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A balance between positive and negative regulation of the Toll-like receptor (TLR) signaling pathway is required to prevent harmful or inappropriate inflammatory responses. Although TLR9 has been reported to be expressed in many mammalian tissues and cells, its function and exact mechanism are not fully understood. Some protein post-translational modifications (PTMs), such as phosphorylation and ubiquitination, are involved in the development of tumors. An important PTM, methylation, which controls the TLR9 signaling pathway, still remains unclear. Using human prostate cancer (PCa) cells PC3 and clinical PCa samples, this study employed LipidTOX staining, RNA interference, Western blot, immunoprecipitation, GST fusion protein sedimentation, and immunofluorescence techniques to investigate the molecular mechanism of TLR9 protein arginine methylation modification in PCa ferroptosis. In this study, we found that the total level of methylation was reduced in PCa, the expression of TLR9 was decreased, and the level of reactive oxygen species (ROS) was increased in PCa cells, indicating that TLR9 may be involved in the regulation of ferroptosis in PCa. In addition, protein arginine methyltransferase 5 and 9 (PRMT5 and PRMT9) are recruited to mediate methylation modification of TLR9 after stimulation of unmethylated cytosine guanine [oligodeoxynucleotide (ODN)], but PRMT9 has the strongest effect, which prompted us to focus on PRMT9. Decreased expression of PRMT9 down-regulates arginine (R) methylation levels of TLR9. Methionine 260 (G260) mediates PRMT9 to catalyze arginine methylation of TLR9 on R216. In vitro transcriptomic results showed that the expression level of acyl synthetase medium chain family 1 (ACSM1) in cancer tissues was significantly higher than that in the para-cancer group. BODIPY-C11 immunofluorescence results indicated that TLR9 methylation could regulate the growth of PC3 cells mediated by ACSM1. In addition, arginine methylation enhancement of TLR9 induced by PRMT5 or 9 increased the transcription activity of nuclear factor erythroid 2-related factor 2 (NRF2), and arginine methylation of TLR9 at sites 216 and 305 mediated the interaction between TLR9 and NRF2 and enhanced the transcription activity of NRF2. PRMT9 mutation and (R216K) mutant TLR9 decreased NRF2 transcriptional activity, and R216 mutation decreased PRMT9-mediated arginine methylation GPX4 and other related iron-death protein levels. Our study reveals a key role of TLR9 protein arginine methylation in the regulation of ferroptosis, which may provide a therapeutic strategy for controlling the development and progression of PCa.

Computational protein subcellular localization prediction is vital for understanding cellular mechanisms and disease treatments. However, current methods lack interpretability: they predict where a protein localizes but fail to explain why. Moreover, understanding protein behaviour requires costly, time-consuming three-dimensional structures. Here, we propose BioGraphX, a novel encoding framework that constructs protein interaction graphs directly from sequences using biochemical rules, providing a constraint-based structural proxy. Building upon this, BioGraphX-Net demonstrates superior performance on the DeepLoc 2.0 benchmark by integrating ESM-2 (Evolutionary Scale Modeling) embeddings with the proposed features via a gating mechanism. Gating analysis shows that while ESM-2 embeddings contribute strongly, BioGraphX features function as high-precision filters. SHAP (SHapley Additive exPlanations) analysis reveals feature importance patterns consistent with a sophisticated biophysical logic: sequence signals act as universal exclusion filters, while organelle-specific biophysical combinations enable precise compartment discrimination. Notably, Frustration features resolve targeting ambiguities in complex compartments, reflecting evolutionary constraints while preventing mislocalization from sequence mimicry. Cross-dataset validation on a protein solubility prediction task confirms the structural proxy captures genuine biophysical signal. Additionally, BioGraphX promotes Green AI in bioinformatics, matching state-of-the-art performance with a minimal parameter count of 13.46 million. In summary, BioGraphX provides accurate predictions and new insights into the language of life. Source code is available at https://github.com/Abubakar-Saeed/BioGraphX.

