Search Results (4,537)

Background and Clinical Significance: Congenital tufting enteropathy (CTE), or autosomal recessive congenital diarrhea type 5 (DIAR5), is a rare intestinal epithelial disorder characterized by severe neonatal-onset watery diarrhea, failure to thrive, and intestinal failure. Most cases are caused by biallelic EPCAM variants. Case Presentation: A 53-day-old female infant presented with severe watery diarrhea and failure to thrive from the first days of life. She was born at term with a birth weight of 3.4 kg and had 10–20 watery stools daily. At admission, she was dehydrated, dystrophic, and below the third weight percentile. Diarrhea persisted despite an amino acid-based formula and cessation of enteral feeding. Duodenal biopsy showed disturbed villous–crypt architecture, variable lamina propria inflammation, absence of intraepithelial lymphocytosis, epithelial tufts, and regenerative epithelial changes, supporting CTE. Whole-exome sequencing identified compound heterozygous EPCAM variants: a maternally inherited likely pathogenic frameshift variant, c.687_688del, p.(Lys230Asnfs*23), and a paternally inherited missense variant, c.757G>A, p.(Asp253Asn), classified as a variant of uncertain significance. TPN was initiated for intestinal failure. Follow-up was complicated by catheter-related sepsis, cholelithiasis, and recurrent pancreatitis requiring laparoscopic cholecystectomy. She subsequently tolerated limited enteral feeding but did not achieve enteral autonomy and remained dependent on TPN, while maintaining normal growth with nutritional support. Conclusions: CTE should be considered in infants with severe neonatal-onset diarrhea. Histopathology combined with genetic testing is essential for diagnosis. Long-term TPN and multidisciplinary management are required. Full article

Mycoplasma synoviae (M. synoviae) is an avian pathogen responsible for respiratory disease and synovitis. The VlhA (variable lipoprotein hemagglutinin) family of surface adhesins plays a critical role in host cell attachment, yet the specific residues and structural determinants governing this interaction remain incompletely understood. In this study, we selected the C-terminal lipid-associated membrane hemagglutinin (LAM HA) domain within the VlhA family as the bait protein, based on its conserved C-terminal region. Yeast two-hybrid screening identified 18 LAM HA-interacting host proteins, and molecular docking pinpointed five residues (S83, R85, Y88, N124, K192) as the most frequent interaction hotspots. To assess their collective functional relevance, we constructed a combined deletion mutant lacking these five candidate residues. At the optimal pH of 6.0–6.5, wild-type LAM HA showed the highest titer (1:2), significantly exceeding that at pH 7.0–7.5 (no activity) and pH 5.0–5.5 (1:1) (p < 0.05), whereas the deletion mutant displayed a reduced titer (from 2 to 1; p = 0.05). Secondary structure analysis at the same pH revealed decreased α-helix content (from 7.90% to 7.57%), along with increased β-sheet (from 38.92% to 38.83%) and random coil (from 10.83% to 10.44%). Molecular dynamics simulations revealed that the deletion mutant exhibited elevated RMSF (from 2.83 ± 1.88 Å to 4.18 ± 2.65 Å) and Rg (from 40.48 ± 1.31 Å to 54.16 ± 4.47 Å) at pH 6.0–6.5, while RMSD showed a slight decrease (11.17 ± 1.33 Å vs. 12.14 ± 0.21 Å), collectively indicating compromised structural stability of the mutant. Collectively, these findings suggest that the LAM HA domain contributes to hemagglutination activity through pH-sensitive conformational stability and specific residue clusters—a property that may be relevant to M. synoviae colonization in the acidic microenvironments of the respiratory tract and synovial fluid during infection. Full article

