Search Results (1,934)

Congenital Myasthenic Syndrome represents a complex and heterogeneous group of inherited neuromuscular disorders, which result from variants in genes involved in different pathophysiological mechanisms related to the neuromuscular junction. LRP4 (Low-density lipoprotein receptor-related protein 4) represents one of the most important proteins involved in this complex signaling pathway, acting in a complex with agrin and Muscle Skeletal Receptor Tyrosine Kinase (MuSK) proteins. LRP4 became known to most neurologists due to the description of anti-LRP4 antibody-related Myasthenia Gravis. There are, however, different neurological and neuromuscular disorders that result from pathogenic variants in LRP4 gene, especially a rare and potentially treatable Congenital Myasthenic Syndrome. The authors performed a detailed narrative review, including descriptions of the main pathophysiological, clinical, and therapeutic aspects of LRP4-related Congenital Myasthenic Syndromes. Full article

Cross-material continuous tool wear prediction is difficult because a model must preserve the physical wear scale, not only align high-dimensional sensor features. This limitation is critical in milling, where the target variable is the continuous flank wear width ($\mathrm{VB}$) and material shift can distort the mapping from sensor response to wear magnitude. We address this problem by recasting cross-domain tool wear prediction as monotone wear-scale adaptation. We propose Multi-Physics Monotone Score Transport (MPMST), a monotone score transport framework that constructs a tool-wear-oriented score from sensor-derived candidate cues, transports the target-domain score onto the source-domain wear scale, and then predicts wear through isotonic regression. We also evaluate One-Physics Monotone Score Transport (OPMST), a force-only variant that uses the same score-transport pipeline with a restricted cue family. On Mondragon Unibertsitatea–Tool Condition Monitoring (MU-TCM) with two cross-material transfer tasks, the validation-driven MPMST configuration reduces mean absolute error by approximately 63% relative to Correlation Alignment (CORAL) and by approximately 31% relative to a physics-informed Gaussian process baseline. The results support monotone score construction and score transport as practical mechanisms for continuous tool wear prediction under domain shift, while also showing that MU-TCM is strongly force dominated. Full article

Scheduling in multi-layer industrial networks must remain stable even when the feedback mechanism of the environment changes inside a single production episode. The system can switch between a step-continuous regime with dense process feedback and a task-driven regime with sparse milestone feedback, so that the same state requires different behaviour before and after the switch. A regime-oblivious policy may therefore optimise the wrong action preference after a switch. We formulate this setting as a mode-switched multi-industrial-chain Markov decision process (MS-MIC-MDP) and prove that a single fixed action preference is necessarily suboptimal in at least one regime. We then propose BHERA, a belief-guided homeostatic estimation framework for regime adaptation. BHERA builds cross-layer representations, performs structured variational inference of slow and fast latent beliefs, estimates the posterior probability of the task-driven regime, and uses that posterior to regulate sample weights, entropy strength, return-prediction emphasis, and latent information capacity. A homeostatic feedback rule on the Kullback–Leibler (KL) divergence keeps the latent representation informative without allowing uncontrolled information growth, and we analyse it as a two-timescale stochastic approximation with an associated convergence argument and a per-iteration complexity bound. Experiments in a multi-layer industrial scheduling simulator show that BHERA achieves higher return, lower cost, and higher utility than CReSCENT, HiTAC-MuSE, Informed Switching, and WToE across all tested perturbations, with paired statistical tests confirming significance. Expanded ablations and parameter-sensitivity studies confirm the importance of regime belief, regime-balanced weighting, bootstrap prediction, homeostatic capacity control, and the dual-timescale latent split. Full article

