Search Results (36,631)

Klebsiella pneumoniae infection following H9N2 Influenza A virus (IAV) infection causes severe pneumonia. But the underlying pathogenic mechanisms of H9N2 IAV and K. pneumoniae co-infection are complex and need to be further explored. In this study, the lung transcriptomes of mice with H9N2 IAV and K. pneumoniae co-infection were characterized by transcriptomic profiling. As a result, GO enrichment analysis revealed that the differential genes were primarily involved in the activation of immune responses, cellular components of membranes and extracellular spaces, and defense responses against pathogen infections. According to KEGG enrichment, the differentially expressed genes (DEGs) were concentrated in TLR signaling pathways, RLR signaling pathways, TNF signaling pathways and NLRP3 signaling pathways. Furthermore, in vitro cell models were established to investigate the innate immune responses induced by H9N2 IAV and K. pneumoniae CPS co-stimulation. K. pneumoniae CPS stimulation influenced the cytokine profiles of mink lung epithelial cells infected with H9N2 IAV, worsened cell viability, and aggravated apoptosis, indirectly inhibiting H9N2 IAV replication. The findings demonstrated that K. pneumoniae superinfection modulated the innate immune responses induced by H9N2 IAV infection, contributing to its pathogenesis. Full article

Background/Objectives: Ki67 is a well-established histologic proliferation marker across many cancers; however, its clinical application in pancreatic ductal adenocarcinoma (PDAC) has remained limited. Multiple studies have demonstrated that Ki67 is prognostic in PDAC, with higher Ki67 expression associated with worsened outcomes. In this study, we aimed to characterize the underlying biology of Ki67-enriched tumors. Methods: Clinical and transcriptional data from PDAC patients were obtained from The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. Mutational analysis from the TCGA cohort was also performed. Patients within each study were stratified into low- and high-expression groups based on the median transcript levels. Each dataset was analyzed independently, and differences between groups were subsequently compared across studies. Results: Consistent with their enhanced proliferative capacity, MKI67-high tumors were consistently enriched in pro-proliferative cellular pathways including E2F targets, MYC targets, and mitotic spindle formation as well as pro-growth metabolic pathways across all studies. MKI67-high PDAC is associated with higher histologic grading with similar pathologic staging. High expression was associated with worsened overall and disease-free survival in the TCGA cohort, although this was not consistently observed across external validation datasets. MKI67-high tumors exhibited a significantly higher mutational burden than the MKI67-low tumors. Conclusions: MKI67 enrichment in PDAC correlates with aggressive tumor biology, enhanced proliferative signaling, genomic instability, and distinct microenvironmental and immune features. MKI67-high tumors demonstrate a reproducible association with proliferative signaling, genomic instability, and aggressive biological features across multiple transcriptomic datasets. Further validation is required to determine the clinical utility of MKI67 as a biomarker in PDAC. Full article

Personalized recommendation has become an essential component of intelligent information systems and electronic multimedia platforms. However, cold-start items with limited user–item interactions remain difficult to model, especially when collaborative signals are sparse and heterogeneous side information is underutilized. To address this problem, this paper proposes Heterogeneous Graph Contrastive Recommendation (HGCRec), a heterogeneous graph contrastive learning framework for cold-start multi-modal recommendation. HGCRec constructs a heterogeneous structural graph containing users, items, categories, brands, and semantic entities, while visual and textual information is incorporated as item-side feature views. A relation-aware heterogeneous graph encoder captures relation-specific structural semantics, and a cross-modal graph contrastive learning objective coordinates structural, visual, and textual item representations. An interaction-sparsity-aware weighting strategy allocates stronger contrastive supervision to items with fewer training interactions. Furthermore, an item-specific adaptive fusion module integrates collaborative, structural, visual, and textual representations according to interaction sparsity and learned multi-source representation states. Experiments are conducted on three Amazon multi-modal recommendation datasets, including Baby, Sports, and Clothing. The results show that HGCRec consistently outperforms representative graph-based and multi-modal recommendation baselines. Compared with the strongest baseline, Freezing and Denoising Graph Structures for Multimodal Recommendation (FREEDOM), HGCRec improves Recall@20 by 9.65%, 10.44%, and 12.00% on Baby, Sports, and Clothing, respectively, and improves NDCG@20 by 11.14%, 11.35%, and 13.10%. Sparsity-aware analysis further shows larger relative improvements for items with extremely limited training interactions, demonstrating the effectiveness of HGCRec under the evaluated interaction-sparse and few-shot settings. Full article

