Search Results (412)

The green transition in agriculture is a key issue for achieving sustainable development. Based on panel data from 30 Chinese provinces covering the period from 2011 to 2022, this paper examines the relationship between environmental enforcement and agricultural green total factor productivity (AGTFP), with a focus on analyzing the moderating effects of land transfer and agricultural insurance, as well as their synergistic threshold characteristics. The study employs two-way fixed-effects models, moderating effect models, and Hansen threshold regression methods for empirical analysis. The baseline regression results show a significant positive association between environmental enforcement and AGTFP. This conclusion remains robust after various tests, including truncation, replacement of core explanatory variables, difference GMM, and instrumental variables. The decomposition test shows that this positive correlation is mainly reflected through the channel of technological progress, rather than the improvement in technical efficiency. Heterogeneity analysis indicates that the positive association is more pronounced in regions with high GDP, strong law enforcement capacity, and in northern regions. Moderation analysis reveals that both the land transfer rate and insurance depth positively moderate the relationship between environmental enforcement and AGTFP, and the two exhibit a synergistic effect. However, this synergistic effect exhibits nonlinear characteristics and may weaken or even reverse at extreme value intervals. A threshold model further reveals an asymmetric complementary relationship between the two institutional conditions. The moderating effect of land transfer is activated only after insurance depth crosses a threshold value, while the moderating effect of insurance depth is most effective during the small-scale farming stage. These findings suggest that environmental regulation policies should be advanced in coordination with land transfer and agricultural insurance systems, with a focus on institutional alignment and coordination. Full article

Friction at the cold rolling interface is affected jointly by the surface roughness, lubrication state, local pressure, and relative sliding. A constant friction coefficient is therefore insufficient to describe its non-uniform distribution along the contact arc. Accordingly, this study proposes a macro–micro two-scale mixed-lubrication and dynamic friction model based on the measured roll roughness. First, the measured roll roughness profile was represented within a finite effective scale interval by a scaled and truncated Weierstrass–Mandelbrot (W–M) function. The parameters D and G were obtained as finite-scale W–M roughness parameters and were introduced into a mixed-lubrication load-sharing model to calculate the local mixed-lubrication friction coefficient. The pressure distribution along the contact arc was calculated using the Karman equation, and the local macroscopic pressure was mapped to a representative microscopic contact load. Finally, the mixed-lubrication friction coefficient was used to calibrate the dynamic friction factor separately in the forward-slip and backward-slip zones, and the friction stress distribution along the contact arc was calculated. For the selected effective scale interval and preprocessing procedure, the fitted W–M roughness parameters were D = 1.528 and G = 9.15 × 10⁻⁸ m. The W–M parameter D had a more significant influence on the mixed-lubrication friction coefficient and load-sharing behavior than the scale parameter G. Increasing the rolling speed strengthened the oil-film load-carrying effect and reduced the equivalent interfacial friction coefficient. The friction stress was positive in the backward-slip zone and negative in the forward-slip zone, with a direction reversal near the neutral point. Field forward-slip inversion showed that both the simulated and measured equivalent friction coefficients decreased with increasing rolling speed, with a difference of approximately 0.009~0.017. The proposed model can capture the main trend of cold rolling interfacial friction with variations in the rolling speed and contact state. Full article

Background: Pheochromocytomas and paragangliomas (PPGLs) can be metastatic in up to 30% of cases. To assess this risk, scoring systems like PASS and GAPP were developed, yet it is unclear whether these scores correlate with somatic genetic alterations. Methods: A retrospective pilot study. Twenty patients with sporadic pheochromocytoma, stratified into high- and low-risk groups based on GAPP and PASS scores. Somatic variant burden, derived from whole-exome sequencing, and clinical variables were compared between groups. Results: Six patients (30.0%) comprised the high-risk group; all had PASS scores >4 and GAPP scores indicating moderately differentiated PPGLs. Compared with the low-risk group, the high-risk group had larger tumors (4.7 vs. 3.4 cm, p = 0.03) and non-significant association with higher diastolic blood pressure (90 vs. 79 mmHg, p = 0.09), normetanephrine (8.5 vs. 2.3 X upper limit of normal [ULN], p = 0.08), and metanephrine (22.9 vs. 9.25 X ULN, p = 0.09) levels. The high-risk group also demonstrated a higher somatic variant burden, particularly for truncating variants (32 vs. 26, p = 0.04). As a continuous variable, only the GAPP score, not PASS score, showed a significant positive correlation with variant burden, observed for both non-missense (r = 0.57, p = 0.009) and frameshift (r = 0.47, p = 0.04) variants. Conclusions: Higher pathological severity scores are associated with increased rates of severe molecular somatic variants. The stronger link between GAPP score and genetic alteration rates suggests it may better reflect the genomic complexity of sporadic PPGLs. Full article