The improvement of sucrose yield in sugarcane is impeded by the crop’s complex polyploid genome and slow progress in breeding. To clarify how arginine (Arg) regulates sugar metabolism and identify key genes associated with sucrose transport and accumulation in sugarcane, a screening experiment was performed by spraying L-arginine hydrochloride on the leaves and leaf sheaths of three sugarcane varieties (YZ05-51, YZ08-1609, and YT93-159), which differ in growth vigor, leaf morphology and other phenotypic traits. YZ05-51 exhibited the most prominent sugar-increasing effect, and subsequent optimization experiments on its leaf sheaths revealed that 20 g/mu L-arginine hydrochloride at pH 7.0 was optimal, significantly enhancing stem sucrose content. Transcriptomic analysis revealed the upregulation of genes related to sucrose synthesis and transport, with candidate genes enriched in pathways such as starch-sucrose metabolism, glycolysis/gluconeogenesis, and ATP-binding cassette (ABC) transporters. Metabolomic analysis detected 32 sugar metabolites across three categories, of which 24 were differentially abundant (e.g., glucose, galactose, fructose, and mannose). Integrated multi-omics analysis identified key regulatory genes, including SBEs and TPS1 (sucrose synthesis and carbon flux regulation), RBSK, α-amylases, GH28 (starch breakdown, glycolysis, and sugar mobilization), ABC transporters, GTs, and TIM10/TIM12 (sucrose transporter). Collectively, these analyses demonstrate enhanced activity of genes and metabolites involved in sucrose synthesis/transport in leaf sheaths, accompanied by reduced synthesis of other monosaccharides and oligosaccharides. Vigorously metabolizing leaf sheaths is more conducive to sucrose transport. This study provides valuable insights into the molecular mechanisms underlying Arg-mediated sucrose accumulation specifically in the sugarcane YZ05-51 sugarcane, highlighting its critical regulatory roles. Full article

In smallholder-dominated agricultural systems, farm expansion is often expected to improve agricultural performance, yet a larger operated area does not necessarily translate into higher returns per unit of land. This issue is particularly relevant in rice farming, where land fragmentation, labor constraints, and uneven access to agricultural services may limit the return-enhancing effect of farm-scale management (FSM). Using 2024 household survey data from 732 rice-farming households in Jiangxi Province, China, this study examines how FSM, service-scale management (SSM), and their organizational matching affect rice-farming returns (RFR). We apply ordinary least squares (OLS) regression models with interaction-term specifications and further conduct mechanism, moderation, and heterogeneity analyses. The results show that FSM alone does not automatically increase per-mu net operating returns, whereas SSM is positively associated with RFR. More importantly, the interaction between FSM and SSM is significantly positive, indicating that farm expansion generates return advantages mainly when supported by agricultural socialized services. Mechanism analysis suggests that this synergistic effect operates partly through higher land consolidation (LC) and more formalized service contractualization (SC), while smart agricultural technology (SAT) further strengthens the return-enhancing effect. Heterogeneity analysis further shows that the effect differs across farmers with different operating scales. These findings suggest that smallholder modernization should not be understood as land expansion alone but as the organizational matching between farm scale and the service-based division of labor. Policy efforts should therefore aim to improve agricultural socialized service systems, promote land consolidation, strengthen service contracts, and integrate smart agricultural technologies into service provision. Full article

The paper details the implementation and experimental validation of an IEC 61850-9-2 sampled value (SV)-based distance protection scheme for a 132 kV transmission line. Instead of conventional analog interfaces, we propose a scheme that uses a digital process bus to stream time-synchronized voltage and current measurements from instrument transformers to protection relays. A laboratory-scale setup was developed, in which an SEL 401 merging unit samples currents and voltages injected by an OMICRON CMC 356 and publishes them as SV messages to an SEL 421 distance relay. This work demonstrates how IEC 61850-9-2 can be practically applied to modernize transmission line protection and enhance overall grid reliability and resilience. Full article

Indigenous goat populations are valuable genetic resources for livestock production in arid and semi-arid environments, yet many remain insufficiently characterized at the phenotypic and genomic levels. This study investigated phenotypic variation and genome-wide associations in two local Ardi goat lines in Bahrain: Ardi Bahraini and Ardi Mu’atar, the latter being distinguished by a characteristic facial marking pattern. A total of 280 goats were phenotypically characterized for qualitative traits and body measurements, and 76 animals were genotyped using the Illumina Caprine 60K single nucleotide polymorphism (SNP) BeadChip. After quality control, 49,716 autosomal SNPs were retained for genome-wide association analysis. Phenotypic analysis showed that the two lines differed significantly in body weight, body length, hip height, face width, tail length, ear width, and tail circumference, while discriminant analysis identified tail length, ear width, tail circumference, and facial patterns differentiating the lines. Principal component analysis (PCA) showed partial genomic clustering of the two lines, and genome-wide significant and suggestive SNPs based on Bonferroni and false discovery rate (FDR) thresholds on chromosomes 6, 13, 14, and 29. The strongest association was observed for rs268277393 on chromosome 13, located near DOK5 (Docking Protein 5) and TRNAC-GCA (transfer RNA cysteine, anticodon GCA), and was associated with the Ardi Mu’atar facial pattern. Additional candidate regions were located near genes with possible roles in pigmentation, development, or morphological variation. These findings provide preliminary genomic evidence supporting the phenotypic distinctiveness of Ardi Mu’atar goats and identify candidate markers that may contribute to future conservation and breeding programs. Further validation in larger populations and functional studies will be required to confirm the biological role of these candidate regions. Full article

