Search Results (265)

The interplay between the environmental exposome and the cancer genome remains a critical gap in precision oncology. While somatic mutational signatures—genomic fossils imprinted by exposures such as ultraviolet radiation; tobacco smoke; and industrial pollutants—are well characterised for their etiological significance; their functional impact on therapeutic efficacy remains largely unexplored. We hypothesised that these environmental genomic scars induce distinct pharmacogenomic vulnerabilities and resistance mechanisms that vary by geographical exposure patterns. This study employs two complementary analytical frameworks. First, a linear regression-based pharmacogenomic screen across four datasets (GDSC1, GDSC2, CTRP, CCLE; 1001 cell lines, 31 cancer types) identified 608 statistically significant (p < 0.01) mutational signature–drug interactions, revealing that UV-associated signature SBS7a is associated with broad-spectrum therapeutic resistance, including to BRAF inhibitors (PLX-4720, p < 10⁻⁴), while pollution-driven oxidative stress (SBS18) is associated with sensitivity to p38 MAPK inhibition (VX-702, r = −0.45, p < 10⁻⁹). Second, an XGBoost predictive model trained exclusively on 33,679 GDSC2 records using a 1265-feature matrix integrating 40 SBS signatures, drug chemistry descriptors, proteomic features, and two satellite-derived environmental variables (NASA PM_2.5 and UV)—achieved R² = 0.7973 on a 20% holdout set (grouped cross-validation R² = 0.7296). SHAP analysis revealed that satellite-derived PM_2.5 (Zone_PM25) ranked 7th of 1265 features, exceeding all 40 individual SBS mutational signatures. Synthesising these findings with satellite-derived atmospheric data, we constructed an exploratory spatially interpolated risk surface spanning 122 nations, generating the hypothesis that uniform drug efficacy assumptions may not apply globally. These findings suggest that a patient’s environmental exposure history may constitute a measurable pharmacogenomic variable. This exploratory framework warrants validation in independent datasets and with individual-level geographic data before clinical application. Full article

Elemental mercury (Hg⁰) in coal-fired flue gas has become a focal yet challenging issue in mercury pollution control due to its high toxicity, bioaccumulation potential, and high volatility. There is an urgent need to develop a technology of Hg⁰ catalytic oxidation that is both low-cost and highly efficient. On the other hand, waste fluid catalytic cracking (WFCC) catalysts generated from the petroleum refining industry are classified as hazardous solid waste, necessitating effective harmless disposal and resource recovery. Herein, a composite support (A-P) was constructed by combining an activated WFCC catalyst (AFCC) with the natural mineral palygorskite, followed by the loading of VO_x active species to prepare a Vx/A-P catalyst for Hg⁰ removal from flue gas. Moreover, the effects of the preparation process and conditions of the Vx/A-P catalyst on the Hg⁰ removal performance were systematically studied. This work aims to provide a theoretical basis and technical support for the development of low-cost, high-performance mercury removal catalysts, while also promoting the green recycling and value-added utilization of waste catalysts. Full article

We investigate the effects of post-annealing in oxygen (O₂) and nitrogen (N₂) on tin-doped vanadium oxide (V_xSn_yO_z) films for microbolometer applications. The films were deposited using magnetron sputtering in an Ar:O₂ environment. We demonstrate that low Sn doping combined with N₂ post-annealing provides an effective approach to optimize the temperature coefficient of resistance (TCR), resistivity, and 1/f-noise. Compared to undoped VO_x, V_xSn_yO_z films exhibit an enhanced TCR, moderate resistivity, and reduced 1/f-noise. The 135 nm thick V_0.46Sn_0.03O_0.51 film after post-annealing in N₂ shows a TCR of −4.08%/K and a resistivity of 7.3 × 10⁻² Ω⋅cm at 300 K, an absorptance of 63–68% in the 900–2500 nm wavelength range, and low noise voltage power spectral density (1.77 × 10⁻¹⁶ V²/Hz at 100 Hz under 0.3μA bias current). These results indicate that Sn-doped VO_x films are promising sensing materials for microbolometer applications. Full article

