Search Results (7,330)

Hepatocellular carcinoma (HCC) is sustained by coordinated interactions among malignant hepatocytes, immune cells, and stromal populations that collectively drive tumor growth, immune evasion, and vascular remodeling. Using integrative single-cell transcriptomics on 93,032 cells from tumor and healthy human liver, we characterized cell-type-specific transcriptional programs underlying immunometabolic reprogramming and reconstructed the intercellular communication circuits that maintain the tumor microenvironment. Malignant hepatocytes displayed upregulation of genes encoding both glycolytic and oxidative phosphorylation (OXPHOS) metabolic enzymes, consistent with metabolic plasticity, while concurrently suppressing genes involved in antigen presentation—a transcriptional pattern indicative of coordinated metabolic and immune-evasive reprogramming. Tumor-associated macrophages acquired TREM2-enriched, lipid-handling phenotypes consistent with immunosuppressive polarization, and tumor endothelial cells upregulated angiocrine and extracellular matrix programs while silencing innate immune outputs. Ligand–receptor inference revealed a qualitative rewiring of intercellular communication: the antigen-presentation-centered network of the healthy liver was replaced by a tumor-driven architecture dominated by pro-angiogenic, ECM–integrin, inflammatory chemokine, and lipid-associated signaling circuits, with malignant hepatocytes, TAMs, and TECs collectively assuming the dominant signaling burden. These findings establish that HCC progression is an emergent property of a stabilized multicellular network, rather than the autonomous behavior of malignant cells, and define cooperative immunometabolic modules that constitute tractable targets for combinatorial therapeutic intervention. Full article

Background: Platinum-based chemotherapy is the frontline treatment for high-grade serous ovarian cancer (HGSOC); however, the development of therapy resistance greatly limits clinical response. Increasing evidence suggests that platinum agent-driven metabolic programming, particularly within redox-associated pathways, may contribute to chemoresistance. Methods: A syngeneic pair of patient-derived HGSOC cell lines representing cisplatin-sensitive (SE) and cisplatin-resistant (CR) states were evaluated using a multi-omics approach. Differential metabolite abundance and gene expression were assessed, followed by gene set and pathway enrichment analyses to identify coordinated metabolic shifts. In silico analysis of an additional sensitive and resistant HGSOC cell line validated the glutathione pathway upregulation seen in the patient-derived model. The functional contribution of the glutathione pathway on cisplatin resistance was evaluated following glutathione inhibition. Results: Chronic cisplatin exposure induced extensive metabolic rewiring in CR cells, characterized by enrichment of glutathione metabolism at both the metabolite and gene levels. Increased reduced glutathione was observed alongside upregulation of key enzymes involved in its de novo biosynthesis, recycling, and utilization, consistent with enhanced detoxification capacity relating to cisplatin-induced oxidative stress. Additionally, taurine was highly enriched, further highlighting a metabolic shift towards enhanced antioxidant mechanisms. CR cells also demonstrated an increase in NADPH-generating pathways, including amino acid metabolism and fatty acid β oxidation, to support redox balance and biosynthetic demands of increased glutathione metabolism. Transcriptional remodeling of the γ-glutamyl cycle further indicated a shift toward increased glutathione turnover, suggesting that the coordinated changes seen may define a metabolic state enhanced in oxidative stress tolerance and therapeutic resistance. These transcriptional changes were also seen in another model of platinum sensitivity/resistance, indicating a conserved response associated with platinum-induced resistance. Finally, concurrent cisplatin treatment and glutathione inhibition significantly increased sensitivity within the CR cells. Conclusions: These findings suggest that cisplatin-resistant cells, previously exposed to a platinum-based agent, may undergo distinct metabolic rewiring towards antioxidant pathways to survive chronic chemotherapeutic stress. Targeting components of these systems may represent a viable strategy to overcome platinum resistance and improve therapeutic outcomes. Full article