Amyotrophic lateral sclerosis (ALS) remains an intractable motor neuron (MN) disease with a growing patient population and few effective treatments. Here, we review how extracellular phosphoglycerate kinase 1 (ePgk1) improves neurite outgrowth of MNs (NOMN) and axonal growth, both in vitro and in vivo. Our group first elucidated a novel non-canonical function of ePgk1 as a cross-tissue mediator between nerve and muscle tissues. We then discovered that neural membranous Enolase 2 (Eno2) serves as a receptor of ligand ePgk1 and that ePgk1-Eno2 interaction suppresses the Rac1-GTP/p-Pak1-T423/p-P38-T180/pMK2-T334/p-Limk1-S323 axis, reducing p-Cofilin and promoting NOMN and axonal growth, finally suggesting that the 419th aspartic acid residue of Eno2 mediates this interaction. In a crucial preclinical step, we truncated two short 16-amino-acid derivatives from Pgk1, FD-1/-2, each mediating neuroprotection comparable to that of full-length 417-amino-acid Pgk1 in ALS animal models, in terms of improvements of innervated neuromuscular junction, MN cell bodies, motor performance, and endpoint prolongation. In this context, we also discuss the opposite function driven by Eno1-plasminogen interaction and by Eno2-ePgk1 interaction; the latter results in unfavorable for tumorigenesis. Unlike intracellular Pgk1 roles, ePgk1 is an extracellular factor with anti-angiogenic properties, further positioning ePgk1 and its FD-1/-2 as promising protein/peptide drugs for ALS treatment. Full article

Based on their domain organisation, four proteins from the protist Dictyostelium discoideum have been assigned to the IQGAP family of scaffold proteins. Although these proteins are shorter than animal IQGAPs, their involvement in the regulation of the actin cytoskeleton in cell motility, macroendocytosis, cytokinesis, and adhesion appears to be broadly conserved between these evolutionarily distant organisms. In this article, we show that the putative three-dimensional structure of Dictyostelium IQGAP-related proteins, as predicted by AlphaFold 3, closely corresponds to the C-terminal half of human IQGAP1, thus supporting their common origin. IqgD is the largest IQGAP-related protein in Dictyostelium, with an overall domain organisation similar to human IQGAPs. IqgD is localised in the cell cortex, interacts with F-actin and Rac1 GTPases, and primarily supports cell adhesion to the underlying surface and cell growth on bacterial lawns. DGAP1 and GAPA are truncated proteins that have retained a 700-residue-long C-terminal region of homology compared to their animal relatives. They play important, yet opposite, roles in regulating contractile cortical assemblies comprising F-actin, myosin II, and the actin-bundling proteins cortexillins, which are especially important for cytokinesis and epithelial morphogenesis. Finally, IqgC, although structurally resembling other IQGAPs, turns out to be more closely related to GAP1 proteins from fungi. This multifaceted protein carries RasGAP activity, interacts with several other small GTPases, and positively regulates macroendocytosis and cell–substratum adhesion. Full article

