Ferroptosis and cuproptosis are promising anti-tumor treatment strategies. Elesclomol (ES) is a kind of common cuproptosis inducer, and cisplatin (DDP) is a commonly used drug in liver cancer chemotherapy, which can induce cells to undergo ferroptosis. Both of these cell death processes require inducing cells to generate oxidative stress. Therefore, elesclomol and cisplatin may have a synergistic effect in anti-tumor treatment. Here, we designed an active oxygen-responsive nano-delivery system and conducted in vitro and in vivo to study the synergistic anti-liver cancer effect of elesclomol and cisplatin. Our data showed that the elesclomol nanoparticles can effectively inhibit the growth of liver cancer cells and showed extremely low organ toxicity. Elesclomol exhibited a synergistic effect with cisplatin in vitro, but the combined treatment of the two did not outperform single drug treatment in vivo. The reason might be that the nuclear factor erythroid 2-related factor 2 (Nrf2) protein in liver cancer cells is feedback-expressed, inhibiting the oxidative stress effects induced by elesclomol and cisplatin. Therefore, this study provides reference data for exploring the mechanism of elesclomol’s synergistic anti-liver cancer treatment with cisplatin and offers a feasible strategy for future precise liver cancer treatment and improving chemotherapy efficacy.

IntroductionThe aim of this study was to explore the prognostic significance of necrotic cell death triggered by sodium overload (NECSO)-related genes in lung adenocarcinoma (LUAD) and construct a prognostic model with high predictive efficiency. The findings will enable a precise stratification of the prognostic risk of patients with LUAD. Analysis of the constructed prognostic model, immune cell infiltration, and tumor mutational burden (TMB) will facilitate the development of individualized precision medical protocols.MethodsBased on the LUAD data obtained from TCGA and GEO databases, a prognostic prediction model for LUAD containing 15 key genes (including arginyl aminopeptidase like 1 [RNPEPL1] and beta-1,3-N-acetylglucosaminyltransferase 3 [B3GNT3]) coexpressing with the key NECSO gene, TRPM4, was established.ResultsRisk score was identified as an independent prognostic factor. High-risk patients had the following characteristics: high frequency of mutations in TP53 and TTN genes, high TMB, high number of immunosuppressive cells with impaired immune cell function, and abnormally active metabolism. Nomograms developed by integrating clinical features and risk scores displayed high predictability.DiscussionThe findings provide new molecular markers and potential therapeutic targets for the prognosis of LUAD and lay a theoretical foundation for the development of therapeutic approaches targeting the NECSO mechanism in patients with LUAD.

As a major occupational hazard, crystalline silica (SiO2) poses a severe risk of pulmonary toxicity. While the irreversible fibrosis of late-stage silicosis has been extensively studied, the cellular and molecular mechanisms by which SiO2 reprograms macrophage metabolism to drive early pathogenesis remain poorly understood. To elucidate this early immune-inflammatory response, we combined targeted metabolomics, pharmacological treatments, and nutrient deprivation in murine alveolar macrophages. Our results demonstrate that SiO2 exposure severely impairs the master antioxidant regulator, nuclear factor erythroid 2-related factor 2 (Nrf2), triggering excessive reactive oxygen species (ROS) accumulation and upregulated glutamine catabolism to drive pro-inflammatory M1 macrophage polarization. We demonstrated that Nrf2 activation with tert-butylhydroquinone (TBHQ) redirected glutamine metabolic flux from pro-inflammatory catabolism to antioxidant anabolism, significantly attenuating SiO2-induced M1 polarization. Conversely, Nrf2 inhibition via ML385 exacerbated the inflammatory response. Furthermore, introducing a glutamine deprivation (−Gln) model revealed that restricting glutamine availability significantly attenuated the ability of Nrf2 to reverse M1 polarization, suggesting that its immune-protective effects largely depend on an intact glutamine metabolic pathway. Ultimately, our findings underscore the severe risks of silica exposure and identify the Nrf2–glutamine metabolic axis as a promising target, providing novel mechanistic insights and a robust basis for “antioxidant–metabolic” dual-target interventions in early-stage silicosis.

