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Gender-specific pathways linking body dissatisfaction, self-disgust, and social anxiety in Chinese adolescents: A three-wave longitudinal study.

Adolescence is a critical period for physical and psychological development. Body dissatisfaction is a significant concern during this stage, contributing to psychological issues such as social anxiety. However, the longitudinal relationships among body dissatisfaction, self-disgust, and social anxiety, as well as the potential role of gender differences in these dynamics, remain unclear. A total of 1109 junior high school students in China completed the baseline survey, with data collected at three time points (Mage = 12.67 years, SD = 0.68; 51.9% girls). Data were collected using the Body Areas Satisfaction Scale (BASS), the Self-Disgust Scale (SDS), and the Social Anxiety Scale for Children (SASC). Structural equation modeling (SEM) was employed to examine the longitudinal mediating effects among body dissatisfaction, self-disgust, and social anxiety, as well as to explore gender differences in these relationships. After controlling for autoregressive effects of self-disgust and social anxiety across waves, body dissatisfaction at T1 was found to indirectly predict social anxiety at T3 through self-disgust at T2, while indirectly predicting self-disgust at T3 through social anxiety at T2. Multi-group analyses revealed significant gender differences: for females, only the mediating pathway with self-disgust as the mediator was significant; for males, only the pathway with social anxiety as the mediator was significant. These findings contribute to a more nuanced understanding of the emotional mechanisms linking body dissatisfaction to social anxiety and highlight the importance of considering gender-specific pathways in prevention and intervention efforts.

Adolescent

In silico identification of DNMT1 inhibitors from the PlantCyc database through computational approach to assess the anti-cancer potential of nutraceutical compounds in breast cancer.

Breast cancer accounts for a disproportionate share of global cancer-related deaths, with 670,000 fatalities and 2.3 million new diagnoses recorded in women during 2022 alone. Existing treatment modalities carry considerable toxicity burdens, and resistance to available agents remains an unresolved clinical problem. DNA methyltransferase 1 (DNMT1), the enzyme chiefly responsible for maintaining genome-wide methylation patterns during DNA replication, has been mapped out as a high-value target in breast cancer because its dysregulation silences tumour suppressor genes through promoter hypermethylation. The present work involves hierarchical in silico workflow to screen 4549 plant-derived compounds from the PlantCyc database (v16.0.3) against the human DNMT1 catalytic domain (PDB ID: 4WXX). Ten top-scoring compounds were taken forward for molecular docking via AutoDock Vina; Quercetin and Kaempferol both recorded the highest binding affinities at -9.5 kcal/mol, Wogonin (-9.3 kcal/mol) and Xanthohumol (-8.1 kcal/mol) also emerged as strong binders. Pharmacokinetic evaluation using ADMET-AI confirmed that all 10 compounds met Lipinski's rule of five, with human intestinal absorption values at or above 0.98. Wogonin and Xanthohumol were selected for a 100 ns all-atom molecular dynamics (MD) simulation in GROMACS due to their well-rounded ADMET profiles and limited existing data on their specific interactions with DNMT1 in breast cancer. Across all measured trajectory metrics, backbone RMSD, residue fluctuation, radius of gyration, solvent-accessible surface area, and intermolecular hydrogen bond count, Wogonin formed a more stable, compact complex. These findings suggest that Wogonin and Xanthohumol are non-toxic nutraceutical candidates suitable for DNMT1 targeted epigenetic therapy, with computational foundation strong enough to facilitate future in vitro and in vivo validation work.

Humans

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P&#x2009;=&#x2009;0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent

Applications of quantum AI in brain disorder diagnosis: A systematic review.

BACKGROUND AND OBJECTIVE: Brain disorder diagnosis and prediction remain challenging because neuroimaging, electrophysiological, behavioral, and multimodal data are high-dimensional, noisy, heterogeneous, and limited by small clinical cohorts. This systematic review synthesised applications of quantum artificial intelligence (QAI) for brain disorder diagnosis, prediction, detection, and monitoring. METHODS: Following PRISMA guidelines, studies published from 2016 to 13 January 2026 were retrieved from Scopus, Web of Science, and IEEE Xplore. After screening, 36 studies met the eligibility criteria and were qualitatively analysed according to disorder category, data modality, QAI method, implementation setting, validation strategy, and performance. RESULTS: At the broader disease-group level, neurodegenerative disorders were the most frequently investigated, followed by mental health and psychiatric disorders. At the individual level, Parkinson's disease and schizophrenia were the leading applications, followed by depression, anxiety, Alzheimer's disease, and stress-related tasks. MRI-based modalities were the most frequently used data source, followed by multimodal data and EEG. Methodologically, primary QAI approaches were dominated by quantum neural and QDL architectures, followed by quantum-inspired optimization or feature-selection methods and quantum-kernel/conventional QML classifiers. Qiskit/IBM Quantum and PennyLane were the most frequently reported quantum software frameworks. However, most studies relied on simulators, classical quantum-inspired implementations, or unclear implementation settings, with limited real-hardware evaluation. CONCLUSIONS: QAI shows emerging potential for brain disorder analysis, particularly through hybrid quantum-classical learning, quantum neural architectures, quantum-kernel methods, and quantum-inspired optimization. Nevertheless, current evidence remains preliminary and requires larger datasets, subject-level and external validation, fair classical benchmarking, noise-resilient circuits, real quantum hardware evaluation, explainability, and clinical validation.

