Search Results (13,077)

Background: Intuitive inquiry meditation (Can-Hua-Tou) is a unique mental practice which differs from relaxation-based practices by continuously demanding intuitive inquiry. It emphasizes the doubt-driven self-interrogation, also referred to as Chan/Zen meditation. Nonetheless, its electrophysiological signature remains poorly characterized. Methods: We recorded 128-channel EEG from 20 male Buddhist monks (5–28 years Can-Hua-Tou experience) and 18 male novice lay practitioners (<0.5 year) during three counter-balanced eyes-closed blocks: Zen inquiry meditation (ZEN), a phonological control task silently murmuring “A-B-C-D” (ABCD), and passive resting state (REST). Power spectral density was computed for alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–45 Hz) bands and mapped across the scalp. Mixed-design ANOVAs and electrode-wise tests were corrected with false discovery rate (p < 0.05). Results: Alpha power increased globally with eyes closed, but condition- or group-specific effects did not survive FDR correction, indicating comparable relaxation in both cohorts. In contrast, monks displayed a robust beta augmentation, showing significantly higher beta over parietal-occipital leads than novices across all conditions. The most pronounced difference lay in the gamma band: monks exhibited trait-like fronto-parietal gamma elevations in all three conditions, with additional, though sub-threshold, increases during ZEN. Novices showed negligible beta or gamma modulation across tasks. No significant group × condition interaction emerged after correction, yet only experts expressed concurrent beta/gamma amplification during meditative inquiry. Conclusions: Long-term Can-Hua-Tou practice is associated with frequency-specific neural adaptations—stable high-frequency synchrony and state-dependent beta enhancement—consistent with Buddhist constructs of citta-ekāgratā (one-pointed concentration) and vigilance during self-inquiry. Unlike mindfulness styles that accentuate alpha/theta, Chan inquiry manifests an oscillatory profile dominated by beta–gamma dynamics, underscoring that different contemplative strategies sculpt distinct neurophysiological phenotypes. These findings advance contemplative neuroscience by linking intensive cognitive meditation to enduring high-frequency cortical synchrony. Future research integrating cross-frequency coupling analyses, source localization, and behavioral correlates of insight will further fully delineate the mechanisms underpinning this advanced contemplative expertise. Full article

To investigate how sweating–drying processing affects the components, antioxidant activity, and hepatoprotective mechanisms of Eucommia ulmoides (EUB) against acute liver injury (ALI), this study constructed a “processing–active components–ALI targets” network. Eight processed EUB samples were analyzed using HPLC fingerprinting, multi-assay antioxidant tests (DPPH/ABTS·+/pyrogallol), network pharmacology, and molecular docking. Sweating–drying significantly altered EUB’s chemical profile, with HPLC fingerprint similarities ranging from 0.715 to 1.000, the lowest being for FG4 (40 °C dried after sweating) and FD (freeze-dried after sweating). Key components (chlorogenic acid (CA), pinoresinol diglucoside (PDG), aucubin (AU), geniposidic acid (GPA)) varied: XS (sun-dried) had the highest CA/PDG, while FG4 showed increased AU/GPA. FY (shade-dried after sweating) exhibited the strongest free radical scavenging (DPPH/ABTS·+/pyrogallol IC₅₀ = 0.828, 0.134, 14.200 mg/mL), which correlated with CA/PDG/liriodendrin (PD) synergy. Network pharmacology identified 205 EUB-ALI intersection targets (core: TNF, PTGS2, GAPDH) and the AGE-RAGE pathway; molecular docking confirmed strong CA/PDG binding to GAPDH/PTGS2. This study clarifies how processing regulates EUB’s components and their links to antioxidant and hepatoprotective effects, providing scientific support for EUB’s clinical application against ALI. Full article

