Search Results (597)

Reprogramming is a hallmark of cancer, enabling tumour cells to sustain rapid proliferation, resist cell death, and adapt to hostile microenvironments. This review explores the expression profiles of key metabolic enzymes and transporters involved in glucose, amino acid, and lipid metabolism across the five most deadly cancers worldwide: lung, breast, colorectal, liver, and gastric cancers. Through a comparative analysis, we identify consistent upregulation of glycolytic enzymes such as LDHA, PKM2, and HK2, as well as nutrient transporters like GLUT1, ASCT2, and LAT1, which contribute to cancer progression, metastasis, and therapy resistance. The role of enzymes involved in glutaminolysis (e.g., GLS1, GDH), one-carbon metabolism (e.g., SHMT2, PHGDH), and fatty acid synthesis (e.g., FASN, ACLY) is also examined, with emphasis on their emerging relevance as diagnostic, prognostic, and predictive biomarkers. While several metabolic proteins show strong potential for clinical translation, only a few, such as tumour M2-pyruvate kinase (TuM2-PK) and serum LDH measurement, have progressed into clinical use or trials. This review addresses some of the challenges in biomarker development. Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology. Full article

In this paper, we propose a quantitative evaluation method for navigation safety in coastal waters based on unstructured grids. Initially, a comprehensive analysis was conducted on various factors affecting navigation safety, including natural conditions, traffic conditions, and marine hydro-meteorological conditions, to construct a multi-source fused spatiotemporal dataset. Subsequently, channel boundary extraction was performed using Constrained Delaunay Triangle–Alpha-Shapes, and the precise extraction of ship navigation areas was performed based on Constrained Delaunay Triangle–Voronoi diagrams. Additionally, temporal feature grids were constructed based on the spatiotemporal characteristics of marine hydro-meteorological data. Finally, unstructured grids for evaluating navigation safety were established through spatial overlay analysis. Based on this foundation, a quantitative analysis and evaluation model for comprehensive navigation safety assessment was developed using the fuzzy evaluation method. By calculating the fuzzy relation matrix and weight vectors, quantitative assessments were conducted for each grid cell, yielding safety risk levels from both spatial and temporal dimensions. An analysis was performed using maritime data within the geographic boundaries of lon.119.17–120.41° E and lat.34.40–35.47° N. The results indicated that the unstructured grid division and channel boundary extraction in the demonstrated sea area were closely related to parameters such as the ship traffic flow patterns and the spatiotemporal characteristics of the marine environmental factors. A quantitative evaluation and analysis of the 186 unstructured grid cells revealed that the high risk levels primarily corresponded to restricted navigation areas, the higher-risk grid cells were mainly anchorages, and the low to lower risk levels were primarily associated with channels and navigable areas for ships. Full article

Plant functional traits (PFTs) serve as key predictors of plant survival and adaptation to environmental gradients. Studies on intraspecific variation in PFTs are crucial for evaluating species’ adaptation to projected climate change and developing long-term conservation strategies. This study systematically investigated PFT responses in Polyspora chrysandra (Theaceae, Yunnan, China) through an integrated multivariate analysis of 20 leaf functional traits (LFTs) and 33 environmental factors categorized into geographical conditions (GCs), climate factors (CFs), soil properties (SPs), and ultraviolet radiation factors (UVRFs). To disentangle complex environmental–trait relationships, we employed redundancy analysis (RDA), hierarchical partitioning (HP), and partial least squares structural equation modeling (PLS-SEM) to assess direct, indirect, and latent relationships. Results showed that the intraspecific coefficient of variation (CV) ranged from 7.071% to 25.650%. Leaf tissue density (LTD), specific leaf area (SLA), leaf fresh weight (LFW), leaf dry weight (LDW), and leaf area (LA) exhibited moderate intraspecific trait variation (ITV), while all other traits demonstrated low ITV. Reference Bulk density (RBD) and Silt emerged as significant factors driving the variation. Latitude (Lat), altitude (Alt), and mean warmest month temperature (MWMT) were also identified as key influences. HP analysis revealed Silt as the most important predictor (p < 0.05). Latent variable analysis indicated descending contribution rates: SPs (31.51%) > GCs (11.52%) > CFs (11.04%) > UVRFs (10.29%). Co-effect analysis highlighted significant coupling effects involving RBD and cation exchange capacity of clay (CECC), as well as organic carbon content (OCC) and UV-B seasonality (UVB2). Path analysis showed SPs as having the strongest influence on leaf thickness (LT), followed by GCs and UVRFs. These findings provide empirical insights into the biogeographical patterns of ITV in P. chrysandra, enhance the understanding of plant environmental adaptation mechanisms, and offer a theoretical foundation for studying community assembly and ecosystem function maintenance. Full article

