Search Results (459)

Oxidative stress is considered one of the cancer hallmarks, influencing tumor initiation, progression, and metastasis. High levels of reactive oxygen species (ROS) impair the effectiveness of the immune response in cancer patients. We examined changes in oxidative stress during immunotherapy, exploring the relationship between the immune system and clinical parameters related to oxidative burden. Several T-cell and myeloid subsets from 79 metastatic non-oncogene-addicted non-small-cell lung cancer (NSCLC) patients were analyzed using flow cytometry. Additionally, 20 cytokines were measured in serum samples, and sNox2-dp levels, an indicator of NOX2 activity, were assessed by ELISA. Seventy-nine healthy donors served as controls. The data showed that cancer patients had higher levels of sNox2-dp compared to healthy donors (p < 0.0001). Elevated sNox2-dp levels were associated with inflammation-related comorbidities (p = 0.008) and platelet counts (p = 0.03) in NSCLC patients. Furthermore, sNox2-dp displayed a negative correlation with immune cells involved in activation, such as proliferating (Ki67⁺) CD8⁺, PD1⁺ and effector lymphocytes, and a positive correlation with immunosuppressive PMN-MDSCs and inflammatory soluble immune factors, including IL1α, IL1β, IL6, IL10, CCL3, and CCL4. Oxidation levels decreased after immunotherapy (p = 0.04) and increased only in non-responder patients (p = 0.02). Oxidative stress may be indirectly affected by immunotherapy and could serve as a novel tool to identify responding patients in the NSCLC setting. Full article

In low-amplitude and low-frequency vibration environments, the energy harvesting efficiency of self-powered wireless sensor nodes is insufficient, limiting their long-term autonomous operation. To address this issue, a micro piezoelectric–electromagnetic hybrid energy harvester is designed, aiming to enhance energy capture efficiency through structural integration and parameter optimization. The study is conducted entirely through numerical simulations. A coaxial integrated architecture is adopted, combining a piezoelectric cantilever beam array with an electromagnetic induction module. The piezoelectric layer uses lead magnesium niobate–lead titanate (PMN-PT) solid solution material with a thickness of 0.2 mm. The electromagnetic module employs copper wire coils with a diameter of 0.08 mm, winding 1500–3000 turns, paired with N52-type neodymium–iron–boron (NdFeB) permanent magnets. To improve energy conversion efficiency, the optimization parameters include the length-to-thickness ratio of the cantilever beam, the mass of the tip mass, the number of coil turns, and the spacing of the permanent magnets. Each parameter is set at four levels for orthogonal experiments. A multi-physics coupling model is established using ANSYS Workbench 2023, covering structural dynamics, piezoelectric effects, and the electromagnetic induction module. The mesh size is set to 0.1 mm. The energy output characteristics are analyzed under vibration frequencies of 0.3–12 Hz and amplitudes of 0.2–1.0 mm. Simulation results show that the optimized hybrid harvester achieves 45% higher energy conversion efficiency than a single piezoelectric structure and 31% higher than a traditional separated hybrid structure within the 0.3–12 Hz low-frequency range. Under a 6 Hz frequency and 0.6 mm amplitude, the output power density reaches 3.5 mW/cm³, the peak open-circuit voltage is 4.1 V, and the peak short-circuit current is 1.3 mA. Under environmental conditions of 20–88% humidity and −15–65 °C temperature, the device maintains over 94% stability in energy output. After 1.2 million vibration cycles, structural integrity remains above 96%, and energy conversion efficiency decreases by no more than 5%. The proposed coaxial hybrid structure and multi-parameter orthogonal optimization method effectively enhance energy harvesting performance in low-amplitude, low-frequency environments. The simulation design parameters and analysis procedures provide a reference for the development of similar micro hybrid energy harvesters and support the performance optimization of self-powered wireless sensor nodes. Full article

Biopsy procedures are essential for definitive cancer diagnosis but remain limited by the risk of accidental blood vessel puncture, which can lead to hemorrhage and procedural failure. Conventional imaging guidance often provides insufficient vascular contrast, making vessel avoidance during needle insertion challenging. A rotational oblique spectral ultrasound (ROSUS) imaging system was developed to improve vessel detection and needle guidance during biopsy procedures. The device integrates a high-frequency PMN-PT 1–3 composite transducer mounted at a 45° angle within the 18-gauge needle tip, enabling simultaneous forward- and side-looking capability. By combining synchronized rotational–axial scanning with multifrequency signal ratio (MFSR) processing, ROSUS achieved volumetric images with blood–tissue contrast ratio improvement over 1.2 dB compared to conventional B-mode signal processing while maintaining high spatial resolution of 85 µm and 424 µm in axial and lateral directions, respectively. These results demonstrate that frequency-domain spectral processing can improve vessel and tissue differentiation, offering an 18-gauge needle-integrated platform for safer and more accurate biopsy needle-based procedures. Full article