Continuous objective assessment of pig motor condition, including recovery after anesthesia, requires the joint analysis of posture, locomotion, transitions between states, and short-term adverse events. This study aimed to develop and algorithmically evaluate a multi-camera pipeline for the quantitative analysis of simulated recovery states in a fully synthetic virtual environment. Procedural generation was used to produce 150,000 images annotated with fifteen anatomical keypoints while varying the pose, size, and appearance of the model, camera viewpoints, illumination, environment, and image post-processing parameters. The YOLO11m-pose model was used for two-dimensional pose estimation, after which observations from three synchronized cameras were combined using weighted triangulation. The reconstructed three-dimensional trajectories were processed using a quality-control system, a finite-state machine, and temporal rules for detecting falls, prolonged immobility, and convulsion-like movements. After repartitioning the dataset by three-dimensional pose index, the retrained YOLO11m-pose model achieved a keypoint ${\mathrm{mAP}}_{50--95}$ of 0.8968, a precision of 0.9985, and a recall of 0.9986 on the independent pose-level test set. During the processing of a 15-minute three-camera sequence, 98.993% of 405,000 reconstructions satisfied the geometric acceptance criteria, and the median reprojection error was 2.420 pixels. On a first manually annotated 5-minute synthetic sequence, the state machine achieved a strict frame-level accuracy of 91.20%, a macro-F1 score of 90.10%, and Cohen’s $\kappa$ of 0.860; accuracy outside $\pm 1$ s neighborhoods of state transitions was 97.43%. On a second 5-minute synthetic evaluation sequence with exact Unity-world geometric ground truth, direct three-dimensional evaluation yielded an MPJPE of 31.86 mm at 99.993% landmark coverage. A limited temporal assessment on this second sequence detected both of the two lying-derived prolonged-immobility reference intervals; fall and convulsion-like-movement events were not independently annotated. All training, validation, and end-to-end evaluation data were generated in a virtual environment; therefore, these results establish algorithmic feasibility within the synthetic domain but do not establish performance on real animals. Full article

Re₃Zr has recently been proposed in the cubic Pm-3n structure. Its alternative atomic arrangements and thermodynamic position within the Re–Zr system have not been systematically resolved. In this work, CALYPSO particle-swarm structure searches combined with density functional theory identify five Re₃Zr polymorphs with Cmcm, Fmmm, Immm, P4/mmm, and Fm-3m symmetries and compare them consistently with the reported Pm-3n phase. Formation enthalpies, a selected-phase partial convex hull, phonon dispersions, elastic properties, sound velocities, elastic Debye temperatures, electronic structures, and bonding characteristics are evaluated. All five CALYPSO structures lie below Pm-3n in fixed-composition energy, with Cmcm being the lowest. The Cmcm phase has a formation enthalpy of −0.257 eV atom⁻¹ and lies approximately 0.042 eV atom⁻¹ above the selected-phase partial hull, identifying it as a low-lying off-hull metastable candidate at 0 K. AIMD simulations at 300 and 1000 K show no obvious structural reconstruction of the Cmcm framework over the simulated time scales. All six structures exhibit no imaginary phonon frequencies and satisfy the corresponding mechanical-stability criteria. Their elastic responses are strongly structure dependent: P4/mmm has the largest Chen–Tian hardness estimates and elastic Debye temperature, whereas Fm-3m shows the weakest elastic anisotropy. All six polymorphs are metallic, with Fermi-level states dominated by Re-5d orbitals and predominantly delocalized bonding. These results provide a thermodynamically constrained 0 K reference for future synthesis, phase identification, and finite-temperature or kinetic investigations of hypothetical Re₃Zr polymorphs. Full article

Background/Objectives: A recent feature in the Invisalign^® system allowed integration of cone-beam computed tomography (CBCT) with intraoral scans, thereby enabling visualization of the tooth roots and surrounding alveolar bone. Here, we aimed to compare differences between anatomical measurements obtained from integrated CBCT using Invisalign^® software and conventional CBCT images. Methods: In this cross-sectional study, we included 45 adult patients (mean age 29.53 ± 7.66 years). Alveolar bone width was measured at the crestal, mid-root, and apical levels and the root length, maxillary and mandibular outer and inner transverse widths, and symphyseal width were assessed. Intra-examiner reliability was assessed using intraclass correlation coefficients. Paired t-tests were used to compare the two methods, and Bland–Altman analysis was used to evaluate agreement. Results: Intra-examiner reliability demonstrated excellent agreement for all measurements (intraclass correlation coefficients > 0.90). Integrated CBCT models showed greater alveolar bone width, symphyseal width, and interbuccal transverse measurements than conventional CBCT, whereas the root length and interlingual transverse widths were underestimated. Most of the differences between the two methods were statistically significant (p < 0.05), although 5 of the 12 crestal measurements did not reach statistical significance (p > 0.05). For most measurements, the mean absolute differences were below 0.7 mm, except for root length, which showed larger discrepancies. Bland–Altman analysis revealed good agreement between the methods, with most observations lying within the 95% limits of agreement and no evident proportional bias. Conclusions: Most measured variables showed significant differences between integrated and conventional CBCT (p < 0.05), ranging from 0.7 mm to 1.3 mm; however, at the crestal level, 5/12 measurements showed no statistically significant difference between methods (p > 0.05). Full article