Objectives: This study aimed to identify core genes associated with mitochondria-related transcriptomic signatures and evaluate their potential as computational biomarkers, immune characteristics, regulatory mechanisms, and potential therapeutic relevance. Methods: Obesity-related transcriptome datasets were obtained from the GEO database. Differentially expressed genes (DEGs) were intersected with mitochondria-related genes (MRGs) to identify obesity-related MRGs. Functional enrichment, protein–protein interaction (PPI) analysis, CytoHubba, LASSO and random forest algorithms were used to screen core genes. External validation, ROC analysis, immune infiltration analysis, regulatory network construction, candidate drug prediction, and molecular docking were further performed. Results: A total of 527 DEGs and 15 differentially expressed MRGs were identified. Enrichment analysis suggested that these mitochondria-related genes were mainly associated with disrupted mitochondrial energy metabolism, lipid metabolic remodeling, and altered substrate utilization. ECHDC2, FASN, NAT8L, and AASS were identified as core MRGs; these genes are respectively associated with mitochondrial metabolic regulation, de novo fatty acid synthesis, N-acetylaspartate-related mitochondrial metabolism, and lysine degradation. These genes were significantly downregulated in obesity and showed good diagnostic performance. Immune infiltration analysis revealed alterations in the immune microenvironment, and the core genes were negatively correlated with multiple immune cell types. Molecular docking showed that Genistein had the lowest predicted binding free energy with NAT8L (−8.89 kcal/mol), suggesting relatively favorable binding among the tested ligand–target pairs. Conclusions: ECHDC2, FASN, NAT8L, and AASS may serve as candidate computational biomarkers, among which FASN represents a known lipid metabolism-related gene, supporting the biological plausibility of the workflow. Full article

Pegmatite dikes are important prospecting indicators for rare-metal deposits, whereas traditional methods for pegmatite dike identification are constrained by the limited capability of human visual interpretation to capture information from remote sensing imagery, resulting in low identification accuracy and efficiency. In recent years, global research on semantic segmentation of different surface features and remote sensing-based mineral exploration using deep learning methods and high-resolution remote sensing imagery has made significant progress; however, studies on surface-exposed geological bodies such as pegmatite dikes remain highly insufficient. To address the key problem of efficiently identifying pegmatite dikes in remote sensing imagery, this study proposes an improved model based on UNet++, termed GAD-UNet++. In the field of remote sensing geology, this study constructed a pegmatite dike semantic segmentation dataset based on high-resolution RGB imagery by using 0.66 m RGB imagery for visual delineation and ZY1F hyperspectral data for spectral constraint and label refinement; on this basis, semantic segmentation of surface pegmatite dikes in the Yilanlike area of the South Tianshan Mountains, Xinjiang, was conducted using RGB remote sensing image patches as model input. Specifically, because pegmatite dikes are small targets characterized by slender structures, indistinct boundaries, and sparse regional distribution, this study introduced a lightweight feature extraction structure (GhostNetV2) and a long-range dependency attention module (DFC) at the encoder stage, and further incorporated the Coordinate Attention module (CA) to enhance spatial localization and boundary representation of the targets. Finally, focal cross-entropy loss and a deep supervision strategy were adopted to improve the accuracy of semantic information extraction for pegmatite dikes, as well as the training stability and segmentation accuracy under class-imbalance conditions. The results show that the proposed model achieved an mIoU of 93.11% and an F1-score of 94.95% on the test set. Compared with existing semantic segmentation models, the proposed model achieved superior performance in both identification accuracy and computational efficiency for pegmatite dikes. In addition, this study delineated 18 potential pegmatite dike enrichment zones in the Yilanlike area, providing technical support for remote sensing-based rare-metal prospecting and geological interpretation in the study area. Full article

