Search Results (1,658)

Levodopa-induced dyskinesia (LID) is a severe motor complication associated with long-term levodopa (L-DOPA) treatment for Parkinson’s disease (PD). Its underlying mechanisms remain unclear, and candidate biomarkers lack consistency. To investigate cortico-striatal network alterations associated with LID, we simultaneously recorded single-neuron spikes and local field potentials (LFPs) from the dorsolateral striatum (DLS) and the primary motor cortex (M1) in LID rats. Our results showed that in the DLS, the LID group had a greater number of putative fast-spiking interneurons (FSIs) with lower firing rates, and fewer putative medium spiny neurons (MSNs) with higher firing rates. In M1, pyramidal neurons were fewer but fired faster, while interneurons were more numerous with no change in firing rate. Although gamma power increased and delta power decreased in both regions in LID rats, delta-gamma phase-amplitude coupling (PAC) was present in the DLS but absent in M1. Furthermore, cross-regional PAC analysis revealed significantly stronger coupling between the low-frequency phase of M1 and the high-frequency amplitude of the DLS than in the opposite direction, indicating an asymmetric pattern of cortico-striatal coupling in LID. These findings demonstrate region-specific alterations in neuronal activity and oscillatory coupling associated with LID and suggest that asymmetric cortico-striatal PAC may serve as a promising electrophysiological marker for characterizing abnormal network dynamics underlying dyskinesia. Full article

Background: Autism spectrum disorder (ASD) is characterized by widespread aberrations in brain scalp-level synchronization. Phase-amplitude coupling (PAC), which reflects cross-frequency neuronal oscillatory interactions, serves as a crucial metric for assessing functional brain integration. However, the specific patterns of PAC at both intra-region and inter-region scalp levels in young children with ASD, as well as their precise associations with clinical symptoms, remain unclear. Methods: This study enrolled 237 children with ASD aged 3–9 years and 201 age-matched typically developing (TD) children. Resting-state electroencephalography (EEG) data were acquired from all participants. The analysis systematically examined low-frequency oscillation phase (δ, θ, α) modulation of high-frequency oscillation amplitude (β and low γ) from both intra-region and inter-region dimensions. The PAC strength was quantified using the modulation index (MI). Multiple comparisons were corrected using the Bonferroni method. Finally, correlations between PAC metrics and Autism Behavior Checklist (ABC) scores were analyzed. Results: Compared to the control group, children with ASD exhibited significant frequency-specific PAC abnormalities: (1) Multi-regional γ hyper-coupling: There was a significant enhancement in the modulation of γ amplitude by δ/θ/α phase across the measured scalp regions, suggesting abnormal high-frequency synchronization. (2) Dissociated β modulation patterns: The ASD group showed increased δ–β coupling (predominantly in frontal, temporal, and occipital lobes) alongside significantly reduced α–β coupling (localized to frontal and central regions). This reflects both an abnormal locking of slow-wave activity to the β band and a diminished regulatory role of α oscillations. (3) Clinical correlation: Notably, abnormally elevated PAC strength (particularly in the δ/θ/α–γ bands) showed a negative correlation with clinical symptom severity—that is, stronger coupling was associated with lower scores on the ABC. Conclusions: Leveraging a large-sample dataset, this study characterizes the landscape of aberrant cross-frequency interactions in young children with ASD. Our findings indicate that the neuroelectrical activity in ASD goes beyond mere connectivity anomalies by demonstrating altered PAC strength at both the intra-region and inter-region levels. Notably, the strength of this aberrant intra-region PAC is correlated with clinical symptoms. Full article

