Search Results (130)

Background/Objectives: Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive intervention for overactive bladder (OAB) typically utilized in patients for whom behavioural and pharmacological therapies do not work. The aim of this study is to identify predictors of progression to alternate minimally invasive treatment options following PTNS in patients with OAB refractory to medical and behavioural therapy. In addition, the aim of this study is to determine predictors of maintenance therapy after completing PTNS induction. Methods: This study is a retrospective cohort analysis of patients that underwent PTNS between March 2018 and June 2023 for management of overactive bladder. The primary outcome of this study is progression to alternate minimally invasive treatment options following PTNS, such as sacral neuromodulation or intradetrusor onabotulinum toxin injections. The secondary outcome of this study is the continuation of maintenance therapy following the initial 12-week PTNS treatment course. Results: A total of 49 patients were included for analysis. Overall, 33% (16/49) of patients had further alternate minimally invasive treatment. Multivariate logistic regression analysis identified only age (odds ratio (OR) = 1.06; p = 0.05) as a significant predictor of progression to alternate minimally invasive OAB treatment following PTNS. Overall, 27 (55%) patients continued with ongoing monthly maintenance PTNS after completing initial weekly treatment for OAB. Multivariate logistic regression only identified sex as a predictor of ongoing maintenance PTNS (OR = 13.2; p = 0.017). Conclusions: The present study identifies younger age as a significant predictor of progression to further minimally invasive OAB treatments after PTNS. Furthermore, female sex was found to be a significant predictor of ongoing maintenance PTNS. Full article

The Ili River Valley and adjacent Xinjiang regions contain introduced cattle, local cattle, and yak and therefore provide a useful regional system for examining cattle–yak genomic differentiation. Using whole-genome resequencing data from 79 individuals, we analyzed Angus (ANG), Simmental (SIM), Holstein (HOL), Xinjiang Brown Cattle (XH), Kazakh Cattle (KAZ), Altay White-headed Cattle (AWH), and yak (WY). The six domestic cattle groups were merged into a composite domestic cattle group (PTN, n = 69) and compared with WY (n = 10). Sequencing generated 2996.28 Gb of raw data and 2939.56 Gb of clean data. Alignment to the Bos taurus ARS-UCD1.2 reference genome yielded mapping rates of 96.71–99.78% and depths of 5.98×–17.26×. Genome-wide PTN-WY comparisons showed extremely high differentiation: the median weighted F_ST was 0.846 and the 95th percentile was 0.943. The joint F_ST–π scan identified 832 candidate highly differentiated windows and 533 unique ENSBTAG gene IDs, whereas the low-differentiation set contained only five windows and three genes. The longest contiguous highly differentiated segments were located on chromosomes 26, 29, 8, 21, and 7. WY had the highest median Tajima’s D (1.173) and the slowest LD decay, while KAZ had the lowest median Tajima’s D (0.345) and the fastest LD decay. Treemix supported non-tree-like covariance components, and PSMC indicated broadly similar deep-time demographic profiles across individuals. Overall, the dominant genomic signal between PTN and WY is deep phylogenetic divergence, with locally enhanced highly differentiated segments superimposed on this background. These segments were enriched for functions and pathways related to reproductive behavior, neuroendocrine regulation, circadian rhythm, and membrane transport, but they are not interpreted here as recent within-species selective sweeps. The results provide a cautious regional framework for conservation and breeding of bovine genetic resources in Xinjiang. Full article