The Syrian golden hamster (Mesocricetus auratus) is a universally accepted model for visceral leishmaniasis (VL) due to its ability to mimic human disease pathology. Mus musculus (BALB/c) is preferred for evaluating pharmaceutical and immunological responses. This study focuses on the precise role of gene signatures in L. donovani-infected M. auratus and M. musculus, using transcriptomic analysis. Principal component analysis (PCA) revealed distinct clustering among the four groups (uninfected vs. infected spleen samples from M. auratus and M. musculus). After differential expression analysis, 2054 genes in M. auratus and 1108 in M. musculus were found to be differentially expressed, with 153 genes common to both species. Except for 31 genes, most of the commonly dysregulated genes show a similar expression pattern. Although Th1-mediated immune signaling was observed in both cases, the overexpression of LAG3 in both infected groups underscores the important role of T cell exhaustion. Immunological responses against parasite infection in M. auratus appear to be more aggressive, while M. musculus seems more intense. Interestingly, only the M. musculus-infected group shows overexpression of IL-10. Without a definitive role for IL-10, the overexpression of Tgm2, Clec7a, and Adora2b in both species may drive disease outcome. These findings elucidate the immunological mechanisms driving the pathogenesis of VL in rodent models. Full article

Background/Objectives: IL23R encodes a pivotal component of the IL-23/Th17 signaling axis and represents a validated genetic susceptibility locus for inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Despite extensive GWAS data, the functional consequences of the full spectrum of IL23R missense single-nucleotide variants (SNVs) have not been systematically characterized. This study aimed to identify high-risk missense SNVs through a multi-tool in silico pipeline. Methods: A total of 723 missense SNVs from NCBI dbSNP were verified against transcript NM_144701.3/Q5VWK5-1 (629 aa) using Ensembl VEP (GRCh38). Sequential filtering was performed using applied SIFT, PolyPhen-2, PROVEAN, E-SNPs&GO, MutPred2, and ConSurf (grade ≥ 7); AlphaMissense and FATHMM-MKL were used as independent annotation layers. Protein stability was assessed with MuPro and DynaMut2 (AlphaFold2 AF-Q5VWK5-F1-v6; pLDDT = 68.19); structural characterization was performed with Project HOPE, and interaction networks were constructed using STRING and GeneMANIA. Results: Sequential filtering identified 37 high-risk missense variants. MuPro predicted destabilizing effects for 36/37 variants, with concordant DynaMut2 results for 35/37. Project HOPE identified disulfide bond disruption in 11 variants, charge-altering substitutions in 8, and glycine/proline backbone conformational changes in 11. STRING analysis identified IL12RB1 (0.999), IL23A (0.999), JAK2 (0.995), IL12B (0.986), and STAT3 (0.980) as the leading IL23R interactors. The protective variant R381Q was appropriately characterized as neutral by PROVEAN (−1.16) and AlphaMissense (likely_benign), supporting the specificity of the pipeline. Conclusions: Comprehensive in silico analysis identified 37 high-risk IL23R missense candidates with convergent computational evidence of predicted deleteriousness, predominantly involving cysteine bridge disruption, charge alteration, and glycine/proline backbone conformational changes. These variants are presented as prioritized candidates for future functional validation and may inform subsequent investigations of IBD susceptibility and IL-23 pathway pharmacogenomics. Full article

Future wireless systems such as 5G-Advanced and 6G are expected to rely increasingly on multi-user MIMO and distributed multi-antenna transmission, where accurate channel direction information (CDI) is essential for interference management. In limited-feedback downlink systems, however, finite-rate CDI feedback introduces quantization error, resulting in residual interference and rate loss in zero-forcing beamforming. This paper proposes a quantization-error-threshold-based user admission scheme for limited-feedback MU-MIMO downlink systems. In the proposed scheme, each user feeds back its quantized CDI and channel quality information only when its CDI quantization error is below a predefined threshold, and the base station performs semi-orthogonal user selection and zero-forcing beamforming over the admitted users. The proposed threshold controls the tradeoff between feedback-overhead reduction and candidate-user availability while improving the reliability of the CDI used for precoding. An analytical framework is developed to characterize the threshold-dependent scheduled-user count, ergodic sum-rate, and feedback overhead. Simulation results show that the proposed scheme improves the sum-rate compared with conventional SUS and substantially reduces the feedback overhead, especially as the number of users increases. Full article

