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A Dynamic Nomogram to Predict Metabolic Dysfunction-Associated Fatty Liver Disease in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) involves multiple metabolic disorders. This study aimed to identify high-risk populations for metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with MetS and to establish a dynamic predictive nomogram. METHODS: A total of 627 patients with MetS from six regions in Zhejiang Province were enrolled and categorized into MAFLD and non-MAFLD groups, then randomly assigned to training and validation sets at a ratio of 7:3. Independent predictors of MAFLD were identified using least absolute shrinkage and selection operator regression and multivariable logistic regression analyses. These predictors were then used to construct a dynamic nomogram. RESULTS: A total of 627 patients with MetS were included in the final analysis, of whom 77.0% (483/627) were diagnosed with MAFLD. Multivariable logistic regression analysis identified body mass index (BMI), waist circumference (WC), total cholesterol (TC), alanine aminotransferase (ALT), MetS-defined dysglycemia, and education level as independent risk factors for MAFLD. MetS-defined dysglycemia showed the highest odds ratio (OR) for MAFLD development [OR = 1.87, 95% confidence interval (CI): 1.07-3.29]. Although the number of MetS components and the metabolic syndrome score were significantly associated with MAFLD in univariate analysis, they were not independently associated with MAFLD in the multivariate model. A dynamic nomogram for predicting MAFLD risk in patients with MetS was developed and internally validated. The area under the receiver operating characteristic curve was 0.834 (95% CI: 0.787-0.880) in the training set and 0.839 (95% CI: 0.771-0.899) in the validation set, indicating strong predictive performance. Bootstrap internal validation demonstrated good agreement between predicted and observed outcomes in calibration curves. Decision curve analysis further indicated favorable clinical applicability of the nomogram. CONCLUSION: BMI, WC, TC, ALT, MetS-defined dysglycemia, and education level are independent risk factors for MAFLD. A dynamic nomogram for predicting MAFLD risk in patients with MetS was successfully developed and validated.

Humans

Pathogenic Variants in HEPACAM Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry HEPACAM pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b. HEPACAM encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte-enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in HEPACAM alter hepaCAM protein function in vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity-based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM-interacting proteins Connexin 43 and CLC-2. Moreover, we identified the epilepsy-associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.

Animals

Retinoid dynamics in immune cells during age-related diseases.

Retinoids comprise vitamin A and its structurally related natural and synthetic derivatives. Retinoid dynamics involves multiple retinoid forms, carrier proteins, and enzymes that orchestrate the absorption, transport, storage and biotransformation of dietary vitamin A. Beyond their canonical metabolic functions, metabolites and proteins involved in retinoid metabolism also play distinct roles in signal transduction and transcriptome reprogramming, broadening the mechanisms that influence immune cell fate decisions. Age‑related changes in retinoid bioavailability and signaling intensity alter immune cell polarization and function, thereby contributing to the pathogenesis of chronic inflammation in neurodegenerative diseases, cardiovascular diseases, osteoarthritis, and other age-related diseases. In this review, we focus on age-related alterations in the retinoid metabolic pathway and their impact on inflammation and the progression of age-related diseases. This review highlights the pivotal role of retinoid metabolism in anti-ageing interventions and considers future directions and challenges in this field.

Humans

Utility of Dynamic MRI in Surgical Outcome of Patients With Degenerative Cervical Myelopathy: A Single-Center, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The utility of dynamic MRI (dMRI) in surgical planning and outcomes for degenerative cervical myelopathy (DCM) has not been validated in any prospective randomized trials. METHODS: In this hospital-based randomized controlled trial conducted between February 2023 and December 2024, patients with DCM were randomized into 2 groups: the Static MRI Group, where surgery was guided by conventional static MRI alone, and the dMRI Group, in which dMRI was performed, with the potential to alter the surgical approach. The primary outcome was recovery rate (RR) at 3 months. Secondary outcomes included postoperative changes in modified Japanese Orthopaedic Association scores and Nurick grades, surgical plan alterations, comparison of surgical approaches, and complication rates. RESULTS: Seventy-four patients were analyzed at a 3-month follow-up. The dMRI group had a significantly higher mean RR (55.42% ± 29.05%) than the Static group (46.76% ± 29.51%) ( P = .044). A RR of ≥50% was observed in 91.9% of patients in the dMRI group, compared with 59.4% in the static MRI group ( P = .002). Modified Japanese Orthopaedic Association scores improved more in the dMRI group (15.47 ± 2.62 vs 13.77 ± 2.66, P = .007). While Nurick grades improved in both groups, the intergroup difference was not statistically significant ( P = .151). dMRI altered the surgical plan in 59.5% of cases. Anterior approaches yielded better RR but had more complications. By contrast, posterior approaches had fewer but more severe complications including mortality. CONCLUSION: dMRI enhances the detection of clinically significant cord compression and may aid in surgical decision-making, potentially contributing to superior functional outcomes in DCM. Further studies are required to determine its impact on long-term functional outcomes.

Humans

Dynamics of antibiotic resistance genes co-occurrence with pathogenic and non-pathogenic bacteria throughout wastewater treatment processes.