Ulcerative colitis (UC) is a complex chronic inflammatory bowel disease, and its pathogenesis is closely related to immune imbalance, intestinal flora disorder and intestinal barrier damage. In recent years, a novel form of programmed cell death, PANoptosis, has been confirmed to play a core role in the pathological process of UC. PANoptosis is driven by the PANoptosome complex, which is assembled by key molecules such as ZBP1, NLRP3, and RIPK1, which can simultaneously activate pyroptosis, apoptosis, and necroptosis. This not only leads to damage to the intestinal epithelial barrier, but it also aggravates the dysfunction of immune cells by releasing a large amount of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs), thus forming a vicious cycle of “cell death and inflammation”. Given the complexity of the PANoptosis signaling network, the efficacy of single-target inhibitors is limited. This review systematically expounds the mechanism of action of PANoptosis in UC and focuses on discussing multi-target combination treatment strategies represented by smart hydrogels loaded with multiple inhibitors (such as MCC950, GSK772, VX-765, disulfiram, etc.). This strategy achieves synergy through “vertical blocking” and “horizontal coverage”, and in combination with targeted delivery to the lesion, provides a highly promising innovative direction for fundamentally breaking the pathological cycle of UC. Future research should focus on the development of new inhibitors, the optimization of delivery systems, and in-depth clinical translation to promote this strategy as a breakthrough therapy for refractory UC. Full article

The rapid growth of 5G necessitates wireless receivers capable of high-speed, low-latency communication under complex channel conditions. Traditional receivers struggle with the performance–complexity trade-off in massive MIMO systems, where linear detectors underperform and maximum likelihood (ML) detection becomes computationally prohibitive. Deep-learning-based model-driven approaches have demonstrated a favorable balance between detection performance and computational cost. However, despite their algorithmic promise, the transition of these learned detectors into practical, real-time systems is critically hampered by inefficient hardware mapping, resulting in suboptimal throughput, high resource overhead, and limited scalability. To bridge this gap, this paper presents LwAMP-Net, a dedicated FPGA accelerator for a lightweight learned AMP detector. We propose a modular and multi-mode hardware architecture for LwAMP-Net, featuring an outer-product-based dataflow that mitigates pipeline stalls and multi-mode processing elements that adapt to diverse computation patterns. These innovations jointly enhance computational parallelism and resource utilization on the FPGA. Implemented on a Xilinx XC7VX690T FPGA for a 128 × 8 MIMO system with 16QAM, the accelerator achieves a 49.2% higher normalized throughput per iteration, an 85.4% improvement in throughput per LUT slice, and a 12.7% improvement in throughput per DSP compared to the state-of-the-art methods. This work provides a complete architectural solution for deploying high-performance, hardware-efficient learned MIMO detectors in real-world systems. Full article

Background/Objectives: LINAC-based single-isocenter (SIT) stereotactic radiosurgery (SRS) enables efficient treatment of multiple brain metastases but may compromise target conformity and increase low-dose brain exposure, particularly for spatially distributed lesions. Dual-isocenter techniques (DITs) may mitigate these limitations, while Gamma Knife (GK) remains the reference standard for high-selectivity radiosurgery. This study compares SIT- and DIT LINAC-based SRS with GK, focusing on target conformity and low-dose brain exposure under equivalent, zero-margin targeting assumptions. Methods: Twenty-eight patients with multiple brain metastases (197 lesions) were included in this retrospective planning study. For each patient, three plans were generated: a GK plan and LINAC-based SIT and DIT plans using automated dynamic conformal arc optimization (Elements Multiple Brain Metastases). All plans were generated using a zero-millimeter GTV-to-PTV margin strategy. For DIT, lesions were automatically clustered and assigned to two isocenters. Target coverage required ≥99% of each GTV to receive the prescription dose. Plan quality was evaluated using the Paddick Conformity Index (PCI) on a per-lesion basis and low-dose brain volumes (V12, V10, V5, V4, and V3 Gy) on a per-patient basis. Paired non-parametric tests and multivariable models were used to assess technique-related differences and associations with total target volume and lesion count. Results: GK achieved the highest median PCI (0.83), followed closely by DIT (0.77), while SIT plans demonstrated significantly lower conformity (0.73). Compared with GK, the median PCI difference was −0.05 for DIT and −0.08 for SIT. Conformity for DIT remained stable across lesion volumes and lesion counts, whereas GK conformity increased modestly with lesion size. Low-dose brain exposure differed significantly between techniques at all dose levels (p < 0.001). GK consistently yielded the lowest Vx volumes, SIT the highest, and DIT intermediate values. Relative to GK, SIT plans showed progressively larger increases in low-dose exposure at lower dose levels (mean ΔV3 ≈ +149 cc), while DIT reduced this low-dose spread (mean ΔV3 ≈ +117 cc). Total target volume was the dominant predictor of low-dose brain exposure across all techniques, with a smaller additional contribution from lesion count. Conclusions: DIT LINAC-based SRS significantly improves target conformity and reduces low-dose brain exposure compared with SIT delivery, achieving dosimetric performance that closely approximates Gamma Knife under equivalent zero-margin targeting assumptions. While Gamma Knife remains the reference standard for low-dose sparing, dual-isocenter planning represents a clinically robust and scalable alternative that effectively balances plan quality and treatment efficiency in patients with multiple brain metastases. Full article