Folate-mediated one-carbon metabolism supports nucleotide biosynthesis, methylation reactions, and redox homeostasis, and the mitochondrial enzyme MTHFD2 has emerged as a cancer-associated metabolic target. However, the development of MTHFD2-preferential inhibitors remains challenging because MTHFD2 is structurally and functionally related to other folate-metabolism enzymes, including the cytosolic enzyme MTHFD1 and the mitochondrial isoenzyme MTHFD2L. In this study, a curated library of 115 phytochemicals was screened against the folate/substrate-binding pockets of MTHFD2 and MTHFD1 using a redocking-controlled molecular-docking protocol. Three compounds, dehydrotrametenolic acid, eburicoic acid, and rutaecarpine, met the docking-based prioritization criteria for predicted MTHFD2-preferential binding. Subsequent ADME, drug-likeness, and toxicity profiling indicated that the two triterpenoids had unfavorable physicochemical and pharmacokinetic properties and were therefore not advanced to biochemical testing, whereas rutaecarpine showed the most balanced predicted profile. In vitro enzyme-inhibition assays showed that rutaecarpine inhibited both MTHFD2 and MTHFD1 in a concentration-dependent manner. Rutaecarpine inhibited MTHFD2 with an apparent IC₅₀ of 31.35 μM and MTHFD1 with an apparent IC₅₀ of 54.20 μM, corresponding to a modest 1.73-fold preference for MTHFD2. In contrast, the reference antifolate LY345899 preferentially inhibited MTHFD1. These findings identify rutaecarpine as a natural-product scaffold with statistically supported but modest MTHFD2-preferential activity and support its further structure-guided optimization, including future profiling against MTHFD2L. These results should be interpreted as evidence of exploratory scaffold-level activity rather than identification of a potent, optimized, or broadly validated MTHFD2 inhibitor. Full article

Staphylococcus aureus is an ESKAPE pathogen, defined by its ability to evade antibacterial treatment, and together with S. epidermidis is a leading Gram-positive cause of wound infection. The emergence of methicillin- and vancomycin-resistant strains further limits conventional antibiotic treatment. The staphylococcal endolysin LysSte134_1 was produced recombinantly, its proper folding confirmed by zymography, and its lytic activity demonstrated against planktonic cultures of both S. aureus and S. epidermidis. The combination of LysSte134_1 with 10% 1,3-propanediol and Zn²⁺ increased CFU reduction in both species relative to LysSte134_1 with Zn²⁺ alone. In a murine wound model, topical application of LysSte134_1 significantly reduced the bacterial burden in wound tissue, achieving a 2–3-log reduction in MRSA and below the detection limit for S. epidermidis. Treatment was accompanied by normalization of peripheral leukocyte counts and a shift in the serum cytokine profile from a sustained pro-inflammatory state with elevated IL-6, IL-17 and IL-10 toward levels comparable to non-infected controls. These results suggest the potential utility of LysSte134_1 as a component of topical antibacterial formulations and support further investigation in models of staphylococcal wound infection. Full article

