Search Results (2,528)

Population aging has markedly increased the burden of cancer in older adults, in whom frailty, sarcopenia, and reduced physiological reserve limit tolerance to treatment and worsen clinical outcomes. Aging is accompanied by progressive functional decline and by biological processes such as cellular senescence, characterized by irreversible cell cycle arrest, chronic low-grade inflammation, and impaired immune surveillance. The accumulation of senescent cells and the persistence of a senescence-associated secretory phenotype contribute to tissue dysfunction and generate a microenvironment that favors tumor initiation and progression. Physical exercise has been associated with attenuation of inflammation, improvements in metabolic and immune function, and with lower levels of senescence-related biomarkers. Although aerobic exercise has been extensively studied in this setting, resistance training holds relevance for older adults due to its capacity to counteract sarcopenia, preserve muscle strength and power, and sustain functional independence. Structured and periodized approaches to resistance exercise may further enhance these benefits by delivering targeted stimuli aligned with age-related physiological deficits. Block strength training (BST), a periodized model that concentrates training adaptations into sequential phases of maximal strength, power, and muscular endurance, has demonstrated consistent improvements in functional performance and reductions in frailty risk in community-dwelling older adults. BST improves physical function. It may also influence biological processes related to aging and cancer; however, mechanistic evidence specific to BST remains to be established. We hypothesized that the exercise in block as a targeted, a structured and physiologically grounded resistance training intervention highlights the potential of BST to promote functional aging and healthy. In the case of cancer biology, and the environment near to tumour, the relationship between aging mechanisms in older adults and controlled exercise effects are currently in advance, but mechanistic trials are still lacking. Finally, we propose a novel training method, structured and personalized, that could impact different clinical outcomes in older patients with cancer. Full article

To systematically investigate the combined effects of moisture content, confining pressure, and loading rate on the mechanical properties of weakly cemented soft rock, this study focuses on the Jurassic coal measures from the Hoxtolgay coalfield in Xinjiang. A series of uniaxial and triaxial compression tests were conducted under varying moisture states, loading velocities, and confining pressures. Complementary X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brazilian splitting tests were performed to analyze the microstructural evolution and tensile failure characteristics. The experimental results demonstrate that moisture content acts as the primary governing factor for mechanical degradation; increased hydration promotes clay mineral swelling and attenuates inter-granular cementation, leading to a continuous reduction in both compressive and tensile strengths, as well as the elastic modulus. Conversely, confining pressure consistently enhances these macroscopic mechanical parameters by restricting lateral deformation. While the loading rate alters the mechanical response, its impact is secondary compared to the definitive effects of moisture and stress constraints. Furthermore, by utilizing established stress–strain-based indices, the study quantitatively evaluates the brittleness characteristics, confirming that hydration fundamentally drives the rock mass from a brittle state toward ductility. This research elucidates the coupled degradation mechanisms of highly sensitive soft rock, providing a theoretical foundation for stability design and risk assessment in underground geotechnical engineering. Full article

This study investigates the potential of Fischer–Tropsch (FT) waxes, synthesized from natural gas, as high-performance and sustainable alternatives to conventional ester waxes in cosmetic applications. To evaluate their technical viability, a series of FT waxes with varying hydrocarbon chain lengths were synthesized and characterized. Safety was rigorously assessed through human patch tests and irritation surveys, while sensory attributes, including gloss and transparency, were compared against beeswax and carnauba wax. Furthermore, the impact on the skin barrier was analyzed using Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy to determine lipid packing characteristics. The results demonstrated that FT waxes possess an excellent safety profile with irritation levels comparable to traditional waxes. Sensory evaluations revealed that adjusting the hydrocarbon chain length allows for precise control over melting points and texture, offering significant formulation flexibility. Crucially, lipid packing analysis indicated that FT waxes promote an orthorhombic organization, effectively mimicking and reinforcing the native crystalline structure of the human skin barrier. These findings conclude that FT waxes provide both superior sensory properties and functional skin-barrier benefits, positioning them as versatile and innovative ingredients for advanced dermo-cosmetic formulations. Full article