Nursery-plant grading relies on morphological traits, but leaf metabolic variation associated with nursery-plant grade remains unclear. In this study, untargeted HPLC-QTOF-MS metabolomics was applied to mature and young leaves of Grade I, II, and III apple nursery plants to explore grade-associated metabolic variation and its relationship with growth performance. After quality filtering, 198 positive-ion features were retained from mature leaves, while 259 positive-ion and 8 negative-ion features were retained from young leaves. Multivariate analysis showed clear grade-associated separation in both leaf types, with stronger discrimination in young leaves. A combination of orthogonal partial least squares (OPLS) modeling and trend analysis identified 20 and 28 differential features in mature and young leaves, respectively. Cross-model prioritization further highlighted key metabolites putatively annotated as methyl nicotinate and 1-palmitoyl-sn-glycero-3-phosphocholine in mature leaves, and methyl nicotinate, nicotinamide riboside, cis-jasmone, and methyl (9Z,14Z)-12,13,16-trihydroxyoctadeca-9,14-dienoate in young leaves. These key metabolites were potentially associated with NAD precursor metabolism, membrane lipid remodeling, and oxylipin-related signaling. Correlation analysis showed that they were associated with both initial grading traits and post-transplant growth performance. These metabolites represent candidate molecular correlates of grade-associated physiological variation and growth performance in apple nursery plants. Full article

In this work, we study the joint performance of the quality and reliability in terms of quality–reliability (JQR) performance of an intelligent reflecting surface (IRS)-assisted wireless communication system under severe multipath fading and shadowing. The wireless channel model is given by the Inverse Power Lomax (IPL) fading model, representing a heavy-tailed fading channel, which can describe the hyper-Rayleigh fading and is verified using two different experimentally obtained measurement scenarios, namely, the LTE-case for high-frequency, long-range cellular communications and the device-to-device (D2D) case for lower-frequency short-range communications. For the considered channel model and communication scheme, analytical expressions for the outage probability (a metric related to the reliability) and the average bit error rate for both coherent and non-coherent modulation schemes (metrics associated with the quality of the communication system) are provided. By combining the aforementioned expressions, a unified JQR curve, together with its asymptotic forms in the high signal-to-noise ratio regime and asymptotically large number of IRS elements, is derived. It is proved analytically that the use of IRS with infinite elements can remove fading, while for a finite number of IRS elements, a closed-form signal-to-noise ratio (SNR) penalty factor is presented. The numerical analysis demonstrates that coherent modulations outperform non-coherent ones, higher-order quadrature amplitude modulation (QAM) systems are highly sensitive to the multipath fading, and the LTE-case exhibits better performance compared to the D2D-case for equal settings. Moreover, the joint quality–reliability approach highlights the existence of regions where quality is more preferable than reliability, allowing the allocation of resources based on these regions. All expressions have been verified using Monte Carlo simulations with excellent agreement. Full article