CXCL8, a pro-inflammatory chemokine, which can be induced by TNF-α or IL-1, is responsible for the recruitment and activation of neutrophils. Chemokines interact with glycosaminoglycans on endothelial cells and are thus protected from degradation and sequestration, holding them in an optimal position for recruiting immune cells. Inhibiting the interaction of chemokines with their glycosaminoglycan co-receptors represents an attractive approach for the treatment of chemokine-mediated diseases. Two polyketide-pyrone compounds, PA501 and PA502 were synthesized, which bind to CXCL8 with affinities higher than the natural glycosaminoglycan ligand heparan sulfate, and in a similar range as heparin. Significant structural changes were induced in the chemokine by interacting with the two compounds, as expressed in fluorescence and far-UV CD experiments. In filter binding assays, both compounds were found to displace heparan sulfate efficiently from CXCL8, with PA501 displaying the highest competition efficacy. Using a C-terminally truncated form of the chemokine, CXCL81-58, which lacks the main glycosaminoglycan-binding α-helical domain, the two compounds are suggested to use—to a varying degree—different binding sites on the protein, which have also been proposed for the natural heparan sulfate ligand. In a transmigration assay, PA501 and PA502 exhibited dose-dependent modulation of CXCL8-induced neutrophil mobilization and migration. The compounds PA501 and PA502 may thus be regarded as early novel lead compounds in the quest for anti-inflammatory, chemokine-targeting drugs. Full article

Existing single-image super-resolution methods for remote sensing images suffer from insufficient global receptive fields, weak high-frequency texture recovery, and excessive computational complexity. To address these issues, this paper proposes DFSMamba, a novel spatial–frequency collaborative modeling framework. First, Semantic Continuous-Sparse Attention enhances semantic perception through dynamic chunking and sparse connections while maintaining linear complexity, effectively alleviating the semantic truncation problem caused by fixed window partitioning. Second, the Adaptive State-Space Module employs parallel forward and backward state-space model branches to achieve bidirectional long-range dependency modeling and introduces an activation-guided feature fusion mechanism to adaptively enhance semantically relevant regions. Third, the Discrete Fourier Transform Module maps images to the frequency domain, establishes a global lossless receptive field, and explicitly enhances high-frequency details, compensating for the insufficient utilization of frequency-domain information in pure spatial-domain methods. Experiments on five public datasets demonstrate that DFSMamba outperforms mainstream CNN, Transformer, and Mamba-based methods across ×2 to ×4 scales. On the AID×3 task, it achieves a PSNR of 31.48 dB, exceeding MambaIRv2 by 1.07 dB. Ablation studies verify the positive synergistic effect of the three modules, with the full configuration achieving a PSNR improvement of 0.85 dB over the single-module setup. Fine-grained category, multi-scale input, and loss function experiments further confirm its robustness and generalization capability, particularly in edge and texture detail reconstruction. Full article

Background and Objectives: Among CNS malignancies arising in infancy, ATRT stands out as the most frequently diagnosed in children younger than six months. Disruption of the SMARCB1 gene underlies the overwhelming majority of cases. Progress toward effective treatment has been hampered by two persistent challenges. Current mouse models, while informative, fall short of reproducing the full clinical and biological picture of human ATRT, and their ability to predict therapeutic outcomes in patients remains uncertain. Compounding this, the rarity of the disease makes it difficult to assemble patient cohorts of sufficient size for meaningful clinical trials. At the molecular level, germline loss of SMARCB1 exons 4 and 5 has emerged as a particularly penetrant predisposing event, with affected individuals presenting at an earlier age than those harboring other mutation types. The porcine SMARCB1 gene offers a compelling basis for translational modeling as its protein product is identical to the human ortholog at every amino acid position across isoforms, a degree of conservation that exceeds what is seen in the mouse. Methods: Thus, we hypothesized that germline deletion of exons 4 and 5 would predispose heterozygote swine to ATRT development. In this manuscript, we describe the creation of an ATRT porcine model through a CRISPR/Cas9 mediated gene-editing approach. Results: 15 piglets were produced, two of which had confirmed SMARCB1 targeted excisions. However, none developed tumors. To induce further tumorigenicity, one pig with confirmed exons 4 and 5 excision was crossed with a pig with TP53 exon 2 truncation. In total, 11 piglets were born, of which one contained the original excision without a TP53 mutation. This piglet developed a spinal mass at the T1 level. Conclusion: To our knowledge, this is the first ATRT porcine model ever developed and provides proof-of-concept feasibility for large animal modeling of SMARCB1-deficient rhabdoid tumors. These findings support the continued development of porcine RTPS-1 models toward preclinical application. Full article