Introduction: Cutibacterium acnes, a component of normal skin flora and a common commensal Gram-positive bacterium, presents a diagnostic challenge for arthroplasty surgeons. While Cutibacterium acnes (C. acnes) as a source of infection has been well characterized in shoulder surgery, its presentation and clinical significance in total hip (THA) and total knee arthroplasty (TKA) remain less understood. Methods: A retrospective chart review identified patients with C. acnes culture positivity following THA or TKA. Demographics, laboratory values, and microbiologic data were collected. Statistical comparisons were performed using t-tests and chi-squared analysis. One-year outcomes were evaluated using the Musculoskeletal Infection Society Outcome Reporting Tool (MSIS ORT) criteria among patients undergoing further surgical intervention. Results: Twenty-nine patients with C. acnes-positive cultures were identified (21 THA, 8 TKA); 15 (52%) were polymicrobial. Ten THA patients (47.6%) and seven TKA patients (87.5%) met MSIS criteria for infection at the time of presentation. Mean time to culture positivity was similar between THA (6.8 days) and TKA (7.4 days; p = 0.57). Sonicated cultures were positive in 24% of THA and 12.5% of TKA cases. Mean ESR was 36.4 mm/h for THA and 51.5 mm/h for TKA (p = 0.21); mean C-reactive protein (CRP) was 35.2 and 36.8 mg/dL, respectively (p = 0.95). Mean synovial cell counts were 27,055 for THA and 22,194 for TKA, with polymorphonuclear cells (PMN) percentages of 68% and 73.9% (p = 0.72, 0.70). Monomicrobial infections demonstrated a mean cell count of 24,143 with 58.9% PMNs, compared to 25,903 and 78.8% in polymicrobial cases. At one year, 72% of patients undergoing subsequent surgery achieved successful outcomes. Higher ASA classification was the only significant predictor of failure (mean 3.0 vs. 2.75). Conclusions: C. acnes-associated THA and TKA infections often present with delayed culture growth, mild inflammatory markers, and frequent polymicrobial involvement. At one-year, patients with available follow-up who undergo surgical management experience favorable outcomes, with 72% achieving MSIS ORT success. Full article

Prostate cancer remains largely refractory to immunotherapy, implying the existence of context-specific immune landscape programs that diverge between circulation and tumor. Here, we integrate bulk RNA sequencing from three cohorts (patient peripheral mononuclear cells, primary prostate tissue, and biochemical-recurrence tumors) with multiparameter flow cytometry, unsupervised UMAP/T-REX (Tracking Responders Expanding) mapping, and de novo discovery of long non-coding RNAs (lncRNAs) to characterize context-specific immunoregulation. Patient PBMCs revealed a coherent IL-1/TNF/IL-17 inflammatory architecture with strong chemotactic programs and an unexpected neutrophil-like signal despite density-gradient isolation, consistent with low-density PMN-MDSCs. In contrast, tumors broadly repressed chemokines and innate immune mediators, yet upregulated prostate cancer-associated lncRNAs, indicating local immune quiescence coupled with non-coding regulatory programs. Recurrent tumors acquired epithelial–mesenchymal transition and metabolic remodeling, accompanied by relapse-associated lncRNA signatures, whereas long-term nonrecurrent tumors preserved epithelial and stress-response networks. High-dimensional cytometry confirmed discrete, cancer-enriched myeloid clusters expressing CD47, SIRPα, PD-L1, CD73, and Galectin-9. Network analysis highlighted inflammatory hubs (CXCL2, PTGS2) in PBMCs and loss of mechanotransduction modules in tumors. Structural modeling uncovered a three-way junction and 3′ triple helix in lncRNA. Collectively, these data suggest that circulating inflammatory rewiring is associated with checkpoint-rich suppressor expansion and tumor immune quiescence, outlining integrated myeloid- and RNA-directed strategies for cancer research. Full article

