Search Results (222)

The study of Ultra-High-Energy Cosmic Rays is made possible by space telescopes that allow for the recording of signals generated by Extensive Air Showers (EAS) on the night side of the Earth’s atmosphere. One of the requirements for these telescopes is the detection of very low photon fluxes, achievable using the latest generation SiPMs characterized by high intrinsic gains, low power consumption, low weight, and robustness against accidental exposure to light. Despite these advantages, some technological issues still need to be addressed, such as the radiation hardness for operation in space. Therefore, the design of a SiPM-based focal surface for UHECR detection must consider the space qualification of SiPM arrays, with the development of compact arrays optimized for low dead-area focal surfaces. SiSMUV (SiPM-based Space Monitor for UV light) is a project dedicated to developing a compact and modular UV detector for use in space telescopes designed to study the fluorescence and Cherenkov signals produced by Ultra-High-Energy Cosmic Rays (UHECRs). Each SiSMUV module incorporates a matrix of SiPMs, a readout ASIC (Radioroc by Weeroc), and an FPGA into a monolithic block. This design enables the acquisition and processing of signals from the sensors. The system can connect to a PC for standalone operation or with back-end electronics for integration into more complex systems. In this paper, we will describe the prototype electronics, the experimental setup and the measurements performed to obtain parameters such as the gain of the SiPMs, and their photon detection efficiency (PDE). We will also present the firmware developed to interface with the readout ASIC and to transmit data to other peripherals. Full article

Cellular senescence is an irreversible cell cycle arrest, triggered by stressors like telomere shortening, DNA damage, and oncogenic signaling. These cells, often referred to as ‘zombie cells’ because they cease dividing yet resist apoptosis, drive the Senescence-Associated Secretory Phenotype (SASP), releasing pro-inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes. While senescence is a protective mechanism against malignant proliferation, its persistence in tissues contributes to aging and age-related diseases (inflammaging). Recognizing this dual role forms the basis for developing therapies that bridge anti-aging, regenerative medicine, and oncology, as precise molecular regulatory mechanisms remain incompletely understood. This review interrelates these disciplines, focusing on targeted interventions against senescent cells (SnCs). These interventions include senolytics (agents that selectively eliminate SnCs) and senomorphics (agents that suppress the SASP), offering translational insights from anti-aging/aesthetic applications into integrated treatment models. The framework addresses cancer therapeutics via immunologic modalities such as monoclonal antibodies (mAbs) and CAR T-cell therapy, alongside nucleic acid-based therapeutics (mRNA and siRNA), and is used in combination with broad-spectrum therapeutics. The novelty lies in synthesizing these disparate fields, unified by cellular senescence as a central mechanistic target. Ultimately, the goal is to identify targets that induce tumor regression, mitigate age-related vulnerabilities, promote tissue homeostasis and regeneration, and improve quality of life and overall survival. Full article

Background/Objectives: The milieu of inflammatory cytokines present in the prostate cancer (PCa) tumor microenvironment exerts various effects on cancer progression. Chronic exposure to the inflammatory cytokine interleukin-1 (IL-1) has been shown to impact signaling via the RELA/NF-kB pathway; however, the effects of chronic inflammation on the integration of different inflammatory signaling pathways, such as the interleukin-6 (IL-6)/STAT3 axis, requires further exploration. Methods: We generated in vitro subline models by exposing the C4-2 and LNCaP PCa cell lines to either IL-1α or IL-1β for several months. We then treated the resulting sublines with acute IL-1 alone, IL-6 alone, or IL-1/IL-6 in combination and assessed for sensitivity to cytokine signaling. We observed changes in proliferation and quantified using Ki-67 immunostaining. Cell proliferation was assessed after siRNA silencing RELA or STAT3. Results: IL-1/IL-6 signaling in combination enhanced the signaling effects of either cytokine alone, particularly cytostasis. While the chronic IL-1 sublines maintained sensitivity to acute IL-6 signaling, they lost sensitivity to acute IL-1 signaling and did not show the enhanced IL-1/IL-6 cytostatic response. Inhibition of RELA and STAT3 rescued cytostasis after IL-1/IL-6 treatment in parental PCa cell lines, but only STAT3 inhibition rescued proliferation in the chronic IL-1 sublines. Conclusions: Our work shows that IL-1/RELA and IL-6/STAT3 work in parallel to synergistically induce cytostasis. However, chronic IL-1 exposure selects for cells that attenuate IL-1/RELA signaling, subsequently attenuating IL-1/IL-6 synergy. Full article

