Search Results (689)

Crimean–Congo hemorrhagic fever virus (CCHFV) remains a major public health threat due to its high mortality rates and the absence of approved antiviral therapies. The viral ovarian tumor (OTU) protease is a critical virulence factor that suppresses host innate immunity through its deubiquitinase activity, making it an attractive therapeutic target. In this study, we employed a structure-guided approach to identify and validate novel small-molecule inhibitors targeting the non-catalytic Y89-W99 pocket of the OTU protease. Recombinant OTU protease was successfully expressed, purified, and refolded, yielding a soluble and enzymatically active protein. Cellular assays confirmed that the enzyme retains robust deubiquitinase activity, significantly reducing global ubiquitin conjugates in mammalian cells. In silico analysis of a putative DUB inhibitor library identified several candidate inhibitors with favorable binding interactions within the Y89-W99 pocket. Biochemical validation using a fluorometric Ub-AMC assay revealed that multiple small molecules strongly inhibit OTU activity, including OTUi-10 (~93% inhibition), OTUi-13 (~87%), OTUi-1 (~85%), OTUi-4 and OTUi-11 (~81%), and OTUi-9 (~76%). Additional moderate inhibitors included OTUi-12 (~67%), OTUi-19 and OTUi-21 (~66%), and OTUi-5 (~57%). In silico drug-likeness and toxicity profiling filtered the library to four fully compliant candidates, OTUi-4, OTUi-10, OTUi-11, and OTUi-12, all free of predicted toxicity alerts. These findings suggest that the Y89–W99 pocket may be a pharmacologically relevant site worthy of further investigation and identify OTUi-10, OTUi-4, and OTUi-11 as promising preliminary hit compounds. The results also provide initial insights that may guide future optimization and mechanistic studies of OTU protease inhibitors targeting CCHFV. Full article

Background/Objectives: Multilevel lumbar spinal stenosis (MLSS) is frequently encountered in patients undergoing surgery for lumbar spinal stenosis, yet the optimal extent of decompression remains debated. While multilevel decompression (MLD) may address all radiological stenotic levels, it may also increase surgical invasiveness and operative time. Minimally invasive endoscopic techniques such as unilateral biportal endoscopy (UBE) allow for targeted decompression and facilitate staged surgical strategies. The aim of this study was to evaluate the clinical outcomes of selective single-level decompression (SLD) using UBE in patients presenting with MLSS. Methods: This retrospective monocentric observational study included consecutive adult patients with MLSS who underwent decompression using UBE between December 2022 and July 2025. MLSS was defined as the presence of at least two lumbar levels with Schizas grade B or higher stenosis. Patients undergoing prior lumbar surgery or presenting with non-degenerative pathology were excluded. Patients underwent either SLD targeting the symptom-driving level or MLD, depending on the surgical strategy. Patient-reported outcomes included the Oswestry Disability Index (ODI), lumbar visual analog scale (LVAS), and radicular visual analog scale (RVAS). Results: Among 305 patients operated on for lumbar spinal stenosis, 83 (27%) presented with MLSS and were included in the study. Seventy-four patients (89%) underwent initial SLD and nine (11%) underwent MLD. Among patients treated with SLD, 9 (12%) required a second decompression during follow-up, whereas 65 patients (88%) achieved favorable outcomes without further surgery. Across the entire cohort, ODI, LVAS, and RVAS improved significantly after surgery. Operative time was significantly longer in the MLD group (122 ± 28.1 min vs. 58.1 ± 12.0 min; p < 0.001). These findings support the feasibility of a symptom-driven selective decompression strategy for MLSS using UBE. In our cohort, most patients experienced meaningful functional improvement after SLD without requiring additional surgery. Although a staged approach may necessitate secondary intervention in a minority of patients, selective decompression may help limit surgical extent in carefully selected patients while preserving favorable clinical outcomes. Conclusions: Selective SLD using UBE was associated with significant clinical improvement in most patients with MLSS while reducing operative time and surgical extent. A stepwise strategy targeting the dominant symptomatic level may represent a feasible minimally invasive approach for selected patients with MLSS. Prospective studies are needed to confirm these findings. Full article

