IM vaccination is optimal for systemic and cellular responses, while IN delivery enhances mucosal immunity. These findings support the advancement of adenoviral platforms for influenza control in swine and pandemic preparedness. Full article

Background/Objectives: Radiotherapy can cause severe and irreversible brain damage, including cognitive impairment, increased dementia risk, debilitating depression, and other neuropsychiatric disorders. Current radioprotective drugs face limitations, such as single-target inefficacy or manufacturing hurdles. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice root, exhibits broad bioactivities. It exhibits anti-inflammatory, anti-cancer, immunoregulatory, hepatoprotective, and cardioprotective activities. This study aimed to elucidate ISL’s neuronal radiation mitigation effects and key targets. Methods: In vitro and in vivo models of radiation-induced neuronal injury were established. ISL’s bioactivities were evaluated through cellular cytotoxicity assays, LDH release, ROS, ATP, glutamate, and GSH levels. In vivo, ISL’s radiation mitigation effect was evaluated with sucrose preference test, IL-β level, histopathological analysis, and Golgi-Cox staining analysis. Proteomics, pathway enrichment, and ensemble models (four machine learning models, weighted gene co-expression network, protein–protein interaction) identified core targets. Molecular docking and dynamic simulations validated ISL’s binding stability with key targets. Results: ISL attenuated radiation-induced cellular cytotoxicity, reduced LDH/ROS, restored ATP, elevated GSH, and mitigated glutamate accumulation. In rats, ISL alleviated anhedonia-like phenotypes and hippocampal synaptic loss. ISL also significantly suppressed radiation-induced neuroinflammation, as evidenced by reduced levels of the pro-inflammatory cytokine IL-1β. Proteomic analysis revealed that ISL’s main protective pathways included the synaptic vesicle cycle, glutamatergic synapse, MAPK signaling pathway, SNARE interactions in vesicular transport, insulin signaling pathway, and insulin secretion. Grm8, Grik3, and Grin3a were identified as key targets using the integrated models. The expression of these targets was upregulated post-radiation and restored by ISL. Molecular docking and dynamic simulations indicated that ISL showed stable binding to these receptors compared to native ligands. Conclusions: ISL demonstrates multi-scale radiation mitigation activities in vitro and in vivo by modulating synaptic and inflammatory pathways, with glutamate receptors as core targets. This work nominates ISL as an important natural product for mitigating radiotherapy-induced neural damage. Full article

Under the context of global climate change, the frequent occurrence of extreme low-temperature events poses a severe challenge to plant distribution and ecosystem stability. The arid and semi-arid regions of Northwestern China, as a sensitive response area to global change, have proven to possess significant development potential with their unique desert vegetation systems. This study focuses on the ecological adaptability mechanisms of Nitraria tangutorum Bobr., a key species of the desert ecosystem in Northwestern China, and systematically analyzes the evolution patterns of its geographical distribution under the coupled effects of climate change and human activities through a MaxEnt model. The research conclusions are as follows: (i) This study constructs a Human Footprint-MaxEnt (HF-MaxEnt) coupling model. After incorporating human footprint variables, the AUC value of the model increases to 0.914 (from 0.888), demonstrating higher accuracy and reliability. (ii) After incorporating human footprint variables, the predicted area of the model decreases from 2,248,000 ${km}^2$ to 1,976,000 ${km}^2$, with the High Suitability experiencing a particularly sharp decline of up to 79.4%, highlighting the significant negative impact of human disturbance on Nitraria tangutorum. (iii) Under the current climate baseline period, solar radiation, precipitation during the wettest season, and mean temperature of the coldest month are the core driving factors for suitable areas of Nitraria tangutorum. (iv) Under future climate scenarios, the potential distribution area of Nitraria tangutorum is significantly positively correlated with carbon emission levels. Under the SSP370 and SSP585 emission pathways, the area of potential distribution reaches 172.24% and 161.3% of that in the current climate baseline period. (v) Under future climate scenarios, the distribution center of potential suitable areas for Nitraria tangutorum shows a dual migration characteristic of “west–south” and “high altitude”, and the mean temperature of the hottest month will become the core constraint factor in the future. This study provides theoretical support and data backing for the delineation of habitat protection areas, population restoration, resource management, and future development prospects for Nitraria tangutorum. Full article

Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that γδ T cells contribute to EILV/CHIKV-induced host protection against WT CHIKV infection. TCRδ^−/− mice, which are deficient of γδ T cells, had impaired CHIKV-specific CD8⁺ T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8⁺ T cells of EILV/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, γδ T cells expanded quickly in response to EILV/CHIKV vaccination. TCRδ^−/− mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, γδ T cells contribute to EILV/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV/CHIKV vaccination. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article