Influenza viruses are respiratory pathogens of the family Orthomyxoviridae. Among the four recognized types, influenza A virus (IAV) is the primary cause of seasonal epidemics and pandemics. Continuous antigenic drift facilitates immune evasion, whereas occasional antigenic shift drives the emergence of novel hemagglutinin (HA) and neuraminidase (NA) subtype combinations. Although influenza is primarily characterized by respiratory manifestations, it can also cause severe central nervous system (CNS) complications, including encephalitis, collectively referred to as influenza-associated encephalopathy (IAE), which is associated with poor clinical outcomes and remains frequently overlooked. The neurotropic potential of influenza viruses remains controversial. Although vaccination and antiviral therapies effectively reduce influenza-related morbidity and mortality, specific preventive and therapeutic strategies for influenza-associated CNS complications remain limited. This review synthesizes current evidence on the neuroinvasive characteristics of influenza viruses, including susceptibility factors, viral determinants, host responses, pathogenic mechanisms, therapeutic strategies, and prognostic indicators. Particular emphasis is placed on the mechanisms underlying CNS injury, including both direct viral invasion and indirect injury mediated by dysregulated immune and inflammatory responses. By integrating these emerging mechanistic insights, this review proposes a lung–brain axis framework to explain the bidirectional communication between pulmonary infection and neurological injury during influenza. This framework provides an updated perspective on the pathogenesis of IAE, identifies potential therapeutic targets, and may facilitate future studies aimed at improving early diagnosis, risk stratification, and the development of mechanism-based interventions.

Pneumonia is the most common complication of influenza virus infection and is associated with a high mortality rate in immunocompromised individuals. Currently, neither vaccination nor antiviral therapy has achieved satisfactory therapeutic outcomes. Unlike other organs, the lungs harbor a distinct microbial community due to their unique exposure patterns to airborne particulates and pathogens. However, the characteristic alterations of the pulmonary microbiota and its metabolic products, as well as their potential association with immune suppression in influenza pneumonia, remain inadequately investigated. Mice were rendered immunocompromised through administration of the immunosuppressant cyclophosphamide. Mouse models of influenza pneumonia were established under both immunocompetent and immunosuppressed conditions. Body weight was routinely monitored, and lung histopathology was assessed via hematoxylin and eosin staining. Viral load in lung tissue, serum inflammatory cytokine levels, pulmonary microbiota composition, and lung metabolites were analyzed using RT-qPCR, enzyme-linked immunosorbent assay, 16S rRNA gene sequencing, and untargeted metabolomics, respectively. Spearman correlation analysis was performed to evaluate significant associations between pulmonary microbial taxa and specific metabolites. Influenza virus infection led to a marked reduction in body weight and significantly increased viral load in lung tissue, as well as elevated serum levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α). These effects were more pronounced in immunosuppressed mice, which also exhibited more severe inflammatory and pathological changes in lung tissues. Characteristic shifts in the pulmonary microbiota were observed in the immunosuppressed influenza pneumonia model, particularly involving increased abundance of Bacteroides and Agathobacter. In addition, key metabolites such as adenosine, adenosine 5'-monophosphate, and xanthine were significantly altered, indicating perturbations in the purine metabolism pathway. Immunosuppressed influenza pneumonia results in more severe inflammatory and pathological lung damage. The observed characteristic changes in the pulmonary microbiota and associated metabolites provide potential microbial and metabolic targets that may contribute to the pathogenesis of severe lung injury in immunocompromised individuals following influenza virus infection.IMPORTANCETaking lung tissue as the entry point, this study directly observes the microbial and metabolite changes in the lungs, distinguishing the effects of different immune states. From this novel perspective, it aims to identify new targets for the treatment of influenza pneumonia.