High-resolution surface soil moisture (SM) is needed for local hydrological and agricultural applications, but reliable retrieval at 100 m remains challenging. Within this broader methodological context, radiometer-constrained SAR change detection remains a practical and interpretable option for high-resolution soil moisture retrieval. It uses SAR-derived temporal changes to describe fine-scale wetting and drying processes, while passive microwave observations provide volumetric moisture references. This study proposes an improved SMAP-anchored Sentinel-1 change-detection framework (ISSF) for 100 m SM mapping. ISSF addresses these limitations by fitting NDVI-binned upper-envelope samples with a nonlinear quadratic function to normalize the vegetation-dependent backscatter-change range and by using multi-year SMAP dry/wet quantiles to scale the normalized relative wetness into volumetric SM. ISSF was evaluated using in situ measurements, a near-concurrent airborne reference, SMAP-based products, and direct transfer to OzNet. In the Shandian River Basin, ISSF achieved R = 0.549 and ubRMSE = 0.062 m³ m⁻³ at the point scale. Relative to three benchmark change-detection methods, ISSF increased R by 11–53% and reduced ubRMSE by 7–15%. For the airborne-referenced event, ISSF showed R = 0.635 and ubRMSE = 0.027 m³ m⁻³. Under direct transfer to OzNet, ISSF achieved mean R = 0.55 and mean ubRMSE = 0.05 m³ m⁻³. These results indicate that ISSF provides a practical and interpretable approach for 100 m soil moisture mapping in semi-arid regions with sparse to moderate vegetation. Full article

This study evaluates the potential of L-band passive microwave data for monitoring soil moisture (SM) in boreal and temperate forests using SMAP and SMOS AM and PM overpasses. SMAP and SMOS Level 3 SM products were first assessed for spring and summer seasons. SMOS showed lower accuracy (r² = 0.04–0.24, ubRMSE = 0.09–0.13 m³/m³), while SMAP performed better (r² = 0.18–0.62, ubRMSE = 0.05–0.07 m³/m³) across sites and overpasses. Given the larger number of SMAP TB observations at a fixed incidence angle and greater temporal coverage over the study area, SMAP was selected for SM estimation using ML models. Feature importance analysis identified brightness temperature (TB) as the most influential variable, followed by vegetation water content (VWC), air and soil temperatures, and the microwave polarization difference index (MPDI). Soil and air temperatures were interchangeable during AM overpasses, whereas PM overpasses showed distinct differences, likely due to thermal absorption by dense vegetation. Using optimal features, SM was estimated with CatBoost, Gradient Boosting (GB), Random Forest (RF), and Principal Component Regression (PCR), using stratified shuffle split (SSS) and leave-one-year-out cross-validation (LOYOCV). In SSS, CatBoost achieved slightly higher accuracy than the other ensemble models (AM: r² = 0.73; PM: R² = 0.74), while PCR yielded substantially lower accuracy across both overpasses. LOYOCV showed closer rankings among models, with CatBoost ranking highest overall (r² = 0.58 for AM and 0.54 for PM). Results highlight the feasibility of improved SM estimation in forests using L-band TB, VWC, temperature variables, and MPDI. Full article

Objective: This study aimed to compare the clinical and radiological outcomes between microscopic and unilateral biportal endoscopic (UBE) posterior cervical foraminotomy (PCF). Methods: This study included 73 patients who underwent microscopic PCF (n = 40) or UBE PCF (n = 33) for single-level cervical foraminal disc herniation or stenosis between January 2018 and December 2021. Clinical outcomes were measured using the Visual Analog Scale (VAS) and Neck Disability Index (NDI). Radiologic outcomes were evaluated with cervical range of motion (ROM) using computed tomography and flexion-extension dynamic radiography. Results: The mean follow-up period for microscopic and UBE PCF was 33.0 ± 7.6 months and 29.9 ± 5.9 months, respectively. The postoperative neck VAS until postoperative 2 weeks was significantly lower in the UBE PCF group than in the microscopic PCF group (p < 0.05). The estimated blood loss and operative time were significantly lower in the UBE PCF group than in the microscopic PCF group, while the length of hospital stay was numerically shorter but did not reach statistical significance. The two groups had no significant difference in the NDI on the preoperative and postoperative 3 months. The recurrence occurred in 1 patient (2.5%) of the microscopic PCF group and 1 patient (3%) of the UBE PCF group. The revision surgery was performed in 2 patients (5%) of the microscopic PCF group and in 1 patient of the UBE PCF group. There were no significant differences in motion and instability between the two groups. Conclusions: Both microscopic and UBE PCF are effective and safe procedures for treating cervical radiculopathy due to cervical foraminal disc herniation or stenosis. The UBE approach may provide advantages mainly in early postoperative recovery, including lower early postoperative neck pain, while long-term clinical and radiologic outcomes appear comparable to those of microscopic PCF. Full article