Over the past decade, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has significantly improved owing to the development of anti-angiogenic targeted drugs such as sunitinib, pazopanib, and sorafenib. However, biomarkers that can identify patients with mRCC who may rapidly develop drug resistance are still lacking. Approximately 25% of patients experience rapid disease progression [progression-free survival (PFS) ≤3 months]. Currently, there is a lack of effective noninvasive biomarkers to identify resistant patients prior to treatment. This study aimed to identify plasma biomarkers associated with therapeutic resistance and develop a predictive model for clinical decision-making. Plasma proteomic analysis was conducted in 159 patients with mRCC treated with targeted therapy. Patients were divided into training and validation cohorts. Candidate protein biomarkers were initially screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and further validated using enzyme-linked immunosorbent assay (ELISA). A predictive nomogram was subsequently developed using logistic regression analysis and assessed for discrimination and calibration performance. Immunohistochemistry (IHC) was performed to compare protein expression levels in corresponding tumor tissue samples. Four plasma proteins-chitotriosidase-1 (CHIT1), interleukin-6 receptor (IL-6R), neuronal cell adhesion molecule (NRCAM), and ecto-5'-nucleotidase (NT5E)-were identified as significant predictors of intrinsic resistance. The nomogram incorporating these biomarkers exhibited a high predictive accuracy, with a concordance index (C-index) of 0.956 and 0.869 for the training and validation cohorts, respectively. Notably, while the plasma concentrations of these proteins were significantly elevated in resistant patients, their expression levels in tumor tissues showed no significant differences, underscoring their utility as circulating, noninvasive biomarkers. We developed and validated a plasma protein-based nomogram to predict mRCC resistance to targeted therapy. The four identified biomarkers allow noninvasive identification of high-risk patients and offer a practical tool for early clinical stratification. This model may assist clinicians in avoiding ineffective treatment and optimizing therapeutic strategies for patients with mRCC.

Calmodulin-binding transcription activators (CAMTAs) are a key family of transcription factors that regulate gene expression involved in plant development and mediate plant responses to a wide range of biotic and abiotic stresses. Although CAMTA genes have been surveyed in several crop species, their comprehensive characterization in Brassica rapa remains limited. In this study, we performed a genome-wide analysis and identified 12 BrCAMTA genes, dispersed across 10 chromosomes of the B. rapa genome. Phylogenetic analysis of 84 CAMTA proteins from seven plant species grouped them into four major clades, with BrCAMTAs exhibiting conserved exon-intron structures and motif compositions within their respective phylogenetic groups. Domain analysis revealed that the major CG-1 domain is conserved across all the genes. Protein-protein interaction analysis indicated that the predicted interacting proteins contain diverse domains and exhibit a variety of functions. Promoter analysis revealed a wide array of cis-regulatory elements linked to hormone signaling, stress responses, and developmental regulation. RNA-seq-based expression profiling revealed tissue-specific expression patterns, with BrCAMTA genes showing high expression in roots, stems, and callus tissues. Notably, BrCAMTA6, BrCAMTA8, and BrCAMTA11 exhibited significantly higher expression across all examined tissues. Collectively, these findings highlight the structural conservation and functional diversity of CAMTA genes in B. rapa and provide a valuable framework for future validation studies that are aimed at understanding their roles in growth, development, and environmental adaptation.

Hydrogenotrophic methanogens are promising biocatalysts for biomethanation and carbon dioxide utilization, yet their robustness under bioprocess perturbations remains insufficiently defined. We quantified robustness in a Methanothermobacter archaeal strain with proven potential for industrial application across temperature shifts, oxidative exposure, nitrogen depletion, and hydrogen starvation, measured five key cellular functions in batch culture, and derived a Fano factor based robustness metric that links data dispersion to functional stability. Thermal and oxidative stress were the primary constraints on robustness, most notably for methane productivity and lag phase duration, whereas hydrogen starvation increased productivity in some cases without large losses in robustness, and nitrogen depletion had limited effects. Global proteomics revealed coordinated changes consistent with these patterns, including increased ribosomal proteins, trehalose synthesis, chaperones, and redox regulators under thermal stress, and enrichment of PAS and histidine kinase domain proteins under oxidative stress. Structure-guided predictions using Alpha Fold 3 supported the hypothesis that stress responsive proteins may associate with canonical methanogenesis core subunits, as FmdE was predicted to associate with FmdE-like paralogs under thermal stress, while several Mtr subunits decreased in abundance. The combined results identify actionable targets for engineering robustness in methanogenic archaea, including stabilizing multi subunit methanogenesis complexes such as Mtr, tuning PAS and HK sensors to improve redox response, and modulating chaperone and osmoprotection capacity to regulate metabolic functions during temperature fluctuations. As derived future work, mapping protein interactions with abundance profiling may help move proteomics from description to prediction, providing network-informed design rules that complement conventional genome-centered proteomics and guide strain optimization of robust archaeal biocatalysts for biomethanation.