The corneal epithelium serves as the outermost transparent barrier of the eye and depends on rapid and coordinated cellular responses for wound repair. Although negative pressure (NP) has been shown to accelerate wound healing in other tissues, its cellular and molecular effects on corneal epithelium remain undefined. This study investigates how NP regulates corneal epithelial cell physiology and identifies the molecular mechanisms underlying NP-induced migration. Human corneal epithelial cells were exposed to normal or NP conditions, and cell motility was quantified using scratch-wound and transwell migration assays. Nuclear and cytoplasmic fractions were isolated for proteomic profiling to identify NP-responsive proteins. G3BP1 was selected as a candidate regulator and subsequently examined using molecular, biochemical, and functional assays to determine its role in NP-mediated signaling. Proteomic analysis revealed a significant NP-induced upregulation of G3BP1. Mechanistically, G3BP1 suppressed epithelial junctional proteins, including E-cadherin, p120-catenin, and ZO-1, while activating key pro-migratory signaling pathways involving AKT, ERK1/2, FAK, and Paxillin. These coordinated changes enhanced cytoskeletal dynamics and promoted corneal epithelial cell migration under NP stimulation. G3BP1 functions as a critical mechanotransduction mediator of NP, orchestrating adhesion remodeling and activating pro-migratory signaling cascades to facilitate corneal epithelial cell motility. These findings reveal a previously unrecognized cellular mechanism through which NP promotes epithelial repair and highlight G3BP1 as a potential therapeutic target for persistent corneal epithelial defects. Full article

This paper aims to address the challenge of identifying early-stage short-circuit faults in lithium-ion battery modules through conventional voltage and current signals. The perturbation injection method is employed to inject low-amplitude AC disturbances into battery circuits under constant-current charging cases. By synchronously capturing voltage and current responses and performing frequency-domain analysis, the system achieves real-time impedance spectrum acquisition. A comparative analysis is given based on linear frequency-modulated signals and multiple sine wave signals. The results demonstrate superior performance in wide-band impedance measurement regarding spectral distribution and measurement accuracy. A MATLAB/Simulink-based impedance measurement model including individual cells and battery modules is developed. Simulation results show that within the 1~1000 Hz frequency range, the maximum impedance amplitude errors are 0.0129 Ω for individual cells and 0.077 Ω for battery modules. Further experiments utilizing parallel short-circuit resistors with varying values verify that increased short-circuit severity can lead to reduced impedance amplitude and expanded phase angle. It also validates that module impedance characteristics are closely correlated to the number and spatial distribution of short-circuited cells. These results validate the feasibility and effectiveness of the proposed method in detecting short-circuit faults in battery modules. Full article

We report on electric field measurements recorded onboard the China Seismo-Electromagnetic Satellite (CSES). In this study, we emphasize the whistler and transmitter very low frequency (VLF) radiations recorded in the frequency range between 1.8 kHz and 25 kHz. The electric field detector (EFD) instrument onboard the CSES works as a double probe instrument and allows access to the three electric components of VLF waves. Three frequencies were selected, two related to whistler hiss (i.e., 2.5 kHz channel) and chorus (i.e., 5 kHz channel) radiations and one to the NAA ground-based transmitter signal (i.e., 24 kHz). We investigate the corresponding power spectral density variations, from which we derive the Stokes intensity I and normalized q linear polarization components. This leads us to study their statistical fluctuations and to emphasize the behaviors of natural whistler hiss and chorus radiations and man-made transmitter emissions. The Stokes intensities of the natural whistler and NAA transmitter radiations are estimated, respectively, to be about 1 mV² m⁻² Hz⁻¹ and 0.05 mV² m⁻² Hz⁻¹. The correlation coefficients of the Stokes intensity polarizations are in the order of 98% powerfully coupled, contrary to the Stokes normalized linear polarizations, which are found to be relatively paired, i.e., less than 60%. The signal-to-noise ratio is estimated considering three intensity levels (i.e., high, medium, low). This analysis leads us to characterize the Stokes normalized linear components of VLF radio waves and to show different behaviors of the polarization when considering the Northern and Southern Hemispheres. The regions of enhanced whistler Stokes intensities of whistler hiss and chorus emissions are confined to the sub-auroral regions in both hemispheres, particularly at geomagnetically ranges linked to the NAA transmitter station and its conjugate region in the Southern Hemisphere. In this investigation, we point out the Stokes polarization parameters, which are essential for the characterization of whistler VLF radio waves, particularly when considering the CSES mission objectives and commitments. Full article