In complex low-altitude environments, unmanned aerial vehicles (UAVs) require reliable positioning, yet Global Navigation Satellite System (GNSS) signals are vulnerable to occlusion and interference. Pseudolite-augmented cooperative localization, which combines ground base-station signals with inter-UAV relative observations, can complement GNSS in such environments. However, two practical issues remain in real-world deployment: UAV-to-base-station (U-B) and UAV-to-UAV (U-U) observations have markedly different error statistics that a unified noise adjustment cannot handle, and the conservative covariance estimates produced by Covariance Intersection (CI) fusion bias the innovation-based adaptive noise estimation in distributed architectures. To address these issues, this paper proposes a Distributed Group Covariance Compensation Adaptive Kalman Filter (DGCC-AKF) for collaborative enhancement of UAV regional localization. DGCC-AKF establishes a group adaptive mechanism that independently adjusts the noise covariance matrices of U-B and U-U observations, enabling observation-type-level adaptive weighting that suppresses anomalous U-B or U-U measurements at the group level. In addition, a bounded covariance compensation factor is incorporated to alleviate the CI-induced conservatism in the adaptive noise estimation. The proposed method is evaluated on a 2800 km² semi-physical testbed based on the Ground-based High-precision Local Positioning System (GH-LPS) pseudolite network using measured U-B observations and high-dynamic (>300 km/h) flight trajectories collected from a fixed-wing platform across three independent flight sessions. Results demonstrate that under observation fault periods, the proposed method improves 3D positioning accuracy by up to about 75% over single-UAV extended Kalman filter (EKF). Compared with two advanced algorithms in this field, variational Bayesian adaptive Kalman filter (VBAKF) and maximum correntropy criterion Kalman filter (MCC-EKF), it is the only scheme that remains accurate and stable across all UAVs and fault types. The framework provides a practical step toward field deployment for resilient multi-UAV cooperative navigation in pseudolite-augmented GNSS-denied regions. Full article

Soil moisture (SM) is a key variable for assessing plant water availability, especially in rain-fed systems where imbalances strongly affect crop development. Satellite missions such as SMAP provide global SM estimates, though representing vertical SM variability remains challenging. This study evaluates the performance of SMAP Level 4 Global 3-hourly 9 km grid EASE-Grid Surface and Root-Zone Soil Moisture Geophysical Data (SPL4SMGP, version 7 and the new and scarcely evaluated version 8) using field observations from the Argentine Pampas, a region dominated by Typic Argiudolls soils (~16 million ha). The analysis covered normal-wet and dry conditions across several crop seasons. Surface (SSM, ~5 cm) and root zone (RZSM, 0–100 cm) soil moisture were compared against field data using Pearson’s correlation (r), bias, and unbiased root mean square deviation (ubRMSD). Both SSM and RZSM achieved ubRMSD values close to the SMAP accuracy target (≈0.04 m³/m³). SSM correlated moderately with observations (r = 0.57–0.72) and showed a consistent negative bias (−0.08 ± 0.05 m³/m³). In contrast, RZSM exhibited low sensitivity to soil profile variability and a narrow dynamic range. Version 8 showed similar performance to version 7, with a tendency toward overestimation, mainly during dry periods. Overall, SPL4SMGP products effectively capture SSM dynamics but show limited skill in representing root zone variability in Typic Argiudolls. Full article

L1 transfer is well-attested in SLA; negative transfer is common when learners encounter a typologically distinct language. English-speaking learners often struggle with Japanese passives, which differ significantly from English passives both conceptually and grammatically. While English passives primarily defocus the agent, Japanese passives serve multiple semantic and discourse functions, often maintaining a focus on (and empathy toward) the experiencer. This small study examines how conceptual understandings drawn from usage-based (UB) analyses influence the acquisition of Japanese passives. Using corpus studies and acquisition research as a foundation, we developed concept-based language instruction (C-BLI) integrating UB-focused concepts. Our analysis of students’ oral languaging, gesture, and story-writing data from an immediate post-test and two delayed (3 weeks and 6 months post-instruction) post-tests show individual differences and demonstrate how a UB-based C-BLI approach facilitated developmental processes in Japanese over time; students improved their grasp of concepts taught via multi-modal materials, including visual materializations of concepts and ocean wave gestures. Conceptual and linguistic development were evidenced via oral languaging and story-writing. The most frequently used passive verb was iu ‘say,’ which has been found to be often passivized in L1 speakers’ production and previous SLA research. Findings contribute to broader discussions of how conceptual restructuring may affect L2 acquisition of complex grammatical constructions. Full article