Natural killer (NK) cells contribute to the development of Rheumatoid Arthritis (RA). Increased expression of programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, indicates NK cell exhaustion, a process that may be influenced by microRNAs (miRNAs). In this study, we examined PD-1 expression on NK cells from RA patients and evaluated whether miRNAs modulate this pathway. Although antibiotics are critical for treating infections, they can provoke harmful immune responses by releasing bacterial components that overstimulate the immune system. Such responses may lead to excessive inflammation or cytokine storms. To address this risk, we assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, and compared its effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses. We analyzed public gene and protein expression datasets from antibiotic-treated human cells and performed in silico studies on ZAM-MSC. Differential expression analysis and pathway enrichment were conducted, alongside structural modeling of the endolysin and its predicted interactions with immune receptors. Antibiotic treatment strongly activated inflammatory genes and pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In contrast, ZAM-MSC minimally affected immune-related gene expression, with downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A). Structural modeling showed weak interactions with Toll-like receptors, and epitope analysis predicted low immunogenicity. These results suggest ZAM-MSC may offer a safer antimicrobial alternative, though all protein-level findings are based on computational predictions and require experimental validation.

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by granulosa cell dysfunction, including impaired proliferation, excessive apoptosis, and ferroptosis, which contribute to abnormal follicular development and ovarian dysfunction. This study aims to investigate the effects of Osteoglycin (OGN) on proliferation, apoptosis, and ferroptosis in human ovarian granulosa cells, and to analyze its regulation of follicle stimulating hormone receptor (FSHR), providing insights into granulosa cell dysfunction associated with PCOS. Methods This study investigated the function of OGN in KGN granulosa cells by transfecting them with OGN-plasmid for overexpression or OGN-siRNA for knockdown. Cell viability was assessed using the MTT assay, while apoptosis was analyzed by flow cytometry. Ferroptosis was evaluated by measuring intracellular ROS and MDA levels, and protein expression was examined via Western blotting. Additionally, RT-qPCR and Western blotting were used to assess mRNA and protein levels of FSHR to determine the regulatory effect of OGN on FSHR expression. Results Overexpression of OGN significantly promoted granulosa cell proliferation and inhibited apoptosis, whereas knockdown of OGN suppressed proliferation and induced apoptosis. Mechanistic studies revealed that knockdown of OGN upregulated cleaved-Caspase3 expression, increased intracellular ROS and MDA levels, and reduced GPX4 expression, indicating the activation of both apoptotic and ferroptotic pathways. Furthermore, OGN positively regulated FSHR expression, as FSHR levels were increased with OGN overexpression and decreased following OGN knockdown at both mRNA and protein levels. Conclusion This study demonstrates that OGN plays a critical role in regulating granulosa cell survival and ferroptosis and may contribute to follicular development and PCOS-related ovarian dysfunction by modulating FSHR.

IgA nephropathy (IgAN) is one of the leading causes of end-stage renal disease (ESRD). Telitacicept has been demonstrated significant efficacy in IgAN, but its comparative efficacy versus the recommended regimens in the 2025 KDIGO guideline remains unclear. The aim of this study was to investigate the clinical efficacy and safety of glucocorticoids, telitacicept, and nefecon&#xa0;in patients with IgAN, in order to determine the optimal treatment regimen. We recruited 101 patients with IgAN confirmed by renal biopsy. The patients were categorized into three groups according to the treatment they received: the GC group, the Telitacicept group, and the Nefecon group. Treatment responses, including complete remission (CR) and partial remission (PR), and adverse events were compared among the three groups after 9 months of follow-up. At the 9-month follow-up, the CR rates were 93.5%, 86.2%, and 70.7% for the GC group, Telitacicept group, and Nefecon group, respectively (p=0.035). During the follow-up, proteinuria in all three groups decreased significantly from baseline (p < 0.05), while eGFR remained stable At the 3rd, 6th, and 9th months, the median percentage reduction in proteinuria in the GC group was significantly greater than that in the Nefecon group (p<0.001; p=0.001; p<0.001). The GC group also showed greater reductions compared to the Telitacicept group (p=0.057; p=0.101; p=0.103), and the Telitacicept group also demonstrated higher proteinuria reduction rates than the Nefecon group, although neither difference was statistically significant. Furthermore, the incidence of adverse events, particularly infections, was significantly lower in the Nefecon group than in the GC group (p < 0.05). Our study confirmed that glucocorticoids have superior efficacy to nefecon, but are associated with a higher incidence of adverse events. Telitacicept offered both efficacy and safety, and can be recommended for high-risk IgAN patients who are intolerant to glucocorticoids.

Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons in the substantia nigra, with ferroptosis emerging as critical pathogenic mechanisms. Recent evidence suggests that STING activation can induce neuronal ferroptosis through autophagic degradation of GPX4. Taurochenodeoxycholic acid (TCDCA), a naturally occurring bile acid, has demonstrated neuroprotective properties through activation of Takeda G protein-coupled receptor 5 (TGR5). However, whether TCDCA can improve PD by modulating the cGAS-STING-ferroptosis axis remains unexplored. We investigated the effects of TCDCA treatment on motor function, dopaminergic neuronal survival, oxidative stress markers, ferroptosis-related proteins (GPX4, SLC7A11, ACSL4), and cGAS-STING signaling components in the substantia nigra of male mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration and in MPP&#x207a;-treated SH-SY5Y cells. Behavioral assessments demonstrated that TCDCA significantly improved motor dysfunction in both open field and pole tests. TCDCA treatment markedly increased tyrosine hydroxylase-positive neurons and reduced oxidative stress markers including malondialdehyde and ferrous iron levels while restoring superoxide dismutase activity and glutathione content in the substantia nigra. Results showed that TCDCA upregulated TGR5 expression and concurrently suppressed cGAS and STING activation in both in vivo and in vitro PD models. Importantly, TCDCA treatment significantly enhanced the expression of anti-ferroptotic proteins GPX4 and SLC7A11 while reducing pro-ferroptotic ACSL4. These neuroprotective effects were associated with TGR5 upregulation and cGAS-STING pathway suppression. Our findings demonstrate that TCDCA alleviates PD-related neurodegeneration by inhibiting cGAS-STING-mediated ferroptosis through TGR5 activation, suggesting that TCDCA holds promise as a candidate drug for the treatment of PD.

Bisphenol A (BPA), a widespread environmental endocrine-disrupting chemical, is suspected to contribute to liver injury, yet the underlying mechanisms, particularly for cholestatic liver injury (CLI), remain poorly defined. This study aims to systematically elucidate the molecular pathways by which BPA induces CLI. We applied an integrated network toxicology approach. BPA targets were predicted using chemical databases (ChEMBL, SwissTargetPrediction, TargetNet), while disease targets for CLI were sourced from GeneCards and OMIM. Bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were conducted on overlapping genes. A protein-protein interaction network was constructed to identify hub genes, followed by molecular docking simulations to validate BPA's binding affinity to these key targets. We identified 200 common genes linking BPA exposure to CLI. Pathway analysis revealed that BPA perturbs multiple biological processes, including chemical detoxification, energy metabolism, inflammation, and bile secretion. Ten core genes (TP53, TNF, and key CYP450 enzymes) were pinpointed as central players. Molecular docking confirmed that BPA binds strongly to these hub targets, substantiating their mechanistic role. Our findings provide a comprehensive mechanistic framework explaining how BPA exposure may lead to cholestatic liver injury. The study establishes a novel predictive strategy for evaluating the hepatotoxicity of environmental pollutants.

