Search Results (4,056)

Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its physiological adaptations to fluctuating salinity gradients. We used high-throughput mRNA sequencing and differential gene expression profiling to analyze transcriptional dynamics in intestinal and kidney tissues of grass carp exposed to heterogeneous salinity stressors. Concurrent serum biochemical analyses showed salinity stress significantly increased Na⁺, Cl⁻, and osmolarity, while decreasing lactate and glucose. Salinity stress exerted a profound impact on the global transcriptomic landscape of grass carp. A substantial number of co-regulated differentially expressed genes (DEGs) in kidney and intestinal tissues were enriched in immune and metabolic pathways. Specifically, genes associated with antigen processing and presentation (e.g., cd4-1, calr3b) and apoptosis (e.g., caspase17, pik3ca) exhibited upregulated expression, whereas genes involved in gluconeogenesis/glycolysis (e.g., hk2, pck2) were downregulated. KEGG pathway enrichment analyses revealed that metabolic and cellular structural pathways were predominantly enriched in intestinal tissues, while kidney tissues showed preferential enrichment of immune and apoptotic pathways. Rigorous validation of RNA-seq data via qPCR confirmed the robustness and cross-platform consistency of the findings. This study investigated the core transcriptional and physiological mechanisms regulating grass carp’s response to salinity stress, providing a theoretical foundation for research into grass carp’s resistance to salinity stress and the development of salt-tolerant varieties. Full article

Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for alopecia. This study aimed to systematically investigate the efficacy and mechanisms of PA extracts in promoting hair regeneration. A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of a Periplaneta americana extract was validated by evaluating hair regrowth status and skin pathological staining in C57BL/6J mice. Transcriptomics, metabolomics, RT-qPCR, and 16s rRNA techniques were integrated to dissect the underlying mechanisms of its hair-growth-promoting effects. PA-011 significantly promoted hair regeneration in depilated mice via multiple mechanisms: enhanced skin superoxide dismutase activity and upregulated vascular endothelial growth factor expression; modulated FOXO/PI3K/AKT signaling pathway and restored skin microbiota homeostasis; and accelerated transition of hair follicles from the telogen to anagen phase. PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and the skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation. Full article

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

Schizophrenia (SZ) is a complex neuropsychiatric disorder characterized by heterogeneous symptoms, relatively poor clinical outcome, and widespread disruptions in neural connectivity and oscillatory dynamics. This article attempts to review current evidence linking genomic and proteomic alterations with aberrant neural oscillations observed in SZ, including aberrations in all oscillatory frequency bands obtained via human EEG. The numerous genes discussed are mainly involved in modulating synaptic transmission, synaptic function, interneuron excitability, and excitation/inhibition balance, thereby influencing the generation and synchronization of neural oscillations at specific frequency bands (e.g., gamma frequency band) critical for different cognitive, emotional, and perceptual processes in humans. The review highlights how polygenic influences and gene–circuit interactions underlie the neural oscillatory and connectivity abnormalities central to SZ pathophysiology, providing a framework for future research on common genetic-neural function interactions and on potential therapeutic interventions targeting local and global network-level neural dysfunction in SZ patients. As will be discussed, many of these genes affecting neural oscillations in SZ also affect other neurological disorders, ranging from autism to epilepsy. In time, it is hoped that future research will show why the same genetic anomaly leads to one illness in one person and to another illness in a different person. Full article