During periodontitis, Porphyromonas gingivalis and its lipopolysaccharides (LPS) may translocate into the bloodstream and alter adipocyte function, aggravating obesity-related disorders. This study aimed to evaluate the inflammatory and metabolic effects of P. gingivalis in obese db/db mice, and to decipher the molecular mechanisms targeted by P. gingivalis or its LPS in 3T3-L1 adipocytes. Then, we determined the ability of three major dietary polyphenols, namely caffeic acid, quercetin and epicatechin, to protect adipocytes under LPS conditions. Results show that obese mice exposed to P. gingivalis exhibited an altered lipid profile with higher triglyceride accumulation, an enhanced pro-inflammatory response and a reduced antioxidant SOD activity in the adipose tissue. In adipose cells, P. gingivalis and LPS induced the TLR2-4/MyD88/NFκB signaling pathway, and promoted IL-6 and MCP-1 secretion. Bacterial stimuli also increased ROS levels and the expression of NOX2, NOX4 and iNOS genes, while they deregulated mRNA levels of Cu/ZnSOD, MnSOD, catalase, GPx and Nrf2. Interestingly, caffeic acid, quercetin and epicatechin protected adipose cells via antioxidant and anti-inflammatory effects. Overall, these findings show the deleterious impact of P. gingivalis on inflammation, oxidative stress and lipid metabolism in obese mice and adipose cells, and highlight the therapeutic potential of polyphenols in mitigating periodontal bacteria-mediated complications during obesity. Full article

Sea grape kombucha has been known to exhibit high antioxidant activity due to its elevated total polyphenol content. This study aims to identify and characterize the active microbial community involved in the fermentation of kombucha using sea grapes (C. racemosa) as the primary substrate. Furthermore, it evaluates the effects of different Symbiotic Culture of Bacteria and Yeast (SCOBY) starter concentrations on the physicochemical properties and antioxidant activity of sea grape kombucha. Our results showed that the pH of the kombucha was higher after 7 days of fermentation compared to later time points. The microbial community was composed of 97.08% bacteria and 2.92% eukaryotes, divided into 10 phyla and 69 genera. The dominant genus in all samples was Komagataeibacter. Functional profiling based on 16S rRNA data revealed that metabolic functions accounted for 77.04% of predicted microbial activities during fermentation. The most enriched functional categories were carbohydrate metabolism (15.70%), cofactor and vitamin metabolism (15.54%), and amino acid metabolism (14.24%). At KEGG Level 3, amino acid-associated pathways, particularly alanine, aspartate, and glutamate metabolism (4.24%), were predominant. The fermentation process in sea grape kombucha is primarily driven by carbohydrate and amino acid metabolism, supported by energy-generating and cofactor biosynthesis pathways. Our findings indicate that different metabolic pathways lead to variations in kombucha components, and distinct fermentation stages result in different metabolic reactions. For instance, early fermentation stages (Day 7) are dominated by amino acid metabolism, whereas the late stages (Day 21) show increased activity in carbohydrate and sulfur metabolism. Metabolomic analysis revealed that increasing the SCOBY starter concentration significantly influenced pH, soluble solid content, vitamin C, tannin, and flavonoid content. These variations suggest that fermentation duration and microbial composition significantly influence the spectrum of bioactive metabolites, which synergistically provide functional benefits such as antimicrobial, antioxidant, and metabolic health-promoting activities. For example, sample K1 produced more fatty acids and simple sugar alcohols, sample K2 enriched complex lipid compounds and phytosterols, while sample K3 dominated the production of polyols and terpenoid compounds. Full article

MYCN amplification without concurrent RB1 mutations characterizes a rare yet highly aggressive subtype of retinoblastoma; however, its precise developmental origins and therapeutic vulnerabilities remain incompletely understood. Here, we modeled this subtype by lentiviral-mediated MYCN overexpression in human pluripotent stem cell-derived retinal organoids, revealing a discrete developmental window (days 70–120) during which retinal progenitors showed heightened susceptibility to transformation. Tumors arising in this period exhibited robust proliferation, expressed SOX2, and lacked CRX, consistent with origin from primitive retinal progenitors. MYCN-overexpressing organoids generated stable cell lines that reproducibly gave rise to MYCN-driven tumors when xenografted into immunodeficient mice. Transcriptomic profiling demonstrated that MYCN-overexpressing organoids closely recapitulated molecular features of patient-derived MYCN-amplified retinoblastomas, particularly through activation of MYC/E2F and mTORC1 signaling pathways. Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype. Full article

