Search Results (117,247)

Context: Different studies on football players with fifth metatarsal stress fractures have found that hip internal rotation (HIR)range of motion is significantly reduced, while lateral forefoot pressure is significantly increased; therefore, the purpose of this study was to determine whether HIR range of motion is related to lateral plantar pressure. Methods: The study included 120 college students (60 males and 60 females). HIR was measured using a smartphone inclinometer app in the prone position and a compass app in the supine position. Plantar pressure was assessed using the Gaitview AFA-50 system during standing and walking. Correlation analysis was performed using SPSS 27.0. Results: Among all subjects, HIR activity in the prone position was significantly negatively correlated with standing second through fourth metatarsophalangeal joints(MTPJ2-4), fifth metatarsophalangeal joint (MTPJ5), and midfoot (FM)pressures and significantly positively correlated with standing first toe (T1)pressure. During walking, there is a significant negative correlation between HIR in the prone position and MTPJ2-4, MTPJ5, FM, and lateral heel (LH). Similarly, in the supine position, HIR is significantly negatively correlated with MTPJ2-4, MTPJ5, FM, medial heel (MH), and LH. Conclusion: There is a significant negative correlation between HIR and lateral plantar pressure, indicating that reduced HIR is associated with increased lateral plantar pressure. Improving HIR through targeted rehabilitation may reduce lateral plantar pressure, offering new approaches for non-surgical treatment of little toe capsulitis and reducing the risk of fifth metatarsal stress fractures. Full article

With a typical floodplain in Poyang Lake selected as the study area, this paper employed the remote sensing Waterline Extraction Method (WEM) to invert its topographic changes based on 264 Landsat images from 1987 to 2024. The research systematically revealed the spatiotemporal variations in sediment accretion rates over the past 40 years and their influencing factors. By comparing different WEMs, the object-based method was identified as the most suitable for this study area. Accuracy validation of the topographic inversion showed that when using no fewer than 13 images, the average elevation error rate remained below 7.0%, indicating good reliability. The period from 1987 to 2024 was divided into 15 sub-periods, and digital elevation models of the floodplain were reconstructed for each. Results indicated that: (1) natural floodplain unaffected by sand mining experienced continuous accretion, with an average rate of approximately 3.1 ± 0.7 cm yr⁻¹ (surface elevation change) between 1987 and 2024; (2) in areas impacted by sand mining, the sediment accretion rate after mining (about 1.7 ± 0.8 cm yr⁻¹) was lower than that before mining (about 2.6 ± 2.7 cm yr⁻¹), likely due to the loss of vegetation cover reducing sediment retention capacity; (3) different vegetation types notably influenced accretion rates, with mixed Carex–T. lutarioriparia communities showing a consistently higher rate (about 3.5 ± 0.9 cm yr⁻¹) than pure Carex communities (about 1.7 ± 0.7 cm yr⁻¹), primarily attributable to differences in plant morphology, root architecture, and inundation tolerance. Further analysis revealed that riverine sediment supply was the fundamental material source for floodplain accretion. The phased decline in sediment discharge from the Ganjiang and Xiushui rivers since 1996 generally corresponds to the decreasing trend in sediment accretion rates observed after 2004. Full article