Background and Clinical Significance: SWI/SNF chromatin remodeling complex-deficient malignancies constitute an aggressive group of undifferentiated tumors defined by inactivation of core subunits including SMARCA4 (BRG1) or SMARCB1 (INI1). In the head and neck, these tumors predominate in the sinonasal tract; oral cavity presentations are exceedingly rare, with reported cases predominantly representing metastatic disease. Peri-implant gingival masses in clinical practice are overwhelmingly reactive, but their occasional malignant nature mandates timely biopsy and thorough pathologic workup. We report the first comprehensively molecularly characterized case of a peri-implant gingival SWI/SNF complex-deficient tumor with confirmed biallelic SMARCA4 inactivation. Case Presentation: A 75-year-old man presented with a one-week history of a rapidly enlarging exophytic erythematous peri-implant gingival mass in the right posterior mandible (region 44–47). Incisional biopsy demonstrated an undifferentiated high-grade tumor with epithelioid, plasmablastoid, and focally rhabdoid morphology with necrosis. Immunohistochemistry showed complete loss of BRG1 (SMARCA4) with retained INI1 (SMARCB1), EMA positivity, Ki-67 of approximately 100%, and negativity across all lineage-specific markers (hematolymphoid, epithelial, melanocytic, endothelial, squamous). Comprehensive next-generation sequencing (Oncomine Comprehensive Assay Plus) confirmed biallelic SMARCA4 inactivation via a truncating nonsense mutation (p.Trp1346Ter; VAF 73.85%) combined with copy number loss, establishing the molecular mechanism underlying BRG1 protein loss. Co-occurring alterations included homozygous CDKN2A/CDKN2B deletion, MTAP loss (9p21.3), clonal TP53 and KEAP1 mutations, and intermediate–high tumor mutational burden (13.3 mutations/Mb) with microsatellite stability. The patient initiated carboplatin–paclitaxel and achieved a partial response at one month with further shrinkage by four months. This case illustrates a rare oral cavity manifestation of SWI/SNF complex deficiency arising in a peri-implant location, with a diagnostic workup that required integration of immunohistochemistry and molecular profiling for definitive characterization. The MTAP deletion co-occurring with homozygous CDKN2A/B loss identifies a potentially actionable synthetic lethal vulnerability to MAT2A and PRMT5 inhibitors currently under clinical investigation. An occult primary site could not be fully excluded due to absence of a dedicated staging workup. Conclusions: Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class. Full article

Systematic spatiotemporal records of the International Roughness Index (IRI) for South American Andean rural corridors remain scarce, and available deterioration models, calibrated mostly under temperate or arid conditions, transfer to Andean tropical contexts with considerable uncertainty. This exploratory baseline study addresses that gap on the 36.50 km Loja–Catamayo corridor in southern Ecuador under three a priori constraints: eleven IRI campaigns, one meteorological station whose record starts ten months after the first campaign, and a traffic series anchored on a base-year count conducted ten years before the monitoring window. The campaigns, conducted with a Roughometer III between 2023 and 2025, were integrated with daily climate records from the INAMHI Villonaco station, a yearly AADT series cross-validated against a contemporary classified count, and the as-designed pavement structural section. The non-parametric framework combined the Mann–Kendall trend test with a 25-cell Antecedent Moisture Index sensitivity grid, AASHTO 1993 Structural Number computation, Sayers-derived Present Serviceability Index, and linear, exponential, and Gompertz modelling. The results revealed a statistically significant positive monotonic trend robust to post-peak truncation (H₁ supported) and no detectable short-term climate–IRI association under any of the twenty-five AMI specifications tested (H₂ not supported at the available resolution). The corridor exhibits a structural reserve exceeding projected cumulative ESAL demand by an order of magnitude yet reached the functional intervention threshold at one-third of its design service life. This decoupling between structural adequacy and functional decay locates the dominant deterioration mechanism in the bituminous surface and the drainage regime, supporting surface preservation interventions as the operationally appropriate response. Full article