Antimicrobial resistance (AMR) presents a global health challenge, necessitating comprehensive surveillance and intervention strategies. Wastewater-based epidemiology (WBE) is a promising tool that can be utilized for AMR monitoring by offering population-level insights into microbial dynamics and resistance gene dissemination in communities. This review (n = 29 papers) examines the current landscape of utilizing WBE for AMR surveillance with a focus on methodologies, findings, and gaps in understanding. Reported methods from the reviewed literature included culture-based, PCR-based, whole genome sequencing, mass spectrometry, bioinformatics/metagenomics, and antimicrobial susceptibility testing to identify and measure antibiotic-resistant bacteria and antimicrobial resistance genes (ARGs) in wastewater, as well as liquid chromatography-tandem mass spectrometry to measure antibiotic residues. Results indicate Escherichia coli, Enterococcus spp., and Pseudomonas spp. are the most prevalent antibiotic-resistant bacterial species with hospital effluent demonstrating higher abundances of clinically relevant resistance genes including bla, bcr, qnrS, mcr, sul1, erm, and tet genes compared to measurements from local treatment plants. The most reported antibiotics in influent wastewater across studies analyzed include azithromycin, ciprofloxacin, clindamycin, and clarithromycin. The influence of seasonal variation on the ARG profiles of communities differed amongst studies indicating additional factors hold significance when examining the conference of AMR within communities. Despite these findings, knowledge gaps remain, including longitudinal studies in multiple and diverse geographical regions and understanding co-resistance mechanisms in relation to the complexities of population contributors to AMR. This review underscores the urgent need for collaborative and interdisciplinary efforts to safeguard public health and preserve antimicrobial efficacy. Further investigation on the use of WBE to understand these unique population-level drivers of AMR is advised in a proposed framework to inform best practice approaches moving forward. Full article

CD19-targeted therapies, including monoclonal antibodies, antibody–drug conjugates, and chimeric antigen receptor (CAR) T-cell products, have significantly improved outcomes in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Despite their clinical efficacy, resistance and antigen modulation pose substantial challenges, especially in patients requiring sequential therapy. This review provides a comprehensive overview of CD19 biology and its relevance as a therapeutic target. We examine mechanisms of resistance such as antigen loss, epitope masking, and T-cell exhaustion, as well as the implications of tumor microenvironmental immunosuppression. Future efforts should prioritize the integration of real-time diagnostics, such as flow cytometry, immunohistochemistry, and transcriptomic profiling, and AI-assisted predictive models to optimize therapeutic sequencing and expand access to personalized immunotherapy. Full article

The Long Interspersed Element-1 (L1) retrotransposon is an ancient genetic parasite that comprises a significant part of the human genome. ORF2p is a multifunctional enzyme with endonuclease (EN) and reverse transcriptase (RT) activities that mediate target-primed reverse transcription of RNA into DNA. Structural studies of LINE-1 ORF2p consistently show a single Mg²⁺ cation in the reverse transcriptase active site, conflicting with the common DNA polymerase mechanism which involves two divalent cations. We explored a reaction pathway of the DNA elongation based on the recent high-resolution ternary complex structure of the ORF2p. The combined quantum and molecular mechanics approach at the QM (PBE0-D3/6-31G**)/MM (CHARMM) level is employed for biased umbrella sampling molecular dynamics simulations followed by umbrella integration utilized to obtain the free energy profile. The nucleotidyl transfer reaction proceeds in a single step with a free energy barrier of 15.1 ± 0.8 kcal/mol, and 7.8 ± 1.2 kcal/mol product stabilization relative to reagents. Concerted nucleophilic attack by DNA O3′ and proton transfer to Asp703 occur without a second catalytic metal ion. Estimated rate constant ∼60 s⁻¹ aligns with RT kinetics, while analysis of the Laplacian of the electron density along the cleaving P-O bond identifies a dissociative mechanism. Full article

Camelina sativa is an oilseed crop that has shown strong promise as a biofuel feedstock. The profile of fatty acids greatly influences the oil quality; however, genetic mechanisms that determine the natural variation of fatty acid composition in camelina are not fully understood. A genome wide association study (GWAS) was performed to uncover genetic loci that may contribute to the contents of major fatty acids such as oleic and linolenic acids in camelina seed. Two approaches were taken to improve the GWAS efficiency. First, growing a diversity panel of 212 accessions in four locations and two nitrogen fertilization conditions revealed great variation in fatty acid contents in seeds. Second, using an improved reference genome, abundant markers, including 203,320 single nucleotide polymorphisms (SNPs) and 99,067 insertions/deletions (indels), were developed, which refined the population structure of the diversity panel. GWAS resulted in 118 genetic markers across 31 trait/treatment conditions. Closely linked markers were determined based on linkage decay and by comparing secondarily associated markers when highly associated ones were removed. Candidate genes were examined by comparing the pangenomes of 12 high-quality reference genomes. This study provides new resources to understand seed lipid metabolism and improve camelina oils through molecular breeding. Full article