In this study, Pt/N-Mo/TiO₂ and Pt/Mo/TiO₂ catalysts were prepared by the two-step impregnation method for catalytic CO oxidation, with the obtained Mo/TiO₂ pretreated or not with NH₃ before Pt loading. The Pt/N-1Mo/TiO₂ catalyst exhibited superior catalytic activity compared to Pt/1Mo/TiO₂ and Pt/N-xMo/TiO₂ (x = 0, 0.5, 2, 3, 5), indicating the essential role of N-modification of Mo/TiO₂ with an optimal MoO₃ loading. The T₉₀ decreased from 133 °C for Pt/1Mo/TiO₂ to 105 °C for Pt/N-1Mo/TiO₂ under a feed gas consisting of 8000 ppm CO, 16% O₂, 3% H₂O and balanced N₂. For both Pt/1Mo/TiO₂ and Pt/N-1Mo/TiO₂ catalysts, the H₂O in the feed gas showed promotive effects on CO oxidation, while SO₂ caused some deactivation at low temperatures. Under the same feed gas composition (8000 ppm CO, 16% O₂, 10% H₂O, 50 ppm SO₂ and balanced N₂) and temperature (185 °C), Pt/N-1Mo/TiO₂ demonstrated superior SO₂ resistance compared to Pt/1Mo/TiO₂. CO conversion on Pt/N-1Mo/TiO₂ remained above 99% during a 12-h SO₂ resistance test, while that on Pt/1Mo/TiO₂ gradually decreased to 26%. Characterization results show that NH₃ pretreatment of 1Mo/TiO₂ significantly improved the dispersion of Pt and enhanced the dissociation of adsorbed H₂O into highly reactive hydroxyl (*OH) species, partially explaining the better activity of Pt/N-1Mo/TiO₂ compared with Pt/1Mo/TiO₂. H₂O might promote CO oxidation by facilitating the formation of easily decomposable bicarbonate and formate intermediates. SO₂ impeded the Pt reduction process on Pt/1Mo/TiO₂ while it hardly affected that on Pt/N-1Mo/TiO₂, explaining their difference in SO₂ resistance. Full article

The present study investigated the effect of a 3D-printed nanocomposite scaffold on bone healing in vivo. The scaffolds used were made from the bioresorbable thermoplastic polycaprolactone polymer, blended with Multi-Walled Carbon Nanotubes functionalized with chitosan, and manufactured with a rectilinear infill pattern and interconnected pores of 500 μm in size. The study included three groups of 10 Wistar rats, in which a 2 mm bone defect was created in the middle of the right femur. In the scaffold/peptide group, the gap was filled with the scaffold loaded with a peptide corresponding to human pleiotrophin amino acids 48-56 (PTN_48-56), and the fracture was stabilized with a 12 mm K-wire as an intramedullary nail. In the scaffold group, the scaffold did not contain the peptide, and in the control group, the bone defect was stabilized without the use of a scaffold. Radiological examination revealed that bone healing was achieved on average in 6.6 weeks in the scaffold/peptide group, 7.2 weeks in the scaffold group, and 8.1 weeks in the control group. Histopathological examination performed 2 weeks postoperatively showed that angiogenesis in the scaffold/peptide group was 1.5 times higher than in the scaffold group and 2.5 times higher than in the control group. In conclusion, our osteo-inductive 3D-printed scaffold covered with PTN_48-56 is a promising option for accelerating bone defect healing. Full article

Pleiotrophin (PTN), a heparin-binding growth factor with potent mitogenic and angiogenic activity, has emerged as a key regulator of mammary gland biology and a potential driver of breast cancer progression. This review integrates current evidence on PTN’s roles from normal mammary development, where it can delay ductal outgrowth, to triple negative breast cancer, where it promotes lung metastasis and correlates with poor survival. Though frequently reported as being overexpressed in breast cancer, the published data indicates that PTN transcription is reduced in cancer relative to normal breast cells. By contrast, serum PTN protein levels have been shown by multiple studies to be elevated in breast cancer patients relative to healthy controls. We examine the expression and function of PTN at a cellular level and explore the interplay between PTN and the tumour microenvironment. We evaluate preclinical models, clinical correlations, and emerging biomarker data that position PTN as a candidate prognostic indicator and therapeutic target. Despite growing interest, significant gaps remain regarding context-specific signalling. By integrating developmental and oncogenic perspectives, this review highlights PTN as a pivotal but underexplored factor in mammary gland physiology and breast cancer and outlines future research directions needed to translate PTN-targeted strategies into clinical benefit. Full article