We investigate scalar perturbations of a rotating asymptotically anti-de Sitter (AdS)-Teo traversable wormhole with a controlled non-separable angular deformation. The geometry retains a regular wormhole throat and the required AdS asymptotics, while an explicit quadrupolar deformation generates angular-channel coupling in the intermediate region. A sufficient condition is derived for an ergoregion-free parameter regime in which the spectral analysis is performed. Projecting the geometry-derived Klein–Gordon equation onto spherical harmonics yields a matrix-valued Sturm–Liouville system and an associated quadratic operator pencil. Throat regularity together with normalizable AdS boundary conditions leads to a determinant quantization condition for the discrete normal-mode spectrum. Two-, four-, and six-channel calculations demonstrate systematic numerical convergence of the retained low-lying normal-mode frequencies under enlargement of the angular basis. The complete finite generalized eigenspectrum is also examined without imposing a near-reality selection criterion, and no growing scalar mode is found within the ergoregion-free parameter range and numerical resolutions studied. The six-channel rotation continuation exhibits a finite interior level-repulsion feature accompanied by collective redistribution of the multichannel eigenvectors. The same coupled spectral framework formally defines a matrix-valued two-boundary response whose poles are selected by the normal-mode matching condition; the response plots presented here illustrate this structure using the reduced two-channel effective model rather than a numerical reconstruction of the full six-channel response. We further derive the geometry-dependent short-distance Hadamard subtraction and identify the finite inter-channel structure entering a truncated local quantum mode sum, without claiming a complete numerical evaluation of ${⟨{\mathrm{\Phi }}^2⟩}_{\mathrm{ren}}$. Together, these results establish a geometry-to-spectrum framework in which the spacetime geometry determines the coupled operator, the global boundary conditions determine its normal-mode spectrum, and the same coupled spectral framework organizes the associated asymptotic response and local quantum mode-sum structure. Full article

Hawthorn (Crataegus spp.), a horticultural crop with significant edible, medicinal, and ornamental values, has garnered increasing attention from breeders to markets, leading to continuous emergence of new varieties. Accurate phenotypic characterization and robust Distinctness, Uniformity, and Stability (DUS) testing are fundamental for plant variety protection and breeding innovation. Employing the Chinese DUS Test Guidelines for Hawthorn (LY/T 3208-2020) as an analytical framework, this study systematically evaluated 197 germplasm accessions from the Chinese National Field Genebank. Results demonstrated: (1) Coefficients of Coincidence (COC) for example varieties and test traits ranged between 0.980 and 1.000, fully meeting the testing requirements; (2) the 22 qualitative (QL) and pseudo-qualitative traits (PQ) were categorized into 2–5 classes with Shannon-Wiener indices of 0.032–1.174, indicating high polymorphism; (3) correlation analysis of 11 quantitative traits (QN) revealed coefficients from 0.006 to 0.922, with 23 trait pairs showing statistical significance, while principal component analysis identified fruit and leaf traits as primary drivers of phenotypic variation; (4) grading schemes were established by using Least Significant Difference (LSD) for eight normally or near-normally distributed traits (5–7 classes) and range-based grading approach for three non-normal traits (5 classes). Based on the above results, this study evaluated China’s current DUS testing guidelines for hawthorn. Subsequently, 197 hawthorn accessions were used to evaluate the QL, PQ, and QN traits, based on which corresponding optimization recommendations were proposed. Ultimately, an optimized testing framework for hawthorn DUS testing was established. The resulting analytical insights and phenotypic grading system will enrich the current descriptor framework and provide a foundational dataset for trait-DNA association and marker-assisted breeding. Notably, this optimization strategy serves as a methodological template for updating DUS guidelines in other taxa. Overall, these insights strengthen the protection, development, and breeding of new hawthorn varieties while advancing the standardization of DUS testing. Full article

Land subsidence amplifies the impacts of sea-level rise (SLR) in low-lying deltas, yet some Coastal Vulnerability Index (CVI) assessments omit this or rely on global estimates, drastically understating deltaic vulnerability. This study presents the first CVI assessment along Ghana’s coast to integrate validated, spatially resolved land subsidence derived from Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR). Nine geological, geomorphological, hydrodynamic, and anthropogenic variables were quantified across 72 contiguous grid cells spanning ~150 km of the Volta Delta’s coastline and ranked on a 1–5 vulnerability scale. Three composite indices were computed using a common quantile distribution: an index excluding subsidence (CVI_-sub), an index with a spatially uniform regional vertical land motion (CVI_+(u-sub)), and an index incorporating spatially resolved local InSAR subsidence (CVI_+(v-sub)). High to very high vulnerability ranks rose from 28% of cells without subsidence, through 44% with the regional estimate, to 75% with the local InSAR; every grid cell recorded a higher CVI once subsidence was incorporated (Wilcoxon signed-rank test, p < 0.001). Vulnerability peaked along the Keta and Songor lagoonal margins. Omitting measured subsidence understates deltaic vulnerability, and this approach offers a transferable method for data-sparse deltas. Full article