Immunoglobulin light chains (AL) and transthyretin (ATTR) characterize most cardiac amyloidosis cases. Several proteomic studies have analyzed microdissected amyloid plaques. However, they did not capture the molecular dysfunctions triggered in surrounding tissue. We, therefore, holistically investigated the protein profiles of endomyocardial biopsies from patients with AL&#x3bb; and ATTR conditions. Both conditions showed extracellular matrix remodeling and downregulation of proteostasis, signaling, and mitochondrial energetics. The results also suggested vesicle-mediated transport and complement activation as hallmarks of patients with AL&#x3bb; and ATTR conditions, respectively. These findings corroborate previously proposed pathological mechanisms, namely, direct mitochondrial toxicity of light chain fibrils internalized via macropinocytosis and massive extracellular deposition of ATTR. Notably, protein quantification and network topology enabled the identification of potential disease markers. Although the selection criteria were robust, validation in larger cohorts is needed. Nevertheless, given the challenging accessibility of the analyzed samples, the proposed landscape of results provides a valuable resource to encourage further studies on cardiac amyloidosis.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains a major neurological complication in people living with HIV despite effective antiretroviral therapy. Neurotoxicity caused by viral proteins, particularly the HIV-1 transactivator of transcription (Tat), contributes significantly to HAND. Although N-methyl-D-aspartate receptors (NMDARs) in astrocytes are known to regulate aquaporin-4 (AQP4) the mechanisms by which Tat influences NMDAR signaling and AQP4 expression remain unclear. This study investigated how HIV-1 Tat regulates AQP4 expression in astrocytes through the NMDAR/CaMKII/AC/cAMP/PKA signaling pathway and how secondary Ca2+ dynamics modulate this process. Astrocytic Ca2+ influx was measured using the Fluo-3 AM probe. Western blotting quantified AQP4, NR1, NR2A/B, CaMKII, p-CaMKII, PKA, and PKG expression. Real-time quantitative polymerase chain reaction (RT-qPCR) assessed mRNA levels of AQP4 and NMDAR-related genes. Enzyme-linked immunosorbent assay (ELISA) evaluated nitric oxide synthase activity, adenylate cyclase activity, and intracellular cAMP levels. Pharmacologic inhibitors-MK-801 (NMDAR blocker), H89 (PKA inhibitor), and KT5823 (protein kinase G [PKG] inhibitor)-were applied to investigate pathway interactions. HIV-1 Tat induced robust activation of NMDAR, resulting in increased Ca2+ influx and sequential activation of the CaMKII/AC/cAMP/PKA pathway, ultimately elevating AQP4. After prolonged Tat exposure (approximately 36 hours), a secondary surge in Ca2+ activated PKG, which acts as a protective negative feedback mechanism to inhibit excessive NMDAR activity, thereby stabilizing Ca2+ influx and preventing abnormal overexpression of AQP4. Cotreatment with MK-801, H89, or KT5823 suppressed Tat-induced Ca2+ influx and attenuated AQP4 upregulation, although persistent Tat exposure gradually restored Ca2+ elevations through compensatory mechanisms. HIV-1 Tat dynamically regulates AQP4 expression in astrocytes via the NMDAR/CaMKII/AC/cAMP/PKA pathway, with PKG-mediated feedback contributing to later stabilization. These findings highlight AQP4 as a potential therapeutic target for HAND.

Global delivery of gene therapies demands scalable manufacturing, yet the field is limited by the genome-deficient empty capsids. While the baculovirus expression vector system (BEVS) serves as a leading platform for industrial scale-up, its packaging efficiency is frequently compromised. This failure is largely driven by an imbalanced expression of Rep and Cap proteins. Here, we showed that the conventional back-to-back arrangement of p10 and polh promoters induced transcriptional interference, which suppressed viral protein stoichiometry and limited genome encapsulation. Using systematic dual-fluorescence reporter system, we discover an unexpected non-linear response, in which specific spacer lengths (133-161 bp) paradoxically enhance bidirectional transcription rather than simply relieving transcription repression. Nucleotide-resolution mapping identified a sharp structural optimum at 153 bp that triggered transcriptional enhancement beyond separated promoter controls. Integrating this 153 bp configuration into functional rAAV2 packaging systems restored Rep and Cap expression. Consequently, genome replication efficiency tripled, and the accumulation of empty capsids dropped precipitously from 84.9% to 20.1%, while transduction efficiency in mammalian cells remained uncompromised. These findings define a design rule for dual-promoter expression vector that is readily implementable in rAAV manufacturing. This work establishes a translatable engineering strategy to enhance both product quality and manufacturing efficiency for rAAV-based gene therapies.