This review describes the immunosuppressive effect of secreted phosphoprotein 1 (SPP1)+ tumor-associated macrophages (TAMs) in coordinating the tumor microenvironment (TME) as a functionally unique myeloid cell subgroup. SPP1+ TAMs transcend the traditional M1/M2 paradigm and represent a group of cells that are widely found in various cancer types. SPP1+ TAMs have the characteristics of high expression of SPP1 and promoting immune escape, matrix remodeling and metastasis. We clarify the dual developmental source of SPP1+ TAMs, and introduce the activation process of SPP1+ TAMs through recruitment, polarization and epigenetic locking. After SPP1+ TAMs are activated, they are strategically enriched in the tumor core and tumor marginal area to play their functions. Functionally, SPP1+ TAMs mainly promote the progression of tumors through three mechanisms: (1) Interacting with cancer-associated fibroblasts (CAFs): constructing an immunoexcluded fibrotic niche; (2) Multiple regulation of immune cells; (3) Promoting tumor metastasis and the construction of pre-metastatic niche (PMN). Overall, this review aims to provide a comprehensive overview of the mechanisms mediated by SPP1+ TAMs in the TME, and emphasize their unique role in cancer progression. At the same time, the treatment strategies targeting them are further explored, highlighting their potential as precise therapeutic targets for tumor treatment. Full article

It is broadly realized that the body’s metabolism has a profound impact on tumor progression. However, pathophysiological mechanisms underlying the metabolic modulation of the tumor immune microenvironment remain incompletely understood. Here, we report that long-chain fatty acids (LCFAs) can directly modulate the function of myeloid-derived suppressor cells (MDSCs), a central component of establishing the tumor immune microenvironment. In vitro or in vivo exposure to LCFAs significantly reduces the expression levels of signature immunosuppressive genes of both monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). As a result, mice fed with a diet of high LCFA content exhibit delayed tumor progression and prolonged survival in different cancer models. Furthermore, this LCFA-mediated inhibition of M-MDSCs and PMN-MDSCs correlates with enhanced CD8⁺ T antitumor immunity, which is abolished in tumor-bearing nude mice. These results have revealed a previously under-recognized role of LCFAs in the tumor immune microenvironment, implicating novel therapeutic strategies for cancer treatment. Full article

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Since numerous studies highlight the significance of cholinergic system components in tumor development, acetylcholine (ACh) and the differential activation of its receptors could play a crucial role in GBM progression. The aim of this study was to test this hypothesis by assessing the relevance of the cholinergic system in GBM cells and their microenvironment. We analyzed bulk RNA-seq expression data using the TIMER2.0 web server, focusing on the impact of patient survival in relation to muscarinic receptors (CHRM) and neutrophil infiltration in low-grade glioma (LGG) and GBM. Our analysis revealed a marked decrease in survival associated with all CHRMs, particularly in LGG. Moreover, GBM showed higher neutrophil infiltration and reduced survival, especially in relation to CHRM3. These findings were validated in the U251 cell line and in human GBM tumor biopsies (GBM-b), which also displayed CHRM3 expression. Additionally, we show that GBM cells exposed to cholinergic stimulation exhibited increased vascular endothelial growth factor (VEGF), IL-8 production, and PD-L1 expression, while the VEGF increase was blocked by tiotropium (Tio), a CHRM3 antagonist. Similarly, polymorphonuclear cells from GBM patients (PMN-p) displayed increased PD-L1 expression and IL-8 production upon cholinergic stimulation. Finally, as we previously reported on the relevance of thymic stromal lymphopoietin (TSLP) in GBM pathophysiology, here, we found that TSLP upregulated CHRM3 expression. Our findings highlight the importance of the cholinergic system in the tumor microenvironment, where it may act directly on tumor cells or influence neutrophil physiology, thereby modulating tumor progression. Full article

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, elevated systemic levels of CXCL10 overwhelm the localized chemokine gradient at the primary tumor site, creating a potent immune decoy that diverts anti-tumor CXCR3+ T cells away from the tumor. The resulting immune desertification permits unchecked tumor growth and an increased metastatic burden. We also discuss the therapeutic implications of this model, proposing that disrupting the chemokine axis offers a roadmap for developing rational, stage-specific therapies to effectively combat metastatic OS. Full article