Background: Biallelic loss-of-function variants in LAMC3, encoding laminin gamma-3, cause occipital cortical malformation (OMIM#614115). White matter disease and intracranial neoplasia have not been reported in this spectrum. We report a novel homozygous LAMC3 frameshift variant, expanding its phenotypic and molecular spectrum. Methods: Two adolescent siblings from a consanguineous Turkish family underwent whole-exome sequencing, with segregation confirmed by NGS/IGV and classification per ACMG/AMP criteria. In silico analyses included multiple sequence alignment, AlphaFold modeling of wild-type and mutant proteins, and docking against nidogen-1 (NID1). Results: Both siblings had a novel homozygous LAMC3 variant frameshift variant (NM_006059.4: c.1852_1882del; p.(Pro618Serfs*5)), classified as pathogenic (PVS1, PM2, PP3, PP1) with full cosegregation. Proband II.III, a 17-year-old female, developed postoperative epilepsy after resection of a tectal low-grade glioneuronal tumor harboring a somatic KRAS (NM_004985.3) p.(Gln61Lys) variant (VAF 42.9%), with periventricular white matter gliosis. Proband II.IV, a 15-year-old male, presented with confluent leukoencephalopathy, occipital pachygyria, parietal polymicrogyria, and subcortical band heterotopia, illustrating striking intrafamilial discordance. Conclusions: Docking analysis revealed that the cleavage removes the C-terminal nidogen-binding region, eliminates the predicted wild-type interface (residues 906–1029), and shifts the binding to an unnatural N-terminal surface. This finding is a hypothesis-generating result consistent with loss of function. This study expands the LAMC3 phenotype to include leukoencephalopathy and reports a co-occurring low-grade tectal glioneuronal tumor as a novel, single-case observation, supporting inclusion of LAMC3 in the differential diagnosis of pediatric leukoencephalopathies, particularly with consanguinity. Full article

Urban pluvial flooding shows clear temporal accumulation, delayed response, and spatial heterogeneity. Better flood-depth prediction from a spatiotemporal coupling perspective can support urban flood risk identification and refined management. This study develops a spatiotemporal prediction model that integrates a Transformer and graph neural network (GNN). The Transformer module captures temporal dependencies in rainfall processes and flood-depth evolution. The graph attention network (GAT) represents spatial associations constrained by terrain, drainage networks, and neighboring spatial relationships. A fusion attention mechanism then adaptively couples temporal and spatial features. This study uses multi-source data, including hourly meteorological observations, terrain, land cover, drainage networks, and water-system data. It selects the heavy rainfall event caused by Typhoon In-Fa in Huai’an City in July 2021 as a typical case. The study analyzes the temporal evolution of regional average flood depth and the spatial differentiation of inundated grid cells at the municipal scale. The results show three main findings. First, during the typical heavy rainfall event, regional average flood depth follows a continuous process of low-level stability, sustained rise, rapid increase, delayed peak, slow recession at a high level, and rapid recession. The flood peak lags behind the rainfall peak by about 3 h. This result indicates clear accumulation and delayed response in urban pluvial flooding. Second, at the municipal scale, inundated grid cells show a pattern of concentrated distribution in urban built-up areas, secondary distribution in county-level built-up areas, and scattered distribution in non-construction land. Different depth grades also show clear hierarchical differentiation. Mild and moderate inundation covers a wider area. Medium-high inundation concentrates locally. High-grade inundation appears as a small number of nested high-value cells. Third, the spatial differentiation of medium- and high-grade inundated grid cells does not result from low-lying terrain or construction land alone. It forms under the combined effects of low-lying terrain, local relative depressions, and impervious surfaces in construction land. This pattern shows clear built-up-area clustering, grade differentiation, and land-cover correspondence. The results provide methodological support and decision references for urban flood risk identification, grid-based risk management, and emergency dispatch during extreme rainfall. Full article