Dybowski’s frog (Rana dybowskii) supports a multi-billion-dollar aquaculture sector in northern China and plays a critical ecological role in forest ecosystems. Despite its immense economic value, germplasm degradation and the mystery surrounding its homomorphic sex-determination system present major bottlenecks for the industry. Here, we integrated PacBio HiFi long-read sequencing, Illumina short-read sequencing, and High-Throughput Chromosome Conformation Capture (Hi-C) technologies to assemble the first chromosome-level reference genome of R. dybowskii. The final assembled genome size is 3.77 Gb, with a contig N50 of 16.27 Mb and a scaffold N50 of 41.54 Mb. A total of 97.82% of the sequences were successfully anchored onto 12 definitive pseudochromosomes corresponding to haploid chromosome number. Repetitive elements account for 65.61% of the genome, characterized by an unusual dominance of DNA transposons (37.19%) over retrotransposons, suggesting a genomic landscape shaped by extreme cold adaptation. Combining multi-tissue transcriptomic evidence, we structurally predicted 26,862 protein-coding genes, and the predicted gene set showed a BUSCO completeness of 96.1%. Functional annotation successfully categorized 96.55% of the total genes. This genomic resource successfully fills a crucial phylogenetic gap in the Rana genus, driving high-efficiency molecular breeding and sustainable conservation of this economic amphibian. Full article

Forecasting multi-asset volatility spillovers and turning the forecasts into risk-aware portfolios requires methods that uncover directional information flow between assets, compress the state into a minimal sufficient representation, deliver calibrated uncertainty, and respect explicit tail-risk limits. We propose TDV (Transfer-entropy, Dynamic-graph-attention, Variational-information-bottleneck), an information-theoretic artificial intelligence framework that couples a time-varying transfer entropy network with a graph attention encoder regularised by a variational information bottleneck, and demonstrates the practical value of the calibrated predictive distribution through a downstream entropy-regulated, CVaR-constrained portfolio application. We establish three theoretical results: $L^2$ consistency of the k-nearest-neighbour transfer entropy estimator on $\alpha$-mixing returns with rate $O_P\left(n^{-2/(2+d)}\right)$, a PAC–Bayes generalisation bound of order $O\left(\sqrt{\left(I\right(X;Z)+log(1/\delta \left)\right)/n}\right)$ for the bottleneck-encoded forecaster, and asymptotic CVaR feasibility of the plug-in allocation. In simulations across sparse Granger networks, contagion DCC–GARCH ensembles, and regime-switching factor models, the framework cuts spillover forecasting errors by 24 to 42 percent against LSTM, vanilla GAT, and Transformer baselines, and it recovers 1.6 additional nats of mutual information with the realised connectedness matrix. On a 32-asset global panel covering 2014 to 2025, the model delivers an out-of-sample $R^2$ of 0.331, an annualised Sharpe ratio of 1.46 against 0.83 for an equally weighted benchmark, a maximum drawdown of 7.8 percent, and 95 percent CVaR reductions of 28 to 36 percent across sub-periods relative to a shrinkage minimum-variance baseline. Full article

Background:Pectobacterium brasiliense-mediated soft rot severely threatens the production of diverse cash crops worldwide and brings severe yield reduction risks. A virulent strain BS1113 was separated from diseased cigar tobacco plants collected in Yunnan, yet its virulence regulatory genes and copper resistance-related genetic background have not been fully analyzed so far. This study aims to decipher the genomic features of BS1113 and clarify its pathogenic and copper-tolerant characteristics via whole-genome sequencing, comparative genomics and indoor phenotype verification. Methods: Hybrid sequencing strategies combining Illumina short reads and PacBio long reads were adopted to obtain the complete circular genome sequence of strain BS1113. Subsequent comparative genomic analysis and multiple phenotypic identification experiments were conducted to characterize its genetic architecture and physiological traits. Results: Genome assembly results showed that the circular chromosome of BS1113 spans 4,916,962 bp with a GC content of 51.96%, which encodes a total of 4369 functional protein-coding genes. Genomic comparison revealed that BS1113 completely lacks the T3SS gene cluster, while it conserves intact T2SS, T6SS and I-F CRISPR-Cas systems; the chromosomal copper resistance operon copRSAB was also detected in this isolate. Pathogenicity tests validated that BS1113 satisfies all criteria of Koch’s postulates on cigar tobacco hosts. In addition, BS1113 displayed prominent tolerance against eight mainstream copper bactericides widely used for tobacco disease management. Conclusions: This research generates the first complete high-quality genome of P. brasiliense isolated from cigar tobacco hosts. The genomic data explain the infection mechanism of this pathogen independent of intact T3SS, and also reveal the genetic basis supporting its persistent survival under long-term copper fungicide pressure in field cultivation environments. Full article