Background/Objectives: Fibromyalgia is a painful syndrome with biopsychosocial components that predominantly affects middle-aged women. This study aimed to evaluate changes in sleep quality and quality of life following intravenous (IV) lidocaine treatment in patients with fibromyalgia (FM). Methods: This retrospective observational study included patients diagnosed with fibromyalgia who underwent intravenous lidocaine treatment at a tertiary pain clinic between June 2023 and June 2024 and had a Pittsburgh Sleep Quality Index (PSQI) score > 5. The patients’ demographic data, Fibromyalgia Impact Questionnaire (FIQ) scores at baseline and at 1 and 3 months post-treatment, Numerical Rating Scale (NRS-11) scores, Short Form-12 (SF-12) mental and physical component scores (MCS-12, PCS-12), and PSQI scores were recorded. Results: Overall, 51 patients were included. 92.2% of the patients were women, with a mean age of 41.6 ± 9.5 years. Statistically significant reductions in NRS-11, FIQ, and PSQI scores and increases in SF-12 component scores were observed at 1 and 3 months compared with baseline (p < 0.001). Negative correlations were found between NRS-11 and PCS-12 and MCS-12, and a positive correlation was found between FIQ and PSQI. Sleep quality showed a marked improvement at 1 month; however, attenuation of this benefit was observed at the 3-month follow-up. Conclusions: Sleep quality appeared to be associated with short-term functional outcomes, whereas pain intensity was associated with mid-term clinical status in patients with fibromyalgia. Prospective randomized controlled trials are required to confirm these findings and to determine optimal dosing and treatment schedules. Full article

In the existing research on information propagation modeling in social networks, hypergraphs have been widely applied to characterize the high-order interaction relationships involving multiple nodes. However, most models are still based on the assumption of undirected connections, which leads to certain limitations in depicting the information flow direction and the structural characteristics of propagation chains. To address the above problems, a social hypernetwork propagation model with directional constraints is constructed in this paper by introducing the directed hypergraph structure and combining it with the improved SEIR model. The strength of social relationships is measured by intimacy in the model, and a comprehensive characterization of the information propagation process is achieved by integrating the threshold mechanism of the directed hypergraphs with the attenuation function of information timeliness. In addition, the effectiveness of the proposed model is verified by taking the event of “imposing additional tariffs” as an example, and the evolutionary characteristics of propagation in different network structures, as well as the impacts of user confidence and information timeliness, are analyzed using simulation experiments. The results indicate that the model is applicable to characterizing the information propagation trends and dynamic characteristics in real social networks, and can provide theoretical references and methodological support for the prediction and regulation of network public opinion. Full article

Viral infections remain a global public health challenge. Stimulating the innate immune system is a potent therapeutic strategy that promotes pathogen clearance, directly impacting disease severity and clinical outcomes. Interferons and interferon-stimulated genes (ISGs) are critical components of this antiviral defense system. Neomycin, an aminoglycoside antibiotic, can induce ISG expression and help establish an antiviral state. In this study, we demonstrated that neomycin induces the production of pro-inflammatory cytokines (IL1β, TNFα, IL6, GM-CSF, and IFN-γ) in peripheral mononuclear blood cells (PBMCs) and activates key antiviral ISGs, including MxA, OAS1, and IRF7. The protein expression profiles elicited by neomycin were comparable to those induced by poly(I:C). Intranasal delivery of neomycin to CBA and BALB/c mice induced various ISGs in both the respiratory tract and splenic tissues. Prophylactic administration of neomycin significantly inhibited influenza B virus replication in the lung and nasal turbinates of CBA mice in a sublethal infection model. Overall, our data suggest that neomycin, when used prophylactically alone or combined with other antiviral strategies, shows considerable potential for the attenuation of influenza B virus infections. Full article