As typical environmental hormones, endocrine-disrupting chemicals (EDCs) have become a global environmental health issue of high concern due to their property of interfering with the endocrine systems of organisms. As a commonly used substitute for bisphenol A (BPA), bisphenol E (BPE) has been frequently detected in environmental matrices such as soil and water in recent years. Existing research has unveiled the developmental and reproductive toxicity of BPE; however, only one in vitro cellular experiment has preliminarily indicated potential neurotoxic risks, with its underlying mechanisms remaining largely unelucidated in the current literature. Potential toxic mechanisms and action targets of BPE were predicted using the zebrafish model via network toxicology and molecular docking, with RT-qPCRs being simultaneously applied to uncover neurotoxic effects and associated mechanisms of BPE. A significant decrease (p < 0.05) in the frequency of embryonic spontaneous movements was observed in zebrafish at exposure concentrations ≥ 0.01 mg/L. At 72 hpf and 144 hpf, the larval body length began to shorten significantly from 0.1 mg/L to 1 mg/L, respectively (p < 0.01), accompanied by a reduced neuronal fluorescence intensity and a shortened neural axon length (p < 0.01). By 144 hpf, the motor behavior in zebrafish larvae was inhibited. Through network toxicology and molecular docking, HSP90AB1 was identified as the core target, with the cGMP/PKG signaling pathway determined to be the primary route through which BPE induces neurotoxicity in zebrafish larvae. BPE induces neuronal apoptosis and disrupts neurodevelopment by inhibiting the cGMP/PKG signaling pathway, ultimately suppressing the larval motor behavior. To further validate the experimental outcomes, we measured the expression levels of genes associated with neurodevelopment (elavl3, mbp, gap43, syn2a), serotonergic synaptic signaling (5-ht1ar, 5-ht2ar), the cGMP/PKG pathway (nos3), and apoptosis (caspase-3, caspase-9). These results offer crucial theoretical underpinnings for evaluating the ecological risks of BPE and developing environmental management plans, as well as crucial evidence for a thorough comprehension of the toxic effects and mechanisms of BPE on neurodevelopment in zebrafish larvae. Full article

Concrete mix design plays a pivotal role in ensuring the mechanical performance, durability, and sustainability of construction projects. However, the nonlinear interactions among the mix components challenge traditional approaches in predicting compressive strength and optimizing proportions. This study presents a two-stage hybrid framework that integrates deep learning with reinforcement learning to overcome these limitations. First, a Convolutional Neural Network–Long Short-Term Memory (CNN–LSTM) model was developed to capture spatial–temporal patterns from a dataset of 1030 historical concrete samples. The extracted features were enhanced using an eXtreme Gradient Boosting (XGBoost) meta-model to improve generalizability and noise resistance. Then, a Dueling Double Deep Q-Network (Dueling DDQN) agent was used to iteratively identify optimal mix ratios that maximize the predicted compressive strength. The proposed framework outperformed ten benchmark models, achieving an MAE of 2.97, RMSE of 4.08, and R² of 0.94. Feature attribution methods—including SHapley Additive exPlanations (SHAP), Elasticity-Based Feature Importance (EFI), and Permutation Feature Importance (PFI)—highlighted the dominant influence of cement content and curing age, as well as revealing non-intuitive effects such as the compensatory role of superplasticizers in low-water mixtures. These findings demonstrate the potential of the proposed approach to support intelligent concrete mix design and real-time optimization in smart construction environments. Full article

Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. 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

In this paper, the accuracy of basic and advanced spiral inductor models for gallium nitride (GaN) integrated inductors is evaluated. Specifically, the experimental measurements of geometrically scaled circular spiral inductors, fabricated in a radio frequency (RF) GaN-on silicon technology, are exploited to estimate the errors of two lumped geometrically scalable models, i.e., a simple π-model with seven components and an advanced model with thirteen components. The comparison is performed by using either the standard performance parameters, such as inductance (L), quality factor (Q-factor), and self-resonance frequency (SRF), or the two-port scattering parameters (S-parameters). The comparison reveals that despite a higher complexity, the developed advanced model achieves a significant reduction in SRF percentage errors in a wide range of geometrical parameters, while enabling an accurate estimation of two-port S-parameters. Indeed, the correct evaluation of both SRF and two-port S-parameters is crucial to exploit the model in an actual circuit design environment by properly setting the inductor geometrical parameters to optimize RF performance. Full article