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

Oncogenic driver mutations in non-small cell lung cancer (NSCLC) activate defined signaling pathways that sustain tumor growth and influence the immune landscape. Yet, how coordinated interactions among diverse cell populations within the tumor immune microenvironment (TIME) contribute to this process remains largely unresolved. To address this, we profiled approximately 200,000 single cells from 45 treatment-naïve NSCLC patients representing seven major driver mutations. This analysis uncovered five multicellular modules (CM1–5) with distinct functional properties, each linked to specific malignant regulatory programs. Among them, CM2 and CM5 exhibited pronounced invasive features and were associated with unfavorable clinical outcomes. CM2 was predominantly observed in EGFR- and MET-driven brain metastases and was defined by strong crosstalk between astrocytes and myofibroblasts. Factors such as SPP1, PTN, and PSAP, together with metabolic alterations, contributed to a microenvironment supportive of metastatic colonization in the brain. By contrast, CM5 was enriched in ROS1-, KRAS-, and EGFR-mutant tumors and consisted of diverse myeloid and endothelial subsets characterized by immunosuppressive and pro-angiogenic signaling, including MIF, GALECTIN, and RETN, collectively facilitating immune escape and vascular remodeling. We further constructed and validated a driver mutation-specific prognostic signature (DMSP.sig) model integrating receptor–ligand interactions and core transcription factors, which effectively stratified patient survival. Leveraging this model, we also identified potential therapeutic candidates linked to these prognostic features, highlighting opportunities for clinical intervention. In summary, our study delineates how oncogenic drivers give rise to distinct TIME architectures, providing a framework for prognostic assessment and precision immunotherapy in high-risk NSCLC. Full article

Depression is a prevalent mental health disorder characterized by persistent sadness, loss of interest, and impaired daily functioning. Wearable monitoring systems have emerged as promising tools for continuous mental health assessment; however, they face challenges such as data privacy concerns, misclassification risks, and limited ability to capture complex emotional states. To address these limitations, this study proposes a Self-Supervision-Enabled Compounded Multi-Modal Feature-Learning Network (S2-CFL) for depressive state classification using wearable sensor data and psychological self-reports. The framework integrates a Twin-Path Encoder–Decoder Network (TP-EDN) for extracting temporal features from raw signals and a Densely Connected Convolution Pyramidal Transformer Network (DC2-PTN) for learning spatial representations from signal-to-image transformations. A fusion mechanism combines multi-modal features to predict depressive states, valence, and arousal levels, while a Fine-Grained Emotion Classification Network (FGECN) is employed to categorize emotional states into multiple classes using supervised learning models. Experimental results demonstrate that the proposed multi-modal approach improves classification performance and provides interpretable insights into emotional and depressive patterns. Full article

Quantitative evaluation of public transit networks (PTNs) with complex-network models informs route optimization and operational adjustments. Prior studies emphasize large cities and pay limited attention to small-sized urban systems. This study examines the bus network of Cangzhou City, Hebei Province, China, to broaden the empirical scope and characterize PTNs in smaller cities. The dataset for this study comprises route and stop records, passenger boarding logs, and bus GPS traces. We develop a general workflow for bus data cleaning and completion. To characterize the dynamic bus network and compare it with the static network, we construct a static network and Directed Weighted Dynamic Network I (DWDN I) using the L-space method, and we construct Directed Weighted Dynamic Network II (DWDN II) using the P-space method. We calculated network metrics including degree, weighted degree, clustering coefficient, path length, network diameter, network efficiency, and small-world coefficient. The principal results show that: (1) at the macroscopic level, the dynamic PTN tracks passenger demand, as the average degree, weighted average degree, and clustering coefficient fluctuate in concert with passenger flows; (2) key stations concentrate in the urban core, and stations with high weighted degree display pronounced spatial autocorrelation; (3) the exponential form of the weighted-degree distribution indicates that the examined bus network is not scale-free, while the dynamic network’s small-world coefficient exceeds that of the static network across time periods, reflecting stronger small-world characteristics. This study integrates network and spatial attributes of the PTN to offer an exploratory case for investigating public transit networks in third-tier cities. The findings can inform comparable studies and offer practical guidance for bus operators. Full article

Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery. Full article

Alzheimer’s disease (AD) involves a constellation of molecular processes that extend well beyond amyloid-β (Aβ) accumulation. Recent anti-amyloid antibodies provide limited clinical benefits, highlighting the need for additional strategies due to their modest efficacy and safety concerns. Increasing proteomic evidence reveals that proteins such as midkine (MDK), pleiotrophin (PTN) and clusterin (CLU) accumulate within amyloid plaques and may shape disease progression, although their precise contributions—protective, pathogenic, or both—remain unknown. In this Perspective, we examine how emerging targeted protein degradation (TPD) technologies, including Proteolysis-Targeting Chimeras (PROTACs), Lysosome-Targeting Chimeras (LYTACs) and molecular glues (MGs), could provide a means to selectively eliminate these co-aggregating proteins. We also discuss advances in degrader design, artificial intelligence (AI)-assisted screening, and strategies aimed at enhancing Central Nervous System (CNS) delivery. We finally outline how integrating TPD modalities with antibody-based and multi-target therapeutic approaches may promote more effective, systems-level interventions for AD. Full article

In the maize systems of Liaonan, China, soil compaction and inefficient nitrogen use are key constraints to sustainable productivity. To enhance nitrogen (N) use efficiency and sustainable productivity in the maize systems of Liaonan, China, a field split-plot trial was conducted from 2018 to 2022 to investigate the synergistic effects of rotational tillage and N rates on root physiology and yield. Three straw return practices were tested as follows: NT (1 year no-tillage + 1 year subsoiling), PT (continuous subsoiling), and RT (continuous rotary tillage), each under three nitrogen levels: 150 (N150), 210 (N210), and 240 kg ha⁻¹ (N240). Root length density (RLD) and root surface area density (RSD) were monitored in situ, while root protein content, cellulose/lignin composition, root activity, and photosynthesis were analyzed at the tasseling (VT) and milk stage (R3). The results showed that NT-N210 treatment maximized deep root (30–50 cm) growth, increasing RLD by 54.5% compared to PT-N150 and RSD by 62.0% compared to RT-N150. NT was also associated with a stronger protein-associated FTIR signal and greater lignin accumulation, collectively correlating with delayed senescence. Photosynthesis and yield were strongly correlated with deep RLD (*r* = 0.82, p < 0.01). NT-N210 achieved the highest yield (12,896 kg ha⁻¹, 38.0% higher than PT-N150) with 12.5% less N than conventional practice. These findings indicate that combining the NT rotation with moderate N (210 kg ha⁻¹) optimizes deep root functionality and delays senescence. This improvement was correlated with shifts in protein-associated FTIR signals and cell wall composition (e.g., lignin accumulation), which collectively contributed to significantly improved resource use efficiency and yield. Therefore, adopting a biennial no-tillage/subsoiling rotation combined with moderate nitrogen application (210 kg ha⁻¹) is recommended as an effective strategy to alleviate soil compaction, enhance deep root growth, delay senescence, and achieve high maize yield with improved nitrogen use efficiency in similar agricultural systems. Full article