The widely used oximeter design was adopted and improved as the configuration mainframe in this study to acquire PPG signals. When users wear a finger probe and input their height, the device acquires PPG signals through the probe circuit, then filters and amplifies the signals to remove unnecessary noise, and uses an ARM-M4 to analyze the main peak, dicrotic wave, and wave valley of the PPG waveform to calculate related indexes for the final assessment. After 100 s, the HRV, sine wave ratio, and SI results are estimated, and a cardiovascular disease risk assessment is presented using a risk level from 0 to 5. This study uses the stiffness index (SI), sine wave ratio (SIN), and heart rate variability (HRV) to assess cardiovascular status. The SI is derived from PPG signal characteristics and reflects vascular stiffness based on blood flow rebound time. However, some PPG signals lack a dicrotic wave (sine waves), which is often caused by severe arterial stiffness. These waveforms lead to errors in SI calculation due to misidentification of the dicrotic wave. The appearance of a sine wave indicates that blood pulsation is abnormal; however, it will make the SI calculation algorithm produce a seemingly normal health performance. To address this, the auxiliary line method was introduced to identify sine waves, and the SIN ratio occurring in contiguous PPG waves was incorporated to calculate their proportion in PPG signals, aiding SI analysis and arterial stiffness evaluation. The total power (TP) value obtained via HRV frequency-domain analysis reflects autonomic nervous activity. As reduced autonomic function may relate to cardiovascular diseases, TP is included as an evaluation indicator. By analyzing PPG signals, calculating SI and SIN, and integrating the HRV indicator, this study evaluates arterial stiffness and cardiovascular health, helping participants understand their physical condition more quickly and conveniently, and potentially preventing cardiovascular diseases at an early stage. Full article

In situ process monitoring systems (IPMSs) are rapidly gaining importance in quality assurance of laser powder bed fusion (L-PBF) parts, yet standardized methods for their objective evaluation are lacking. This study introduces a novel, system-independent assessment method for IPMSs based on a specially designed Energy Step Cube (ESC) test specimen. The ESC enables systematic variation in volumetric energy density (VED) by adjusting laser scan speed, without disclosing complete process parameters. Two industrially relevant IPMSs—PrintRite3D by Divergent and Trumpf’s integrated system—were evaluated using the ESC approach with AlSi10Mg as the test material. System performance was assessed based on sensitivity to VED changes and correlation with actual porosity, determined by metallographic analysis. Results revealed significant differences in sensitivity and effective observation windows between the systems. PrintRite3D demonstrated higher sensitivity to small VED changes, while the Trumpf system showed a broader stable observation range. The study highlights the challenges in establishing relationships between IPMS signals and resulting part properties, currently restricting their standalone use for quality assurance. This work establishes a foundation for standardized IPMS evaluation in additive manufacturing, offering valuable insights for technology advancement and enabling objective comparisons between various IPMSs, thereby promoting innovation in this field. Full article

The uptake and accumulation of nanoplastics by plants have emerged as a major research focus. Exogenous selenium nanoparticles (SeNPs) are widely used to mitigate the toxicity of abiotic stresses, such as nanoplastics (NPs) and polyethylene (PE—NPs) nanoplastics, and represent a feasible strategy to enhance plant performance. However, the molecular mechanisms by which SeNPs alleviate the phytotoxicity of microplastics and nanoplastics remain poorly defined. To address this gap, we used Pistia stratiotes L. (P. stratiotes) as a model and silicon dioxide nanoparticles (SiO₂NPs) as a comparator, integrating physiological assays, ultrastructural observations, and proteomic analyses. We found that NP stress caused ultrastructural damage in root tips, exacerbated oxidative stress, and intensified membrane lipid peroxidation. SeNPs treatment significantly mitigated NP-induced oxidative injury and metabolic suppression. Compared to the NPs group, SeNPs increased T-AOC by 38.2% while reducing MDA and ·OH by 33.3% and 89.6%, respectively. Antioxidant enzymes were also elevated, with CAT and POD rising by 47.1% and 39.2%. SeNPs further enhanced the photosynthetic capacity and osmotic adjustment, reflected by increases in chlorophyll a, chlorophyll b, and soluble sugar by 49.7%, 43.8%, and 27.0%, respectively. In contrast, proline decreased by 17.4%, indicating stress alleviation rather than an osmotic compensation response. Overall, SeNPs outperformed SiO₂NPs. These results indicate that SeNPs broadly strengthen anti-oxidative defenses and metabolic regulation in P. stratiotes, effectively alleviating NP-induced oxidative damage. Proteomics further showed that SeNPs specifically activated the MAPK signaling cascade, phenylpropanoid biosynthesis, and energy metabolic pathways, enhancing cell-wall lignification to improve the mechanical barrier and limiting NPs translocation via a phytochelatin-mediated vacuolar sequestration mechanism. SiO₂NPs produced similar but weaker alleviative effects. Collectively, these findings elucidate the molecular basis by which SeNPs mitigate NPs’ phytotoxicity and provide a theoretical foundation and practical outlook for using nanomaterials to enhance phytoremediation in aquatic systems. Full article