Bitter taste receptors (TAS2Rs) are increasingly recognised as extraoral chemosensors that modulate diverse biological processes, including cancer cell behaviour and drug responsiveness. Many TAS2R ligands correspond to therapeutic compounds; however, their contribution to the response of brain tumours to chemotherapy remains unexplored. Here, we investigated whether the bitter taste signalling pathway is modulated by temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma, with an impact on treatment efficacy in glioblastoma cells. We show that TMZ elicits intracellular Ca²⁺ responses compatible with activation of G-protein-coupled receptor signalling and induces anti-proliferative and pro-apoptotic effects in multiple human glioblastoma cell lines. Pharmacological inhibition of bitter taste receptors, as well as genetic silencing of the taste transduction G protein GNAT3, significantly attenuated TMZ-induced cytotoxicity, suggesting that bitter taste signalling is involved in this process. In silico ligand prediction combined with receptor expression profiling identified TAS2R43 as a candidate modulator of these effects, and TAS2R43 knockdown markedly reduced TMZ-induced loss of cell viability and apoptosis. Moreover, TMZ enhanced intracellular accumulation of the ABC transporter substrate doxorubicin, suggesting modulation of multidrug efflux mechanisms. Collectively, our findings identify TAS2R43 as a potential biomarker that warrants further validation to improve responses to TMZ and other ABC transporter-limited anticancer drugs. Full article

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather a mismatch between trial design and the inflammatory biology of the perioperative period. Surgical resection provokes an acute and intense inflammatory surge characterized by sympathetic activation, cytokine release, neutrophil extracellular trap formation, endothelial activation, and transient suppression of cellular immunity. During this perioperative inflammatory window, circulating tumor cells encounter a biologically permissive microenvironment that may facilitate immune evasion, adhesion, and early metastatic niche establishment. The magnitude of this inflammatory response varies across patients and may represent a critical, yet under-recognized, determinant of tumor–host dynamics. Anesthetic and analgesic strategies influence this inflammatory cascade. By attenuating nociceptive signaling and sympathetic activation, regional anesthesia may modulate perioperative immune and immunometabolic pathways. However, it should not be framed as an anti-cancer therapy per se, but rather as a potential regulator of the transient inflammatory milieu that shapes early oncologic biology. We propose that prior neutral trials may reflect methodological misalignment, including heterogeneous tumor populations, absence of inflammatory stratification, and reliance on distant survival endpoints without mechanistic correlates. Future investigations should integrate perioperative immune phenotyping, inflammatory biomarkers, and tumor subtype stratification to determine whether modulation of acute surgical inflammation meaningfully alters early tumor–host interactions. Reconceptualizing the perioperative period as a biologically active inflammatory interface may refine the anesthesiologist’s role within perioperative oncology and open new avenues for precision-based perioperative modulation. Full article

Background: The neutrophil-to-lymphocyte ratio (NLR) is a simple biomarker that reflects the balance between innate immune response and adaptive immunity. Currently, the genetic basis and clinical implications of NLR in relation to inflammatory gastrointestinal diseases have not been extensively explored. Methods: We carried out a genome-wide association study (GWAS) on European individuals from the UK Biobank to detect genetic variants related to NLR, followed by post-GWAS analyses including colocalization analysis, transcriptome-wide association studies (TWAS), and LD score regression. Logistic regression, Cox regression, and gene–environment interaction analysis were used to evaluate the impact of NLR polygenic risk scores (PRS) on inflammatory gastrointestinal disease risks. Results: GWAS of 395,442 Europeans identified 306 genomic regions (731 lead SNPs) associated with NLR, mapping to 1542 genes enriched for immune pathways. Colocalization revealed shared genetic signals with TWAS prioritization of 59, 19, 14, 22 and 28 genes in the whole blood, spleen, terminal ileum, transverse colon and sigmoid colon, respectively. LD-score regression showed significant positive genetic correlations with CD (rg = 0.132), coeliac disease (rg = 0.124), peptic ulcer (rg = 0.138) and duodenal ulcer (rg = 0.220). One-SD increase in NLR PRS predicted higher risk of IBD (OR = 1.05, 95% CI 1.03–1.08), Crohn’s disease (OR = 1.06, 1.02–1.10), ulcerative colitis (OR = 1.05, 1.02–1.08) and coeliac disease (OR = 1.07, 1.03–1.11). Restricted cubic splines demonstrated non-linear relationships of NLR PRS for IBD, CD and UC. Gene environment analyses showed smoking and diabetes amplified the risks, while cardioprotective diet, oily fish intake and polyunsaturated fatty acid level attenuated NLR PRS-associated risk in IBD (mainly CD). Conclusions: Our study delineates the polygenic basis of NLR and establishes its genetic correlation with inflammatory gastrointestinal diseases, offering a genetically informed indicator for disease risk stratification with potential utility in population-level prevention strategies. Full article