Background/Objectives: Sexual health is shaped by lifestyle factors alongside biomedical determinants. This review synthesises evidence on physiotherapy, balneology/peloidotherapy, and diet therapy as preventive and therapeutic adjuncts for female sexual dysfunctions and related gynaecological conditions. Methods: A structured narrative review of PubMed and Google Scholar (June–July 2025) was conducted by three independent reviewers using predefined keywords in English and Polish. Case reports, preprints, and studies before 2015 were excluded. From 7322 records, 47 studies met the inclusion criteria for qualitative synthesis. Results: Physiotherapy—particularly pelvic floor muscle training, multimodal manual therapy, neuromuscular electrical stimulation (including PTNS), magnetostimulation, short-wave diathermy, and capacitive–resistive monopolar radiofrequency—was consistently associated with reductions in dyspareunia, chronic pelvic pain, and urinary symptoms, with parallel improvements in sexual function and quality of life. Balneological procedures (brine baths/irrigations, crenotherapy, selected radon/sulphide/iodine–bromine applications) and peloidotherapy demonstrated analgesic, anti-inflammatory, and perfusion-enhancing effects, with signals of benefit in vulvodynia, endometriosis, and infertility support. Dietary measures—higher fruit intake (notably citrus), adequate vitamin D, targeted omega-3 use in PCOS, a Mediterranean dietary pattern, and prudent red-meat limitation—were associated with favourable endocrine–metabolic profiles and, in selected contexts, reduced disease risk. Conclusions: Integrating lifestyle–medicine modalities with standard care may meaningfully prevent and manage female sexual dysfunctions by addressing pain, perfusion, neuromuscular control, and endocrine–metabolic drivers. Implementation frameworks and high-quality trials are warranted to refine indications, dosing, and long-term effectiveness. Full article

Multiple sclerosis (MS), the most prevalent chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults, exhibits marked sexual dimorphism, with a 3:1 female-to-male ratio, but more severe symptoms and greater neurological damage in males. Increasing attention has focused on identifying circulating molecules that reflect inflammatory activity within the central nervous system and could clarify the mechanisms underlying MS. Pleiotrophin (PTN), a cytokine implicated in autoimmune and neurological diseases, is significantly elevated in patients with relapsing-remitting MS (RRMS). To explore the potential contribution of PTN and its receptors to neuroinflammatory signaling, we quantified the mRNA expression of PTN receptors in peripheral blood mononuclear cells from RRMS patients compared to untreated RRMS patients and healthy control subjects. We further performed an in silico molecular docking and molecular dynamics analysis to assess the possible functional significance of PTN-receptor interactions. Our results show a significant overexpression of integrin subunit beta-3 (ITGB3) mRNA in peripheral blood mononuclear cells from RRMS patients compared to healthy control subjects. Molecular docking shows that PTN could binds to the metal ion-dependent adhesion site domain of ITGB3 via Mg²⁺/Ca²⁺-mediated stabilization and has a higher binding affinity than fibrinogen, the canonical endogenous ligand. These findings suggest that ITGB3 could be a dynamically regulated integrin receptor in RRMS that may participate in PTN-driven neuroinflammatory pathways in peripheral blood immune cells, influenced by disease stage, sex, and immunotherapy. While our results support the biological plausibility of PTN–ITGB3 engagement, they remain hypothesis-generating and require functional validation. The integration of molecular expression data and computational modeling underscores the potential involvement of ITGB3 as a possible participant in MS and warrants further investigation of its clinical and mechanistic role. Full article

Objectives: We aimed to evaluate the effect of non-invasive NESA neuromodulation compared to posterior tibial nerve stimulation (PTNS) in patients with an overactive bladder (OAB), also given the same exercises and patient education, on quality of life, symptoms, discomfort and sleep quality. Method: Twenty-four women, aged 38–85 years with OAB, were included in this preliminary randomized controlled trial. Each patient attended ten sessions, twice a week. Patient pelvic floor function and urinary incontinence symptoms were collected throughout ICIQ-SF and B-SAQ questionnaires. Patient QoL and sleep quality were reported using SF-36 and PSQI, respectively. All outcomes were measured using three assessments: previous treatment (T1), immediately after treatment (T2) and two-month follow-up (T3). Results: Both groups showed significant improvements in pelvic floor function and urinary incontinence symptoms, as well as in sleep quality (p < 0.05). Although no significant differences between the groups were observed for any of the variables (p > 0.05), only the NESA group showed compelling improvements in quality of life (p < 0.05). Conclusions: The two treatments improved OAB symptoms, discomfort, and sleep quality in the short term yet only the non-invasive NESA group improved quality of life in women with OAB. These findings warrant further investigation in larger trials. Full article