This study proposes a high-contrast photoacoustic (PA) imaging methodology based on a dual-wavelength confocal metalens, designed to monitor the dissemination of cancer cells and to inform subsequent cancer treatment strategies. The metalens is composed of two metasurfaces that perform filtering and focusing functions, effectively reducing the cross-talk between the two wavelengths of light in space and achieving a confocal effect. Furthermore, to minimize process complexity, a uniform material system of silicon dioxide (SiO₂) and titanium dioxide (TiO₂) is employed across the different metasurfaces of the metalens. The designed metalens has a radius of 25 µm and an operational focal length of 98.5 µm. The results confirm that this dual-metasurface design achieves high focusing efficiency alongside precise focusing capability, with the deviations of the actual focal lengths for both beams from the design values being within 1.5 µm. Additionally, this study developed a skin tissue model and simulated multi-wavelength photoacoustic imaging of cancer cells within the human body by integrating theories of radiative transfer, photothermal conversion, and the wave equation. The results demonstrate that the enhancement trend of the reconstructed signal closely matches the original signal, confirming the model’s excellent fitting performance. The sound pressure values generated by cancer cells are significantly higher than those of normal cells, proving that this method can effectively distinguish cancerous tissue from healthy tissue. This research provides new theoretical support and methodological foundations for the clinical application of multi-wavelength photoacoustic imaging technology. Full article

In the application of ceramic dielectric filters, to achieve electromagnetic shielding of signals and subsequent integrated applications, it is necessary to carry out metallization treatment on their surfaces. The quality of metallization directly affects the performance of the filter. However, when in use, the filter may encounter harsh environmental conditions. Therefore, the surface-metallized film needs to have strong corrosion resistance to ensure its long-term stability during use. In this paper, Cu films and copper–chromium alloy films were fabricated on Si (100) substrates and BaTiO₃ ceramic substrates by HiPIMS technology. The effects of different added amounts of Cr on the microstructure, electrical conductivity, and corrosion resistance of the Cu films were studied. The results show that with an increase in Cr content, the preferred orientation of the (111) crystal plane gradually weakens, and the grains of the Cu-Cr alloy film gradually decrease. The particles on the film surface are relatively coarse, increasing the surface roughness of the film. However, after doping, the film still maintains a relatively low surface roughness. After doping with Cr, the resistivity of the film increases with the increase in Cr content. The film–substrate bonding force shows a trend of first increasing and then decreasing with the increase in Cr content. Among them, when the Cr content is 2 at.%, the film–substrate bonding force is the greatest. The Cu-Cr alloy film has good corrosion resistance in static corrosion. With the increase in Cr content, the Tafel slope of the cathode increases, and the polarization resistance R_p also increases with the increase in Cr content. After the addition of Cr, both the oxide film resistance and the charge transfer resistance of the electrode reaction of the Cu-Cr alloy film are greater than those of the Cu film. This indicates that the addition of Cr reduces the corrosion rate of the alloy film and enhances its corrosion resistance in a NaCl solution. 2 at.% Cr represents a balanced trade-off in composition. While ensuring the film is dense, uniform, and has good electrical conductivity, the adhesion between the film and the substrate is maximized, and the corrosion resistance of the Cu film is also improved. Full article