Wastewater treatment plants (WWTPs) are recognized hotspots for antibiotic resistance genes (ARGs) and pathogenic bacteria. Despite advancements in treatment technologies, the persistence of ARGs and pathogenic bacteria remains a concern. In this study, we analyzed the dynamic changes in ARGs and bacterial communities throughout the treatment processes within an anaerobic-anoxic-oxic (AAO) WWTP over one week by using HT-qPCR coupled with 16S rRNA gene amplicon sequencing. The connectedness index, based on network analysis, showed that the dynamics of ARGs and mobile genetic elements (MGEs) were more strongly associated with potentially pathogenic bacteria than with non-pathogenic bacteria, suggesting that ARG immigration and dissemination in the WWTP were likely driven by potentially pathogenic taxa. The AAO treatment significantly reduced ARGs in final effluent (EF) (∼64 %) and residual sludge (RS) (∼81 %); however, potential hosts of ARGs such as Comamonas testosteroni and Clostridioides difficile persisted with minimal changes in relative abundance and remained detectable in EF and RS. Notably, the abundance of ARGs was lower in RS than in EF, and source tracking analysis identified influent as the primary source of ARGs and potentially pathogenic taxa in EF, underscoring the greater health risks associated with effluent discharge.

Wastewater

Integrated widely targeted metabolomics and GC-IMS reveal dynamic flavor, nutritional, functional, and metabolic profiles in macadamia kernels during processing.

Different processing stages influence the color, flavor, and antioxidant activities of macadamia kernels. However, the biochemical mechanisms that occur during processing are not well known. This study integrated widely targeted metabolomics (UPLC-MS/MS) with GC-IMS to systematically characterize non-volatile and volatile compounds in macadamia kernels across key three sample groups: fresh kernels (FMN), low-temperature-dried kernels (DMN), and roasted kernels (BMN). A total of 622 non-volatile metabolites and 52 volatile compounds were identified. Low-temperature drying promoted the accumulation of phenolic acids and flavonoids, enhancing antioxidant capacity. Roasting degraded heat-sensitive nutrients but generated flavor compounds via Maillard reaction and lipid oxidation, shifting aroma from green to nutty notes. Nutritional assessment confirmed that roasting significantly reduced antioxidant activities and bile acid binding capacity. Pearson correlation analysis verified the key metabolite-antioxidant relationships. These findings provide critical insights into metabolic dynamics during nut processing and establish a scientific basis for optimizing thermal processing strategies.

Metabolomics

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans

Exercise-associated epigenetic remodeling and TCR repertoire dynamics in Lynch syndrome carriers.

Lynch syndrome (LS) carriers are at elevated cancer risk. Emerging evidence suggests that exercise may serve as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers undergoing a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Integrative transcriptomic analysis highlights ISL1 as a key exercise-repressed, epigenetically regulated gene, and identifies FLCN as a colorectal cancer (CRC)-associated methylation target. TCR analysis reveals an exercise-associated increase in systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. Collectively, these findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.

Lynch syndrome

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p&#x2009;<&#x2009;0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p&#x2009;<&#x2009;0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2&#xa0;weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p&#xa0;=&#xa0;0.04) and extension (46.67%, p&#xa0;=&#xa0;0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p&#xa0;<&#xa0;0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans

Individual differences in brain dynamics across a social cognition network induced by cortico-cerebellar tDCS in adults with autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core diagnostic domains of social communication impairments, restricted interests and repetitive behaviors. Idiosyncratic brain organization is a potential hallmark of ASD. Previous transcranial direct current stimulation (tDCS) studies often targeted dorsolateral prefrontal cortex, with changes oin brain dynamics averaged across the cohort. We utilized a magnetoencephalographic (MEG) array to characterize individual differences in brain dynamics induced by cortico-cerebellar tDCS across nodes of a social cognition network. A randomized, sham-controlled, double-blind, within-subject clinical trial was conducted in a cohort of 24 young adults with ASD or high autistic traits. Two separate sessions of computerized social learning activities were combined with verum/sham tDCS, with anodal electrode over right temporoparietal junction (TPJ) and cathode on right deltoid. Following stimulation, theta- and alpha-band activity were evaluated within nodes of a social cognition network: bilateral TPJ, fusiform, medial prefrontal cortex and Crus I/II of cerebellum. Idiosyncratic participant-specific up- and down-regulation of theta- and alpha-band activity occurred across the network. Activity in right Crus I/II, a region inundated by the stimulation current, strongly correlated with the change of activity summed across all cerebral cortical nodes in theta- but not alpha-band. Intrinsic theta-band activity is believed to mediate input/output relationships in cerebellar cortex and to drive synaptic plasticity. These results suggest that theta-band stimulation of cerebellar cortex might be an effective therapy for individuals on the autism spectrum who present with cerebellar hyperactivity.

Humans

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy

Understanding Dynamics: A Systematic Review of the Attitudes, Knowledge, and Competencies of European Frontline Professionals Toward Domestic Abuse.