Coumarins are heterocyclic compounds with diverse biological activities and potential applications as alternative acaricidal agents. In this study, nine coumarin derivatives were synthesized through a solvent-free Pechmann reaction using Preyssler heteropolyacid as a reusable catalyst under green chemistry conditions. The synthesized compounds were evaluated against adult females of Rhipicephalus (Boophilus) microplus using the adult immersion test. Survival analysis was performed using the Cox proportional hazard model, while molecular docking studies were carried out on triosephosphate isomerase (TIM). In addition, post hoc analysis of the structures predicted to be most active by the QSAR model suggested an association between higher predicted activity, the presence of hydroxyl groups, and the polarity of C7 side chains, although the topological descriptor identified by the model does not admit a direct physicochemical interpretation. The results showed that hydroxylated coumarins, particularly those substituted at C5 and C7, exhibited the highest acaricidal activity, with IC₅₀ values between 7.24 and 8.78 mg/mL. Docking analysis suggested plausible interactions with residues located at the TIM interface cavity, mainly Lys-112, Asn-65, and Glu-77. The QSAR model indicated that hydroxyl substitution and side-chain polarity contributed positively to activity. This study integrates Preyssler heteropolyacid-catalyzed green synthesis of coumarins with Cox proportional hazard survival modeling, TIM molecular docking, and QSAR analysis within a single acaricidal evaluation against R. (B.) microplus, providing a multi-pronged framework for prioritizing structural modifications in future coumarin-based acaricide development. Full article

Background/Objectives: Atrial fibrillation (AF), the most prevalent form of clinical cardiac arrhythmia globally, is associated with markedly increased morbidity, mortality, and socio-economic expenditure. Accumulating strong evidence highlights genetic abnormalities underpinning its etiopathogenesis. A recent investigation has demonstrated that mutations in the TBX20 gene, which codes for a T-box transcription factor essential for proper cardiovascular development and structural remodeling, contribute to familial AF. Nevertheless, the mutational prevalence and spectrum of this gene in patients with sporadic AF remain unknown. Methods: A cohort of 352 individuals suffering from sporadic AF and a group of 376 healthy subjects without AF history were recruited prospectively. Sanger sequencing examination of TBX20 was implemented in all research participants. The functional impacts of the discovered TBX20 variations were quantitatively measured by dual-reporter gene analysis. Results: Two novel heterozygous truncating TBX20 variations, NM_001077653.2: c.725C>A; p.(Ser242*) and NM_001077653.2: c.826A>T; p.(Lys276*), were detected in two of the 352 cases with sporadic AF, respectively, with a mutational prevalence of approximately 0.57%. The two TBX20 variants were absent from the 752 control chromosomes. Functional measurements revealed that both Ser242* and Lys276* variants lost transactivation on KCNH2 and NPPA, two genes responsible for AF. In addition, each of the two variations abrogated the synergistic transactivation of NPPA by TBX20 together with NKX2.5, another gene reported to cause AF. Conclusions: The current data indicate haplo-insufficient TBX20 variations as new genetic defects predisposing to sporadic AF and hence are conducive to improving the prophylaxis and treatment strategies of sporadic AF in a subset of patients. Full article

Agricultural pest and disease images often lose diagnostically important textures during transmission and storage, while conventional codecs struggle to balance high compression ratios and information fidelity. This study proposes YOLOv11n-SWAQ, a lightweight adaptive compression framework integrating shared feature encoding and critical-region-aware quantization. The YOLOv11n backbone and feature fusion network are reused as a shared encoder to reduce redundant feature extraction. A lightweight window-based attention module enhances lesion boundaries, insect contours, and local textures. Detection boxes and attention weights are combined to construct a three-level quantization map for background, ordinary critical, and high-importance texture regions, while a hyperprior entropy model improves latent probability estimation. At an actual complete-stream bitrate of approximately 0.31 bpp, the proposed method achieved an ROI-PSNR of 36.970 dB and an ROI-MS-SSIM of 0.9652. Compared with the YOLOv11n+CAE cascaded baseline, the reconstruction error in complex-texture regions decreased by 4.8%, indicating preferential bitrate allocation to diagnostically important regions. The proposed method achieved an end-to-end processing time of 13.44 ms, representing an average reduction of approximately 72% compared with representative advanced learned image compression models. Overall, YOLOv11n-SWAQ provides a favorable trade-off between critical-region fidelity and computational efficiency for high-ratio agricultural image compression, with its principal advantage lying in lightweight task-oriented processing rather than a large absolute gain in global reconstruction quality. Full article