Humans

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy &#xd7; intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy &#xd7; randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced &#x223c;10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay

Clinical outcomes of fusion vs excision in the treatment of painful type II accessory naviculars: A matched cohort study.

BACKGROUND: For painful Type II accessory naviculars, whether to remove or fuse them remains unclear based on the current literature. This study aimed to investigate the clinical outcomes of fusion versus excision in treating painful type II accessory naviculars. METHODS: This retrospective comparative study included and followed 54 eligible patients (from May 2017 to March 2023). After 1:1 propensity score matching (PSM), 34 patients (17 fusion versus 17 excision) were analyzed. Outcomes included Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score, Tegner score, complication rates, and radiographic measurements. Receiver operating characteristic (ROC) curve analysis was performed to identify the appropriate accessory navicular size cutoff for predicting nonunion following fusion. RESULTS: The mean follow-up was 35.0&#x202f;&#xb1;&#x202f;9.9 months. The fusion and excision groups showed significant and comparable VAS and AOFAS score improvements (p&#x202f;<&#x202f;.001). The fusion group had a higher complication rate (41.2% vs. 5.9%, p&#x202f;=&#x202f;.039), primarily nonunion and persistent pain. ROC curve analysis identified 50.3&#x202f;mm&#xb2; as the cutoff for nonunion risk; sizes <&#x202f;50.3&#x202f;mm&#xb2; predicted high nonunion likelihood. CONCLUSIONS: Both fusion and excision are effective treatments for painful type II accessory naviculars, demonstrating acceptable pain and functional improvement during midterm follow-up. However, the lower complication rate along with relatively superior functional recovery favors the excision technique. For accessory naviculars smaller than 50.3&#x202f;mm2, excision may be a better choice. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Humans

The future of pediatric vesicoureteral reflux management.

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition in pediatric urology, yet important uncertainties persist regarding risk stratification, imaging strategies, and prevention of long-term renal damage. Emerging technologies may help address these challenges. This review provides a forward-looking overview of recent advances in artificial intelligence (AI) and immunomodulation that may influence future management of pediatric VUR. METHODS: A forward-looking literature review was performed using the PubMed database (January 2000-March 2025), focusing on studies addressing AI, immunomodulation, or vaccination in the context of VUR and urinary tract infections. Criteria of inclusion were the relevance to pediatric VUR, the novelty of the proposed concept, the potential clinical implications and, for the AI literature, the existence of a clinical evaluation of the algorithm on a dataset from patients. KEY FINDINGS AND LIMITATIONS: AI-based models show promising performance in supporting clinical decision-making, including prediction of the need for voiding cystourethrography, automated grading of VUR, estimation of recurrent urinary tract infection risk and prediction of chemoprophylaxis. These tools may facilitate more individualized diagnostic and therapeutic strategies, although current evidence is largely retrospective and requires prospective validation. Immunization and immunomodulatory approaches aim to reduce infection burden and modulate inflammatory pathways associated with renal scarring. While early experimental and adult clinical data are encouraging, pediatric-specific evidence remains limited, and clinical applicability in children with VUR is not yet established. CONCLUSION: Artificial intelligence and immunologically targeted strategies represent complementary, emerging approaches that may contribute to more personalized management of pediatric VUR. At present, both should be regarded as exploratory tools whose clinical impact will depend on further validation and appropriately designed pediatric studies.

Humans

Gloeotrichia echinulata genomes from the United States are nontoxigenic and likely geosmin producers.