Nitrous oxide (N₂O), commonly known as laughing gas, is widely used for its anesthetic and analgesic properties in medical settings. However, its recreational abuse has escalated, leading to severe neurological complications including cognitive impairment, yet the underlying mechanisms remain poorly understood. In this study, male C57BL/6 J mice were exposed to either normal air inhalation or nitrous oxide inhalation for 28 days to evaluate the effects of repeated nitrous oxide exposure on cognitive function. We employed hippocampal transcriptome sequencing, real-time PCR, Western blotting, and non-targeted plasma metabolomics to explore potential regulatory mechanisms. Repeated nitrous oxide exposure impaired motor skills, learning, and cognitive abilities in mice. Integrative multi-omics analysis revealed that differentially expressed metabolites and genes synergistically disrupted energy metabolism through co-regulation of the TCA cycle, MAPK signaling pathway, and pyrimidine metabolism, ultimately leading to impaired cellular signaling, nucleic acid synthesis, and cognitive dysfunction. Our study provides novel multi-omics insights into the MAPK/ERK/CREB-mediated neurotoxicity and energy metabolism collapse induced by nitrous oxide as a recreational drug of abuse, offering new directions for clinical intervention. Full article

Roasting time strongly influences almond oil yield, flavor and oxidative stability. This study investigated almond oils obtained by pressing almond kernels roasted at 130 °C for 0, 5, 10 and 20 min, corresponding to cold-aroma, light-aroma, strong-aroma and sauce-aroma groups, respectively, by combining physicochemical analysis, fatty acid quantification, gas chromatography–ion mobility spectrometry (GC-IMS), machine learning and lipidomics. Increasing roasting time enhanced oil yield from 45.81% to 50.34%, with no further significant increase after 10 min. Stronger roasting moderately reduced the free radical level. In contrast, acid value, peroxide value and thiobarbituric acid reactive substances (TBARS) increased from 0.28 to 0.38 mg KOH/g oil, 1.20 to 1.46 meq O₂/kg oil and 0.38 to 0.46 mg malondialdehyde/kg oil, respectively, indicating limited oxidative deterioration. Fatty acid analysis showed that oleic acid remained relatively stable at 644.37–647.03 mg/g oil, whereas linoleic acid decreased significantly from 150.42 to 140.19 mg/g oil. GC-IMS detected 59 volatile signals and clearly separated the four processing groups, indicating substantial roasting-induced changes in volatile fingerprints. A positive–unlabeled (PU) learning model used 27 literature-supported aroma-active compounds as the positive class and 32 compounds without confirmed aroma-activity evidence as the unlabeled class. The model showed good cross-validated discrimination, with a mean area under the receiver operating characteristic curve (ROC-AUC) of 0.866 and a mean area under the precision–recall curve (PR-AUC) of 0.756, and prioritized eight unlabeled compounds, mainly alcohols and methional, as candidate aroma-active compounds requiring further sensory validation. Lipidomic analysis showed that accelerated oxidation caused broad lipid remodeling, with 327 differential lipids between cold-aroma oxidized and unoxidized oils, mainly involving glycerophospholipids, glycerol lipids, sphingolipids and fatty acyls. Overall, increasing roasting time improved oil recovery and promoted aroma differentiation while causing only limited initial oxidative deterioration, providing a theoretical basis for optimizing roasting conditions in industrial processing. Full article