Acute lung injury (ALI) is a severe respiratory disease accompanied by diffuse inflammatory responses induced by various clinical causes. Many fresh medicinal plants have shown better efficacy than their dried forms in preventing and treating diseases like inflammation. As a classical Chinese herb, platycodon grandiflorum (PG) has been demonstrated effective in treating pneumonia, but most of previous studies focused on the efficacy of processed or dried PG formats, while the specific benefits of its fresh form are still underexplored. Exosome-like nanoparticles derived from medicinal plants are expected to point out an important direction for exploring the material basis and mechanism of this fresh herbal medicine. The fresh form of PG could effectively improve ALI induced by lipopolysaccharide (LPS), relieve lung histopathological injury and weight loss, and reduce levels of inflammatory factors in mice, exhibiting better efficacy than dried PG in the treatment of ALI. Further extraction and purification of PG exosome-like nanoparticles (PGLNs) demonstrated that PGLNs had good biocompatibility, with characteristics consistent with general exosome-like nanoparticles. Besides, proteomic analysis indicated that PGLNs were rich in a variety of proteins. Animal experiments showed that PGLNs improved the pathological changes in LPS-induced lung tissues, inhibited the expression of inflammatory factors and promoted the expression of anti-inflammatory factors, and exerted a regulatory effect on the polarization of lung macrophages. Cell experiments further confirmed that PGLNs could be effectively taken up by RAW264.7 cells and repolarize M1 macrophages into M2 type, therefore reducing the secretion of harmful cytokines. Moreover, non-targeted metabolomics analysis reveals that PGLNs reduce inflammation and control macrophage polarization in a manner closely linked to pathways including glycolysis and lipid metabolism, highlighting a potential mechanism by which PGLNs protect the lungs from inflammatory damage like ALI. Fresh PG has better anti-inflammatory and repair effects than its dried form. As one of the most effective active substances in fresh PG, PGLNs may regulate macrophage inflammation and polarization by regulating metabolic pathways including lipid metabolism and glycolysis, so as to reduce inflammation and repair lung injury.

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial strain resistant to multiple antibiotics frequently encountered in clinical settings. Excessive antibiotic use has increased bacterial resistance, leaving a lack of effective treatments for MRSA infections. MRSA often colonizes the surface of skin wounds, resulting in chronic inflammation and protracted wound healing. The biofilm formation hinders the complete eradication of the bacteria, exacerbating the local inflammatory response and impeding wound healing. This study presents an innovative methodology for managing MRSA-infected skin wounds. The novel immunomodulatory hydrogel composed of Berberine, silver nanoparticles (AgNPs), and carboxylated chitosan (designated as Ber@AgNPs@CHI hydrogel) demonstrates enhanced therapeutic efficacy in a murine model of MRSA skin infection. This hydrogel is effective in eradicating MRSA and preventing biofilm formation. Furthermore, it modulates the local immune microenvironment by facilitating the transition of macrophages from the M1 to M2 phenotype and increasing the production of vascular endothelial growth factor (VEGF). These actions collectively facilitate the progression of the wound from the inflammatory to the proliferative phase, enhancing the early stages of wound healing. Hence, this safe and effective hydrogel mediates wound healing from multiple perspectives and targets, providing a new potential avenue for treating persistent infected wounds caused by clinical MRSA.

Malignant tumors of the digestive system are widespread and pose a serious threat to humans. Immune escape is an important factor promoting the deterioration of malignant tumors in the digestive system. Natural killer cells (NK cells) are key members of the anti-tumor and immune surveillance system, mainly exerting cytotoxic effects by binding to the activating receptor natural killer cell group 2D (NKG2D) on their cell surface with the corresponding ligands (major histocompatibility complex class I chain-related protein A/B, MICA/B) on the surface of tumor cells. Malignant tumors of epithelial origin usually highly express NKG2D ligands such as MICA, which can attract NK cells to kill tumor cells and also serve as an important basis for NK cell-based immunotherapy. Tumor cells highly express hypoxia-inducible factor-1α (HIF-1α), which promotes the expression of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs). These metalloproteinases hydrolyze MICA and other ligands on the surface of tumor cells to generate soluble molecules. These soluble ligands, when binding to NKG2D, cannot activate NK cells and also block the binding of NKG2D to MICA on the surface of tumor cells, enabling tumor cells to evade the killing effect of NK cells. Almost all organs in the digestive system originate from epithelial tissue, so the soluble ligands generated by the HIF-1α/MMPs or HIF-1α/ADAMs signaling pathways play a crucial role in evading NK cell killing. A comprehensive understanding of this immune escape process is helpful for a deeper understanding of the molecular mechanism of NK cell anti-tumor activity. This article reviews the molecular mechanisms of common digestive system malignancies evading NK cell killing, providing new insights into the mechanism of tumor immune escape.