Sarcopenia is highly prevalent among stroke patients and is associated with poor functional outcomes; however, differences across stroke stages and age groups remain unclear. This cross-sectional study enrolled 80 stroke patients from a regional teaching hospital in Taiwan, categorized into chronic (n = 40) and post-acute care (PAC) groups (n = 40), and further stratified into younger (40–64 years, n = 44) and older (≥65 years, n = 36) groups. Assessments included body composition, muscle strength, ultrasound-measured muscle thickness, gait speed, calf circumference, sarcopenia screening (SARC-F), nutritional status, and health-related quality of life. No significant differences were observed in muscle mass, muscle strength, or ultrasound-derived muscle thickness between the chronic and PAC groups. However, the PAC group demonstrated poorer functional outcomes and health-related quality of life, including lower gait speed (p = 0.018), and lower EQ-5D index and visual analogue scale scores (p = 0.006 and p = 0.002, respectively). In contrast, the chronic group showed a higher prevalence of sarcopenia (p < 0.001), a higher mean SARC-F scores (p = 0.004), a greater proportion of low appendicular skeletal muscle mass index (ASMMI, p = 0.025), and reduced calf circumference (p < 0.001). Age-stratified analysis revealed that older patients had lower muscle mass and structural parameters, including ASMMI (p < 0.001), fat-free mass (p < 0.001), quadriceps thickness (p < 0.001), and calf circumference (p = 0.002), along with a higher prevalence of sarcopenia (p < 0.001). These findings indicate that stroke stage is more closely associated with functional impairment, whereas aging predominantly affects muscle mass and sarcopenia severity. Full article

Sinotaia angularis is a freshwater viviparid snail with limited genomic resources. Here, we report a chromosome-level reference genome generated using PacBio HiFi sequencing and Hi-C scaffolding, with mitochondrial marker -based screening (16S rRNA and COI (cox1)) and phylogenetic analysis supporting the taxonomic assignment. A total of 74.08 Gb of HiFi reads were obtained, providing approximately 65.7-fold genome coverage. The final assembly spans 1.127 Gb, with a scaffold N50 of 141.87 Mb and a GC content of 34.47%. Hi-C scaffolding anchored 978.89 Mb (86.85% of the assembly) onto eight chromosome-level scaffolds. BUSCO analysis using the mollusca_odb10 dataset recovered 86.9% complete orthologs from the genome assembly. Repeat annotation identified 378.75 Mb of repetitive sequences (33.60% of the genome), with unclassified repeats and LTR elements as the dominant components. Gene annotation predicted 22,232 protein-coding genes, 209 tRNAs, 72 rRNAs, 88 snRNAs, and 10 snoRNAs. Functional annotation assigned database support to 155,611 predicted proteins or isoforms, corresponding to 98% of the total protein set. CAZy annotation identified 5371 carbohydrate-active enzyme entries, suggesting broad carbohydrate-processing potential. This genome provides a reference resource for comparative genomics, chromosome evolution, repeat dynamics, gene-family evolution, and freshwater adaptation studies in Viviparidae. Full article

Cronartium ribicola is a globally distributed fungal pathogen that infects Pinus armandii Franch., causing widespread tree mortality. In this study, we report a chromosomal-level genome assembly of C. ribicola LQ (262.51 Mb, N50 = 15.4 Mb, GC content = 38.4%) using integrated Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. Ultimately, a total of 94.83% of the assembled sequences were anchored onto 17 pseudo-chromosomes. Genome annotation predicted 10,222 protein-coding genes, and repetitive sequences accounted for 91.67% of the genome. Benchmarking Universal Single-Copy Ortholog (BUSCO) analysis demonstrated 94.03% genome completeness, with functional annotations covering 88.32% of the genes. A total of 352 carbohydrate-active enzyme (CAZyme) genes, predominantly glycoside hydrolases (45.17%), and 8 secondary metabolite biosynthetic gene clusters were identified, indicating strong host tissue degradation capability and diverse virulence factors. Overall, this study provides valuable genomic resources for dissecting the pathogenicity, host interaction mechanisms, and resistance gene discovery of C. ribicola and establishes a foundation for developing virulence-targeted disease control strategies. Full article