Subsea Christmas trees are often deployed in turbid coastal waters or seabed environments. During manipulator operations on Christmas tree panels, conventional optical servoing is severely limited by rapid electromagnetic attenuation and strong scattering from suspended particles, resulting in reduced visibility. Forward-looking sonar (FLS) provides stable imaging, but its unique imaging geometry and low resolution make direct 6D pose estimation challenging. To address this issue, this paper proposes a 6D object pose estimation method for FLS images, in which conventional optical control-point-based pose estimation is restructured to resolve the mismatch between optical-centric network assumptions and acoustic imaging characteristics, and is further integrated with acoustic projection-based pose inversion. First, to address the limited diversity of target appearances and the scarcity of training data, we construct an FLS imaging model based on primary truncation for image simulation, providing data for model pretraining. Second, a multi-task acoustic control-point detection network, Acoustic-Yolo6D, is designed to mitigate localization degradation caused by heavy speckle noise, low boundary contrast, and resolution variations associated with polar-coordinate imaging, through heatmap regression, auxiliary object segmentation, and explicit range-bearing positional encoding. An Acoustic-n-Point (AnP) model is then used to recover the target 6D pose. Finally, simulation and water-tank experiments on the socket target verify the feasibility and robustness of the proposed method under limited-data conditions. The method achieves a 3.1 cm mean translation error, a 10.88° mean orientation error, and 52 FPS in real underwater acoustic environments. Full article

Objectives: Membrane-enveloped virus-like particles (VLPs) constitute a versatile vaccine platform allowing for the display of heterologous viral surface antigens. The density of displayed antigens is paramount for the efficient elicitation of a strong cellular and humoral immune response. SARS-CoV-2 spike protein variants with engineered cytoplasmic tails (CTs) were generated to enhance decoration efficiency on the surface of VLPs formed by the HIV core protein Gag. These HIV (SARS-CoV-2) chimeric particles serve as a vaccine component prototype. Methods: Spike variants were first analyzed for cellular and surface expression as well as incorporation into extracellular vesicles (EVs) and VLPs using flow cytometric analysis and Western blot analysis. Receptor binding, fusogenicity, i.e., mediating the fusion of spike-positive with receptor-containing membranes, and the proteins’ potential to mediate lentiviral vector gene transduction into susceptible target cells was examined by employing syncytia-formation assays and vector titration experiments. The display of a neutralization-sensitive epitope was examined utilizing immuno-precipitation using a neutralizing antibody. Results: All four variants were shown to be cell-surface expressed, to recruit the cognate receptor, to mediate membrane fusion and cell entry of lentiviral pseudotype vector particles and to decorate VLPs and EVs. However, the spike variant encompassing a truncated CT derived from the gibbon ape leukemia virus (GaLV) transmembrane (TM) envelope protein was most efficiently incorporated into HIV Gag-formed VLPs. All variants exposed a neutralization-sensitive epitope in the receptor binding domain. Conclusions: Engineering of the CTs of viral surface antigens can enhance VLP decoration, while required functionality of the ecto-domain such as receptor recognition, fusogenicity and neutralization-sensitive epitope presentation are not abrogated. This indicates the preservation of the structural integrity of the antigen required to elicit a neutralizing humoral immunity upon vaccination. The identified truncated CT of GaLV TM may be of utility to improve the incorporation of other viral surface antigens into a variety of membrane-enveloped VLPs derived from a range of different parental viruses. Full article