Background: Osteoarthritis (OA) is a heterogeneous joint disease characterized by cartilage degeneration. The interplay between extracellular matrix (ECM) remodeling, endoplasmic reticulum (ER) stress, and inflammatory signaling in OA pathogenesis remains incompletely understood. This study aimed to identify robust diagnostic biomarkers and explore the mechanistic convergence of key genes in OA cartilage through an integrated transcriptomic framework. Methods: Three independent cartilage transcriptomic datasets (GSE285234, GSE287861, GSE289464) were integrated after ComBat batch correction. Differentially expressed genes (DEGs) were identified using limma, followed by ORA and GSEA for functional enrichment. LASSO logistic regression identified hub genes for a diagnostic model and nomogram, validated by leave-one-out cross-validation (LOOCV). Consensus clustering stratified OA samples into molecular subtypes. Single-cell RNA-sequencing (scRNA-seq) data (GSE169454, GSE220243) were used to validate cell-type-specific expression. Virtual gene knockout (scTenifoldKnk) and pathway analysis inferred downstream functional consequences. Results: Fifty-eight DEGs (predominantly downregulated) were enriched in ECM and ER protein processing pathways. Six hub genes (EIF2S1, GANAB, STT3A, XBP1, MGP, PMP22) showed robust selection stability. The diagnostic model achieved a LOOCV AUC of 0.769, a well-calibrated nomogram, and superior net benefit. Unsupervised clustering revealed two OA subtypes with divergent unfolded protein response (UPR) and TGF-β pathway activities. scRNA-seq confirmed hub gene expression in chondrocytes and other joint microenvironment cells. Notably, virtual knockout of five hub genes convergently perturbed IL-17, NF-κB, and chemokine signaling pathways. Conclusions: This study identified and validated a six-gene signature reflecting ECM-ER-inflammatory crosstalk in OA cartilage. The convergent perturbation of inflammatory pathways by functionally distinct hub genes reveals a mechanistic core that may serve as a diagnostic panel and a platform for targeted therapeutic investigation in OA. Full article

Background: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus. EJPs (Erjing Pills) are believed in Traditional Chinese Medicine to have the effects of a nourishing essence and a brightening of the eyes, but the specific effect on DR remains unclear. This study aims to investigate the therapeutic effects and underlying mechanisms of EJPs on DR. Methods: The chemical profile of EJPs was characterized by UHPLC-MS. Network pharmacology and molecular docking were employed to predict its active ingredients and potential targets. A DR rat model was induced by streptozotocin. Retinal morphology and function were assessed by OCT, FFA, and H&E staining. The expressions of proteins and mRNAs related to the AGE-RAGE pathway, oxidative stress, inflammation, and tight junctions were detected by Western blot, qPCR, and ELISA. Results: LC-MS and network pharmacology analysis identified 638 common targets between EJPs and DR, with core targets including SRC, AKT1, and MAPK1, primarily enriched in the AGE-RAGE signaling pathway. Molecular docking confirmed strong binding (binding energy < −5.0 kcal/mol) between key EJP constituents and core targets. In vivo, EJP treatment significantly alleviated retinal vascular leakage, improved retinal thickness, and alleviated histopathological damage. In addition, EJPs downregulated the AGEs-RAGE/NF-κB axis and pro-inflammatory cytokines while enhancing antioxidant defenses and tight junction proteins in the retinas of DR rats. Conclusions: EJPs ameliorate DR by protecting the blood–retinal barrier and modulating the AGE-RAGE/oxidative stress/inflammation network, demonstrating a multi-component, multi-target, and multi-pathway mechanism. This study provides a mechanistic basis for the potential application of EJPs in DR management. Full article

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents against H. pylori infection, molecular hybridization has now been applied to the synthesis of the new compound 3. Its structure connects the metronidazole moiety to pectolinarigenin, the latter obtained by acid hydrolysis of glycosylated flavonoids isolated from the plant Linaria reflexa Desf. The NOE effect supported the C-7 functionalization of 3, as evidenced by the energy-minimized DFT-calculated structure. The new molecule enriches the chemical space of known metronidazole–flavonoid analogs, among which the genistein derivative 2 was reported as the most active in inhibiting bacterial strains. The computational analysis of 2 and 3 compared with metronidazole as the reference has provided favorable data for both Absorption, Distribution, Metabolism, and Excretion (ADME) predictions and the probability of anti-H. pylori activity, besides rising docking evaluation on three specific targets and dynamics simulation as inhibitors of the flavodoxin enzyme. The results are promising for further in-depth biological investigation. Full article

Background: Natto, a well-known fermented soybean product beneficial for bone health, remains unclear in its mechanism. Methods: This study investigated its effect on secondary osteoporosis (OP) in mice. Results: Natto significantly inhibited weight loss, bone quality deterioration, and bone morphological damage, and regulated OPG/RANKL pathway protein expression (p < 0.05) in OP mice. Analysis of 16S rRNA revealed that natto increased gut microbiota α-diversity and the abundance of Sutterella, Roseburia, and Coprococcus, while reducing harmful bacteria such as Streptococcus, Shigella, and Helicobacter. These microbial changes positively correlated with body weight, bone size, and serum osteogenic metabolism in OP mice. Serum metabolomics showed differential metabolites of the natto group enriched in PPAR signaling and primary bile acid biosynthesis. Verification by mRNA and ELISA indicated that the upregulated liver and circulating PPARα by natto may regulate downstream bile acid pathways, linking gut microbiota to multi-organ metabolic functions. Conclusions: In summary, natto may act on gut microbiota to alleviate bone loss via the “gut microbiota–bile acid–OPG/RANKL” network, targeting multiple organs including gut, liver, and bone. This provides a theoretical basis for natto dietary intervention in osteoporosis prevention through the gut–bone axis. Full article