While laser-assisted turning (LAT) improves the machinability of GH 4169 through heating-induced thermal softening, revealing the influence of the laser processing parameters on its thermal field and machining efficiency is crucial. In this study, the influence of different laser processing parameters on the thermal field during the preheating process of LAT is systematically investigated by combining finite element (FE) simulation and experimentation, from which the optimal processing parameters of the LAT of GH 4169 are obtained. Firstly, the experimental platform of LAT is established, and a 2D FE model of the LAT of GH 4169 is constructed. Secondly, the absorption coefficient of GH 4169 with a 1064 nm wavelength laser is calibrated through experimentation and FE simulation, which lay an accurate foundation for the subsequent thermal field analysis. Furthermore, the FE simulation of the preheating process of the LAT of GH 4169 is carried out, focusing on the influence of laser power, laser spot diameter, laser spot movement speed and laser spot–tool edge distance on the thermal field, in terms of the peak and final preheating temperatures. The results show that laser power, laser spot movement speed and laser spot diameter have a significant influence on both of the two temperatures, while laser spot–tool edge distance only affects the final preheating temperature. In addition, the regression equations of the peak and final preheating temperatures are obtained based on the FE simulation results, and the optimal processing parameters are determined by combining the boundary conditions (peak temperature of 650–950 °C and initial preheating temperature of ≤190 °C). Comparison experiments with conventional turning (CT) show that under the optimal processing parameters, LAT can effectively reduce the cutting force, surface roughness and tool flank wear, which indicates that a rational selection of laser processing parameters is crucial for improving the capability of LAT of GH 4169. Full article

The high-redshift blazars are important cosmological probes for exploring the early universe and unraveling the fundamental emission processes and the structure of the active galactic nuclei. The high-energy GeV gamma-ray emissions of 38 high-redshift blazars (z > 2.5) observed by Fermi-LAT were analyzed. Along with the Archive multiwavelength data, we employ one-zone leptonic external Compton (EC) models to reproduce the spectral energy distributions (SEDs) of 38 sources. Both the external photons from the molecular torus (MT) and the broad-line region (BLR) are considered. We obtained the best-fitting parameters for describing the characteristics of the jets and accretion disks. The results indicate that high-redshift blazars exhibit higher $\gamma$-ray luminosities, energy densities, jet powers, kinetic powers, accretion disk luminosities, black hole (BH) masses, radiation efficiencies, and mass accretion rates compared to low-redshift blazars. For high-redshift blazars, the influence of the accretion rate on jet power appears to weaken, and in most cases, the jet power exceeds the total accretion power. We speculate that for high-redshift blazars, rapid accretion may lead to magnetic field saturation, thereby reducing the effectiveness of the Blandford–Payne (BP) process. Consequently, the Blandford–Znajek (BZ) process is likely to play a more dominant role in powering jets in high-redshift blazars compared to low-redshift blazars. Naturally, we acknowledge that selection effects cannot be fully eliminated. Full article

Objectives: The lat pulldown machine is one of the most versatile pieces of equipment for back strengthening, allowing variations in grip and load. However, there are significant gaps in the literature regarding the relationship between exercise modality and specific muscle activation. Methods: This study examined the electromyographic (EMG) activity of major back muscles during seven lat pulldown exercise variants that differed in grip type, width, and trunk inclination. Forty male subjects, with at least 5 years of resistance training experience, performed five repetitions of lat pulldown exercise using 70% of their repetition maximum. Prior to the surface EMG analysis, maximal voluntary contraction (MVC) tests were performed for each muscle group analysed, specifically the latissimus dorsi, posterior deltoid, brachial biceps, middle and lower trapezium, and infraspinatus. The normalised root mean square of the EMG (NrmsEMG) activity for each muscle was recorded during full, concentric, and eccentric movements. Results: Multivariate analysis of variance (MANOVA) showed no significant difference in the NrmsEMG muscle activation across the different lat pulldown exercise variations (all p > 0.05). A significant difference was found in the posterior deltoid where the wide-pronated grip with a 30° trunk inclination showed greater EMG activation compared to the wide pronated grip (p = 0.011) and wide neutral grip (p = 0.017). Conclusions: These findings suggest that grip variations may not significantly alter latissimus dorsi recruitment, challenging the assumption that grip effectiveness targets this muscle. The results highlight the need for individualised approaches to exercise selection, given the variability in muscle activation patterns observed. Full article