Acute kidney injury (AKI) is a major complication of lupus nephritis and kidney transplantation, inevitably causing ischemia–reperfusion (I/R) injury. We previously confirmed that high-dose voclosporin induces drug nephropathy through aberrant peroxisome accumulation. The latter induces increased renal indole-3-aceticT acid (IAA) production due to the decreased expression of the IAA-degrading enzyme indolethylamine N-methyltransferase (INMT). Conversely, INMT overexpression prevents this nephropathy, suggesting that high-dose voclosporin could enable a novel therapeutic approach. This prompted us to test whether INMT overexpression with high-dose voclosporin could avert nephrotoxicity and protect against I/R injury. Inmt-overexpressing mice treated with high-dose voclosporin exhibited absence of peroxisomal abnormalities and resistance to I/R injury. RNA sequencing revealed the downregulation of tubular injury markers NGAL (Lcn2) and KIM-1 (Havcr1) concurrent with significant cytokine suppression. Mechanistic analysis revealed the robust induction of Regnase-2, an mRNA decay factor, which directly targeted stem–loop structures within the 3′ untranslated region of Lcn2 and Havcr1, thereby promoting their degradation in proximal tubular cells. Importantly, Regnase-2 knockdown mice showed Lcn2 upregulation, mitochondrial dysfunction, and peroxisomal abnormalities culminating in AKI, underscoring its renal protective effects. High-dose voclosporin under Inmt overexpression promoted Regnase-2-mediated mRNA decay to suppress tubular injury. This protective effect extended beyond I/R to rhabdomyolysis- and lipopolysaccharide-induced AKI to prevent nephropathy. Our findings demonstrate the potential transformative therapeutic approach of administering high-dose voclosporin to promote the prophylactic effect of Regnase-2 augmentation against AKI in both native and transplanted human kidneys. Full article

Triple-negative breast cancer (TNBC) is characterized by prominent neutrophil infiltration; however, its significance remains controversial. Here, we investigated the role of neutrophil chemoattractant receptors in TNBC progression and metastasis. In contrast to wild-type (WT), Fpr^-/-, and Fpr2^-/- mice, neutrophils were almost completely absent in 4T1 tumors from Cxcr2^⁻/⁻ mice, indicating a dominant role for CXCR2 in the recruitment of tumor-associated neutrophils, leading us to use Cxcr2^-/- mice for further studies. Primary tumor growth was comparable between WT and Cxcr2^-/- mice, whereas lung metastasis was significantly increased in Cxcr2^-/- mice, with reduced expression of inflammatory cytokines, chemokines and cytotoxic molecules, including granzyme B and perforin, in primary tumors and metastatic lungs of Cxcr2^-/- mice. In vitro, WT, but not Cxcr2^-/-, neutrophils enhanced CD8⁺ T cell activation, partly via ICAM-1, and directly induced tumor cell death, supporting their anti-tumor function. To assess clinical relevance, transcriptomic data were analyzed. High neutrophil infiltration combined with elevated CXCR2 expression, and to a lesser extent CXCR1 expression, was associated with improved prognosis in patients with basal-like BC that largely overlaps with TNBC. Collectively, these findings suggest that CXCR2-mediated neutrophil recruitment exerts protective, anti-tumor effects and may represent a new prognostic marker for TNBC patients. Full article

Thoracic aortopathies, including aneurysm and dissection, are complex vascular disorders characterized by structural alterations of the aortic wall that disrupt normal haemodynamics. Altered shear stress, turbulent flow, and endothelial dysfunction promote thrombus formation and modulate systemic hemostasis via platelet activation and the von Willebrand factor–ADAMTS13 axis. The Total Thrombus-Formation Analysis System (T-TAS) is a microfluidic, flow-dependent assay that quantitatively evaluates thrombus formation under physiological shear conditions. Although studied in various cardiovascular contexts, its application in aortopathies remains largely unexplored, and no prospective studies have validated its clinical utility. Integrating T-TAS with computational haemodynamic approaches, such as two-way fluid–structure interaction simulations, enables assessment of the interplay between blood flow, vessel wall mechanics, pulse wave propagation, and local shear patterns. Patient-specific modelling, including individualized flow profiles, pressure distributions, and wall properties, may enhance mechanistic insights. Genetic variants in Fibrillin-1 gene (FBN1), Transforming Growth Factor Beta Receptor 1/2 (TGFBR1/2), Actin Alpha 2 (ACTA 2), and Myosin Heavy Chain 11 (MYH11) further contribute to structural vascular heterogeneity and diverse systemic haemostatic phenotypes, highlighting the need for personalized assessment. T-TAS should currently be considered an exploratory research tool rather than a validated diagnostic or prognostic method. This narrative review proposes a hypothesis-generating framework integrating structural, haemodynamic, molecular, and functional perspectives. Combining flow-based thrombosis assays with advanced modelling may inform future translational studies, improve mechanistic understanding of thrombus formation, and support personalized risk stratification and management in patients with thoracic aortopathies. Full article