High-dynamic amusement ride conditions involving impacts, rapid rotations, and abrupt posture changes introduce severe motion artifacts that degrade vital sign quality and destabilize physiological state recognition. This study aims to develop an engineering-ready closed-loop framework for robust passenger monitoring and intelligent diagnosis. A multimodal sensing and modeling pipeline was designed to jointly leverage physiological signals such as heart rate and SpO₂ and kinematic measurements, including acceleration, angular rate, velocity, and attitude. Inertial and PPG signals were preprocessed into supervised samples through wavelet multiresolution denoising and coordinate frame unification, while a strapdown inertial navigation system was used to propagate a 12-channel physical quantity sequence. To ensure interpretability and standards compliance, constraints from GB 8408-2018 were translated into executable threshold rules, enabling standards-driven auto-labeling and rule-based early warning. Building on this foundation, three learning modules were developed: a fusion model for high-dynamic heart rate estimation, a CNN–LSTM dynamic-threshold-enhanced network TAPNet for rapid kinematic anomaly screening, and an attention-augmented hybrid model HS-BANet integrating one-dimensional residual blocks, bidirectional LSTM, and multi-head attention for fine-grained arrhythmia classification. Experimental results demonstrated accurate and consistent heart rate estimation with RMSE of 1.18 bpm on HSSH-I and 1.24 bpm on the independent HSSH-II set, strong agreement with training and testing correlations of 0.9928 and 0.9865, and near-zero bias in Bland–Altman analysis. TAPNet achieved 96.9% validation accuracy and 98.2% test accuracy for kinematic anomaly recognition, maintaining robust generalization under class imbalance. HS-BANet enabled multi-class identification of PVC, PAC, VT, SVT, and AF, achieving an accuracy of 92.37%, an F1-score of 86.87%, a precision of 88.45%, a sensitivity of 88.14%, and a specificity of 89.42%. Overall, the proposed two-stage multimodal closed-loop—fast, interpretable early warning based on physical quantity thresholds followed by fine-grained diagnosis from physiological signals—supports stable feature extraction and reliable decision-making under strong motion artifacts and non-stationary dynamics, balancing responsiveness and diagnostic credibility, while showing potential for practical safety early warning and future deployment-oriented operational support in amusement ride scenarios. Full article

Background: Heart failure (HF) is a major public health problem and a paradigmatic condition for sex differences in cardiovascular disease. However, national population-based evidence describing these differences remains limited. We aimed to provide the first nationwide sex-stratified epidemiologic characterization of HF in Spain, quantifying incidence, prevalence, and clinical characteristics across age groups and left ventricular ejection fraction (LVEF) categories. Methods: We conducted a retrospective population-based study using the BIG-PAC database, integrating electronic health records from primary and hospital care covering approximately 1.8 million individuals across seven Spanish autonomous communities. Adult patients with incident HF between 2013 and 2019 were identified. HF phenotypes were classified according to LVEF as reduced (HFrEF ≤40%), mildly reduced (HFmrEF 41–49%), preserved (HFpEF ≥50%), or unknown (HFuEF). Incidence rates per 1000 person-years and prevalence were estimated and stratified by sex and LVEF phenotype. Results: In total, 19,961 incident HF cases were identified. Overall HF incidence was 3.23 per 1000 person-years and was similar in women and men (p = 0.697). HF prevalence was 2.34% and higher in men than in women (2.67% vs. 2.06%; p < 0.001). Women were older and more frequently presented with HFpEF (38%), whereas HFrEF predominated in men (53%); notably, HFrEF still accounted for approximately one third of HF cases among women. Once stratified by LVEF phenotype, clinical characteristics were broadly similar between sexes. Conclusions: While HF incidence was similar in women and men, substantial sex differences in prevalence, age, and phenotype distribution were identified, establishing the first nationwide epidemiological framework to inform sex-aware HF prevention and healthcare planning in Spain. Full article