Environmental heat stress disrupts cellular homeostasis through coordinated molecular responses involving protein quality control, oxidative stress regulation, inflammatory signaling, and water homeostasis. Although saliva plays an essential role in maintaining oral homeostasis, the molecular pathways underlying salivary adaptation to heat stress remain insufficiently characterized. We hypothesized that integrating the human salivary proteome with systems biology approaches would identify a reproducible heat-stress-responsive molecular signature. Human salivary proteomic datasets retrieved from the Human Salivary Proteome Wiki were integrated into a non-redundant dataset comprising 15,594 protein accessions corresponding to 2540 distinct proteins. Following deduplication, functional annotation, and biological curation, proteins associated with heat stress response, oxidative stress regulation, inflammatory signaling, water homeostasis, salivary secretion, and mucosal protection were assembled into a Salivary Climate Stress Panel (SCSP). Protein–protein interaction and functional enrichment analyses were performed, and the biological relevance of the identified proteins was independently evaluated using a human heat stress transcriptomic meta-analysis comprising 322 comparisons and the GEO dataset GDS3004. Functional filtering identified 2050 heat-stress-associated salivary proteins, from which a curated SCSP of 35 proteins was established. Network analysis identified HSP90AB1, HSP90AA1, and IL1B as the principal hub proteins linking heat stress, oxidative stress, inflammatory signaling, and water homeostasis pathways, while transcriptomic validation confirmed consistent activation of representative SCSP genes under heat stress conditions. These findings provide a reproducible systems-level framework for investigating heat-stress-responsive molecular pathways in the human salivary proteome and support future studies on salivary biomarkers of environmental heat exposure. Full article

Microelectromechanical systems (MEMS) have a widespread use in several applications such as signal filtering, time referencing, and sensing. This paper explores the nonlinear dynamic behavior of a MEMS resonator using a reduced-order modeling approach. The study focuses on how multi-modal formulation and detuning affect the system’s response under primary resonance. Using the method of multiple scales, amplitude–phase response equations are derived, and time-domain simulations are generated with the Runge–Kutta method. Two mode combinations are examined: the first mode combined with the second mode and the first mode with the third mode for multi-modal influence evaluation. Results indicate that the first mode provides the dominant behavior to MEMS response, while the second and third modes exhibit minimal participation despite the nonlinearities retained in the presented multi-modal model. Additionally, a detuning study reveals that the geometric and forcing nonlinear effects are stronger near resonance and diminish as the system moves away from it. The analysis suggests that the significant features of the response can be captured in the case of primary resonance using only the first mode, which offers an effective modeling approach. From a design perspective, finding that the first mode alone is sufficient means that the essential dynamic behavior of the MEMS resonator can be predicted and controlled by focusing on its first mode of vibration. In practical terms, this greatly allows engineers to optimize geometry, driving voltage, or control parameters to target the first mode natural frequency without accounting for higher modes, which reduces computational cost and design complexity. Full article

Background: Lipid mediators (LM), comprising 17S-hydroxy-docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50, were naturally generated from docosahexaenoic acid by soybean lipoxygenase and exhibit potent anti-inflammatory activities. However, their therapeutic potential in periodontitis (PD) remains unclear. Therefore, this study investigated the protective effects of LM against PD in vitro and in vivo. Methods: Human gingival fibroblasts (HGFs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS) to evaluate the anti-inflammatory effects of LM. Nitric oxide (NO) production, prostaglandin E2 (PGE2) level, inflammatory cytokines secretion, matrix metalloproteinase 9 (MMP9) expression, and NF-κB/STAT3 signaling pathways were analyzed. In vivo, a ligature-induced rat model of PD was established, and LM were orally administered at doses of 5, 10, and 20 μg/kg once daily. The effects of LM were evaluated by histopathological examination, micro-computed tomography (micro-CT), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC). Results: In PG-LPS-stimulated HGFs, LM significantly reduced NO and PGE2 production by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, LM decreased the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, and MMP9, accompanied by suppression of the NF-κB and STAT3 signaling pathways. In the ligature-induced rat model of PD, LM significantly attenuated gingival inflammation and alveolar bone loss. Furthermore, IHC analysis revealed that LM markedly reduced the level of IL-6, TNF-α, MMP9, and phosphorylated STAT3 in gingival tissues. Conclusions: LM exerted protective effects against periodontitis by alleviating inflammatory response and reducing alveolar bone loss, which may be associated with suppression of the NF-κB and STAT3 signaling pathways. Full article