Endoscopic spine surgery (ESS)—including full-endoscopic transforaminal and interlaminar techniques, and unilateral biportal endoscopy (UBE)—offers patients smaller incisions, preserved paraspinal muscle, and faster recovery. Because the working corridor is narrow, intraoperative fluoroscopy plays a larger role than in open or microscopic approaches, making radiation exposure worthy of attention for both patients and surgeons. This narrative review aims to be a practical resource for the endoscopic spine surgeon. We synthesize the available literature on typical radiation doses across the main ESS techniques, compare them with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open alternatives, review the factors that drive exposure, and walk through the full menu of dose-optimization options—from simple measures such as collimation, pulsed fluoroscopy, and leaded eyewear, through navigation platforms, to robotic guidance. A consistent practical observation is that the simplest, least expensive interventions often deliver the largest dose reductions. Capital-intensive technologies add real value, particularly for endoscopic interbody fusion, and work best alongside rather than in place of these basics. With routine dosimetry and straightforward as-low-as-reasonably-achievable (ALARA) practices, surgeons can continue to build on the already favourable profile of ESS while keeping radiation exposure low. Conclusions are tempered by the largely retrospective and heterogeneous nature of the underlying evidence. Full article

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) has evolved sophisticated immune-evasion strategies to establish a productive infection in the host, primarily by counteracting the innate antiviral response. Here, we demonstrate for the first time that the PRRSV non-structural protein NSP8 suppresses NF-κB-dependent antiviral signalling by hijacking the host ubiquitin-conjugating enzyme UBE2K and inducing the degradation of IKKα, a pivotal kinase in the NF-κB pathway. PRRSV infection led to significant upregulation of host UBE2K, which in turn facilitated viral replication. Mechanistically, we found that NSP8 interacts directly with IKKα, triggering its degradation by the proteasome. Furthermore, we revealed that this process was facilitated by the host protein UBE2K, which acted as a crucial cofactor by directly interacting with NSP8 and thereby enhancing its activity against IKKα. This disruption blocked the activation of the NF-κB pathway and suppressed the expression of downstream antiviral factors, such as TNF-α, IL-6 and IFN-β, ultimately facilitating PRRSV replication. All of these findings showed that NSP8 is an important part of the process by which the host NF-κB pathway is blocked by viruses. This is a new way in which PRRSV avoids the immune system. Full article

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

Background: Far-Out Syndrome at the lumbosacral junction is caused by extraforaminal compression of the L5 nerve root, frequently involving the lumbosacral ligament (LSL). Conventional piecemeal resection of the LSL may increase the risk of postoperative dysesthesia due to repeated manipulation near the L5 dorsal root ganglion (DRG). This study introduces a novel unilateral biportal endoscopic (UBE) technique for en bloc resection of the LSL. Methods: The technique is based on an osteoclastic release strategy in which the bony attachments of the LSL, including the inferior aspect of the L5 transverse process and the sacral ala, are drilled and released before addressing the ligament itself. This maneuver elevates the LSL away from the underlying L5 DRG and achieves en bloc removal under direct endoscopic visualization. Results: En bloc resection may improve visualization within the narrow extraforaminal corridor and may reduce direct mechanical manipulation of the L5 DRG, which could potentially translate into reduced postoperative dysesthesia. The presented technique enabled effective decompression without repeated instrument insertion beneath the ligament. Conclusions: UBE-assisted en bloc resection of the LSL is a feasible and potentially neuroprotective technique for treating lumbosacral extraforaminal lesions. Full article