This study aimed to investigate the selective anticancer activity of the curcumin analog PAC (3,5-Bis-4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone). Normal gingival epithelial cells (GECs), cancerous gingival cells (Ca9-22) and tongue squamous carcinoma cells (CAL27) were exposed to increasing concentrations of PAC (0–10 µM) for 24 h. Cell viability and cytotoxicity were evaluated using MTT and LDH assays, while apoptosis and caspase activation were analyzed by Annexin V/PI staining and flow cytometry. Gene-expression profiling was performed using RT² Profiler PCR arrays. PAC significantly inhibited Ca9-22 and CAL27 cell proliferation in a concentration-dependent manner, with an IC₅₀ value of 5 µM, while exerting no noticeable cytotoxic effects on normal GEC. PAC treatment induced significant early and late apoptosis associated with increased caspase activity in both oral cancer cell lines. Transcriptomic analyses revealed extensive modulation of apoptosis-related genes. In Ca9-22 cells, PAC predominantly suppressed anti-apoptotic and survival-associated genes, including BCL2, BIRC3, BIRC5, XIAP, CFLAR, and NFKB1. In contrast, CAL27 cells exhibited a more pronounced pro-apoptotic transcriptional profile characterized by upregulation of TP53, APAF1, CASP1, BID, and TNF. Gene interaction network analyses further demonstrated that PAC targets highly interconnected apoptotic signaling pathways. Collectively, these findings demonstrate that PAC exerts potent selective anticancer activity against OSCC cells through modulation of intrinsic and extrinsic apoptotic pathways. These results further support the therapeutic potential of PAC as a promising multitarget candidate for oral cancer treatment. Full article

Harvesting remains one of the main bottlenecks in microalgae-based technologies. Although microalgae hold great promise for industrial biotechnology, their growth in dilute suspensions makes biomass recovery challenging. Conventional harvesting methods are often energy-intensive and costly, limiting large-scale implementation. This study applies a life cycle assessment (LCA) to evaluate the environmental performance of a laboratory-scale magnetic harvesting process of Chlorella vulgaris (C. vulgaris) using Fe₃O₄ microparticles in combination with polyaluminum chloride (PAC) and polyacrylamide (PAM), followed by magnetic oscillation for particle detachment and subsequent reuse. Electricity consumption was identified as the dominant environmental hotspot across most impact categories, with the detachment step accounting for nearly two-thirds of the total energy demand, a step often overlooked in previous LCA studies. The global warming potential (GWP) is consistent with typical laboratory-scale assessments and is mainly driven by energy inefficiencies associated with small processing volumes. The values obtained and the scale-up literature indicate that further optimization and future industrial-scale production will decrease these values into a realistic and competitive range. Sensitivity analysis showed that replacing grid electricity with photovoltaic power significantly reduces environmental impacts. The use of NaOH as a reagent also contributed substantially to environmental impacts. Reusing magnetic particles (4 cycles) reduced material resource depletion by up to fourfold, which is a very relevant result bearing in mind the principles of sustainability and circularity. Full article