The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex’s next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit. This review examines why promising targets and compounds, spanning NaV and TRP channels, often falter and outlines a path toward more reliable target selection and validation. I first summarize the pain pathway, from nociceptor transduction through spinal processing to cortical perception, emphasizing how inflammation and peripheral sensitization reshape excitability. Historically serendipitous, pain drug discovery now prioritizes molecular precision. Most approved chronic pain therapies act in the CNS and are limited by modest efficacy and adverse effects. Nociceptor-enriched targets (NaV1.7/1.8/1.9; TRP channels) remain attractive, yet redundancy among NaV subtypes and the necessity of blocking targets at the correct anatomical sites complicate translation. Human genetics and multi-omics provide a powerful, unbiased engine for target discovery. Rare high-impact variants offer strong causal hypotheses, while common polygenic contributions illuminate broader susceptibility. Large biobanks increasingly reveal a mismatch between legacy pain targets and genetically supported candidates across neuronal and non-neuronal cells. Human DRG transcriptomics highlight NaV channel redundancy. Human in vitro electrophysiology and PK/PD analyses show suzetrigine achieves ~90–95% NaV1.8 engagement, yet neurons can still fire unless additional channels are blocked. Species differences and drug distribution (including BBB/PNS penetration and P-gp efflux) critically influence efficacy; centrally accessible blockade (e.g., for NaV1.7 or TRPA1) may be necessary to achieve robust analgesia, challenging peripherally restricted strategies. Osteoarthritis illustrates how obesity-driven metabolic inflammation, synovial immune activation, subchondral bone remodeling, and specific nociceptor subtypes converge to drive mechanical pain. Multi-omic integration across diseased human tissues can pinpoint causal processes and cell types, enabling more selective and safer target choices. I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics. Full article

The dangerous potential of chemical warfare requires immediate development of new materials capable of detecting and efficiently adsorbing the toxic nerve agents VX and Novichok (A-234). The current adsorbents fail to achieve sufficient detection efficiency and specific binding capabilities. Our research, conducted through advanced computational modeling, predicts that carbon nanocones (CNCs) could function as effective molecular traps for these toxic substances. The research combines density functional theory (DFT) with molecular dynamics (MD) and Monte Carlo (MC) simulations to explain the basic principles of molecular trapping by these agents. The nanocone shape produces two distinct and selective binding areas. MC shows preferential trapping VX molecules within the internal concave surface (P1), while A-234 molecules are strongly adsorbed on the external convex surface (P2). Docking results complement this by showing that A-234 exhibits stronger single-molecule binding on the more open surface, consistent with its preference for P2. The nanocone captures molecules through van der Waals forces, which produce measurable electronic changes that modify its electronic signature. The research demonstrates that carbon nanocones represent a promising candidate material for the future development of chemical defense systems, potentially including sensitive detection systems and advanced filtration technologies. Full article