In resource-poor sandy habitats, alien plant co-invasion often triggers intense belowground competition mediated by rhizosphere microorganisms. However, the mechanisms by which these plants overcome nutrient limitations remain unclear. Here, we conducted an eight-month in situ monitoring of single- and co-invasion plots of Solanum rostratum and Cenchrus pauciflorus Benth. in the Horqin Sandy Land. By integrating soil enzyme assays with 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing, we characterized their rhizosphere microbial community assembly. Co-invasion exposed both species to convergent biotic stress, characterized by the significant enrichment of the pathogenic fungi Didymella and Pseudogymnoascus (linear discriminant analysis (LDA) > 4.0). To mitigate these pressures, the dominant competitor, S. rostratum, specifically recruited a cross-kingdom phosphate-solubilizing consortium comprising Bacillus and Penicillium (LDA > 4.0). This targeted recruitment significantly enhanced rhizosphere activities, increasing phosphatase and sucrase to 86.10 U/g and 2.17 U/g, respectively, thereby maintaining available phosphorus at a high level (35.55 mg/kg). Conversely, the subordinate competitor, C. pauciflorus, lost key native stress-resistant bacteria such as Rubrobacter (relative abundance dropping from 5.39% to 3.27%) and failed to recruit effective microbes, leading to the rapid depletion of available phosphorus (dropping to 21.38 mg/kg). Ultimately, under dual nutrient and pathogenic stress, the precise recruitment and functional integration of cross-kingdom phosphate-solubilizing microbes are strongly linked to the divergent belowground competitive outcomes between these co-invading plants. Full article

Salt stress is a major abiotic stress that threatens citrus yield and quality. To elucidate the molecular mechanisms underlying differential salt tolerance in citrus rootstocks, we performed an integrative transcriptomic and metabolomic analysis of salt-sensitive trifoliate orange (Poncirus trifoliata) and salt-tolerant Goutoucheng (Citrus aurantium) under 60 mM NaCl treatment for 12 h and 24 h. Physiological observations confirmed that Goutoucheng exhibited less growth inhibition and leaf damage than trifoliate orange. Transcriptome sequencing identified 2081 and 1588 differentially expressed genes (DEGs) in trifoliate orange at 12 h and 24 h, respectively, compared with 1166 and 997 DEGs in Goutoucheng. Metabolome profiling revealed 217 and 173 differentially accumulated metabolites (DAMs) in trifoliate orange versus 162 and 239 DAMs in Goutoucheng at the two time points. KEGG pathway analysis showed that DEGs were mainly enriched in the Mitogen-activated protein kinase (MAPK) signaling pathway—plant, plant hormone signal transduction, and flavonoid biosynthesis—and DAMs were mainly enriched in flavonoid biosynthesis, starch and sucrose metabolism, and glutathione metabolism. Integrative nine-quadrant and two-way orthogonal partial least squares analyses further pinpointed flavonoid biosynthesis as a central hub in salt response. Notably, quercetin derivatives accumulated preferentially in the salt-tolerant rootstock Goutoucheng. Several transcription factor families—including HSF, MYB, NAC, HB-HD-ZIP, C2H2, bHLH, AP2/ERF, and Trihelix—may enhance antioxidant capacity under salt stress by regulating flavonoid accumulation. Collectively, these results indicated that coordinated regulation of flavonoids contributed critically to salt stress adaptation in citrus rootstocks. The identified DEGs, DAMs, and transcription factors provide candidate targets for genetic improvement of salt tolerance in citrus. Full article