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as an anti-atherogenic neuropeptide. Maxadilan, a PAC1 receptor agonist, offers atheroprotection by acting downstream of vascular inflammation caused by hypercholesterolemia. This study aims to explore how PACAP and Maxadilan influence migration and apoptosis in human coronary artery smooth muscle cells (HCASMCs). Methods: To investigate the role of PACAP deficiency in the pathogenesis of atherosclerosis under standard chow (SC) in vivo, PACAP^−/−-mice were crossed with ApoE^−/−-mice to generate PACAP^−/−/ApoE^−/−-mice. The whole aorta was isolated and stained with OilRedO (ORO). Atherosclerotic lesions and lumen stenosis in the brachiocephalic trunk were quantified using ImageJ 1.54p (Fiji). To further investigate the role of PACAP and Maxadilan in the pathogenesis of atherosclerosis with special respect to HCASMC under a lipid-enriched environment, HCASMCs were treated with oxLDL, with or without PACAP or Maxadilan. Uptake and accumulation of oxLDL were analyzed using Bodipy^TM493/503, and cell viability was assessed with PrestoBlue^®. Cell migration was evaluated using the scratch assay and the MRI wound-healing tool in ImageJ (Fiji). Mitochondrial morphology was examined with MitoTracker Green and the MiNA tool in ImageJ (Fiji). Apoptotic processes were analyzed by Western blot, immunocytofluorescence staining, and ELISA. Results: In vivo, PACAP^−/−/ApoE^−/−-mice showed increased lumen stenosis and decreased plaque burden compared with ApoE^−/−-mice. In vitro, PACAP enhanced the viability of oxLDL-treated HCASMCs, while neither PACAP nor Maxadilan influenced lipid content in HCASMCs, regardless of oxLDL presence. Both oxLDL and PACAP slowed cell migration, but Maxadilan increased migration in oxLDL-treated HCASMCs. The protein level of the proliferation marker Ki67 was reduced in cells treated with oxLDL and Maxadilan. Additionally, BAX, which promotes intrinsic apoptosis, was elevated in HCASMCs stimulated with Maxadilan and oxLDL. Investigations of mitochondrial morphology indicated that oxLDL and PACAP increased the individual and network structures, with a decrease in branches per network. Conclusion: Our data highlight the complex role of the PACAP/PAC1 system in vascular pathology and suggest that selective modulation—such as targeted PAC1 activation or PACAP supplementation—could lead to new strategies for stabilizing atherosclerotic plaques. In the long term, this could improve the balance between plaque formation and vascular function. Full article

Background/Objectives: Incorporating parent training into cognitive-behavioral therapy for anxious youth has not been shown to significantly improve outcomes perhaps because these interventions have not addressed potential interfering psychological barriers to implementing parenting changes and rarely offer between-session support. There is growing evidence that Acceptance and Commitment Therapy (ACT) can target these psychological barriers and generate more flexible and adaptive behavioral repertoires in parents of children with a variety of presenting challenges. Methods: Following a pilot trial of “Acceptance and Commitment Therapy for Parents of Anxious Children (ACT-PAC)” a six-week group-based intervention focused on targeting psychological barriers to parenting change using mindfulness and acceptance approaches, we collected qualitative feedback from participants in two post-treatment phases by conducting individual interviews and a focus group with participants that completed the intervention. Results: Analysis of interview responses revealed that parents found ACT principles and processes to be helpful, and many also appreciated the ACT-PAC group setting that allowed parents to recognize their experiences were shared by others and to self-disclose in a non-judgmental space. Feedback from the focus group further provides preliminary evidence that ACT-PAC is acceptable to and feasible for parent participants and suggests modifications such as involving additional caregivers, making resources more readily available, and creative structural changes that may facilitate between-session practice. Conclusions: Results suggest that the group-based intervention can be both maintained and improved for future participants. Limitations to generalizability in light of possible selection bias and the small focus group sample size are addressed. Full article

Surfactant-enhanced soil washing is a promising strategy for the remediation of organochlorine pesticide (OCPs) contaminated sites. In this study, we constructed a comprehensive evaluation framework integrating efficient parameter optimization, effluent recovery and ecological restoration assessment. Among the 14 evaluated washing agents, the non-ionic surfactant Triton X-100 exhibited superior solubilization capacity for highly hydrophobic OCPs. Under an optimal dosage of 2.0%, Triton X-100 achieved near-complete extraction of γ-chlordane and over 75% removal of mirex in both moderately and severely contaminated soils. Powdered activated carbon (PAC) demonstrated exceptional selective adsorption performance, significantly outperforming activated carbon fiber (ACF). The optimal PAC dosages (20 g/L) could extract over 90% of OCPs from the soil washing effluents, facilitating potential washing agent recycling. Furthermore, community-level physiological profiling (BIOLOG-AWCD) revealed distinct ecological trajectories post-washing. While nitrogen and phosphorus (N/P) bio-stimulation successfully restored and even surpassed the microbial diversity in moderately contaminated soils, it only partially alleviated the ecological vulnerability in severely contaminated soils (Simpson index < 0.45). These findings underscore that while surfactant-enhanced soil washing combined with selective adsorption constitutes a powerful physicochemical remediation cycle, restoring heavily degraded microhabitats necessitates an integrated approach coupling bio-stimulation with phytoremediation. Full article