The progressive failure of pancreatic beta-cells under chronic glucolipotoxicity drives the pathogenesis of type 2 diabetes mellitus (T2DM). This metabolic stress overwhelms the folding capacity of the endoplasmic reticulum (ER), hyperactivates the unfolded protein response (UPR), engages terminal pro-apoptotic signaling through C/EBP-homologous protein (CHOP), and promotes beta-cell dedifferentiation. In this systematic review and meta-analysis, registered with PROSPERO (CRD420261370436), we evaluated the preclinical efficacy of the low-molecular-weight chemical chaperones tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) in preserving beta-cell exocytotic identity and mitigating ER stress. Following PRISMA 2020 guidelines, a systematic search of PubMed, Scopus, and Web of Science (January 2016–May 2026) identified four eligible experimental studies. Preclinical models (INS-1 and βTC-6 cell lines, Wistar rats, and C57BL/6 mice) exposed to a high-fat diet (HFD), a high-fat/high-fructose diet (HFHFD), cholesterol loading, or protein restriction followed by high-fat feeding showed impaired or dysregulated glucose-stimulated insulin secretion (GSIS) and upregulated ER-stress markers. Co-administration of TUDCA or 4-PBA moved secretory output toward the healthy-control phenotype in every model and reduced pro-apoptotic markers in the three models in which they were measured. A hierarchical Bayesian random-effects meta-analysis of the between-arm GSIS restoration ratio at stimulatory glucose yielded a pooled ratio of 1.85 (95% credible interval [CrI] 1.38 to 2.43), with the entire credible mass above the null (posterior probability of benefit 0.996). This estimate was stable across nine prior specifications for the between-study standard deviation and in every leave-one-out analysis, including exclusion of the single hypersecretion model (1.98, 95% CrI 1.09 to 3.18). Between-study variance was small but weakly identified from only four studies and is reported as exploratory. Pooling instead on the registered within-arm stimulation-index scale, a change in metric declared as a protocol deviation, gave 1.46 (95% CrI 0.73 to 2.58) with substantial heterogeneity (I² = 89.3%), so the evidence supports restoration of absolute glucose-stimulated insulin output rather than of fold glucose responsiveness. Because no source report documents blinding of outcome assessment, the pooled estimate should be read as an upper bound. In conclusion, TUDCA and 4-PBA act as chemical chaperones that alleviate ER stress and may prevent terminal UPR activation and preserve the beta-cell exocytotic machinery, positioning them as candidate disease-modifying agents that merit confirmatory clinical evaluation. Full article

Purpose: This study investigated the molecular mechanisms underlying blue light-induced corneal epithelial toxicity. Methods: C57BL/6J mice were exposed to 460 nm blue light for 1, 2, or 4 weeks, whereas human corneal epithelial (HCE) cells were exposed for 15 or 30 min. RNA-sequencing with bioinformatic analysis identified p53 signaling and ferroptosis as key pathways. p53 knockdown using siRNA and pharmacological inhibition with pifithrin-α (PFT-α) were employed to validate the mechanism in vitro and in vivo. Results: Blue light exposure caused time-dependent corneal epithelial disruption, reduced tear film stability, increased inflammatory cell infiltration, downregulated K12 expression, and upregulated K10 expression. Blue light induced cell death and G1-phase cell-cycle arrest in HCE cells. Ferroptosis hallmarks included intracellular ferrous iron (Fe²⁺) accumulation, reactive oxygen species (ROS) generation, decreased SLC7A11 and GPX4 expression, and increased COX2 expression. RNA sequencing revealed p53 pathway activation as a master regulator of ferroptosis. p53 knockdown reversed blue light-induced SLC7A11/GPX4 suppression and COX2 upregulation. Topical PFT-α administration attenuated corneal epithelial damage, restored K12 expression, suppressed K10 expression, and normalized ferroptosis markers in vivo. Conclusions: Blue light pollution triggers corneal epithelial ferroptosis through p53-mediated SLC7A11/GPX4 axis suppression. Pharmacological inhibition of p53 represents a promising therapeutic strategy for blue light-associated dry eye. Full article