Zebrafish is emerging as a model animal for phenotype-based drug screening. Drugs screened from the zebrafish platform have advanced into clinical trials, underscoring their translational potential. Amyotrophic lateral sclerosis is a progressive motor neurons (MN) degenerative disease with few approved drugs. Previously, supplementation with exogenous recombinant phosphoglycerate kinase 1 (Pgk1) was found to improve MN growth through its interaction with receptor Eno2. To bypass the high complexity and cost of full-length Pgk1 production, a short segment within Pgk1 (M08) was predicted as the key motif interacting with Eno2, and a zebrafish phenotypic screening platform was established to find the most neurotrophic compound(s) among M08 and its mutants. We first found that M08-injected zebrafish embryos significantly increased branched caudal primary MNs (CaPMNs). However, compared to M08 (59.20 ± 1.80%), M039, among 17 mutants further screened, showed even more improvement of branched CaPMNs, up to 74.54 ± 3.73%. Next, when we administered the M039 peptide to C9ORF72-knockdown ALS-like zebrafish embryos, it improved axonal growth and swimming ability. Then, we employed a cellular model as a secondary screen, and M039 exhibited improved neurite outgrowth of MN (NOMN) and reduced p-Cofilin in NSC34 neural cells grown in ALS-like condition. Therefore, by using a zebrafish MN phenotype as a primary screening platform, we identified a mutated short peptide M039 having the most pronounced positive effect on improving neurite growth among all 17 mutants in comparison to parental M08, demonstrating the feasibility of zebrafish screening as a cost-effective strategy for finding promising neuroprotective short peptides that serve as neurotherapeutic potentials. Full article

Alternating-current poling (ACP) is becoming a mainstream method because of its stronger ability in promoting the piezoelectric performance of ferroelectric single crystals than that of direct-current poling (DCP). A novel approach was developed by incorporating alternating-current poling and direct-current poling as modified alternating-current poling (MACP). According to the comparison of performance differences between AC-poled and DC-poled single crystals, the properties of MACP single crystals under specific conditions were systematically investigated. The improvement of single crystal performance by MACP is manifested by the multi-peak increase in piezoelectric coefficient ($d_{33}$) and relative dielectric permittivity (${\epsilon }_{33}^T/{\epsilon }_0$), and the coupling factor ($k_t$) value under higher DC bias is higher than that under DC polarization, rather than a direct superposition of DCP and ACP. Two optimal polarization windows were found: 0.2–0.25 kV/mm and 0.35–0.6 kV/mm. Compared with DCP, MACP increases the $d_{33}$, ${\epsilon }_{33}^T/{\epsilon }_0$ and $k_t$, of single crystals by up to 45.67%, 21.62%, and 24.54%, respectively. This significant performance improvement, combined with its complexity, provides a new direction for customizing the performance of single crystals. Full article

Background/Objectives: Accurately diagnosing a periprosthetic joint infection (PJI) represents a challenging and complex task. Especially in the case of low-grade infections, important diagnostic modalities may be inconclusive and synovial markers such as white blood cell count (WBC) and polymorphonuclear percentage (PMN) gain relevance. We therefore aim to assess WBC and PMN in different clinical and microbiological settings. Methods: We performed a retrospective analysis of 115 patients with a diagnosed PJI. WBC and PMN were compared between patients with low- and high-virulent infections, negative and positive histology, symptom duration ≤ 4 weeks and >4 weeks, and positive and negative pathogen detection. Results: Synovial WBC was significantly higher in patients with successful pathogen detection (42.44 [87.0] G/L vs. 16.35 [32.0] G/L; p < 0.01), as was PMN (86.0 [60.0]% vs. 91.0 [89.0]%; p < 0.01). PJIs with high-virulent pathogens showed higher WBC compared to low-virulent pathogens (58.27 [102.0] G/L vs. 27.27 [46.0] G/L; p < 0.01). Patients with onset of symptoms ≤ 4 weeks demonstrated higher WBC (58.27 [112.0] G/L vs. 16.42 [46.0] G/L]; p < 0.01) as well as higher PMN (91.5 [9.0]% vs. 88.0 [20.0]%); p = 0.042). Cases with negative histology showed significantly lower WBC (16.73 [44.0] G/L vs. 42.86 [87.0] G/L; p < 0.01) and lower PMN (86.0 [67.0]% vs. 91.0 [9.0]%; p = 0.036). Conclusions: WBC and PMN show high variability and appear to be influenced by virulence, histology, onset of symptoms, and pathogen detection. Full article