This retrospective planning study evaluated how arc number (AN) and control-point density (CP) affect VMAT quality, radiobiological endpoints, and workflow efficiency for locally advanced cervical cancer in a resource-conscious setting. Twenty-one patients (FIGO IIB–IIIB) were replanned in Monaco v5.51 (Monte Carlo) for 46 Gy using 6-MV beams (Elekta) with 1–4 coplanar arcs, and dual-arc plans were further analyzed using ≈250, 300, 350, and 400 CP per arc. Target coverage (D98/D95/V95/V98), conformity and homogeneity (CI, HI), and organs-at-risk (OARs) DVH metrics (including D2cc and Vx) were compared alongside monitor units, planning time, and delivery time. Increasing AN improved dose conformity and OAR sparing relative to single-arc plans, whereas increasing CP produced only modest dosimetric changes but substantially increased planning and treatment times. Radiobiological modeling using BED/EQD2 and EUD-based LKB NTCP indicated negligible bladder risk (<0.01%) and low rectal risk (<0.2%), but a higher small-bowel NTCP (~26%) driven by hotspot-sensitive descriptors; Niemierko TCP estimates were similar between leading dual-arc CP settings. Overall, a dual-arc strategy with ~250 CP per arc provided the most practical balance between plan quality, estimated biological effect, and deliverability. Full article

This study addresses the shortcomings of conventional orbital dynamics methods in order to determine initial orbits for short-arc segments of space objects. By integrating the temporal characteristics of observational data, we innovate a multi-scale Informer temporal modeling approach, proposing a high-precision algorithm for short-arc-segment initial orbit determination. The study analyses why Informer models yield differing results across various time windows. First, a radar observation target model accounting for multiple perturbations and a training data generator were established to produce training data for the Informer. Subsequently, an Informer network framework was designed, encompassing data preprocessing, network architecture, and training algorithms. Realistic scenarios and evaluation metrics were then configured for digital simulation. The model’s feasibility for low-Earth-orbit satellites was validated through digital simulation for different scenarios. The results in Scenario 1 demonstrate that compared to DNN methods, this approach achieves improvements in Root Mean Square Error (RMSE) across six dimensions in ECI—x, y, z, vx, vy, and vz—of 84.04%, 80.56%, 41.38%, 60.00%, 89.03%, and 64.17% respectively; compared to the best results of the Gibbs method across different windows, this approach improves the RMSE by 25%, 23%, and 46% in the three velocity dimensions (vx, vy, and vz) in the ECI frame, respectively. The results in Scenario 2 demonstrate the universality of this method. Furthermore, the reasons for differing outcomes across Informer models with varying time windows were analyzed, alongside the rationale for the integrated Informer model outperforming individual Informer models. Full article

The effectiveness of Machine Learning (ML)-based Network Intrusion Detection Systems (NIDS) is critically hampered by the scarcity of realistic and up-to-date malware traffic datasets. To address this gap, we present an automated platform for generating real-world malware traffic datasets. Our solution leverages a production-environment honeynet (T-Pot), deployed within a university network and segmented via a secure WireGuard VPN, to capture live attacks using high-interaction honeypots (Dionaea, Cowrie, ADBhoney). A fully automated pipeline handles traffic capture, transfer, filtering based on honeypot logs, and malware analysis (VirusTotal, VxAPI). The output is the IPN-UAN-23 dataset—a curated, labeled corpus of malicious network traffic. This platform functions as a vital automated security tool, providing the continuous stream of actionable intelligence required to develop and refine robust ML-based NIDS within a DevSecOps lifecycle. Full article

This paper presents a study on the development and optimisation of thin films of nickel-vanadium oxide (NiV_xO_y) deposited by DC reactive magnetron sputtering (RMS) controlled by P.E.M. (plasma emission monitoring). The hysteresis behaviour of the Ni emission signal as a function of oxygen incorporation was analysed using optical emission spectroscopy (OES), enabling the identification of critical working points along the hysteresis loop and their correlation with film growth mechanisms. Compared to the non-monotonic nature of the target discharge voltage signal, OES provided a simplified response for real-time process control. A set of coatings was deposited under various working pressures (0.6 and 2.0 Pa) and plasma emission monitoring (P.E.M.) conditions and was thoroughly characterised in terms of microstructure, composition, optical modulation, and electrochemical performance. Films deposited at high pressure and under 30% P.E.M. conditions showed an optimal balance between optical modulation (21%) and charge density (4 mC/cm²), which was attributed to the increased Ni³⁺ content and the surface cracks at low density. Full article