The diversity and abundance of the brain virome is an active field of investigation. However, how the brain virome relates to the presence of viruses outside of the nervous system remains unclear. The rationale for this study is that analyses across multiple biologically linked compartments within the same individuals provide an important opportunity to evaluate virome discordance and viral burden. To characterize viral prevalence and burden across anatomical compartments, we applied the targeted viral enrichment method ViroFind to matched postmortem brain (n = 66), cerebrospinal fluid (CSF; n = 24), and peripheral samples (spleen, peripheral blood mononuclear cells, and lymph nodes; n = 66) from individuals with and without human immunodeficiency virus (HIV) infection and substance use disorder (SUD) in the National NeuroAIDS Tissue Consortium. We detected nucleic acids from 27 viruses representing 12 taxa. Several viruses, including adenovirus, torque teno virus, Epstein–Barr virus, human herpesvirus 6 and 7, cytomegalovirus, parvovirus, and JC polyomavirus, showed significant inter-compartment differences in prevalence or burden. CSF exhibited lower overall viral diversity than brain or peripheral samples, whereas peripheral samples showed the highest viral burden. CNS viral detection was more likely when the same virus was also detected in the periphery. We also detected HBV and HCV in CNS samples despite them not being classically regarded as neurotropic. Broader virome profiling showed greater peripheral viral burden and diversity in HIV-positive than HIV-negative individuals, whereas SUD was not associated with overall viral burden differences. These findings highlight important cross-compartment differences in viral detection, including occurrence of occult HBV infection within the CNS, and support the value of CNS–periphery comparisons in virome studies. These findings can contribute to improved diagnosis and management of viral infections. Full article

Background: Exercise adaptation is increasingly recognized as an immunometabolic process driven by coordinated interactions among inflammatory signaling, mitochondrial regulation, metabolic homeostasis, and recovery-associated physiology. Within this framework, NLRP3 inflammasome activation and PPARD-mediated metabolic signaling have emerged as biologically relevant pathways potentially involved in exercise-induced physiological adaptation. However, the contribution of regulatory genetic variations linking these pathways remains poorly characterized. Objective: To synthesize current evidence regarding the integration of NLRP3- and PPARD-related pathways in exercise immunometabolism and adaptive physiological responses to exercise, with particular emphasis on the regulatory variants NLRP3 rs10754558 and PPARD rs2267668 as potential contributors to interindividual variability in exercise adaptation. Methods: A structured narrative review complemented by exploratory systems-level in silico analyses was conducted using the PubMed, Scopus, and Web of Science databases until March 2026. Evidence related to exercise physiology, inflammatory regulation, metabolic adaptation, and exercise-associated phenotypes involving the NLRP3 and PPARD pathways was evaluated. Complementary analyses included functional annotation, protein–protein interaction network analysis, and pathway enrichment using STRING, Reactome, KEGG, Gene Ontology, and other publicly available genomic databases. Particular attention was given to the functional and regulatory context of rs10754558 and rs2267668 within the interconnected inflammatory and metabolic pathways relevant to exercise adaptation. Results: The reviewed evidence identified recurrent interactions among the inflammatory and metabolic pathways involved in exercise adaptation and recovery. NLRP3 rs10754558 and PPARD rs2267668 were identified as candidate regulatory variants potentially positioned at the interface between inflammatory responsiveness and metabolic flexibility, providing a biologically plausible framework for understanding the interindividual variability in exercise adaptation. Exploratory system-level analyses identified recurrent associations among inflammatory signaling, mitochondrial function, energy-sensing pathways, and metabolic regulation. These findings primarily reflect the functional annotations and system-level pathway associations identified through exploratory analyses. Conclusions: Current evidence supports a systems-level physiological framework in which inflammatory and metabolic pathways interact dynamically during exercise adaptation and recovery. NLRP3- and PPARD-related pathways, including the candidate regulatory variants rs10754558 and rs2267668, may contribute to interindividual variability in exercise-associated physiological responses and represent promising targets for future hypothesis-driven investigations in exercise immunometabolism, exercise genomics and precision exercise medicine. Full article

