Search Results (4,735)

Hydrogel additive manufacturing underpins soft tissue models, biointerfaces, and soft robotics. The coupled choices of formulation, rheology, and process conditions limit the progress. This review maps how artificial intelligence links composition to printability across direct ink writing, inkjet, vat photopolymerization, and laser-induced forward transfer, and how vision-guided control improves fidelity and viability during printing. Interpretable predictors connect routine rheology to strand stability, data-driven classifiers chart droplet regimes, and optical dose models with learning enhance voxel accuracy. Polymer informatics, including BigSMILES based representations, supports generative screening of precursors and crosslinkers. Bayesian optimization and active learning reduce experimental burden while honoring biological constraints, and emerging autonomous platforms integrate in situ sensing with rapid iteration. A strategic framework outlines a technological progression from current open-loop data gathering toward real-time closed-loop correction and ultimately predictive fault prevention through digital twins. The synthesis provides quantitative routes from formulation through process to function, establishing a practical foundation for predictive, reproducible hydrogel manufacturing and application-oriented design. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies, yet its molecular mechanisms remain poorly defined. The present study employed an analysis of microarray data (GSE7116) from peripheral blood mononuclear cells of patients with multiple myeloma, myeloma patients with MRONJ, and healthy controls. Differentially expressed genes were identified using the limma package, followed by functional enrichment analysis, weighted gene co-expression network analysis, and LASSO regression and CytoHubba network ranking. The predictive performance was validated by means of nested cross-validation, Firth logistic regression, and safe stratified 0.632+ bootstrap ridge regression. The profiling revealed distinct gene expression patterns between the groups: the upregulation of ribosomal and translational pathways, as well as the suppression of neutrophil degranulation and antimicrobial defense mechanisms, and identified key candidate genes, including PDE4B, JAK1, ETS1, EIF4A2, FCMR, IGKV4-1, and XPO7. These genes demonstrated substantial discriminatory capability, with an area under the curve ranging from 0.95 to 0.99, and were found to be functionally linked to immune system dysfunction, cytokine signaling, NF-κB activation, and a maladaptive stress response. These findings link MRONJ to systemic immune-inflammatory imbalance and translational stress disruption, offering novel insights and potential biomarkers for diagnosis and risk evaluation. Full article

Surgical castration, a common practice in animal husbandry, raises animal welfare concerns and adversely affects growth performance. Active immunization against gonadotropin-releasing hormone (GnRH) provides a non-surgical alternative. Both methods ultimately suppress sex hormone production, but their comparative effects on the gut microbiota, a crucial regulator of host health and metabolism, remain unclear. Here, 60 Sprague Dawley (SD) rats were randomly allocated into three groups—control (n = 20; 10 female and 10 male), surgical castration (n = 20; 10 female and 10 male), and GnRH immunocastration groups (n = 20; 10 female and 10 male)—at 4–5 weeks of age to comparatively investigate the impacts of surgical versus GnRH immunocastration on the gut microbiota. Our study demonstrated GnRH immunocastration significantly reduced gonadal weight, effectively suppressing gonadal development to a level comparable to surgical castration. However, the two methods induced distinct, sex-dependent shifts in the gut microbiota. Surgical castration reduced the gut microbial community diversity, whereas the community structure of GnRH immunocastrated rats more closely resembled that of the control group, indicating a milder impact on the microbial diversity and composition. Notably, GnRH immunocastration resulted in higher microbial alpha diversity than surgical castration in both female and male SD rats. Specific bacterial genera, such as Clostridia_UCG014, Lactobacillus, and Lachnospiraceae_UCG006, were similarly altered in both surgical castration and GnRH immunocastration female SD rats, while Intestinimonas and Erysipelatoclostridiaceae_UCG004 were concurrently changed in male SD rats. Conversely, Eubacterium_nodatum_group exhibited opposite responses, increasing with GnRH immunocastration but decreasing with surgical castration in male SD rats. Functional prediction revealed fundamental sex differences in microbial metabolic pathways. In females, nitrogen metabolism, glyoxylate/dicarboxylate metabolism, and mismatch repair were changed, while the pathways involved in siderophore biosynthesis, the citrate cycle (TCA cycle), genetic information processing, and amino acid metabolism were changed in male SD rats. In conclusion, GnRH immunocastration appears to be a less disruptive intervention, better preserving microbial diversity and inducing a unique functional profile. These findings highlighted the importance of considering the castration method’s impact on the gut microbial ecosystem in animal production and provided insights for developing humane and effective approaches to animal population control. Full article