Newton’s law of cooling requires a reference temperature ($T_{ref}$) to define the heat-transfer coefficient ($h$). For external flows with multiple temperatures in the freestream, obtaining $T_{ref}$ is a challenge. One widely used method, referred to as the adiabatic-wall (AW) method, obtains $T_{ref}$ by requiring the surface of the solid exposed to convective heat transfer to be adiabatic. Another widely used method, referred to as the linear-extrapolation (LE) method, obtains $T_{ref}$ by measuring/computing the heat flux ($q_s^{\prime \prime }$) on the solid surface at two different surface temperatures ($T_s$) and then linearly extrapolating to $q_s^{\prime \prime }=0$. A third recently developed method, referred to as the state-space (SS) method, obtains $T_{ref}$ by probing the temperature space between the highest and lowest in the flow to account for the effects of $T_s$ or $q_s^{\prime \prime }$ on $T_{ref}$. This study examines the foundation and accuracy of these methods via a test problem involving film cooling of a flat plate where $q_s^{\prime \prime }$ switches signs on the plate’s surface. Results obtained show that only the SS method could guarantee a unique and physically meaningful $T_{ref}$ where $T_s=T_{ref}$ on a nonadiabatic surface $q_s^{\prime \prime }=0$. The AW and LE methods both assume $T_{ref}$ to be independent of $T_s$, which the SS method shows to be incorrect. Though this study also showed the adiabatic-wall temperature, $T_{AW}$, to be a good approximation of $T_{ref}$ (<10% relative error), huge errors can occur in $h$ about the solid surface where $|T_s-T_{AW}|$ is near zero because where $T_s=T_{AW}$, $q_s^{\prime \prime }\ne 0$. Full article

Glutathione peroxidase (GPX) is crucial in mediating plant responses to abiotic stresses. In this study, bioinformatics methods were used to identify the GPX gene family in quinoa. A total of 15 CqGPX genes were identified at the quinoa genome level and conducted preliminary analysis on their protein characteristics, chromosome distribution, gene structure, conserved domain structure, cis-acting elements, and expression patterns. Phylogenetic analysis showed that the GPX genes of quinoa, Arabidopsis, soybean, rice, and maize were divided into three groups. Most of the CqGPXs had the three characteristic conserved motifs and other conserved sequences and amino acid residues. Six types of cis-acting elements were identified in the CqGPX gene promoter, with stress and hormone response-related cis-acting elements constituting the two main categories. Additionally, the expression patterns of CqGPX genes across various tissues and their responses to treatments with NaCl, PEG, CdCl₂, and H₂O₂ were also investigated. The qRT-PCR results showed significant differences in the expression levels of the CqGPX genes under stress treatment at different time points. Consistently, the activity of glutathione peroxidase enzymes increased under stresses. Heterologous expression of CqGPX4 and CqGPX15 conferred stress tolerance to E. coli. This study will provide a reference for exploring the function of CqGPX genes. Full article

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Background/Objectives: Alterations in DNA damage repair mechanisms can impair the therapeutic effectiveness of cisplatin. MicroRNAs (miRNAs), key regulators of DNA damage repair processes, have been proposed as promising biomarkers for predicting the response to platinum-based chemotherapy (CT) in non-small cell lung cancer (NSCLC). In this study, by using a bioinformatics approach, we identified six miRNAs, which were differentially expressed (DE) between NSCLC patients characterized as responders and non-responders to platinum-based CT. We further validated the differential expression of the selected miRNAs on tumor and matched normal tissues from patients with resected NSCLC. Methods: Two miRNA microarray expression datasets were retrieved from the Gene Expression Omnibus (GEO) repository, comprising a total of 69 NSCLC patients (N = 69) treated with CT and annotated data from their response to treatment. Differential expression analysis was performed using the Linear Models for Microarray Analysis (Limma) package in R to identify DE miRNAs between responders (N = 33) and non-responders (N = 36). Quantitative real-time PCR (qRT-PCR) was used to assess miRNA expression levels in clinical tissue samples (N = 20). Results: Analysis with the Limma package revealed 112 DE miRNAs between responders and non-responders. A random-effects meta-analysis further identified 24 miRNAs that were consistently up- or downregulated in at least two studies. Survival analysis using the Kaplan–Meier plotter (KM plotter) indicated that 22 of these miRNAs showed significant associations with prognosis in NSCLC. Functional and pathway enrichment analysis revealed that several of the identified miRNAs were linked to key pathways implicated in DNA damage repair, including the p53, Hippo, PI3K and TGF-β signaling pathways. We finally distinguished a six-miRNA signature consisting of miR-26a, miR-29c, miR-34a, miR-30e-5p, miR-30e-3p and miR-497, which were downregulated in non-responders and are involved in at least three DNA damage repair pathways. Comparative expression analysis on tumor and matched normal tissues from surgically treated NSCLC patients confirmed their differential expression in clinical samples. Conclusions: In summary, we identified a signature of six miRNAs that are suppressed in NSCLC and may serve as a predictor of cisplatin response in NSCLC. Full article