Malignant bone and soft tissue tumors are often resistant to conventional treatment, and treatment options for unresectable and metastatic cases are limited. L-type amino acid transporter 1 (LAT1) is overexpressed in several malignancies, including sarcomas, making it an attractive target for targeted alpha therapy. In this study, we investigated the therapeutic efficacy of LAT1-targeted alpha therapy using a novel modified 3-astatin-211 Astato-α-methyl-L-tyrosine (²¹¹At-AAMT) for bone and soft tissue sarcomas. LAT1 expression and the specificity of LAT1-mediated uptake of ²¹¹At-AAMT were evaluated in bone and soft tissue sarcoma cell lines. Antiproliferative effects were assessed using cell viability and colony formation assays. DNA damage was assessed using immunostaining with phosphorylated histone γH2AX. In vivo efficacy of ²¹¹At-AAMT, determined using xenograft mouse models, was compared with that of doxorubicin. LAT1 was highly expressed in all cell lines, especially MP-CCS-SY and MG-63 cells. ²¹¹At-AAMT uptake was LAT1-dependent and significant in all cell lines. It inhibited cell proliferation in a dose-dependent manner, comparable to that of doxorubicin. In xenograft models, a single administration of ²¹¹At-AAMT significantly inhibited tumor growth without systemic toxicity, whereas doxorubicin caused weight loss. Histopathological analysis showed reduced cell density, inhibited proliferation, and extensive DNA damage in tumors treated with ²¹¹At-AAMT, whereas LAT1 expression was maintained in residual tumor tissues. LAT1-targeted alpha therapy with ²¹¹At-AAMT demonstrated antitumor efficacy comparable to that of first-line chemotherapy for osteosarcoma and soft tissue sarcoma. Sustained LAT1 expression suggests the potential for repeated or combination treatments, highlighting its promise as a novel therapy for advanced, treatment-resistant sarcomas. Full article

The prevalence of loneliness is rising, with both individual and societal costs, including a substantial mental health toll. Perhaps not surprisingly, given this upsurge, research focused on loneliness is proliferating. Of particular interest are the characteristics of lonely individuals and where to intercede to reduce loneliness. Interventions often focus on enhancing social skills, providing social support, offering opportunities for social interaction, and addressing maladaptive cognitions. In the current study, we seek to add to the literature on the importance of beliefs by focusing on individual differences in the meaning assigned to the nature of loneliness. Specifically, we investigate mindsets, first developing and validating a new Mindsets of Loneliness Assessment Tool (M-LAT) across two studies (N = 243; N = 382) using primarily university students. Analyses revealed four factors, which we call Lonely Attribute Mindset (LM_Attribute), Lonely People Mindset (LM_Person), Loneliness as Enhancing Mindset (LM_Enhancing), and Loneliness as Debilitating Mindset (LM_Debilitating). Lonely People and Debilitating Mindsets tended to correlate the strongest with social and psychological wellbeing. We discuss the need for future work investigating if mindset interventions targeting both of these types of mindsets can be leveraged to improve wellbeing, especially in the face of loneliness. Full article

Osteoarthritis in dogs is commonly managed with non-steroidal anti-inflammatory drugs (NSAIDs), nutraceuticals, and other medications aimed at alleviating pain and inflammation. Although NSAIDs are generally considered the most effective option, their use is contraindicated in certain conditions due to adverse side effects. Consequently, there has been growing interest in alternative or complementary therapies, such as acupuncture, laser therapy, and their combination. Laser acupuncture involves stimulating traditional acupuncture points with low-intensity laser light, producing anti-inflammatory, analgesic, anti-edematous, and bio-stimulatory effects. In this study, 19 dogs with osteoarthritis were assigned to two groups: 10 received laser acupuncture treatment (Group T) using a dual-wavelength system delivering continuous and pulsed, synchronized emissions, while 9 served as controls (Group C). After 30 days, only Group T showed significant improvement (p < 0.01), with reduced pain and improved joint mobility. Significant reductions in LDH and CPK were observed in Group T, along with changes in inflammatory markers (IL-6 and IL-10, though not TNF-α) and a significant increase in biological antioxidant potential. These preliminary findings indicate that laser acupuncture, applied according to a standardized protocol and adapted to the site of disease, may represent a viable non-invasive therapeutic option for canine osteoarthritis, particularly in cases where pharmacological treatment is contraindicated or ineffective. Further large-scale, randomized controlled trials are warranted to confirm these results and establish long-term efficacy. Full article