The effects of different activation functions (sigmoid and hyperbolic tangent), and node numbers in a hidden layer of artificial neural network (ANN) models on urban air quality forecasting were investigated in a coastal city of Korea. The ANN models of multilayer perceptron (MLP) with a back-propagation training algorithm for error calculation in cases of 13, 15, and 17 nodes in each hidden layer were performed using 15 input independent variables (PM, gas, and meteorological data of Gangneung city (Republic of Korea)), affected by PM and gas of an upwind Beijing city (China). Root mean square error (RMSE) and the coefficient of determination (R²; Pearson R) were evaluated to assess the two models’ forecasting abilities between the predicted and measured values. The values of R by ANN-sig (ANN-tanh) with 13, 15, and 17 hidden neuron numbers were 0.930 (0.950), 0.920 (0.947), 0.926(0.953) on PM₁₀, 0.953 (0.956), 0.927 (0.938), 0.949 (0.960) on PM_2.5, and 0.880 (0.959), 0.917 (0.886), and 0.882 (0.939) on NO₂. Regardless of node numbers and activation functions, the prediction abilities of the two models were excellent, showing the highest values of R in the ANN-tanh model with more neuron numbers in the hidden layer. Unlike previous studies’ insistence that smaller nodes (larger) in the hidden layer produce the overfit (underfit) result in the ANN model, the present study proves that more nodes in its hidden layer than the input layer can yield the best prediction than any other, as shown in their temporal distributions and scatter plots of predicted and measured data. Future-time air quality forecasting at Gangneung city can be calculated sequentially using its current time data and previous time data from Beijing city, using the suggested empirical formulas. Full article

Vibrio harveyi (Vh) and Vibrio vulnificus (Vv) are major bacterial pathogens affecting farmed eels, but their comparative virulence mechanisms remain poorly characterized. This study combined histopathology and transcriptomic profiling to investigate organ-specific damage and host responses in American eels (Anguilla rostrata, 20 g per fish, for a total of 60 fish) following experimental infection with LD₅₀ doses of Vh (strain HA_1, 7.5 × 10⁴ CFU/fish) and Vv (strain FJ_4, 5.0 × 10⁵ CFU/fish). Tissue samples from liver, kidney, and spleen were collected at 0, 36, and 60 h post-infection (hpi). Histopathological analysis revealed distinct injury patterns: Vh induced severe hepatic edema and necrosis, whereas Vv caused vacuolar degeneration and vascular congestion in the liver. In the kidney, Vv triggered acute necrosis and vacuolization by 36 hpi, while Vh-induced renal damage was delayed until 60 hpi. Transcriptomic analysis of spleen tissue identified 4779 and 1215 differentially expressed genes (DEGs) in the Vh_36 vs. Vv_36 and Vh_60 vs. Vv_60 comparisons, respectively. Functional enrichment analysis associated these DEGs with 109 Gene Ontology (GO) terms—mainly catalytic activity, biological regulation, and binding—and 51 KEGG pathways, including “tuberculosis” and “pathways in cancer”. Differential alternative splicing (DAS) analysis further uncovered 1579 and 1214 DAS events originating from 12,482 and 12,316 splicing genes in the two comparisons. These were enriched in GO categories such as “binding”, “cellular process”, and “cell part”, as well as KEGG pathways related to “signal transduction”, “infectious diseases”, and “immune system.” Protein–protein interaction network analysis identified 119 cross-DAS-encoded proteins, including 8 that were predicted as key regulators of virulence differences. In summary, this work presents the first integrative study comparing the pathogenicity and host transcriptional dynamics of Vh and Vv in American eels, providing new molecular insights into their distinct virulence strategies. Full article

A series of dimethylpyridine-3-carboxamide derivatives was designed as potential, selective, non-zinc chelating inhibitors of matrix metalloproteinase 13 (MMP-13), and subsequently synthesized. The identity of the obtained compounds was confirmed by FT-IR, ¹H/¹³C NMR, and HR-MS methods. Fluorescence spectroscopy was applied to study the interaction of synthesized compounds with human serum albumin, providing insight into their potential transport properties in plasma. In parallel, the electronic properties and reactivity parameters relevant to enzyme binding of the designed molecules were analyzed using density functional theory. Molecular docking and molecular dynamics simulations revealed the compounds to interact preferentially and stably within the S₁ pocket of MMP-13 via hydrogen bonds and π-stacking interactions. The calculated binding free energy confirmed the stability and persistence of the complexes during simulation, indicating a strong and specific recognition pattern. On the other hand, their affinity towards MMP-8 was considerably weaker, which is consistent with the predicted selectivity profile. In addition, the biological evaluation confirmed MMP-13 inhibition. Finally, in vitro tests revealed their cytotoxic activity against cancer cell lines. Full article