This research investigates resonator width optimization for simultaneously enhancing electrical performance and mechanical reliability in wideband RF MEMS filters through systematic evaluation of three configurations: 0% (L1), 60% (L2), and 100% (L3) matching ratios between cap and bottom wafers using Au-Au thermocompression bonding. The study demonstrates that resonator width alignment significantly influences both electromagnetic field coupling and bonding interface integrity. The L3 configuration with complete width matching achieved optimal RF performance, demonstrating 3.34 dB insertion loss across 4.5 GHz bandwidth (25% fractional bandwidth), outperforming L2 (3.56 dB) and L1 (3.10 dB), while providing enhanced electromagnetic wave coupling and minimized contact resistance. Mechanical reliability testing revealed superior bonding strength for the L3 configuration, withstanding up to 7.14 Kgf in shear pull tests, significantly exceeding L1 (4.22 Kgf) and L2 (2.24 Kgf). SEM analysis confirmed uniform bonding interfaces with minimal void formation (~180 nm), while Q-factor measurements showed L3 achieved optimal loaded Q-factor (Q_L = 3.31) suitable for wideband operation. Comprehensive environmental testing, including thermal cycling (−50 °C to +145 °C) and humidity exposure per MIL-STD-810E standards, validated long-term stability across all configurations. This investigation establishes that complete resonator width matching between cap and bottom wafers optimizes both electromagnetic performance and mechanical bonding reliability, providing a validated framework for developing high-performance, reliable RF MEMS devices for next-generation communication, radar, and sensing applications. Full article

Increased body mass index (BMI) and age are associated with COVID-19 severity. SARS-CoV-2 infection occurs through ACE2 binding, with TMPRSS2, ADAM17, and NRP1 facilitating this process. This study describes how adipose tissue (AT) location, BMI, age, and obesity affect these proteins’ expression. AT was collected from subcutaneous (abdominal superficial [AS], abdominal deep [AD], thigh [T]) and visceral (epiploon [E]) areas from middle-aged women without obesity (BMI 23.9 kg/m², age 48.3 years). Subcutaneous AT was also obtained from middle-aged women with previous obesity (BMI 24.8 kg/m², previously 41.7 kg/m², age 46.9 years), older women with obesity (BMI 32.3 kg/m², age 70.8 years), and older women without obesity (BMI 23.7 kg/m², age 70.6 years). ACE2, TMPRSS2, ADAM17, and NRP1 expression was evaluated by qPCR and Western blotting. All proteins were more expressed in visceral AT. ACE2, TMPRSS2, and NRP1 positively correlated with BMI in AS and/or E, while NRP1 correlated with age in T. In subcutaneous AT, ACE2 and NRP1 were more influenced by obesity while TMPRSS2 was more age-dependent. In women with previous obesity, ACE2 and NRP1 levels decreased, while TMPRSS2 and ADAM17 remained unchanged. These findings highlight the differential influence of visceral AT, obesity, and age on the expression of SARS-CoV-2 cell entry mediators, potentially contributing to COVID-19 severity. Full article