Background: Tumor-associated macrophages (TAMs) are key components of the hepatocellular carcinoma (HCC) microenvironment, but their spatial heterogeneity remains incompletely characterized. We aimed to assess the biological and prognostic relevance of a BAG3-associated TAM program in HCC. Methods: Public single-cell RNA sequencing (scRNA-seq) datasets were analyzed to characterize TAM heterogeneity, and an integrated validation scRNA-seq dataset was used to assess reproducibility. Spatial transcriptomics was used to provide spatial context in a small treatment-exposed cohort. Pseudotime, regulatory network, and cell–cell communication analyses were performed to characterize state transitions and microenvironmental interactions. Survival modeling evaluated the prognostic relevance of the BAG3-associated program. Results: Five TAM subsets were identified, including MARCO⁺, MT⁺ RTM−, MMP9⁺, UBE2C⁺, and BAG3⁺ TAMs. Among them, BAG3⁺ TAMs, a less well-characterized subset, exhibited coordinated stress-adaptive, proteostasis-related, and matrix-remodeling programs that were reproduced in the validation dataset. Pseudotime analysis suggested a continuum of TAM states, with BAG3⁺ TAM stress-remodeling features enriched toward late pseudotime. Communication analysis centered on BAG3⁺ TAMs suggested crosstalk between inflammatory stress cues and angiogenic, stromal-remodeling, and immunomodulatory programs; this pattern was primarily supported by HBV-derived samples and recurrently involved the MIF–CD74 axis. Spatial mapping further supported BAG3⁺ TAM-enriched niches with elevated AP-1, EGR1, and NFKB1 activity. A BAG3-associated risk score derived from a 10-gene signature remained an independent prognostic factor for overall survival after clinical adjustment. Conclusions: These findings characterize a BAG3-associated TAM program with spatial, immunoregulatory, and prognostic relevance in HCC, and support its further evaluation in biomarker and mechanistic studies. Full article

The uterine microbiome plays a critical role in maintaining pH balance, modulating the immune system, and influencing fertility, especially in artificial breeding contexts. This study examined the impact of uterine microbiota on pregnancy success in cows following embryo transfer (ET), using Illumina 16S rRNA gene sequencing of the V4 hypervariable region of samples collected from the uterine horn (UH) and the uterine body (UB) of cows during the estrous cycle preceding synchronization for ET in the Amazon region. Microbiomes from the uterine horn (UH) and the uterine body (UB) were analyzed before embryo transfer. Cows that became pregnant (UH-P and UB-P) and those that did not (UH-NP and UB-NP) were compared. Fifteen cows were grouped as follows: UB-P (three), UB-NP (five), UH-P (three), and UH-NP (four). Linear discriminant analysis effect size and heat tree analyses identified Sphingobacterium and Stenotrophomonas spp. as significantly enriched in the UB-P and UH-NP groups, respectively. Additionally, non-pregnant cows exhibited more distinctive genera than pregnant ones. These findings suggest that cows achieving pregnancy have lower microbial diversity and fewer potentially pathogenic genera. This study contributes to the emerging field of pre-pregnancy uterine microbiome research in cattle, offering evidence that microbial composition may influence reproductive success, and highlights specific taxa as potential biomarkers for pregnancy outcomes following embryo transfer. Full article

Plant polysaccharides can exert immunomodulatory activities. In this study we provided chemical characterization of wheat cell culture-derived polysaccharides (WCCPS) and assessed their capacity to modulate inflammatory responses in mouse macrophages. The total sample (T-010) contained arabinogalactans, arabinans, glucans and xyloglucans. Fractionation by anion-exchange chromatography rendered a bound acidic fraction (B-010) and an unbound neutral fraction (UB-010). The B-010 fraction was enriched in arabinogalactans and arabinans, with some galactans, homogalacturonans, and arabinoxylans. The neutral UB-010 fraction was composed of glucans and xyloglucans. None of the WCCPS preparations triggered cytokine production on their own, but each potentiated different macrophage responses to bacterial lipopolysaccharide (LPS). The total WCCPS in T-010 increased LPS-induced tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 secretion, whereas the acidic arabinogalactan-rich fraction B-010 boosted IL-6 release and selectively upregulated nitric oxide synthase 2 (Nos2) and cholesterol 25-hydroxylase (Ch25h) expression in response to LPS. In contrast, the neutral UB-010 fraction enhanced IL-6 levels and induced Nos2 expression without altering Ch25h expression. These results suggest that WCCPS can modulate distinct aspects of the inflammatory response, with their effects shaped by their composition and structural features. Future research will focus on elucidating the molecular mechanisms underlying the immunomodulatory activity of WCCPS. Full article