Six Gloeotrichia echinulata genomes derived from planktonic harmful algal blooms (HABs) with similar colonial morphology have been sequenced from lakes in the west and northeast regions of USA, four of them to completion. The c. 7 Mbp genomes exhibit a high level of conservation, with 98-99% pairwise genome-wide average nucleotide identity and high levels of synteny, representing a single species cluster. We observed strong conservation of gene clusters responsible for the synthesis of the secondary metabolites and bioactive peptides that are characteristic of HAB-forming cyanobacteria. All six G. echinulata genomes lack genes for the synthesis of classic cyanotoxins, including microcystin, but possess genes responsible for the synthesis of the taste and odor compound geosmin. Interestingly, the geoA geosmin synthase gene in three genomes is homologous to other cyanobacterial geoA genes, while the other three geoA genes are related to actinomyces geoA. Phylogenomic analysis places the G. echinulata genomes within a clade of benthic Nostocales, reflecting an ecological niche featuring extensive growth on the sediment surface before colonies disperse into the epilimnion for planktonic growth. We identify genes conserved in all six genomes that could represent physiological adaptations supporting active growth on sediments and pelagic recruitment independent of wind-driven mixing: phycoerythrin light harvesting complexes for optimal photosynthesis at depth; gliding motility to access patchy nutrient distributions; and gas vesicles with relatively small GvpC proteins that predict resistance to higher hydrostatic pressure. The strong genomic similarity across geographically distant populations suggests that G. echinulata in the United States is a tightly related non-toxigenic species group with predictable properties relevant to public health and drinking water management.

Cyanobacteria

Effect of knee and hip joint positions on passive stiffness of the rectus femoris and vastus lateralis in healthy individuals.

Passive muscle stiffness is a key determinant of musculoskeletal function and is influenced by structural components such as titin, connective tissue, and fascia. However, the effects of joint position, muscle depth, and sex on quadriceps passive stiffness remain unclear. To investigate the passive stiffness of the rectus femoris (RF) and vastus lateralis (VL) under different joint configurations, muscle depths, and between sexes using shear wave elastography (SWE). Thirty-six healthy young adults (18 men and 18 women) participated in this randomized crossover study. Passive stiffness was assessed in four positions of knee flexion: supine with 60&#xb0; (SUP60), supine with 20&#xb0; (SUP20), sitting with 60&#xb0; (SIT60), and sitting with 20&#xb0; (SIT20). SWE measurements (m/s) were obtained from 30 regions of interest (ROIs) per muscle, categorized into superficial, intermediate, and deep levels. Data were analyzed using Generalized Estimating Equations (GEE). A significant effect of position was observed, with higher stiffness values in the SUP60 condition for both RF and VL (p&#x2009;<&#x2009;0.001). Superficial regions consistently exhibited greater stiffness compared to intermediate and deep regions across all positions (p&#x2009;<&#x2009;0.001). Additionally, men demonstrated significantly higher stiffness values than women (p&#x2009;<&#x2009;0.001). Significant interactions were found between position and muscle, as well as position and depth. Quadriceps passive stiffness is influenced by joint position, muscle depth, and sex. The SUP60 position elicits the highest stiffness, while superficial muscle regions are consistently stiffer. These findings highlight the non-uniform mechanical behavior of the quadriceps and may have implications for clinical assessment, rehabilitation, and exercise prescription. Clinical trial registration: This study was registered at Clinicaltrials.gov in June 06th, 2023. Register number NCT05905406. Link to access https//clinicaltrials.gov/study/NCT05905406.

Humans

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-na&#xef;ve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 &#xb1; 3.01mm2 at baseline, 2.86 &#xb1; 2.50mm2 at week 12, 3.59 &#xb1; 3.26mm2 at week 52; monotherapy: 3.77 &#xb1; 2.23mm2 at baseline, 3.27 &#xb1; 2.36mm2 at week 12, and 3.47 &#xb1; 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 &#xb1; 2.08 mm2 at baseline, 1.46 &#xb1; 1.36mm2 at week 12, and 1.53 &#xb1; 1.32mm2 at week 52; monotherapy: 2.39 &#xb1; 1.85mm2 at baseline, 1.87 &#xb1; 1.68mm2 at week 12, and 1.82 &#xb1; 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 &#xb1; 15% vs - 3 &#xb1; 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (&#x3b2;=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (&#x3b2;=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans

[Analysis of a Chinese pedigree affected with Townes-Brocks syndrome due to a novel variant of SALL1 gene and a literature review].

OBJECTIVE: To analyze a novel exonic variant of the SALL1 gene and its impact on the binding site of SALL protein. METHODS: Clinical data of three children diagnosed with Townes-Brocks syndrome and their family members who had presented at the First Affiliated Hospital of Shandong First Medical University in April 2022 were retrospectively collected. The pathogenic variant was identified through whole-genome sequencing (WGS) and validated by Sanger sequencing. Protein structural prediction was performed using AlphaFold and PyMOL software to construct three-dimensional models of the wild-type and mutant proteins. Additionally, previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-386). RESULTS: The proband was one of triplet sisters born at 34+4 gestational weeks. All three cases had presented with anal atresia and rectovaginal fistula, and case 3 also had toe malformation of left foot. WGS revealed a novel heterozygous c.757C>T (p.Gln253*) variant in the SALL1 gene, which was predicted to be pathogenic. Sanger sequencing confirmed co-segregation of the variant with the disease within the family. Protein structural modeling demonstrated that the variant has introduced a premature stop codon at position 253, resulting in a truncated protein. CONCLUSION: Above finding has enriched the mutation spectrum of the SALL1 gene in association with Townes-Brocks syndrome, which also represented a rare case of anal atresia in triplets, and provided a basis for molecular diagnosis, genetic counseling, and further research.