To address the dynamic characteristics of vehicle semi-active suspension systems under special operating conditions and multi-source excitations, this paper proposes a fuzzy adaptive proportional–integral–derivative model predictive control (PID-MPC) strategy aimed at enhancing ride comfort during vehicle operation. The proposed approach employs MPC as the primary controller to optimize suspension performance, incorporating a fuzzy adaptive PID compensation mechanism for real-time adjustment of PID parameters, thereby improving control efficacy. A half-car semi-active suspension model was established on the MATLAB/Simulink (2020b) platform, with simulation validation conducted across diverse road profiles, including speed bump road surface, Class B road surface, and Class C road surface. Simulation results demonstrate that the proposed strategy achieves a significant reduction in both vehicle vertical acceleration and vehicle pitch angle acceleration while maintaining appropriate suspension deflection and tire dynamic loads, effectively elevating occupant ride comfort. Research demonstrates that the fuzzy adaptive PID-MPC control strategy exhibits commendable performance under typical road operating conditions, possessing notable potential for practical engineering implementation. Full article

At onset, myelodysplastic syndrome (MDS) may be complicated by coagulation and fibrinolytic abnormalities, such as disseminated intravascular coagulation (DIC), tumor lysis syndrome (TLS), infection, thromboembolism, hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HPS/HLH), hemorrhage, and hematoma formation. In these cases, the cause may be secondary. On the other hand, it is known that platelet clotting dysfunction and fibrinolysis abnormalities are seen in the background of MDS, and primary fibrinolysis abnormalities may be complicated by adverse events associated with paraneoplastic syndrome (PNS). Coagulation fibrinolysis, as a PNS associated with MDS, is known to take the pattern of either consumptive coagulation abnormality or fibrinolytic coagulation abnormality. One mechanism of coagulation and fibrinolytic abnormalities has been shown to be the immunophenotypical pathway, and aberrant cytokine production is also associated with coagulopathy in MDS. We focused on how to differentiate an MDS-associated bleeding tendency resulting from either secondary or primary causes. In order to make this differentiation, we proposed a useful flowchart for the differentiation of solidified fibrinolysis seen at the initial MDS diagnosis. Additionally, we compared and summarized the molecular pathways of the secondary and primary causes of coagulopathy. Addressing coagulation and fibrinolytic abnormalities in MDS is required to differentiate the complexity and heterogeneity of bleeding and coagulation abnormalities. This review highlights the need to distinguish between the primary (disease-intrinsic) and secondary (reactive or complication-related) causes of coagulopathy. By proposing a diagnostic flowchart tailored to evaluate these causes at initial diagnosis, this study supports individualized risk stratification and management strategies. By comparing the molecular pathways of the two causes of coagulopathy, we provide a clinical discussion of the underlying pathologies. This aligns with the principles of personalized medicine by ensuring that treatment decisions (e.g., supportive care, anticoagulation, and antifibrinolytics) are based on the patient’s specific pathophysiological profile, rather than a one-size-fits-all approach. Full article

Hepatic oxidative stress is a key driver in liver injury pathogenesis, with D-galactose (D-gal) modeling serving as an established inducer of accelerated oxidative damage. Silibinin (SLB), a flavonolignan from milk thistle, shows therapeutic promise through potent antioxidant activity and gut–liver axis modulation. This study investigated whether the hepatoprotective effect of SLB against oxidative stress depends on gut microbiota regulation. Using mouse models with gut microbiota ablation by oral antibiotics or direct oxidative stress induction by D-gal (150 mg/kg), SLB treatment (200 mg/kg) was administered. The protective mechanisms were evaluated through the Nrf2/ARE pathway, target gene expression, gut microbiota profiling, and cecal metabolomics. Results demonstrated that SLB significantly alleviated D-gal-induced hepatic oxidative stress (e.g., reduced MDA by 33.3%), but this protection was markedly weakened after antibiotic-induced microbiota depletion (e.g., a loss of efficacy exceeding 50%). Integrated omics revealed that antibiotics caused a severe reduction in unclassified_Muribaculaceae (a butyrate producer, decreased by 80%), impairing butyrate-mediated Nrf2/Keap1 activation. Simultaneously, the absence of Parabacteroides led to accumulated primary bile acids and inhibited secondary bile acid production (e.g., taurochenodeoxycholate reduced by 75%), further disrupting redox homeostasis. Conclusion: Silibinin’s mitigation of hepatic oxidative stress is gut microbiota-dependent, highlighting the therapeutic potential of microbiota-targeted antioxidant strategies for oxidative stress-related pathologies. Full article