Major histocompatibility complex class I-like related gene A (MICA) is the most polymorphic non-classical HLA gene. MICA proteins are expressed at low levels on the surface of normal cells but are highly expressed on the surface of tumor cells. Its most important biological function is to bind to activating receptors on the surface of natural killer (NK) cells or CD8+ T cells, then activate these immune cells to exert immune killing effects. Multiple studies have shown that the amino acids at specific loci in the MICA molecule can significantly affect its binding ability to NKG2D. The binding strength of MICA-NKG2D significantly affects the anti-tumor effect of NK cells in the body and the prognosis of many tumor patients. However, the strong MICA-NKG2D interaction can trigger negative feedback against this immune response by down-regulating the expression of NKG2D or generating soluble MICA, weakening the overly intense immune response. Therefore, simply evaluating the intensity of the anti-tumor immune response from the perspective of the amino acid polymorphism of MICA affecting its binding ability to NKG2D also has limitations. We review the effects of MICA amino acid polymorphism on the affinity of the NKG2D signal pathway and analyze in detail the specific role of MICA amino acid polymorphism in tumor immunity. The study provides a reference for understanding the mechanism of anti-tumor immune response by NK cells or other immune cells, as well as a theoretical basis for considering the MICA-NKG2D signal axis for anti-tumor immune therapy in future clinical practice.

ETHNOPHARMACOLOGICAL RELEVANCE:Erchen decoction (ECD) has traditionally been employed as an adjunct therapy for respiratory diseases such as tracheitis, bronchitis, and chronic obstructive pulmonary disease (COPD) in China. However, its therapeutic effects and underlying mechanisms in treating silicosis remain unclear. AIM OF THE STUDY:This study aims to elucidate the protective mechanism of ECD against silica-induced pulmonary fibrosis, focusing specifically on ferroptosis in alveolar macrophages (AMs). MATERIALS AND METHODS:Silicosis animal and cellular models were established through silica (SiO2) exposure to evaluate the therapeutic efficacy of ECD. The effects of ECD on fibrosis, polarization, and ferroptosis in AMs were systematically evaluated using histopathology, cytokine assays, and molecular biology techniques. RESULTS:Animal experiments demonstrated that ECD significantly reduced silica-induced inflammatory infiltration, collagen deposition, and fibrosis markers (α-SMA and Collagen-1) expression in mouse lung tissues. Metabolomic analysis identified active components in ECD serum, including quercetagitrin and hinokiol, which exhibited strong binding affinities with key ferroptosis targets (P53 and HMOX1). Co-culture models confirmed that ECD suppressed fibroblast migration and activation via modulating AMs function, thereby reducing secretion of pro-inflammatory (IL-6) and pro-fibrotic (TGF-β) factors. Mechanistically, ECD inhibited silica-induced ferroptosis in AMs, evident by reduced intracellular Fe2+, lipid peroxidation, and malondialdehyde (MDA) levels, increased GPX4 and xCT expression, and antioxidant activity mediated through the P53/HMOX1 axis. CONCLUSIONS:ECD effectively ameliorates silica-induced silicosis progression by targeting ferroptosis in AMs and regulating the P53/HMOX1 signaling pathway, highlighting its potential as an adjunct therapeutic option for silicosis.

Introduction:Influenza A virus (IAV) infection is associated with high morbidity and mortality and can ultimately lead to acute lung injury (ALI). In traditional Chinese medicine, Maxing Shigan Decoction (MXSGD) can treat exogenous wind-cold, toxic heat invading the lungs, and heat-toxicity obstructing the lungs. However, the active components and underlying mechanisms of MXSGD in IAV-induced diseases remain largely unexplored. Therefore, we aimed to investigate the active constituents of MXSGD and its underlying mechanism of action in ALI. Methods:Bioactive components of MXSGD in rat serum were identified using ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-HRMS). Blood-absorbed MXSGD components (i.e., the constituents of MXSGD detectable in serum) in ALI were predicted through network pharmacology and molecular docking analyses. A mouse lung injury model was established using the influenza virus. The degree of lung injury, viral load in lung tissues, serum levels of inflammatory factors, gene expression levels of inflammation-related factors in lung tissue, and macrophage polarization in the lungs were then assessed. Results and discussion:In the rat serum, 242 bioactive components were identified using UPLC-HRMS. Moreover, 56 ingredients, including glycyrrhizin, amygdalin, and ephedrine, were analyzed using network pharmacology, revealing 338 ALI-related targets and 99 core proteins in the protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for core targets, and molecular docking confirmed the binding affinity of the main identified targets with their respective blood-absorbed components. Validation results demonstrated that MXSGD significantly ameliorated lung injury, mitigated lung congestion and inflammation, lowered viral load in mouse lung tissue, promoted macrophage polarization, and downregulated the expression of the PI3K/AKT pathway in IAV-infected mice. Overall, this study revealed the mechanisms and active ingredients underlying the therapeutic effects, highlighting of MXSGD its potential in treating IAV-induced ALI and regulating the polarization of macrophages.