Objectives: This study aimed to develop a prognostic model for isolated moderate-to-severe traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] ≤ 12) using readily available variables and to explore paired blood–cerebrospinal fluid (CSF) metabolomic signatures. Methods: Consecutive TBI patients admitted between January 2019 and June 2025 were retrospectively analyzed. Multivariate logistic regression with bootstrap internal validation identified predictors of 6-month unfavorable outcome and in-hospital mortality. Untargeted metabolomics was performed on paired blood and CSF samples from 30 matched male patients. Results: Among 405 patients, 266 (65.7%) had unfavorable outcomes and 54 (13.3%) died in hospital. Rotterdam CT Score (odds ratio [OR] 10.59, 95% confidence interval [CI] 6.19–18.14), initial lactate (OR 1.81, 95% CI 1.38–2.36), and blood glucose (OR 1.40, 95% CI 1.21–1.64) predicted unfavorable outcome (area under the receiver operating characteristic curve [AUC] 0.97). GCS motor score (OR 0.50, 95% CI 0.37–0.66), initial lactate (OR 1.57, 95% CI 1.31–1.91), and follow-up lactate (OR 1.57, 95% CI 1.34–1.88) predicted mortality (AUC 0.96). Blood metabolomics revealed enrichment in energy and lipid metabolism pathways. CSF metabolomics highlighted neurotransmitter pathway dysregulation and neuroinflammatory markers, with depleted kynurenic acid in both biofluids. Conclusions: Readily available admission variables enable early bedside risk stratification in TBI. Metabolomic profiling links unfavorable outcomes to systemic energy–lipid dysregulation and central neuroinflammatory–neurotransmitter disturbances, with the tryptophan–kynurenine axis as a potential therapeutic target for neuroprotective strategies. Full article

Background: Age at diagnosis and histologic differentiation are clinically relevant in early gastric cancer (GC), as poorly differentiated tumors and those diagnosed in younger patients often demonstrate more aggressive characteristics. Serum microRNAs (miRNAs) may provide insights into the molecular basis of these features. Methods: We compared expression profiles between undifferentiated and differentiated early GC cases to identify differentially expressed miRNAs (DEmiRNAs) and associated enriched pathways. Using Lasso regression, we developed and cross-validated a histologic differentiation classifier based on miRNA profiles from 1399 early GC serum samples. Finally, cancer-specific miRNA differences between adolescent and young adult (AYA) and non-AYA patients were evaluated using samples from cancer cases and normal controls. Results: We identified 75 differentiation-associated DEmiRNAs targeting genes enriched in cancer hallmark pathways such as TP53 and PI3K/AKT/mTOR signaling. In the validation set, the combined Lasso model predicted differentiation status with a sensitivity of 69.2%, specificity of 75.3%, positive predictive value (PPV) of 66.9%, negative predictive value (NPV) of 77.2%, an overall accuracy of 73.1%, and an area under the curve (AUC) of 79.7%. Comparison of AYA and non-AYA groups identified 52 cancer-specific and age-related miRNAs. Notably, three components of a previously reported four-miRNA GC diagnostic signature were significantly associated with age. Conclusions: Age-related variation in miRNA expression suggests that patient age may influence the performance of the existing four-miRNA diagnostic signature in early GC. Overall, our findings demonstrate the utility of miRNA profiling for predicting differentiation status in early GC and reveal age-associated variation in cancer-specific miRNAs. Full article

Shuanghuanglian oral liquid (SHL) is widely used in companion animals and poultry, but its molecular mechanism in pneumonia–myocarditis comorbidity and heart–lung inflammatory crosstalk remains largely unclear. This computational study investigated the conserved AKT1/HIF1A-mediated immunoregulatory mechanism of SHL and its cross-species translational potential in veterinary medicine. Network pharmacology was integrated with GO, KEGG, and Reactome enrichment analyses, protein–protein interaction network construction, ADMET evaluation, cross-species sequence homology analysis (human, dog, cattle, and pig), molecular docking, and molecular dynamics simulation. A total of 61 active compounds, 251 putative targets, and 52 common targets associated with pneumonia and myocarditis were identified. These targets were mainly enriched in inflammation- and immune-related pathways, including TNF, IL-17, AGE–RAGE, and PPAR signaling. AKT1 and HIF1A showed high sequence conservation across species (85–98%). Key compounds exhibited favorable binding affinity to AKT1, and molecular dynamics simulation suggested the stability of the Baicalein–AKT1 complex. ADMET analysis suggested favorable pharmacokinetic properties and low predicted toxicity. These findings suggest that SHL may potentially alleviate pneumonia and myocarditis through modulation of the conserved AKT1/HIF1A axis and support its potential as a complementary therapeutic approach for managing heart–lung inflammatory diseases in multiple livestock species. This entirely computational study highlights promising mechanisms that should be further validated in vivo. Full article