Pain is an unpleasant but essential sensory experience that serves as a protective mechanism, yet it can also manifest maladaptively in a wide range of pathological conditions. Current analgesic strategies rely heavily on opioid medications and non-steroidal anti-inflammatory drugs (NSAIDs); however, concerns regarding addiction, tolerance, and dose-limiting adverse effects highlight the urgent need for safer and more effective therapeutics. Voltage-gated sodium (Na_v) channels, which govern the initiation and propagation of action potentials, have emerged as promising targets for mechanism-based analgesic development. In particular, the Na_v1.7–Na_v1.9 subtypes have attracted substantial interest owing to their enrichment in the peripheral nervous system—despite broader expression elsewhere—and their central roles in nociception, offering the potential for non-addictive, subtype-selective pain modulation. This review summarizes the physiological roles of these channels in nociception, examines how disease-associated mutations shape pain phenotypes, and highlights recent advances in drug discovery targeting Na_v1.7 and Na_v1.8. The recent FDA approval of VX-548 (suzetrigine), a first-in-class and highly selective Na_v1.8 inhibitor, marks a major milestone that validates peripheral Na_v channels as clinically actionable targets for analgesia. We also discuss the remaining challenges and emerging opportunities in the pursuit of next-generation, mechanism-informed analgesics. Full article

In order to improve the wear resistance of titanium alloy and apply it to the high-speed train brake disc, TiNbZrV_x (x = 0, 0.2, 0.4, 0.6, 0.8) refractory medium-entropy alloy coatings were prepared on Ti-6Al-4V (TC4) substrate. The effect of V content on the microstructure, mechanical properties, and friction and wear properties of the coatings was studied. TiNbZrV_x coatings achieved good metallurgical bonding with the substrate, forming BCC and B2 phases and AlZr₃ intermetallic compound (IMC). From TiNbZr coating to TiNbZrV_0.8 coating, V promotes element segregation and new phase formation, which decreased the average grain size from 85.055 μm to 56.515 μm, increased the average hardness from 265.5 HV to 343.4 HV, and reduced the room temperature (RT) wear rate by 97.8%. However, the ductility of the coatings decreased from 15.7% to 5.8% because the grain boundary precipitates changed the dislocation arrangement, and the tensile fracture mode changed from ductile fracture to brittle fracture. Abrasive wear was the main wear mode at RT, and adhesive wear and oxidation wear were the main wear modes at elevated temperature. The COF at elevated temperature was lower than that at RT, because a large number of friction pair components were transferred to the coating surface at high temperature and were repeatedly rolled to form a dense film, which played a certain lubricating role. Full article

The current application of the production data exponentially weighted moving average (EWMA) model can detect PRRSV outbreaks earlier than that of processing fluid (PF) testing; however, its advantages have not been fully reported. This study aimed to analyze various production parameters, including abortion, off-feed, low appetite, and dead sows, on a daily basis following a PRRSV outbreak in an II-vx sow farm. The EWMA method was employed and the results were compared with the early detection of positive PF results. Differences in daily abnormal indicators across the three PRRSV status periods were analyzed. Additionally, this study evaluated the PRRSV detection rates in different sample types (AF, OS, and TBS) from aborted sows and compared the detection rates of different sample combinations using statistical tests. The 187-day study revealed that the first true positive (TP) alarm point for daily abortion sows occurred on day 107 and for off-feed sows on day 110. In contrast, the first RT-qPCR-positive result for PF was obtained on Day 122. The average values of daily abortions and off-feed sows in status I-A were significantly higher than those in status II-vx and I-B. Conversely, the average value of low appetite in status I-A was significantly lower than that in statuses II-vx and I-B. No significant differences were observed in the daily number of dead sows among the three groups. The RT-PCR detection rates varied significantly (p < 0.01) among the different sample types (AF, 43.04%; TBS, 65.82%; and OS, 74.68%), with amniotic fluid (AF) showing the lowest detection rate. Combining AF and oropharyngeal swabs (OS) samples yielded a higher detection rate than combining AF and TBS samples. Using the EWMA to monitor the daily number of aborted sows was effective for the early detection of PRRSV outbreaks. Full article