Drought is a leading constraint on plant productivity and will intensify with climate change. Plant acclimation emerges from a multilayered regulatory system that integrates signaling, transcriptional reprogramming, RNA-based control, and chromatin dynamics. Within this hierarchy, non-coding RNAs (ncRNAs) provide a unifying regulatory layer; microRNAs (miRNAs) modulate abscisic acid and auxin circuits, oxidative stress defenses, and root architecture. This balances growth with survival under water-deficient conditions. Small interfering RNAs (siRNAs) include 24-nucleotide heterochromatic populations that operate through RNA-directed DNA methylation, which positions ncRNA control at the transcription–chromatin interface. Long non-coding RNAs (lncRNAs) act in cis and trans, interact with small RNA pathways, and can serve as chromatin-associated scaffolds. Circular RNAs (circRNAs) are increasingly being detected as responsive to drought. Functional studies in Arabidopsis and maize (e.g., ath-circ032768 and circMED16) underscore their regulatory potential. This review consolidates ncRNA biogenesis and function, catalogs drought-responsive modules across model and crop species, especially cereals, and outlines methodological priorities, such as long-read support for isoforms and back-splice junctions, stringent validation, and integrative multiomics. The evidence suggests that ncRNAs are tractable entry points for enhancing drought resilience while managing growth–stress trade-offs. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM. Full article

A surface molecularly imprinted ratiometric fluorescent sensor (Eu/CDs@SiO₂@IIPs) was constructed for the selective and visual detection of Cu²⁺. The sensor integrates blue-emitting carbon dots as an internal reference and a custom-designed Eu(III) complex, Eu(MAA)₂(2,9-phen), as both the functional and fluorescent monomer within a surface-imprinted polymer layer, enabling efficient ratiometric fluorescence response. This structural design ensured that all fluorescent monomers were located at the recognition sites, thereby reducing background fluorescence interference and enhancing the accuracy of signal changes. Under optimized conditions, the sensor exhibited a detection limit of 2.79 nM, a wide linear range of 10–100 nM, and a rapid response time of 3.0 min. Moreover, the uncoordinated nitrogen atoms in the phenanthroline ligand improved resistance to interference from competing ions, significantly enhancing selectivity. Practical applicability was validated by spiked recovery tests in deionized and river water, with results showing good agreement with ICP-MS analysis. These findings highlight the potential of Eu/CDs@SiO₂@IIPs as a sensitive, selective, and portable sensing platform for on-site monitoring of Cu²⁺ in complex water environments. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Swiprosin-1 (SWS1/EFhd2) is a calcium-binding adaptor protein involved in cytoskeletal regulation, but its physiological role in bone homeostasis remains largely undefined. To elucidate its function in osteoclast biology, we examined SWS1 expression and activity during osteoclastogenesis using primary murine bone marrow-derived macrophages, siRNA-mediated knockdown, and SWS1 knockout (KO) mice. SWS1 was predominantly localized to the nucleus in precursor cells and redistributed to the F-actin ring in mature osteoclasts. Receptor activator of nuclear factor-kappa B ligand stimulation significantly downregulated SWS1 mRNA expression. Loss of SWS1 enhanced osteoclast formation, F-actin ring integrity, and bone resorption, accompanied by elevated expression of osteoclastogenic markers. In vivo, male SWS1 KO mice exhibited deteriorated trabecular bone microarchitecture with increased osteoclast numbers. Mechanistically, SWS1 deficiency intensified αvβ3 integrin-associated cytoskeletal signaling and upregulated Akt, MAPK, NF-κB, and PLCγ2 pathways. These results indicate that SWS1 negatively regulates osteoclast differentiation and function by restraining cytoskeletal reorganization and downstream signaling. Collectively, our findings establish SWS1 as a novel modulator of osteoclast activity and a potential therapeutic target for osteolytic bone disorders. Full article

With the increasing demand for high-performance ceramic guideways in precision industries, accurate flatness measurement of large-scale, rough ceramic surfaces remains challenging. This paper proposes a novel method combining oblique-incidence laser interferometry and sub-aperture stitching to overcome limitations of conventional techniques. The oblique-incidence approach enhances interference signal strength on low-reflectivity surfaces, while stitching integrates high-resolution sub-aperture measurements for full-surface characterization. Numerical simulations validated the method’s feasibility, showing consistent reconstruction of surfaces with flatness values of 1–20 μm. Experimental validation on a 1050 mm × 130 mm SiC guideway achieved a full-surface measurement with PV 2.76 μm and RMS 0.59 μm, demonstrating high agreement with traditional methods in polished regions. The technique enabled quick monitoring of a 39-h lapping process, converging flatness from 13.97 μm to 2.76 μm, proving its efficacy for in-process feedback in ultra-precision manufacturing. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article