Humans

Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.

Humans

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans

Adductor Canal Block and Local Anesthetic Versus Local Anesthetic Alone in ACL Reconstruction: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Effective postoperative analgesia is crucial for early recovery after anterior cruciate ligament reconstruction (ACLR). Local infiltration analgesia (LIA) and adductor canal block (ACB) are common regional techniques, but their combined efficacy remains unclear. PURPOSE: To compare the effectiveness of LIA alone versus LIA combined with ACB in patients undergoing ACLR, with primary outcomes including postoperative opioid consumption and quadriceps function. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A double-blind randomized controlled trial enrolled 100 patients undergoing ACLR under general anesthesia. Patients were randomized into 2 groups: LIA + sham (saline injection) (n = 50) and LIA + ACB (n = 50). The primary outcome was postoperative opioid consumption in the first 24 hours. Secondary outcomes included visual analog scale (VAS) pain score, quadriceps function assessed by straight leg raise (SLR) at 3 hours, Quality of Recovery-15 (QoR-15) score, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 week. Statistical analysis was performed using t tests and chi-square tests with a P value <.05 considered significant. RESULTS: There was no significant difference in 24-hour opioid consumption between the LIA + ACB and LIA-only groups (P = .109). Similarly, VAS pain scores at 24 hours postoperatively showed no significant differences between the groups (P = .0804). Early functional recovery, assessed by SLR performance at 3 hours, was equivalent between groups (P = .6711). Additionally, QoR-15 scores on postoperative day 1 and KOOS values at 1 week demonstrated no significant differences (P = .6486 and P = .9054, respectively). Intraoperative opioid consumption was not different between the groups (P = .127). CONCLUSION: These findings indicate that the addition of ACB to LIA does not yield postoperative analgesic in ACLR. Consequently, LIA alone suffices for routine ACLR, potentially enabling clinicians to optimize perioperative workflows without incurring the additional time, financial burden, and resources associated with routine ACB administration. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04721119.

Humans

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 &#xb1; 0.8 mmHg; GA = 14.62 &#xb1; 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 &#xb1; 0.9 mmHg; GA = 15.88 &#xb1; 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 &#xb1; 0.6. GA: 12.24 &#xb1; 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 &#xb1; 1.2, SA: 12.86 &#xb1; 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 &#xb1; 0.8, GA: 16.50 &#xb1; 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans

Long-term outcomes after a randomized phase II trial of nerve growth factor eye drops for optic pathway gliomas: four-year follow-up findings in children.

PURPOSE: A previous double-blind, randomized, placebo-controlled, phase II clinical trial reported beneficial effects of a short-term treatment (10 days) with murine nerve growth factor (mNGF) eye drops on visual function in children with optic pathway gliomas (OPG). The present study aimed to evaluate long-term changes in clinical and neuroradiological parameters in the cohort of OPG patients who had previously participated in the phase II mNGF trial. METHODS: Fifteen of the 18 patients originally enrolled in the phase II mNGF trial agreed to undergo clinical and neuroradiological monitoring over a 48-month follow-up period. Of these, 9 had originally been randomized to mNGF and 6 to placebo; no additional treatment (mNGF, chemotherapy, or radiotherapy) was administered during the extended follow-up. Every 6 months, patients underwent general clinical and neuro-ophthalmological examination, visual evoked potentials (VEP), and photopic negative response of the electroretinogram (PhNR). Brain MRI was performed every 12 months. RESULTS: Comparison of initial and final follow-up median values revealed no statistically significant changes in visual acuity, VEP amplitude, PhNR amplitude, or visual field radius. No significant differences were observed in any parameter relative to baseline values of the mNGF trial. Brain MRI demonstrated stable disease in all patients throughout the observation period. CONCLUSION: These findings, obtained in an observational extension of the original randomized cohort, indicate favorable long-term safety and tolerability of a short-term course of topical mNGF in children with OPG, with sustained visual and neuroradiological stability over four years, rather than evidence of persistent treatment efficacy. Further prospective, adequately powered and randomized clinical studies are needed to confirm both the short- and long-term clinical efficacy of NGF treatment in preventing OPG-induced visual loss.

Humans