Nonlinear state estimation plays an important role in aerospace sensing applications, where estimation accuracy must be balanced against computational efficiency. In this paper, a sparse-grid Gaussian kernel quadrature Kalman filter (SGKQKF) is proposed for discrete-time nonlinear state estimation by combining Gaussian kernel quadrature (GKQ) weighting with a Smolyak sparse-grid construction. The univariate GKQ rule is constructed on scaled Gauss–Hermite nodes through a truncated Mercer eigendecomposition of the Gaussian kernel and is then extended to multivariate cases via the Smolyak construction to alleviate the curse of dimensionality associated with tensor-product rules. The proposed method is positioned within the established sparse-grid filtering framework, with the specific contribution of integrating kernel-adapted quadrature weights into sparse-grid structures for discrete-time nonlinear Gaussian filtering. For fixed nodes, the exact kernel-quadrature weights minimize the worst-case integration error in the reproducing kernel Hilbert space (RKHS) induced by the Gaussian kernel, whereas the closed-form weights used in the implementation are interpreted as a Mercer-based practical approximation to this exact rule, with the approximation error characterized through the Mercer spectral-tail expression of the Gaussian kernel. For sparse grids, where a closed-form RKHS optimality result is not available, numerical maximum mean discrepancy (MMD) evaluations are presented as empirical diagnostics in the tested configurations. Numerical experiments demonstrate that the proposed filter achieves a favorable accuracy–efficiency trade-off compared with conventional deterministic Gaussian filters. Full article

Background/Objectives: Merkel cell polyomavirus (MCPyV) is a ubiquitous virus strictly associated with Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. MCPyV oncogenic properties are associated mainly with early protein expression, integration, and LT truncation. MCPyV can also interact with DNA Damage Response (DDR) mechanisms, contributing to oncogenesis and tumor progression. In this work, we investigated the correlation between MCPyV and MCC and evaluated the mRNA expression profiles of DDR genes in virus-positive and -negative tumors. Methods: A total of 19 formalin-fixed paraffin-embedded biopsies were acquired from patients diagnosed with MCC. After DNA and RNA extraction, the DNA was used for MCPyV detection via qPCR and for sequencing analysis of the early, late, and non-coding control viral regions and the extracted RNA was used for MCPyV transcripts, miRNA detection and for the evaluation of several DDR genes expression such as ATM, ATR, CHK1, CHK2, H2AX, Rad51, p53, and p21, in MCPyV-positive and -negative samples via reverse transcription, PCR, and qPCR. Results: MCPyV presence was detected in 11/19 samples, all characterized by viral integration, LT truncation, and early region expression only. Furthermore, higher mRNA levels of DDR genes were observed in MCPyV-positive tumors compared with the negative ones. Conclusions: Our findings support the role of MCPyV in MCC formation and suggest its involvement in the transcriptional regulation of DDR genes, which may influence tumor progression. Understanding the molecular interplay between MCPyV and the DDR may guide future research into plausible novel diagnostic and therapeutic strategies for virus-induced tumors. Full article

This paper proposes an adaptive residual extended Kalman filter method optimized by a multi-strategy improved parrot optimization algorithm (MIPO-ARKEKF) to improve the kinematic parameter calibration accuracy and efficiency of robotic polishing systems. To address the limitations of the standard extended Kalman filter (EKF), such as truncation-error accumulation during repeated linearization and sensitivity to manually selected noise parameters, an integrated improvement framework is developed. Specifically, a gradient stabilizer based on state-estimation increments is introduced to alleviate estimation degradation caused by accumulated truncation errors, while the proposed MIPO algorithm is employed to adaptively optimize the process and measurement noise covariance matrices, thereby improving the robustness of parameter identification under practical measurement uncertainty. The calibration process is established on the basis of high-precision external measurement data obtained from the robotic polishing system. In benchmark-function tests, MIPO demonstrates superior convergence performance. In physical experiments based on a KUKA KR210 R2700 robot, the proposed MIPO-ARKEKF method reduces the root mean square positioning error from 0.8927 mm to 0.4858 mm, corresponding to a 45.58% improvement in accuracy. Compared with representative hybrid calibration methods, the proposed method achieves comparable compensation accuracy while reducing computation time by 34.88% to 65.08%. Practical polishing experiments on ultra-low-expansion glass lenses further verify that the proposed method effectively improves end-effector trajectory tracking accuracy and polishing quality, providing an efficient solution for high-precision robotic polishing. Full article