Background/Objectives: Chronic pain is a significant clinical challenge, in part due to the absence of reliable objective biomarkers for its evaluation and treatment. Growing evidence indicates that immune cells, including natural killer (NK) cells, are involved in the regulation of pain processes. NK cells are innate cytotoxic lymphocytes whose functional status may mirror underlying pathological pain states. In this study, we investigated μ-opioid receptor (MOR) expression and functional alterations of NK cells in a murine model of neuropathic pain induced by chronic constriction injury (CCI). Methods: Mice were divided into three groups: Sham (sciatic nerve exposure without ligation), CCI 14-day, and CCI 21-day groups. At the respective time points, animals were sacrificed and spleens were collected for analysis. Splenocytes were isolated by mechanical dissociation followed by centrifugation and erythrocyte lysis. Lymphocytes were analyzed by flow cytometry to evaluate MOR expression in NK cells and their degranulation activity (CD107a assay). Cells were incubated with fluorochrome-conjugated antibodies against NK cell markers (NK1.1, CD3, Ly49A, Ly49C/I) in combination with anti-MOR and anti-Interferon γ antibody (IFN-γ). Immunofluorescence and confocal microscopy analyses were performed to assess MOR localization and granzyme localization, supporting CD107a-mediated degranulation. Results: Flow cytometry analysis revealed a significant reduction in surface MOR expression on total NK cells from CCI mice compared with sham controls at 14 and 21 days post-injury, a finding corroborated by immunofluorescence evidence of MOR cellular internalization. Functionally, CCI induced a marked decrease in CD107a expression and impaired IFN-γ production both under basal conditions and following PMA/ionomycin stimulation, indicating a hyporesponsive state of NK cells. Consistently, confocal microscopy revealed extracellular release of Granzyme A following CCI, suggesting dysregulated degranulation. Conclusions: Neuropathic pain is associated with a remodeling of NK cell phenotype and effector functions, characterized by impaired cytotoxic activity and cytokine production, along with modulation of inhibitory receptor expression. Notably, MOR-reduced surface expression in NK cells emerges as a potential biomarker of neuropathic pain. Further studies are needed to elucidate the molecular mechanisms regulating MOR expression and its relationship with NK cell hyporesponsiveness and degranulation in chronic pain conditions. Full article

Monitoring water surface algal blooms from surveillance perspectives faces challenges such as small objects, low texture contrasts, dynamic background interferences, and limited labeled datasets. In this study, we propose GECA-YOLOv26, a lightweight model that integrates Ghost Convolution (GhostConv) and Efficient Channel Attention (ECA) modules. First, the GhostConv lightweight module is introduced in the first layer of the YOLOv26 backbone, reducing parameters from 4608 to 2704 and achieving a 41% reduction in computational cost. Second, eight ECA modules are embedded at key locations after backbone downsampling and neck feature fusion to enhance feature representation and mitigate degradation caused by model lightweighting. Finally, the MuSGD optimizer is used for training, with adaptive modifications to resolve tensor shape conflicts with the ECA modules. Experimental results indicate that the model achieves a mAP50 of 82.16%. Compared with the YOLOv26 baseline, our model improves mAP50 by 6.42%, while mAP@0.5:0.95 decreases by 0.79% and inference speed reduces from 143 FPS to 123 FPS. The model also reduces parameters and size, achieving 5.19 MB and 1864 fewer parameters. Compared with YOLOv8, YOLOv10, and YOLOv11, the proposed model improves mAP50 by 2.12%, 5.99%, and 2.79%, respectively. To evaluate the stability of the results under small-sample conditions, we conducted 3-fold and 5-fold cross-validation experiments, which demonstrated that the model performs robustly across different folds and random seeds. Ablation studies further confirm the effectiveness of each module. Heatmap analysis demonstrates that the proposed model effectively highlights small object regions, remains robust under limited-sample conditions, and reduces model complexity. This study provides a novel solution for algal bloom detection in surveillance scenarios. Full article