ETHNOPHARMACOLOGY RELEVANCE:Maxing Shigan Decoction (MXSGD), derived from the traditional Chinese medicine (TCM) classic Shang Han Lun, is recognized as an effective TCM herbal formula for treating respiratory diseases, although its precise molecular mechanisms against influenza A virus (IAV) have not yet been fully elucidated. AIM OF THE STUDY:This study aimed to clarify the pharmacological effects of MXSGD on IAV-infected pneumonia mouse models, with a particular focus on its regulatory mechanism through miR-1260. MATERIALS AND METHODS:The chemical composition of MXSGD was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After establishing IAV-infected mouse models, the pathological changes in lung tissues were observed by hematoxylin-eosin (HE) staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expression levels of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. A co-culture system of MLE-12 and RAW246.7 cells was constructed as the research model. Then, the intracellular miR-1260 expression was detected by RT-qPCR, and the Sema3A expression was examined by immunofluorescence. The macrophages were further transfected with miR-1260 mimic, inhibitor, and Sema3A siRNA to determine whether MXSGD exerts its therapeutic effects through the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway. Subsequently, alveolar macrophage-depleted mouse models were established using CL2MBP, and were infected with IAV. To clarify the role of macrophages in the therapeutic mechanism of MXSGD against IAV, the body weight and organ indices of mice were monitored and recorded; the total protein content and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were measured; the histopathological changes were observed by HE staining; the pulmonary epithelial cells and macrophages in lung tissues were examined through immunological assays; and the expressions of miR-1260 and its target genes in lung tissues were evaluated by RT-qPCR and Western blot analysis. RESULTS:MXSGD was found to alleviate IAV-induced pathological injury and suppress macrophage recruitment in mouse lung tissues, while downregulating the viral load and levels of inflammatory factors. The attenuation of macrophage recruitment was closely associated with pulmonary epithelial cells, potentially mediated through the miR-1260-targeted Sema3A-regulated PI3K/AKT/mTOR signaling pathway. In cellular experiments, both cell types in the co-culture system were restored following MXSGD treatment, accompanied by lowered intracellular viral load and levels of inflammatory factors. Additionally, macrophage apoptosis and miR-1260 expression were significantly reduced, whereas the Sema3A fluorescence intensity in macrophages was markedly increased. By transfecting miR-1260 mimic, inhibitor, and Sema3A siRNA into co-cultured macrophages, the therapeutic effects of MXSGD were further confirmed to be associated with the miR-1260/Sema3A-mediated PI3K/AKT/mTOR pathway. In IAV-infected models established after pulmonary macrophage depletion, the therapeutic efficacy of MXSGD was partially weakened following elimination of alveolar macrophages. In general, above in vivo findings are consistent with the cellular experimental results, collectively supporting the involvement of the miR-1260-targeted Sema3A-mediated PI3K/AKT/mTOR signaling pathway in the therapeutic mechanism of MXSGD. CONCLUSIONS:MXSGD was demonstrated to regulate the PI3K/AKT/mTOR pathway through the macrophage miR-1260/Sema3A axis, through which excessive inflammatory responses in IAV-induced pneumonia were effectively suppressed. The findings provide a novel therapeutic target for antiviral treatment in TCM.