Peritoneal carcinomatosis (PC) is a late-stage manifestation of abdominopelvic malignancies with poor prognosis and limited treatment options. Unique biochemical mechanisms within the peritoneal cavity play a key role in disease progression and resistance to therapy. Despite current therapies like systemic chemotherapy and cytoreductive surgery, patients frequently develop severe complications, including bowel obstruction, nutritional decline, and ascites, driving the need to address the pro-tumorigenic niche in the peritoneal cavity. The immune microenvironment in PC is marked by elevated proinflammatory mediators, such as IL-6 and IL-8, which skew the response toward innate rather than adaptive immune responses. IL-8 signaling, through its receptors CXCR1 and CXCR2, promotes neutrophil recruitment, chronic inflammation, angiogenesis, epithelial–mesenchymal transition, and immune evasion, making the IL-8/CXCR1/CXCR2 axis a potential therapeutic target in PC. Pre-clinical models provide evidence that IL-8 or CXCR1/CXCR2 blockade may be a valuable therapeutic strategy. IL-8 targeting agents such as monoclonal antibodies (BMS-986253) and small-molecule inhibitors (SX-682, AZD5069, navarixin) have shown efficacy in mitigating tumor growth and improving the efficacy of immune checkpoint inhibitors. Phase I and II trials have demonstrated encouraging safety profiles and preliminary efficacy when treating multiple abdominopelvic malignancies. In this review, we discuss the influence of the IL-8/CXCR1/CXCR2 axis within the peritoneal immune environment in PC and highlight recent work using IL-8 or CXCR1/CXCR2 blockade as a therapeutic strategy for PC. Continued research into the peritoneal immune microenvironment and the development of targeted therapies are essential for improving the management and prognosis of PC, potentially enhancing antitumor immunity and patient outcomes. Full article

Honeybee populations are increasingly threatened by various environmental stressors, including pesticides, pathogens, and climate change. Emerging research highlights the vital role of pollen polyphenols in supporting honeybee health through a network of antioxidants, immune responses, and detoxification mechanisms. This review synthesizes current findings on the chemical diversity, bioactivity, and functional relevance of polyphenolic compounds in honeybee nutrition. Pollen polyphenols, which include flavonoids and phenolic acids, possess remarkably high antioxidant potential, up to 235 times greater than that of nectar. They also significantly increase the expression of antioxidant enzymes, immune system genes, and detoxification pathways such as cytochrome P450s and glutathione-S-transferases. These compounds also demonstrate antimicrobial effects against key pathogens and mitigate the toxic effects of pesticides. The content and composition of polyphenols vary seasonally and geographically, impacting the resilience of honeybee colonies. Field and laboratory studies confirm that polyphenol-rich diets improve survival, gland development, and stress resistance. Advanced analytical techniques, including metabolomics, have expanded our understanding of polyphenol profiles and their effects on honeybee physiology. However, knowledge gaps remain in pharmacokinetics and structure–function relationships. Integrating this evidence into conservation strategies and good beekeeping practices, such as habitat diversification and targeted feed supplementation, is crucial for maintaining honeybee health and ecosystem services in a rapidly changing environment. Full article

This study investigates the use of suberinic acid residues (SARs), derived from birch outer bark, as a bio-based additive in high-density fiberboard (HDF). Boards with target densities of 800 kg m⁻³ were produced with SAR contents of 0, 1, 5, 10, 20, and 50%. Standardized tests evaluated mechanical properties: screw withdrawal resistance, modulus of elasticity, modulus of rupture, and internal bond, as well as moisture resistance through surface water absorption, water absorption, and thickness swelling. Density profiles were also analyzed. SAR content influenced HDF performance in a concentration-dependent manner. The most notable improvements in mechanical properties occurred at 5% SAR, where fine particles likely enhanced internal bonding and stiffness. However, higher SAR levels led to reduced mechanical strength, possibly due to an excessive particle surface area exceeding the adhesive’s bonding capacity. Moisture resistance declined with increased SAR, attributed to its hydrophilic nature and process parameters, although SAR-modified boards still outperformed those with other biodegradable additives like starch. SAR also affected the density profile, improving core densification at moderate levels. Overall, SAR shows potential as a renewable additive for enhancing HDF performance, particularly at low concentrations, balancing mechanical strength and environmental benefits. Full article