Berberis darwinii is a native Chilean berry distributed across contrasting agro-ecological zones, highlighting its broad ecological amplitude and agronomic relevance. The objective of this study was to identify productive, functional, and balanced elite accessions of B. darwinii by integrating phenotypic, fruit quality, nutritional, and antioxidant traits under contrasting water availability. Ninety-six accessions were evaluated in a common-garden experiment over two consecutive growing seasons (irrigated and rainfed) for morphological, productive, and fruit quality traits. Substantial variation was observed in plant height, shoot number, leaf area, and spine density. Across seasons, some accessions combined high yields (up to 8.5 t ha⁻¹), fruit diameters exceeding 8 mm, and elevated soluble solids (up to 33 °Brix). Because water regime, season, and plant age were not experimentally separated, these contrasts indicate adaptive performance under contrasting water availability rather than direct irrigation effects. Functional analyses revealed high biochemical diversity, with total polyphenols reaching 18,168.7 mg GAE 100 g⁻¹ dry weight, anthocyanins up to 5747.7 mg cyanidin-3-glucoside 100 g⁻¹ dry weight, and ORAC values up to 35.4 mmol Trolox 100 g⁻¹ fresh weight. Multivariate analyses supported the selection of elite candidates for low-input domestication and functional ingredient development. This integrated common-garden framework links intra-specific phenotypic variation with phenolic/antioxidant diversity, supporting trait-based selection and interpretation of stress-associated secondary metabolism. Full article

Background: Current guidelines recommend lobectomy for tumors >20 mm on CT, yet systematic CT–pathology size discordance may contribute to size-threshold–driven surgical decisions. We hypothesized that CT-based tumor diameter differs from pathological size near the 20 mm surgical boundary, potentially leading a proportion of patients to undergo more extensive resection than pathology would indicate under a size-only rule. Methods: We retrospectively analyzed 1096 patients undergoing thoracoscopic surgery for clinical stage I non-small cell lung cancer at a single center (2020–2024). CT–pathology agreement was assessed via Bland–Altman analysis. Optimal CT cut-off was identified using restricted cubic spline (RCS) modeling, internally validated with bootstrap resampling (B  =  2000), and evaluated by decision curve analysis (DCA). Results: CT showed size-dependent bias: overestimation in small tumors (T1a: +4.21 mm) transitioning to underestimation in larger lesions (≥T2: −7.49 mm). At the 20 mm threshold, 15.8% of patients (n = 173) underwent lobectomy despite pathological size ≤20 mm (potential overtreatment). RCS modeling and bootstrap-optimized DCA identified 23 mm as the candidate revised threshold. Adopting CT >23 mm would reclassify 108 patients from lobectomy to sublobar resection, reducing size-threshold–defined potential overtreatment by 51.4% while maintaining sensitivity for true ≥T2 tumors. Conclusions: CT demonstrates size-dependent discordance with pathological size; this discordance likely reflects both CT measurement inaccuracy and specimen shrinkage after fixation, and the relative contributions cannot be separated from these data. A candidate 23 mm CT threshold, supported by DCA and internal bootstrap validation, could reduce size-threshold–defined potential overtreatment by 51% in this cohort. Prospective multicenter validation is required before clinical implementation. Full article