The advent of effective formulations based on RNA encapsulated within lipid nanoparticles has led to the evaluation of this technology for its ability to treat and prevent a wide range of diseases. Expansion of the RNA-based tool kit available to vaccine and drug developers will accelerate this development and hopefully produce more robust and cost-effective therapies. With its more sustained expression profile, self-amplifying RNA offers many advantages to standard messenger RNA, allowing for the administration of lower RNA doses in vivo and potentially reducing dosing frequency for indications where long-term expression of a protein is required. We generated self-amplifying RNA containing the viral replicon from Sindbis virus, which demonstrated robust protein expression in vitro and in vivo. In addition, it showed increased compatibility with a number of modified nucleotides when compared to an equivalent RNA containing the replicon from Venezuelan equine encephalitis virus. These Sindbis-based self-amplifying RNAs containing modified nucleotides have the potential to be used in a variety of experimental and therapeutic applications.

The Hippo signaling pathway represents an evolutionarily conserved regulatory network. It plays a central role in controlling cell proliferation, apoptosis, differentiation, and tissue homeostasis. Increasing evidence indicates that dysregulation of this pathway promotes the development and progression of hematological malignancies. This includes leukemia, lymphoma, and multiple myeloma. Notably, aberrant activation of downstream effectors-Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ)-plays a central role in this process. Abnormal YAP/TAZ signaling promotes malignant cell survival, proliferation, therapeutic resistance, and disease aggressiveness through extensive crosstalk with multiple oncogenic pathways, such as Phosphatidylinositol 3-kinase (PI3K)/ Protein kinase B (AKT), Transforming growth factor-beta (TGF-&#x3b2;), Wnt/&#x3b2;-catenin, and metabolic signaling networks. Notably, the biological functions of YAP/TAZ appear to be highly context-dependent, with both oncogenic and tumor-suppressive roles reported in different hematopoietic lineages and tumor microenvironments. In this review, we summarize the molecular architecture and regulatory mechanisms of the Hippo pathway, discuss its dysregulation and functional significance in major hematological malignancies, and highlight recent advances in Hippo-targeted therapeutic strategies, including YAP/TEA domain transcription factor (TEAD) inhibitors, upstream pathway modulators, and combination treatment approaches. We further outline current challenges and future opportunities for translating Hippo-based precision therapies into clinical practice. Despite promising preclinical findings, hematological malignancy-specific clinical evidence remains limited. Future studies are required to validate Hippo-targeted therapeutic strategies and establish clinically actionable biomarkers. A deeper understanding of Hippo signaling may provide novel insights into disease biology and accelerate the development of precision medicine approaches for hematological malignancies.

Acute microglia-mediated neuroinflammation and oxidative stress play important roles in the pathogenesis of gas explosion (GE)-induced traumatic brain injury (TBI). Curcumin has documented neuroinflammatory protective properties; however, its effects on gas explosion (GE)-induced TBI and the underlying mechanism remain unclear. In this study, we established a male rat model of acute TBI and an in vitro model of acute microglial impact injury using shockwave physiotherapy. The effects of curcumin on the extent of the brain injury, as well as the levels of inflammatory cytokines, oxidative stress indicators, microglia polarization, and toll-like receptor 4 (TLR4) protein expression in model rats and microglial cells were evaluated using histological staining, western blotting, qPCR, immunohistochemistry, immunofluorescence, and biochemical assays. The results showed that curcumin reduced the pathological changes induced by GE and significantly inhibited the expression of neuron-specific enolase (NSE) (P&#x202f;<&#x202f;0.05), a marker of microglial activation. Curcumin treatment also promoted M2 polarization of microglia (P&#x202f;<&#x202f;0.05) and reduced the protein expression levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-&#x3ba;B (P&#x202f;<&#x202f;0.05), and the pro-inflammatory factors tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), interleukin (IL)-1&#x3b2;, IL-6, and NLRP3 (P&#x202f;<&#x202f;0.05). Moreover, curcumin treatment significantly reduced the levels of oxidative stress factors in rat tissues (P&#x202f;<&#x202f;0.05). In summary, our findings indicated that curcumin alleviated acute neuroinflammation and oxidative stress induced by GE in vivo and in vitro by inhibiting TLR4-mediated M2 polarization of microglia, thus providing a new treatment target for the neuroinflammation associated with TBI caused by explosives.