L-arginine and its derivatives L-homoarginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) show distinct (patho-) physiological properties as well as a differential renal handling. L-arginine and L-homoarginine have a lower renal clearance and are largely retained (i.e., reabsorbed) as compared to ADMA and SDMA, which are relatively enriched in the urine and excreted. To obtain a more complete picture of what is known regarding transport proteins involved in renal reabsorption and secretion of these substances, a comprehensive literature review and search of cell-specific gene expression databases were performed. Five transport proteins known to transport L-arginine and its derivatives were included, and the data available regarding their tubular expression pattern and their transport characteristics, as well as experimental and clinical data regarding their possible impact on the renal handling of L-arginine and its derivatives, are presented and discussed in a structured narrative review. Based on their transport properties and links to clinical phenotypes, b^0,+AT-rBAT and y⁺LAT1-4F2hc were identified as the most promising candidates to explain a significant part of the observed differential renal handling. This also makes them promising candidates for further investigations as mediators of possible adverse and beneficial drug effects involving L-arginine, L-homoarginine, ADMA, and SDMA. Full article

Wings are a crucial evolutionary trait of insects and constitute an important part of their sensory system. Phloem-feeding aphids specialising in particular host plant species require an efficient sensory system and locomotive abilities to find an appropriate plant to complete the life cycle. Wings (in winged morphs) play a crucial role in this dispersal, but the sensory part of their structure is neglected. Here, we review campaniform sensilla, responsible for sensing the mechanical deformations of wings, in the aphid subfamily Eriosomatinae, where many species are host-alternating, which requires distant flights. Based on light and scanning electron microscopy, we illustrate sensilla and their arrangement on wings in 10 species. We also provide a broader sensory background by correlating their number with other important olfactory and campaniform sensilla of the antennae and legs. We find a strong relation of forewing sensilla with olfactory receptors on antennae, but their number is specific for particular morphs, depending on the required flight effort, led by the abundance of the host plant. Morphs migrating to less abundant host have 1.15 to 1.77 more campaniform sensilla per 1 mm of forewing length than morphs migrating to more abundant host. Aphids reveal a relatively high number of sensilla on the distal part of the forewings, showing their importance for effective sensing the deformation of wing. Full article

Objectives: Surface-Guided Radiation Therapy (SGRT) has been widely adopted in breast cancer radiotherapy, particularly for improving setup accuracy and motion management. Recently, its application in lung cancer has attracted growing interest due to similar needs for precision. This study investigates the feasibility and clinical utility of SGRT in lung cancer treatment, focusing on its effectiveness in patient setup and real-time motion monitoring under frameless immobilization conditions. Materials and Methods: A total of 204 treatment records from 17 patients with primary lung cancer who underwent radiotherapy at Korea University Guro Hospital between October 2024 and April 2025 were retrospectively analyzed. Patients were initially positioned using the Identify system (Varian) in the CT suite, with surface data transferred to the treatment room system. Alignment was performed to within ±1 cm and ±2° across six degrees of freedom. Cone-beam CT (CBCT) was acquired prior to treatment for verification, and treatment commenced when the Distance to Correspondence Surface (DCS) was ≤0.90. Setup deviations from the Identify system were recorded and compared with CBCT in three translational axes to evaluate positioning accuracy and PTV displacement. Results and Conclusions: The Identify system was shown to provide high setup accuracy and reliable real-time motion monitoring in lung cancer radiotherapy. Its ability to detect patient movement and automatically interrupt beam delivery contributes to enhanced treatment safety and precision. In addition, even though the maximum longitudinal (Lng) shift reached up to −1.83 cm with surface-guided setup, and up to 1.78 cm (Lat) 5.26 cm (Lng), 9.16 cm (Vrt) with CBCT-based verification, the use of Identify’s auto-interruption mode (±1 cm in translational axes, ±2° in rotational axes) allowed treatment delivery with PTV motion constrained within ±0.02 cm. These results suggest that, due to significant motion in the longitudinal direction, appropriate PTV margins should be considered during treatment planning. The Identify system enhances setup accuracy in lung cancer patients using a surface-guided approach and enables real-time tracking of intra-fractional errors. SGRT, when implemented with systems such as Identify, shows promise as a feasible alternative or complement to conventional IGRT in selected lung cancer cases. Further studies with larger patient cohorts and diverse clinical settings are warranted to validate these findings. Full article