Although DNA-based data storage theoretically provides an information density of 2 bits per nucleotide, biochemical constraints transform sequence design into a high-dimensional constrained combinatorial optimization problem. The high computational cost and low encoding efficiency of conventional rule-based approaches make metaheuristic methods an effective alternative. This study proposes the TC-HUR hybrid algorithm to simultaneously optimize information density and conflicting biophysical constraints, including homopolymer (HP) length, GC content, melting temperature ($T_m$), and reverse-complement (RC) similarity. The method escapes local optima using Cauchy jump-enhanced Hunger Games Search (HGS), performs high-precision exploitation via Runge–Kutta (RUN) operators, and refines constraint violations at the nucleotide level through an adaptive intensive mutation mechanism. The algorithm is evaluated on a complex dataset of 1853 nucleotides under different noise regimes. TC-HUR outperforms RUN by 2.5% and HGS by 16.7% in average fitness. While maintaining homopolymer length near the ideal threshold, it reduces reverse-complement similarity to 19.10%, ensuring high sequence diversity. Under high-noise conditions, TC-HUR achieves a normalized edit distance of 0.1290, reducing insertion–deletion (indel) errors by approximately 14%. The results demonstrate that the proposed model effectively generates biophysically synthesizable and noise-resilient DNA codes. Full article

Background: Immunotherapy efficacy in esophageal squamous cell carcinoma (ESCC) is often limited by an immunosuppressive tumor microenvironment (TME). NLRC5, a key regulator of MHC-I antigen presentation, exhibits context-dependent roles in tumor immunity; however, its function in ESCC remains unclear. This study aimed to systematically investigate the expression pattern, prognostic value, and immunological role of NLRC5 in ESCC. Methods: An integrated analysis of bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data was performed using multiple cohorts, including The Cancer Genome Atlas, Gene Expression Omnibus, and an in-house ESCC cohort. Differential expression, survival analysis, immune infiltration estimation, and functional enrichment analyses were conducted to elucidate the role of NLRC5 in the tumor microenvironment. Results: NLRC5 was significantly upregulated in ESCC and its high expression independently predicted poor patient survival. Although NLRC5 expression was associated with increased CD8⁺ T cell infiltration, it was paradoxically accompanied by features of T-cell exhaustion and elevated expression of multiple immune checkpoints. Moreover, NLRC5-high tumors were enriched in transcriptional programs related to PANoptosis, indicating an additional immunosuppressive mechanism within the TME. Conclusions: NLRC5 is not only a prognostic biomarker but also a key modulator of an immune-active yet functionally suppressed tumor microenvironment in ESCC. These findings highlight NLRC5 as a potential therapeutic target for restoring effective antitumor immunity. Full article

Ewing sarcoma (ES) is the second most common primary bone malignancy in children and adolescents and remains one of the most lethal pediatric cancers. Found in more than 85% of patients with ES, EWSR1::FLI1 results from the t(11;22)(q24;q12) chromosomal translocation. This fusion encodes an aberrant transcription factor that dysregulates gene expression and drives oncogenic transformation. Although this oncogene was identified over three decades ago, therapeutic progress has been limited, in part due to the lack of robust and permissive animal models. Prior efforts to generate transgenic mouse models have been unsuccessful, and while zebrafish have emerged as a promising system, a tissue context capable of supporting EWSR1::FLI1-driven tumorigenesis has not been defined. Here, we report that tissue-specific expression of EWSR1::FLI1 in zebrafish induces tumor formation that recapitulates the histologic and molecular hallmarks of human ES, including small round blue cell morphology and characteristic biomarker expression. Tumors were driven by the col2a1a promoter and resulted in ~70% incidence of notochord tumors within the first 72–96 h. Of the surviving fish, ~5% developed CD99-positive small round blue cell tumors at ~9 months post-fertilization. This work establishes a stable tissue-specific transgenic model of ES, providing a powerful in vivo platform to investigate disease pathogenesis and evaluate novel therapeutic strategies. Full article

Background: Breast cancer (BC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide, thereby posing a substantial threat to women’s health worldwide. However, clinically robust diagnostic biomarkers with high sensitivity and specificity, as well as well-validated molecular targets for targeted therapy, remain limited. Methods: BC transcriptomic data from seven GEO datasets and the TCGA-BRCA cohort (n = 1231) were integrated for analysis. After batch-effect correction, candidate genes were screened through DEA, WGCNA, and PPI networks analysis. An ensemble machine learning (ML) framework incorporating 127 algorithmic combinations was constructed, and SHAP analysis was applied to identify hub genes. Further analyses included functional enrichment, immune infiltration, miRNA regulatory network analysis, and SMR analysis. The expression patterns were validated using single-cell transcriptome data. Drug repositioning analysis and AI-assisted virtual screening were performed to prioritize compounds with favorable drug-like properties. The predicted binding modes of candidate compounds with CHEK1 were assessed by molecular docking. Results: Thirty core genes were obtained through differential expression, WGCNA, and PPI screening. Integrated ML (127 algorithms) determined the optimal model (AUC = 0.919), and SHAP identified nine feature genes, among which CHEK1 and KIF23 showed preliminary diagnostic potential across four external cohorts (AUC: 0.625–0.938). Functional enrichment indicated that both are enriched in the cell cycle and p53 pathways, closely associated with BRCA1/ATR; immune infiltration revealed significant correlations with macrophages and CD8⁺ T cells, with hsa-miR-15a-5p and hsa-miR-607 being common upstream regulatory miRNAs. SMR analysis supported a causal relationship between CHEK1 expression and BC genetic susceptibility (p_SMR < 0.05, p_HEIDI > 0.05); single-cell analysis confirms its heterogeneous expression. AI-assisted virtual screening identified 25 A-grade computational candidate compounds from 171 candidates. Molecular docking suggested that Olaparib and LY294002 can form favorable interactions with the CHEK1 active pocket. Conclusions: The study identified CHEK1 as a key diagnostic gene for BC through 127 ML algorithms and SMR causal inference. By combining AI-assisted virtual screening and molecular docking, computational candidate compounds targeting CHEK1 were prioritized. These findings represent hypothesis-generating in silico predictions and require experimental validation before any therapeutic conclusions can be drawn. Full article

Mitochondria regulate nuclear genomes and their own genetic material, primarily to provide energy in eukaryotes. Currently, high-throughput sequencing technologies are being used to resolve the mitochondrial genomes of various edible fungi. However, the application of pan-genomes for the analysis of edible mushroom mitochondrial genomes remains unexplored. In this study, we conducted a comparative mitochondrial genome analysis of 31 Hypsizygus marmoreus strains (four newly sequenced monotypes and 27 public datasets), ranging from 98,284 to 111,087 bp. This variation was determined to be primarily driven by dynamic changes in non-coding regions, particularly intronic polymorphisms in the cox1 gene. Further, transfer RNA (tRNA) secondary structures exhibited atypical globular and elongated conformations alongside copy number variations. Additionally, codon usage showed a pronounced A/T bias, whereas core respiratory chain genes demonstrated an evolutionary pattern of strong purifying selection. Furthermore, the 31 mitochondrial genomes of H. marmoreus were found to harbor eight gene rearrangement patterns and five genetic clusters, and the pan-genome analysis (220,364 bp, 217 nodes) captured abundant single-nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and structural variations. This study provides breeding-relevant genetic markers and a genomic framework for H. marmoreus germplasm classification, genetic improvements, and the molecular breeding of stress-resilient varieties. Full article

Background/Objectives: The incidence of pediatric pathological scars (PPS) has been gradually increasing due to various causes, highlighting the need for accurate scar assessment to monitor disease progression and therapeutic efficacy. Vancouver Scar Scale (VSS) and other scar evaluation systems are relatively subjective evaluation methods that rely on physicians’ or patients’ own judgment. By contrast, when comparing different scar scale evaluation methods, a three-dimensional (3D) camera and dermoscopy may provide relatively objective measurable parameters to avoid possible subjective bias created by the observers. This study aimed to compare the utility of traditional VSS evaluation with that of 3D cameras and dermoscopy in PPS evaluation. Methods: A total of 35 pediatric patients (aged 0–18 years) with PPS were involved, and their scars were assessed via the VSS, dermoscopy, and the Antera 3D^® system. In addition, a subset of 18 patients (36 scar regions) was also evaluated for therapeutic efficacy after 3–6 months of treatment. Briefly, VSS scores were blindly evaluated by two independent dermatologists under standardized conditions. Quantitative assessment was also performed using dermoscopy and the Antera 3D^® system. The former quantified chromatic parameters (pigmentation: L*, vascularity: a*, green value); the latter captured multispectral 3D images to analyze volume, pigmentation, and erythema. Data are presented as means ± standard deviation and analyzed using paired-sample t tests (one-tailed), the Wilcoxon signed-rank test, and standardized response means (SRMs) to assess therapeutic sensitivity, while baseline variability was evaluated using the standard deviation and coefficient of variation (CV). Results: The results showed that Antera 3D^® detected significant reductions in pigmentation (p < 0.01, SRM = −0.46), vascularity (p < 0.001, SRM = −0.59), and volume (p < 0.0001, SRM = −0.83), while dermoscopy indicated similar moderate improvements in vascularity (Green value: p < 0.001, SRM = 0.57; a*: p < 0.0001, SRM = −0.68) and pigmentation (L*: p < 0.0001, SRM = 0.48) after treatments. VSS showed significant gains in pliability (p < 0.0001, SRM = −1.13), height (p < 0.01, SRM = −0.54), and overall impression (p < 0.0001, SRM = −0.86), but minimal changes in pigmentation (p > 0.05, SRM = 0) or vascularity (p > 0.05, SRM = −0.21). At baseline, Antera 3D^® showed the greatest variability in pigmentation (CV 43.41%) and volume (CV 91.21%), followed by VSS in vascularity (CV 52.95%), pliability (CV 34.05%), and overall impression (CV 31.76%). Dermoscopy presented the lowest variability, indicating limited discriminative power. Conclusions: In conclusion, Antera 3D^® offers an objective, sensitive, and spatially precise approach for PPS assessment and may provide additional quantitative information for evaluating subtle and early changes alongside traditional scar assessment scales. Its integration into clinical practice will enhance treatment monitoring and support more accurate timing of therapeutic interventions. Full article

Background/Objective: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes mellitus (T2DM), dysglycemia, and dyslipidemia. However, the role of postpartum weight change in long-term metabolic outcomes remains unclear. Here, we determined the long-term incidence of dysglycemia and dyslipidemia after GDM and evaluated whether postpartum changes in body mass index (BMI) independently predicted these outcomes. Methods: This single-center prospective cohort study included 205 Japanese women diagnosed with GDM. All participants underwent a 75 g oral glucose tolerance test at 6–12 weeks postpartum. The incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM, and dyslipidemia was evaluated over a median follow-up of 3.6 years. Cumulative incidence was estimated using the Kaplan–Meier method, and Cox proportional hazards models identified independent risk factors, particularly postpartum BMI change. Results: During follow-up, 42.4%, 6.3%, and 35.6% of women developed IFG or IGT (prediabetes), T2DM, and dyslipidemia, respectively. The estimated cumulative incidence rates at 6 years postpartum were 57.1% and 50% for IFG/IGT and dyslipidemia, respectively, whereas the 5-year incidence of T2DM was 10.3%. Postpartum BMI increase was independently associated with new-onset dysglycemia. No independent predictor of T2DM progression was identified. Dyslipidemia was independently associated with higher pre-pregnancy BMI and multiparity, whereas postpartum BMI change was not independently associated after multivariable adjustment. Conclusions: Postpartum BMI change was independently associated with dysglycemia in women with a history of GDM. These findings suggest that postpartum weight change may help identify women at higher risk of subsequent metabolic abnormalities, particularly dysglycemia, in this high-risk population, although causal relationships cannot be inferred from this observational study. Full article