Inflammation underpins pulmonary disease progression during tobacco smoke exposure, which may culminate in irreversible pulmonary disease. While primary smoke poses a notable risk, nearly half of the US population is also susceptible due to frequent exposure to secondhand smoke (SHS). In the present study, we assessed the potential role of VYN202, a novel small molecular bromodomain and extra-terminal inhibitor, as a possible means of attenuating SHS-mediated inflammation. We exposed wild-type mice to an acute time course of room air (RA), SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada), or to both SHS and 10 mg/kg VYN202 (efficacious dose from prior inflammatory models) via oral gavage three times a week. Specific smoke exposure delivery to mice involved SHS from two cigarettes over 10 min, equilibration in room air for 10 min, followed by exposure to SHS from one cigarette for an additional 10 min, for a total SHS exposure of 20 min per day, five days a week for 30 days. We evaluated leukocyte abundance and the secretion of inflammatory mediators in bronchoalveolar lavage fluid (BALF). We also assessed general morphology via histology staining and the activation of receptor tyrosine kinase (RTK) family members. While standard hematoxylin and eosin (H&E) staining resulted in unchanged morphology, SHS-mediated increases in BALF protein abundance, total cellularity, and percent PMNs were attenuated with concomitant administration of VYN202. We also discovered SHS-induced activation of RTKs that were pro-inflammatory (JAK1, JAK3, ABL1, and ACK1), as well as RTKs related to endothelial and vascular remodeling (VEGFR3, VEGFR2, EphB4, EphB6, and FAK). Furthermore, inflammatory cytokines including GCSF, IFN-γ, IL-12p70, IL-17A, LIX, and TNF-α were all augmented by SHS exposure. Despite SHS exposure, each of these RTKs and cytokines/chemokines was significantly attenuated by VYN202. In summary, inflammatory responses induced by SHS exposure were mitigated by VYN202. These data reveal fascinating potential for the utility of VYN202 in lessening smoke-induced pulmonary exacerbations. Full article

We study basis-independent structures in the Type-I seesaw mechanism for light Majorana neutrinos, assuming the canonical scenario with three heavy right-handed (sterile) neutrinos. Let $m_{\nu }$ denote the $3\times 3$ mass matrix of light neutrinos, obtained at tree level from heavy Majorana singlets with a diagonal mass matrix $D_N=\mathrm{diag}(M_1,M_2,M_3)$ and a Dirac matrix $m_D$. We show that all right actions F on the seesaw matrix that leave $m_{\nu }$ unchanged form the group $G=D_N^{1/2}O(3,\mathbb{C})D_N^{-1/2}$. While oscillation data determine the PMNS matrix $U_{\mathrm{PMNS}}$ and the mass-squared splittings, they do not fix the F-class within G. We classify basis-invariant quantities into those that are class-blind (e.g., $det \eta$) and class-sensitive (e.g., $\mathrm{Tr}\eta$, $\mathrm{Tr}{\eta }^2$, an alignment measure, and CP-odd traces relevant to leptogenesis), where $\eta$ denotes the non-unitarity matrix of the light sector. We provide explicit formulas and both high-scale and GeV-scale benchmark examples that illustrate these invariant fingerprints and their scaling with $D_N$. This converts the degeneracy at fixed $m_{\nu }$ into measurable, basis-invariant fingerprints. Full article

This work presents a systematic experimental investigation of tapered fiber Bragg gratings (tFBGs) fabricated from standard SMF-28 fiber with waist diameters ranging from 30 to 115 µm. The effects of taper geometry on strain and temperature sensitivities were evaluated using UV inscription through two phase masks to ensure reproducibility. The maximum strain sensitivity achieved was 25.38 ± 0.06 pm/N for the 30 µm waist, corresponding to 20.84 ± 0.05 pm/µε—an enhancement of more than 1600% compared to a standard untapered FBG. In contrast, the thermal sensitivity remained nearly constant at ~12.5 pm/°C for all diameters, confirming that the temperature response is governed by the intrinsic thermo-optic and thermal-expansion properties of silica and is not significantly affected by taper geometry. The measured strain sensitivity exhibited a clear inverse-square dependence on the waist diameter, in excellent agreement with a simple axial-stress model. Consistent Bragg responses obtained using different phase-mask pitches further validated the repeatability of both the tapering and inscription processes. These results demonstrate that tapering standard telecom fiber provides a low-cost, scalable, and robust method to significantly enhance FBG strain sensitivity while preserving thermal stability, enabling compact and high-performance sensors for structural and industrial monitoring applications. Full article