Stage IV colorectal cancer has a poor prognosis, and liver metastases are prone to recurrence, even after resection. This study aimed to identify common cancer antigens, using immunohistochemical staining, as promising targets for antigen-specific immunotherapies in colorectal cancer. We analyzed expression levels and intracellular localization of seven common cancer antigens, CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, and SPARC, and human leukocyte antigen (HLA) class I via immunohistochemical staining of 85 surgical specimens from primaries and liver metastases. Staining intensity and positive staining were scored to evaluate antigen expression. In 25 primaries, seven cancer antigens were expressed in 88–96% of cases, while HLA class I was expressed on the cell membrane in 80.0% of cases. In 60 liver metastases, FOXM1 and SPARC expression were approximately half that observed in the primaries. Other antigens and HLA class I were highly expressed in both. Most of the primaries and liver metastases may benefit from chimeric antigen receptor-T cell therapy targeting CLDN1, EphB4, and LAT1. Cases with high HLA class I expression may be suitable for vaccine-based and T cell receptor-T cell therapy targeting CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, and SPARC for primaries and targeting antigens, excluding FOXM1 and SPARC, for liver metastases. Full article

Type-I Interferon (IFN) is essential for antiviral immunity in both mice and humans; thus, we investigated whether LAT affects HSV-1 infectivity in the absence of IFN by infecting IFNαβR^−/− and wild-type control mice with HSV-1 McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. IFNαβR^−/− mice survived ocular infection with the LAT-plus virus, while no infected mice survived infection with the LAT-minus virus. Increased death in infected mice correlated with a higher expression in the neurovirulence γ34.5 gene but not with gB expression. To determine the region of LAT that contributed to higher mortality, IFNαβR^−/− mice were infected with recombinant viruses expressing the first 1.5 kb or the first 811bp region of 1.5 kb LAT. Similar to LAT-plus infected mice, IFNαβR^−/− mice infected with LAT1.5kb were protected from death, while infection with the LAT811bp virus was similar to that of LAT-minus, suggesting that increased pathogenicity in the absence of LAT depends on the second half of 1.5 kb LAT. To confirm the in vivo upregulation of γ34.5 expression in the absence of LAT, rabbit skin and Neuro2A cells were infected with LAT-plus, LAT-minus, LAT1.5kb, or LAT811bp viruses. γ34.5 expression was significantly higher in LAT-minus- and LAT811bp-infected rabbit skin cells and Neuro2A cells than in LAT-plus- and LAT1.5kb-infected cells, suggesting that sequences after the 811bp of LAT contribute to γ34.5 upregulation. However, except for γ34.5 expression, ICP0, ICP4, and gB expression were not affected by the absence of LAT or truncated forms of LAT. To confirm that higher γ34.5 expression contributes to higher mortality in the absence of LAT, we infected IFNαβR^−/− mice with a recombinant virus lacking LAT and γ34.5 expression, and, in contrast to LAT-minus, all infected mice survived. Our results suggest that LAT controls γ34.5 expression and that higher γ34.5 expression and mortality in infected mice are associated with the second half of 1.5 kb LAT. Full article

Oligometastatic non-small-cell lung cancer (OMD-NSCLC) has emerged as a biologically and clinically distinct subtype of advanced disease, characterized by limited metastatic burden and a more indolent course. In this narrative review, we examine the current definition of OMD-NSCLC, diagnostic tests, possible biomarkers, and current therapeutic strategies. Biological insights highlight the role of microRNAs in differentiating true oligometastatic state from polymetastatic disease. The main local ablative therapies (LAT) include surgery and radiotherapy. The integration of LAT with systemic therapies has been explored in clinical trials, yielding promising but occasionally inconsistent results. As the therapeutic landscape of OMD-NSCLC patients continues to evolve, refining definitions, identifying predictive biomarkers, and individualizing care are essential steps toward achieving the potential of radical-intent therapy. Full article