This study presents an assessment scheme for haptic interaction systems based on Hamiltonian energy prediction, which contributes to procedures applied to neurorehabilitation. It focuses on robotic systems involving human participation in the control loop, where uncertainty may compromise both stability and task performance. To address this, a regression-based model is proposed to predict total mechanical energy using the robot’s position and velocity signals during active interaction. Synthetic data generated via TimeGAN are used to enhance model generalization. Advanced machine learning techniques—particularly Gradient Boosting—demonstrate outstanding accuracy, achieving an MSE of $0.628\times {10}^{-10}$ and $R^2=0.999976$. These results validate the use of synthetic data and passive-mode-trained models for assessing motor performance in active settings. The method is applied to a patient diagnosed with Guillain-Barré Syndrome, using the Hamiltonian function to estimate energy during interaction and objectively assess motor performance changes. The results obtained show that our proposal is of great relevance since it solves a current field of opportunity in the area. Full article

Plasma membrane Ca²⁺-ATPases (PMCA) are activated by calmodulin (CaM) via a C-terminal calmodulin-binding domain, CaMBD. Although specific mutations in this domain have been linked to disease, the broader impact of alternative substitutions across the interface remains unexplored. We applied an integrative in silico workflow to test six substitutions within CaMBD positions 1–18, L5R, N6I, I8T, V14E/D, and F18S, across PMCA isoforms 1–4. CaMBD sequences were aligned across isoforms, and candidates for substitutions were selected by conservation and nucleotide feasibility, prioritizing conserved or co-evolutionarily relevant sites, with substitutions possible by single-nucleotide change. PolyPhen-2 screened the impact of the substitutions on the protein functionality, the DisGeNET database was used to contextualize ATP2B genes with clinical phenotypes, and structural models plus binding free energy changes were estimated with AlphaFold3, FoldX, and MutaBind2. Effects were isoform and subregion dependent, with the strongest weakening toward the CaMBD C-terminus. V14E/D and F18S showed the largest and consistent predicted destabilization, consistent with disruption of conserved hydrophobic anchors. I8T and L5R had mixed outcomes depending on isoform, while N6I presented various scenarios with no clear effect. PolyPhen-2 classified most tested substitutions as damaging. Gene-disease evidence linked ATP2B to neurological, endocrine, and oncologic phenotypes, consistent with roles in Ca²⁺ homeostasis. Overall, CaMBD appears highly sensitive to perturbation, with distal positions 14–18 particularly vulnerable to substitutions that can destabilize CaM binding and potentially impair PMCA-mediated Ca²⁺ clearance in susceptible tissues. Full article

In Myanmar, Russell’s viper (Daboia siamensis) bite is a significant public health problem. In this study, we expend upon our previous RNA-sequencing approach to characterize candidate toxin genes encoding D. siamensis toxins. The mRNA was extracted from Myanmar Russell’s viper venom glands. The RNAseq was performed using Illumina next-generation sequencing. Subsequently, candidate toxin transcripts were recognized by the Venomix pipeline. This study focused on 29 unique cDNA sequences representing eight newly identified venom gene families with low-to-moderate expression levels. These transcripts represented 0.088% of the total number of transcripts in the dataset. The translated protein sequences were analyzed for their conserved motifs and domains to predict their functions. They were neprilysins (bioactive peptide inactivators), cystatins (protease inhibitors with anti-metastatic activities), waprin and vipericidin (antimicrobial peptides), veficolin (platelet and complement activation), vespryns and three-finger toxins (elapid toxin homologs causing neurotoxic activity and tissue damage), and endothelial lipases (unknown function). Their functional activities should be further investigated for potential therapeutic applications, for example, in cancer or antibiotic-resistant infections. Full article