There remains a paucity of European research on attitudes and responses to domestic abuse from frontline workers and professionals who regularly encounter domestic abuse or engage with domestic abuse legislation. This systematic review synthesized qualitative, quantitative, and mixed-method peer-reviewed studies that explored professionals' knowledge, attitudes, and competencies related to domestic abuse. The professionals included medical staff (doctors, nurses, midwives), social care professionals, police officers, and criminal justice practitioners. The review was conducted on current European studies published between 2014 and 2025 and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases consulted included APA PsycInfo, Scopus, Web of Science, PubMed, Sociological Abstracts, International Bibliography of the Social Sciences, Social Services Abstracts, and Google Scholar. Full-text review was performed on 273 articles, of which 36 were deemed appropriate for inclusion. The review included 8 multi-country studies spanning the United Kingdom (England, Scotland, and Wales), and 28 single-country studies conducted in England, Sweden, Turkey, Portugal, the Republic of Ireland, Wales, Bosnia, Spain, Italy, Slovenia, and Hungary. A narrative and thematic synthesis categorized professional attitudes toward domestic abuse into four emergent themes: attitudes toward engagement and responsibility, attitudes toward victims, knowledge and understanding of domestic abuse, and attitudes as predictors of professional practice. This review addresses a dearth of research and provides recommendations for promoting proactive practice among professionals most likely to receive disclosures of abuse.

Humans

Microbial allies in a cotton pest: A descriptive account of associated microbiota dynamics in Dysdercus cingulatus across development.

BACKGROUND: Hemipteran insects harbour several symbiotic partners, mainly bacteria, which play pivotal roles for hosts like dietary provision, support overall physiology, xenobiotic degradation and manipulate/regulate behaviour. Most of these symbionts usually reside and operate from the digestive tracts of the animals. Cotton is one of the major cash crops in India and Dysdercus cingulatus (D. cingulatus) though a secondary pest, is causing significant destruction of cotton bolls, poor lint quality and reduce oil content of seeds. Premature opening of cotton bolls often leads to bacterial and fungal infections, thus resulting in extensive economic loss worldwide. D. cingulatus is a hemimetabolous insect that comprises of developmental stages like egg, nymph (5 instar stages), and adult. The present work explored the ontogeny specific diversity in the associated microbiota and predicted their probable functional inputs in D. cingulatus. RESULTS: The data obtained using 16S rRNA gene sequencing (NovaSeq 6000) revealed presence of members of Proteobacteria (65.83%), Firmicutes (24%), Actinobacteria (10%) phyla throughout the ontogeny of D. cingulatus. Highest alpha diversity of these symbiotic bacteria was recorded in the third instar nymphs in contrast to rest of the developmental stages. Among all the observed genera, Stenotrophomonas, Hungatella and Glutamicibacter were predominant from egg to adult stages. MicFunPred, a tool used for predicting the probable functional inputs of these symbionts, hinted at their probable stage specific contribution in crucial biochemical pathways such as polyketide biosynthesis, ascorbate/aldarate metabolism, pentose phosphate and glyoxylate cycles, steroid hormone and peptidoglycan biosynthesis, and glycolysis/pyruvate metabolism. CONCLUSIONS: The primary investigations on the ontogenetic composition and diversity of associated microbiota, suggest dynamic shifts in D. cingulatus, concurrent with their probable functions/roles in the host development and metabolism. To the best of our knowledge, this is the first report on symbiotic microbiota variation across the developmental stages of D. cingulatus that provides preliminary descriptive observations that may guide future functional and experimental investigations into microbiota-based pest management.

Animals

Dynamics of soil fungal communities restored with biochar from a quarry site.

Quarrying activities have intensified due to population expansion, leading to landscape degradation and ecological destruction. Quarry restoration is usually mandatory in Hong Kong, China. Although biochar is used for sustainable soil amendment, its effectiveness in restoring quarry soil with poor properties has rarely been investigated. A 24-month field study was conducted to evaluate the ecological feasibility of restoring a quarry site by using native species (that is, Castanopsis fissa and Cyclobalanopsis edithiae) and biochar amendment. The results revealed that after 24 months, the application of biochar increased the organic carbon, phosphorus and potassium of the vegetated soil by at least 120 %, 31 % and 12 %, respectively, due to higher cation exchange capacity and better plant growth. The relative abundance of Ascomycota and Basidiomycota increased by 24 % and 47 % with biochar application when C. fissa was planted, which was likely associated with the improved nutrient cycling and soil fertility. Even though adding biochar to bare soil was found to increase the complexity of fungal co-occurrence networks, biochar application only increased fungal diversity in vegetated quarry soil but usually reduced its fungal richness. Moreover, fungal co-occurrence networks in vegetated soil became less complex, suggesting that biochar potentially helped plants to assemble specific, beneficial fungal communities. This effect is most pronounced in the soil planted with C. edithiae, where the structure of fungal communities after 24 months was significantly different from that at other restoration times. This study identifies key fungal phyla enhanced by biochar in quarry soil and provides an effective strategy for facilitating the restoration and management of degraded lands, especially quarry sites.

Charcoal

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H&#x2082;O&#x2082;-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans