Ming Gao, Yilin An, Conghua Feng, Zhiyuan Yang, Zhenyang Xu, Dewei Mao, Qinghui Shang, Zhiyuan Sun
Markerless motion capture (MMC) systems have gained increasing attention in sports science and clinical assessment. However, their accuracy in measuring sagittal-plane lower limb kinematics during running remains unclear. A systematic review and meta-analysis was conducted following established guidelines. MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus were searched for studies comparing MMC with marker-based systems (MBSs). Data were analyzed using a random-effects model in R 4.3.3. Risk of bias was assessed using the COSMIN Risk of Bias checklist for measurement error and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Heterogeneity, sensitivity analyses, and publication bias (Egger’s and Begg’s tests) were also evaluated. Subgroup analyses were conducted to explore potential sources of technical heterogeneity according to sampling frame rate, number of cameras, and running condition. A total of 8 studies were included in this analysis. The pooled root mean square error (RMSE) was 3.84° (95% CI: 2.53–5.15°) for the hip, 4.30° (95% CI: 2.55–6.05°) for the knee, and 3.93° (95% CI: 2.29–5.58°) for the ankle. These findings indicated relatively small measurement errors for sagittal-plane lower limb kinematics, although the magnitude and uncertainty of errors varied across joints. Sensitivity analyses generally supported the robustness of the findings. For knee joint kinematics, funnel plot asymmetry tests did not provide statistically significant evidence of publication bias; however, given the limited number of studies, these findings should be interpreted cautiously. Subgroup analyses indicated that technical characteristics had joint-specific effects on MMC-derived kinematic errors, with no consistent advantage observed for higher frame rates or greater camera numbers. The included MMC systems showed relatively small measurement errors for sagittal-plane lower limb kinematics during running. These findings are specific to the MMC technologies and running conditions evaluated in this review.
Sergey Vladimirov, David Sergeevichev, Maria Bogachek, Alina Kazakova, Anastasia Leonteva, Vladimir Richter, Anna Nushtaeva
Cancer-associated fibroblasts (CAFs) represent a pivotal component of the breast cancer microenvironment. In a paracrine model, CAFs secreted the chemokine CXCL12 (SDF-1α), which bound to CXCR4 and activated the PI3K/AKT and MAPK signaling pathways, stimulating their migration and invasion. TGF-β1 induces myofibroblast differentiation of CAFs by acting through the TGFBR2/ALK5 receptor complex and phosphorylating SMAD2/3, thereby increasing the expression of ACTA2 and FAP. An autocrine loop has been demonstrated in CAF, whereby TGF-β1, via SMAD3, induces the transcription of CXCR4, and subsequently, CXCR4, by binding to the same cell, maintains the myofibroblast phenotype. However, a systematic comparison of paracrine and autocrine variants has not yet been conducted in the context of CAF subtypes. A secondary analysis of 101 bulk RNA-seq samples was performed, with classification into healthNF, riskNF, cancerNF, and CAF S1-S4 using correlation analysis (Spearman), differential expression (DESeq, FDR <0.05), GSEA (FDR <0.25), and a systematic review of the literature (2005–2026). The PCA and the contingency table analysis enabled the description of two patterns of Cancer-associated fibroblasts subtype distribution across clinical and morphological groups: healthNF → cancerNF → CAF and healthNF → riskNF → CAF. Elevated levels of CXCR4 were identified exclusively in CAF (22.7%, FDR = 5.98 × 10 −4 ) and were associated with the CAF-S3 and CAF-S4 fibroblast phenotypes. At CXCR4 High levels, the correlation between CXCL12 and TGFB1 became negative, while the correlation between CXCL12 and ITGAV, FAP, and ITGB1 remained positive. This finding suggests a possible shift from TGF-β-dependent to CXCR4-mediated regulation of CXCL12. GSEA revealed an association of CXCR4 High -CAF with enrichment of gene sets related to the interferon response, inflammation, and apoptosis, as well as with decreased enrichment of proliferation sets, EMT, and TGF-β signaling. A recent systematic review revealed that only 8.6% of publications contain experimental data supporting an autocrine loop, 17.1% describe a paracrine model, and 74.3% do not distinguish between the signaling types. It is hypothesised that the CXCR4 High -CAF transcriptome profile is compatible with a biologically plausible theory of transition between paracrine and autocrine regulatory modes and inflammatory cell states. In vitro validation is a prerequisite for establishing a causal relationship.
Chronic diabetic wounds often fail to heal due to persistent infections and dysregulated immune responses. This study developed a sprayable phage-cocktail hydrogel, a hybrid living material, to provide simultaneous infection control and neuroimmune modulation. A phage-cocktail dressing was formulated using three bacteriophage strains targeting Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa . These bacteriophages were mixed with a 1% sodium alginate solution to create a hands-free spray-produced dressing. The dressing was evaluated for antibacterial activity, cytocompatibility with 3T3 fibroblasts, and efficacy in healing sterile full-thickness skin wounds in db/db mice. The skin wound recovery, macrophage polarization, calcitonin gene-related peptide (CGRP) and substance P (SP) expression were assessed through histological analysis. The dressing achieved approximately 90% antibacterial efficacy while maintaining excellent skin cell cytocompatibility. In db/db mice, the treatment significantly accelerated wound closure (94.2% by day 14), prevented ulceration, and enhanced tissue regeneration. Mechanistic analysis revealed that the dressing induced M2 macrophage polarization and modulated neuropeptide signaling. Specifically, epidermal CGRP sustained M2 macrophages to promote re-epithelialization, while dermal SP facilitated extracellular matrix (ECM) remodeling. This sprayable hydrogel integrates antimicrobial efficacy with neuroimmune modulation to accelerate diabetic wound healing. By modulating pathways associated with the SP/CGRP signaling axis, it supports functional ECM remodeling and re-epithelialization while mitigating dermal fibrosis. This layer-specific regulation provides a potent therapeutic framework for achieving regenerative tissue repair in chronic ulcers.
Customised insoles for paediatric flexible flatfoot are typically designed using static foot postures, which may fail to reflect the dynamic mechanical demands of gait. This study explored an alternative method, evaluating whether dynamically modelled insoles, captured during active locomotion, can effectively provide optimized kinematic control and plantar load distribution while maintaining ergonomic comfort as compared to traditional static designs. Two insoles were customised for 15 children (8–10 years) with flexible flatfeet: a static-based insole (SI), modelled during seated great toe dorsiflexion, and a dynamic-based insole (DI), modelled from the active arch profile during walking. Assessments included geometric characteristics (arch height and medial longitudinal arch [MLA] angle), rearfoot angle (RFA), peak plantar pressure (PPP), and subjective ergonomic comfort. DI exhibited a significantly greater arch height and MLA angle than SI. Kinematically, both designs reduced severe RFA misalignments, with DI demonstrating more consistent bilateral kinematic control. Kinetically, both functioned as effective total-contact devices, attenuating pressure peaks at the heel and lateral forefoot. Notably, despite the more pronounced structural contour of DI, participants reported high subjective comfort scores that were statistically equivalent to SI. Both SI and DI effectively improved rearfoot eversion and reduced localized pressures without compromising subjective comfort. Specifically, the dynamic approach achieved greater total-contact load redistribution across the MLA.
Anna Chiara Siciliano, Stefania Forciniti, Helena Iuele, Federica Carnevali, Giuseppe Gigli, Loretta L. del Mercato
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies due to its late diagnosis, extensive desmoplasia, and strong chemoresistance. Recent advances in three-dimensional (3D) in vitro modelling have provided new insights into tumor-stroma interactions and metabolic adaptations that drive disease progression. This review summarizes the pathogenesis and tumor microenvironment (TME) hallmarks of PDAC, emphasizing the metabolic heterogeneity characterized by altered pH, oxygen, and lactate gradients. It discusses conventional and emerging therapeutic strategies, the molecular basis of drug resistance, and the role of the TME in treatment failure. Furthermore, it highlights the evolution of 3D experimental models as physiologically relevant tools to study PDAC biology and evaluate drug efficacy. Special attention is given to the integration of optical biosensors for non-invasive spatio-temporal monitoring of pH and metabolic fluctuations. These sensing technologies, coupled with advanced bioengineered models, are paving the way for precision oncology and patient-tailored strategies in pancreatic cancer.