Background/Objectives: MicroRNAs are key post-transcriptional regulators involved in various diseases. Despite its status as the gold standard, real-time RT-PCR faces challenges arising from high sequence homology among closely related microRNAs and the substantial biomaterial required to enrich small RNA fractions. This study aimed to develop an optimized protocol for simultaneous analysis of microRNA and mRNA expression from a single total RNA sample using mouse (Mus musculus) brain tissue, avoiding dependence on pre-designed commercial assay panels. Methods: We optimized a real-time RT-PCR workflow enabling simultaneous analysis of mature microRNAs and mRNAs from a single total RNA sample. Modifications include a redesigned universal reverse primer, LNA-modified TaqMan probes, and omission of the 65 °C denaturation step during reverse transcription. The method was validated for five microRNAs in mouse brain tissue. Results: The assay showed high specificity, discriminating closely related miR-125a-5p and miR-125b-5p with a ΔCt difference of 6.7 ± 1.2 cycles. Co-analysis with Oligo(dT)₁₈ and Random hexamer primers did not interfere with microRNA detection. Conclusions: The developed approach enables reliable detection of closely related microRNAs and parallel analysis of different RNA types, which is particularly important for studying regulatory networks when working with limited amounts of biomaterial. This protocol provides a complementary, accessible option for targeted studies in resource-limited settings or for non-cataloged miRNA targets. Full article

Background/Objectives: Type 2 diabetes (T2D)-associated sarcopenia is characterized by impaired insulin signaling, lipotoxicity, oxidative stress, and progressive muscle loss. Although liraglutide improves glucose control and reduces lipid burden, its ability to preserve muscle integrity under diabetic lipotoxic conditions remains limited. This study investigated whether β-hydroxy-β-methylbutyrate (HMB) could enhance liraglutide-mediated protection against high-glucose plus free fatty acid (HG+FFA)-induced injury in skeletal muscle cells. Methods: Differentiated C2C12 myotubes were exposed to HG+FFA to establish a sublethal lipotoxic model and treated with liraglutide, HMB, or their combination. Cell viability, lipid accumulation, myotube morphology, insulin signaling, glucose uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant gene expression, and atrophy-related signaling were assessed. Results: HG+FFA induced marked lipid droplet accumulation, impaired insulin signaling, reduced glucose uptake, disrupted mitochondrial membrane potential, increased ROS production, suppressed antioxidant gene expression, and promoted an atrophic phenotype characterized by increased atrogin-1 and MuRF1 and reduced myogenic markers. Liraglutide alone reduced large lipid droplets and partially improved insulin signaling but showed limited efficacy in preserving the myotube phenotype. HMB alone exerted modest effects on lipid accumulation but preserved myotube area. Notably, combined HMB and liraglutide treatment more effectively reduced lipid burden, restored insulin signaling and glucose uptake, attenuated mitochondrial dysfunction and oxidative stress, restored antioxidant gene expression, and preserved MyHC-positive area and myotube diameter while suppressing atrogin-1/MuRF1 activation. These protective effects were largely attenuated by rapamycin, indicating at least partial dependence on mTOR-associated signaling. Conclusions: Overall, HMB and liraglutide exert complementary protective effects against diabetic lipotoxic and atrophic stress, supporting the potential utility of this combination strategy for T2D-associated sarcopenia. Full article

Impatiens walleriana is a widely cultivated ornamental species extensively used in landscaping and garden design, with its vibrant floral colors constituting one of the primary determinants of its ornamental value. We found in preliminary observations that treatment of I. walleriana seeds with colchicine at 60 mg L⁻¹ induced significant flower color variation, with petals changing from purple to pink. Based on this, the present study used the wild-type (purple) and induced mutant plants (pink) of I. walleriana as materials, and systematically elucidated the molecular regulatory mechanism underlying its flower color variation via integrated analysis of targeted metabolomics and transcriptomics. Metabolomic analysis identified 84 anthocyanin-related metabolites. Metabolite composition and accumulation levels differed significantly between Iw-MU and Iw-WT. Pelargonidin, peonidin, and petunidin were markedly elevated in Iw-MU, while procyanidins accumulated to higher levels in Iw-WT. These metabolic differences may serve as the key metabolic basis for the petal color transition to pink. Transcriptomic analysis identified a total of 689 differentially expressed genes, of which 386 were upregulated and 303 were downregulated. Subsequent functional annotation and enrichment analysis revealed that the flavonoid biosynthesis pathway played a key regulatory role in flower color variation. Among these, the significant downregulation of key anthocyanin biosynthetic genes, DFR and ANS, likely suppressed the production of colored anthocyanins. In contrast, the expression levels of ANR and LAR genes were significantly upregulated, which may drive the metabolic flux to shift toward proanthocyanidin biosynthesis. This study elucidated the metabolomic composition characteristics and key regulatory genes associated with the floral color transition from pinkish-purple to light pink in I. walleriana, as well as clarified the core metabolic pathways and molecular regulatory mechanisms underlying this variation. These findings provide a theoretical foundation for the genetic improvement of flower color and the breeding of new cultivars in I. walleriana. Full article