Tailoring the spin crossover (SCO) effect in molecular materials remains a fundamental challenge, driven by the need to control critical parameters, such as the spin transition temperature (T₁/₂), hysteresis width, cooperativity, and switching kinetics for applications in sensing, memory, and actuation devices. SCO behavior is highly sensitive to small changes in the structure or crystal structure of the surrounding environment. In this context, achieving predictable and reproducible control remains elusive. Embedding SCO complexes into polymer matrices offers a more versatile and processable approach, but understanding how matrix–guest interactions affect spin-state behavior is still limited. In this study, we investigate a polymer-mediated strategy to tune SCO properties by incorporating the well-characterized Fe(II) complex [Fe(1,10-phenanthroline)₂(NCS)₂] into three polymers with distinct structural features: polylactic acid (PLA), polystyrene (PS), and polysulfone (PSF). In terms of potential electrostatic interaction between the complex and the polymeric matrixes, the polymers offer distinct features. Either there does not seem to be any specific interaction (PLA case) or, rather, there is π-π stacking between the aromatic rings of the SCO complex, and the corresponding ones present either in the backbone or in the side chain of the polymer (PSF and PS, respectively). The latter can potentially influence spin-state energetics and dynamics. Importantly, we also reveal and quantify the migration behavior of SCO particles within different polymer matrices, an aspect that has not been previously examined in SCO–polymer systems. Using magnetic susceptibility, spectroscopic, diffraction, and migration studies, we show that the polymer environment, PLA as well, actively modulates the SCO response. PSF yields lower T₁/₂, slower switching kinetics, and enhanced retention of the complex, indicative of strong matrix confinement and interaction. In contrast, PLA and PS composites exhibit sharper transitions and higher migration, suggesting weaker interactions and greater mobility. In addition, the semi-crystalline nature of PLA seems to induce the extension of the hysteresis width. These results highlight both the challenge and the opportunity in SCO polymer composites to tune SCO behavior, offering a scalable route toward functional hybrid materials for thermal sensing and responsive devices. Full article

Pea protein isolates (PPIs) from Pisum sativum have emerged as strategic ingredients at the interface of nutrition, sustainability, and functional food design. This review synthesizes advances linking isolation procedures with molecular structure and techno-functional performance. We compare alkaline extraction–isoelectric precipitation with wet and dry fractionation, as well as green/fermentation-assisted methods, highlighting the purity–functionality trade-offs driven by denaturation, aggregation, and the removal of anti-nutritional factors. We relate globulin composition (vicilin/legumin ratio), secondary/tertiary structure, and disulfide chemistry to interfacial activity, solubility, gelation thresholds, and long-term emulsion stability. Structure-guided engineering strategies are critically evaluated, including enzymatic hydrolysis, deamidation, transglutaminase cross-linking, ultrasound, high-pressure homogenization, pH shifting, cold plasma, and selected chemical/glycation approaches. Application case studies cover high-moisture texturization for meat analogues, emulsion and Pickering systems, fermented dairy alternatives, edible films, and bioactive peptide-oriented nutraceuticals. We identify bottlenecks—weak native gel networks, off-flavors, acidic pH performance, and batch variability—and outline process controls and synergistic modifications that close functionality gaps relative to animal proteins. Finally, we discuss sustainability and biorefinery opportunities that valorize soluble peptide streams alongside globulin-rich isolates. By integrating extraction, structure, and function, the review provides a roadmap for designing PPI with predictable, application-specific performance. Full article

Background/Objectives: The growing demand for functional foods and alternative therapeutic strategies has intensified the search for novel probiotic strains from underexplored ecosystems. This study aimed to isolate and phenotypically characterize lactic acid bacteria (LAB) from spontaneously fermented fruits found in the Legal Amazon (Ananas comosus, Humiria balsamifera, Manilkara zapota, and Platonia insignis) and to perform genome-based analysis of the most promising isolate to evaluate its probiotic potential. Methods: The isolates were identified by MALDI-TOF-MS and screened for tolerance to low pH, bile salts, lysozyme, growth at 39 °C, and antimicrobial activity against five enteric pathogens. The most promising isolate was evaluated by coaggregation and biofilm assays, in silico proteome and CAZyme analysis, bacteriocin cluster mining, and in vivo efficacy testing using Tenebrio molitor larvae. Results: Three isolates from H. balsamifera were identified as Lactiplantibacillus plantarum (M1, M2, M4) by MALDI-TOF-MS. These isolates exhibited high resilience to all tested physiological stressors. Antimicrobial activity was contact-dependent, with no inhibition by cell-free supernatants. M2 showed the strongest pathogen exclusion, moderate biofilm formation, and high coaggregation with S. enterica and E. faecalis. Genome analysis of M2 revealed a 3.40 Mb chromosome, absence of acquired resistance or virulence genes, two plantaricin gene clusters, and 93 CAZymes, including GT families linked to exopolysaccharides biosynthesis. SignalP predicted secretion signals in 10 CAZymes. M2 significantly improved larval survival against E. coli and S. enterica, especially under prophylactic treatment. Conclusions: L. plantarum M2 combines safety, stress tolerance, genomic features, and in vivo efficacy, positioning it as a promising probiotic candidate adapted to tropical niches. These findings highlight H. balsamifera as a reservoir of novel probiotic strains. Full article

Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of inflammation and contribute to the inflammatory cascade that may result in organ failure. We aimed to investigate blood concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 chemokines and their diagnostic and prognostic significance in patients with ALD. In a prospective observational study, 88 individuals were recruited, including 63 patients with ALD (44 men and 19 women, aged 48.49 ± 10.88) and 25 healthy control volunteers matched for age, sex, and ethnicity. In blood samples, concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 were measured using immunoenzymatic ELISAs. Correlations were examined between CXCL levels and (a) traditional inflammatory markers (C-reactive protein, white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio-NLR) and (b) liver dysfunction severity scores: Child–Turcotte–Pugh (CTP), MELD-NA, MELD 3.0, and modified Maddrey’s discriminant function (mDF). Patients’ survival within 30 days of hospital admission was recorded for analysis. CXCL capabilities in predicting the severity of liver dysfunction and ALD outcome were validated. ALD patients showed significant systemic upregulation of all studied chemokines compared to the control group. Patients with advanced liver disease, classified as MELD-Na ≥ 20, MELD3.0 > 19, and CTP class C, as well as poor short-term outcomes, presented with significantly higher CXCL9 and CXCL10 levels compared to their counterparts. ALD non-survivors had significantly higher concentrations of all studied CXCLs in comparison to controls. Positive correlations between CXCL16 and CRP, leukocytosis, neutrophils, and NLR were confirmed (0.67; 0.46; 0.48; 0.54, respectively). Although none of the chemokines correlated with ALT activity, CXCL9, CXCL10, and CXCL16 showed positive correlations with bilirubin and alkaline phosphatase and inverse correlations with albumin levels. Our findings revealed the diagnostic and prognostic value of the studied CXCLs in ALD. In particular, CXCL9 and CXCL10 may have potential for discrimination of severe liver dysfunction and poor short-term prognosis. Further multicenter studies are required to confirm our results. Full article

The die bonding process significantly impacts the yield and quality of IC packaging, and its quality detection is also a critical image sensing technology. With the advancement of machine automation and increased operating speeds, the misclassification rate in die bond image inspection has also risen. Therefore, this study develops a high-speed intelligent vision inspection model that slightly improves classification accuracy and adapts to the operation of new-generation machines. Furthermore, by identifying the causes of die bonding defects, key process parameters can be adjusted in real time during production, thereby improving the yield of the die bonding process and substantially reducing manufacturing cost losses. Previously, we proposed a lightweight model named DSGβSI-YOLOv7-tiny, which integrates depthwise separable convolution, Ghost convolution, and a Sigmoid activation function with a learnable β parameter. This model enables real-time and efficient detection and prediction of die bond quality through image sensing. We further enhanced the previous model by incorporating an SE layer, ECA-Net, Coordinate Attention, and a Small Object Enhancer to accommodate the faster operation of new machines. This improvement resulted in a more lightweight architecture named DSGβSI-SECS-YOLOv7-tiny. Compared with the previous model, the proposed model achieves an increased inference speed of 294.1 FPS and a Precision of 99.1%. Full article

It has been demonstrated that prolonged exposure to stress engenders a plethora of neuropsychiatric, immune and metabolic disorders. However, its pathophysiology transcends the conventional hypothalamic–pituitary–adrenal (HPA) axis. This review addresses the central question of how integrated neural and microbial pathways regulate stress responses and resilience. We present a model in which the parasympathetic nervous system (particularly the vagus nerve) and the gut microbiota interact to form a bidirectional neuroimmune network that modulates the HPA axis, immune function, neurotransmitter balance, and metabolic adaptation. Key molecular pathways include nitric oxide synthesis via the classical nitric oxide synthase (NOS)-dependent and microbiota-mediated nitrate–nitrite routes, inducible nitric oxide synthase (iNOS) regulation, nuclear factor erythroid 2-related factor 2 (Nrf2) signalling, lysosomal function, autophagy and the cholinergic anti-inflammatory reflex. Other pathways include the gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signalling, polyamine metabolism and peroxisome proliferator-activated receptor gamma (PPARγ). Intermittent hypoxia training (IHT) enhances mitochondrial function, oxidative stress responses, autonomic balance and gut microbiota composition. This promotes parasympathetic activity and stress resilience that is tailored to the individual. These adaptations support the concept of personalised stress response profiles based on hypoxic adaptability. Clinical implications include combining IHT with vagus nerve stimulation, probiotics, dietary strategies, and stress reduction techniques. Monitoring vagal tone and microbiota composition could also serve as predictive biomarkers for personalised interventions in stress-related disorders. This integrative framework highlights the therapeutic potential of targeting the parasympathetic system and the gut microbiota to modulate stress. Full article