Preservation of biological specimens over extended periods is essential for morphological research, especially in contexts where sample collection is limited or unrepeatable, such as spaceflight studies. However, the impact of long-term exposure to chemical fixatives remains underexplored. In this study, we used high-resolution X-ray microtomography and X-ray phase contrast tomography to investigate the stability of mineralized tissues subjected to prolonged chemical fixation. We examined the forelimb digits of geckos (Chondrodactylus turneri) preserved for over six years using a protocol involving formalin and ethanol, as well as the humeral bone of gerbils (Meriones unguiculatus) stored in fixative for more than four years. The gecko samples originated from the delayed vivarium control group of the Bion-M No. 1 space mission, offering a valuable chance to evaluate the preservation effects on specimens of significant scientific value. Comparative analysis revealed distinct changes in bone volume and linear attenuation coefficient of bone associated with formalin storage, highlighting the need for optimized storage strategies in long-term biorepositories. These findings offer valuable guidance for maintaining morphological fidelity in chemically preserved skeletal tissues. Full article

This study presents a characterization method for High-Frequency Current Transformers (HFCTs) intended for partial discharge (PD) measurement in on-line acquisition systems designed for AI-based processing and clustering. The primary objective is to analyze how key design parameters, ferrite core material, and number of turns, influence HFCT frequency response, attenuation, and sensitivity, thereby providing a basis for optimized sensor design when data analysis is to be performed by means of AI-based algorithms. The investigation focuses on the influence of different ferrite core materials and varying secondary turn numbers on the frequency spectrum and the response to IEC 60270-compliant calibrator impulses Both concentrated and well-distributed HFCT secondary winding configurations are analyzed to evaluate their impact on signal behavior and sensitivity. The experimental results are compared with a simplified theoretical model to validate performance trends and identify key design factors. The HFCT response to IEC 60270-compliant calibrator impulses is examined to assess its suitability for PD measurement systems and monitoring. The results highlight the critical role of core selection and the number of turns in shaping HFCT bandwidth, attenuation, and impulse response, which are essential for accurate and reliable PD detection in continuous monitoring systems to perform the diagnostic of the electrical insulation condition. This diagnostic approach is based on the detection of partial discharge (PD) activity over time, with the objective of identifying evolving phenomena by monitoring the amplitude and characteristics of the signals associated with different defects. Therefore, accurate separation of signals originating from different defects and from noise is essential. These results provide a foundation for designing HFCT sensors suitable for integration into advanced diagnostic frameworks, AI-aided for Condition-Based Maintenance (CBM). Full article

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma in which complete surgical excision is standard treatment, although some tumors are initially unresectable. Neoadjuvant imatinib has been proposed in these cases, but data on its histopathological and molecular effects and long-term outcomes remain limited. To evaluate the clinical, histopathological and molecular impacts of neoadjuvant imatinib prior to modified Mohs surgery (MMS) in locally advanced DFSP. Single-center, retrospective study. After a mean of 10 months of neoadjuvant imatinib, partial tumor size reduction was observed in 60% of patients (mean reduction 37.8%), while the remaining cases showed disease stabilization; no complete responses were recorded. All tumors exhibited marked volumetric and consistency reduction, with histology revealing extensive hypocellular hyaline regression and attenuated CD34 and nestin expression. Persistence of COL1A1–PDGFB fusion transcripts was detected in post-treatment samples. Following MMS, local recurrence occurred in 30% of patients at long-term after a mean of 10.8-year follow-up since the last surgery. Neoadjuvant imatinib in locally advanced DFSP results in tumor volume reduction without decreasing the final surgical defect. The histological response is typically patchy and may compromise detection of residual disease, potentially increasing the risk of local recurrence. Full article

Hydraulic manipulators face critical challenges due to valve dead-band nonlinearity and state constraints, which can lead to safety hazards and hardware damage. This study proposes a state-constrained controller with valve dead-band compensation to ensure prescribed positioning accuracy and operational safety. Barrier Lyapunov functions ensure that state constraints are maintained and that boundary violations are avoided. Concurrently, a smooth dead-band inverse model is developed to offset asymmetric valve dead-band effects without inducing chatter. Adaptive laws estimate uncertain parameters and dead-band impact in real time, and a disturbance observer attenuates unmatched uncertainties. Dynamic surface control is employed to diminish the explosion of complexity in backstepping design. Comparative simulations under fixed-angle and arbitrary-angle tracking demonstrate that the proposed controller achieves superior tracking accuracy with steady-state errors below 0.04° compared to 0.06° for non-compensated controllers, while significantly reducing pressure fluctuations and control chattering as adaptive parameters converge. The results indicate that the strategy effectively compensates for valve dead zones while strictly maintaining state constraints, thereby achieving the required control precision for hydraulic servo systems. Full article

Background: Infectious hematopoietic necrosis virus (IHNV), a rhabdovirus classified within the genus Novirhabdovirus, continues to be one of the most detrimental pathogens impacting salmonid aquaculture on a global scale. Notable for inducing high mortality rates among fry and fingerlings, IHNV represents a substantial threat to the economic stability of the aquaculture industry. This review offers an in-depth analysis of the contemporary advancements in IHNV vaccine development. Methods: We assess the efficacy and immunological mechanisms of traditional vaccine platforms, including inactivated and live-attenuated vaccines, while emphasizing the groundbreaking success of DNA vaccines, particularly those encoding the viral glycoprotein (G). Although nucleic acid-based therapies provide high levels of protection, they face logistical challenges related to delivery and regulatory obstacles associated with Genetically Modified Organisms (GMOs). Additionally, we examine emerging “next-generation” platforms, such as viral vector vaccines, subunit proteins produced in yeast or plant systems, and RNA-based technologies. We critically analyze technical bottlenecks, including the lack of efficient mucosal delivery systems and the limited understanding of long-term cellular memory in teleosts. Results: We propose future research directions that emphasize the development of multivalent formulations and the incorporation of molecular adjuvants to augment mucosal immunity. Conclusions: This synthesis seeks to integrate fundamental viral pathogenesis with applied immunology to develop a strategic framework for the sustainable, long-term management of IHNV in global salmonid populations. Full article

In this study, an active vibration control (AVC) strategy is effectively used on a system made of a honeycomb polymer–paper core and carbon fiber-reinforced polymer (CFRP) plates. A cost-effective and practical solution based on an AVC system has been developed and tested using a microcontroller unit (MCU) from Texas Instruments. The control system is studied by applying out-of-plane disturbances to the composite panel via an electrodynamic shaker, by exciting the identified mode shapes obtained through experimental modal analysis, i.e., impact tests. The actuator chosen for the AVC system is a Macro Fiber Composite (MFC) patch. Multiple analog signal processing circuits were developed to scale and shift the signal at the input and output of the MCU. The proposed control algorithm is based on a positive position feedback (PPF) technique. Modal analysis was performed to identify the natural frequencies and mode shapes of the structure, which are essential for the design and tuning of the modal-based PPF controller. This analysis also enabled optimal sensor and actuator placement, ensuring effective targeting and control of the dominant vibration modes. Then, a series of tests were performed using pure sine excitations at frequencies of interest, close to the 2nd and 8th mode at 25.13 Hz and 129 Hz, respectively. The results of the experiments revealed a velocity attenuation of 55.8% to 76.9% and a Power Spectral Density (PSD) attenuation of 5.8 dB to 12.8 dB, depending on the mode under study. Owing to the size and mass properties of the Macro Fiber Composite (MFC) patches, the control system is very much suitable for automobile and aerospace applications. Full article