MRSA is an antibiotic resistant bacterium that poses a significant threat to the environment and human health due to its bioaccumulation and potential widespread contamination. The prompt and accurate identification of MRSA is essential for enhancing environmental monitoring and clinical management. Here, we develop a triple-helix molecular switch (THMS) fluorescent aptasensor for the determination of MRSA using Klenow fragment (KF)-assisted target recycling and Ribonuclease H (Rnase H)-powered DNA walker cascade amplification. In this method, the target opens the THMS by specifically binding with the aptamer, resulting in the release of target/aptamer complex and DNA walker. KF then initiates the target recycling process via strand-displacement polymerization reaction under the assistance of carboxyfluorescein (FAM)-labeled primer and dNTPs, creating plenty of double-stranded DNA (dsDNA) products. These dsDNA products show low affinity to graphene oxide (GO) and generate strong fluorescence. This fluorescence is considerably significantly amplified in the presence of SYBR Green I (SGI), attributable to the synergistic interaction between dsDNA and SGI. In the interim, Rnase H drives the released DNA walker to automatically walk on the carboxylated graphene oxide surface by cleaving FAM-labeled RNA signal probe (SP), causing the FAMs to dissociate from the carboxylated graphene oxide (CGO). Therefore, fluorescent signal originating from the two reaction pathways can be detected at excitation/emission wavelengths of 480/514 nm. The target measured by this strategy demonstrates a broad linear working range from 102 colony-forming units (CFU)/mL to 107 CFU/mL, with a detection limit (LOD) of 15 CFU/mL. Moreover, this method performs well in milk and pus sample analysis. These results reveal that this aptasensor is highly specific and sensitive for detecting MRSA and is endowed with good potential for food monitoring and clinical diagnosis applications.

Influenza A virus (IAV) is a major cause of respiratory illness in humans and animals. Secondary bacterial infections, especially those caused by Staphylococcus aureus (SA), significantly increase influenza-related morbidity and mortality. However, the mechanisms underlying these co-infections remain unclear. In this study, we examined how IAV infection influences SA-induced inflammation in lung epithelial cells. Our study was conducted based on in vitro experiments. First, we infected MLE-12 cells with IAV, confirming viral replication and the resulting cell damage. SA was then introduced 24 h or 36 h post-infection, and the cellular responses were measured. We assessed cell viability, cell-free DNA, Citrullinated histone H3, and the mRNA expression of TLR4 and proinflammatory cytokines. Our results showed that IAV+SA stimulation significantly increased upregulated TLR4 expression and inflammatory damage. To further explore TLR4’s role, we used the inhibitor TAK-242 and a TLR4 siRNA knockdown. Both approaches reduced the inflammatory response triggered by IAV and SA stimulation. These findings suggest that TLR4 is a key mediator in the enhanced inflammation observed during IAV and SA co-infection, offering a potential target for therapeutic intervention.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium that causes a wide range of illnesses, necessitating the development of new technologies for its detection. Herein, we propose a graphene oxide (GO)-based sensing platform for the detection of mecA gene in MRSA using flap endonuclease 1 (FEN1)assisted target recycling and Klenow fragment (KF)-triggered signal amplification. Without the target, all the DNA probes were adsorbed onto GO, resulting in fluorescence quenching of the dye. Upon the addition of the target, a triple complex was formed that triggered FEN1-assisted target recycling and initiated two polymerization reactions with the assistance of KF polymerase, generating numerous dsDNA that were repelled by GO. These dsDNAs triggered fluorescence enhancement when SYBR Green I was added. Therefore, the target DNA was quantified by measuring the fluorescence at excitation and emission wavelengths of 480/526 nm. This mecA gene assay showed a good linear range from 1 to 50 nM with a lower limit of detection of 0.26 nM, and displayed good applicability to the analysis of real samples. Thus, a new method for monitoring MRSA has been developed that has great potential for early clinical diagnosis and treatment.

Abstract Background Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. Method The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. Results The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p < 0.05). The results of bioinformatics analysis for transcriptomics results show that these genes are mainly involved in inflammatory factors and inflammation-related signal pathways mediated inflammation biological modules, etc. Intestinal microbiome showed that the intestinal flora Actinobacteriota level and Desulfobacterota level increased in MXSGD group, while Planctomycetota in MXSGD group decreased. Metabolites were mainly involved in primary bile acid biosynthesis, thiamine metabolism, etc. This suggests that MXSGD has a microbial–gut–lung axis regulation effect on mice with influenza A virus pneumonia. Conclusion MXSGD may play an anti-inflammatory and immunoregulatory role by regulating intestinal microbiome and intestinal metabolic small molecules, and ultimately play a role in the treatment of influenza A virus pneumonia.

ContextMa Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has antitussive and expectorant effects, anti-inflammatory, antiviral, regulates the body’s immunity, etc.AimThe aim of this study is to investigate whether MXSGD can ameliorate cyclosporine A (CsA)-induced hypoimmunity lung injury by regulating microflora metabolism. Methods: Establishment of a model for CsA-induced hypoimmunity lung injury. Using 16S rRNA high-throughput sequencing and LC-MS, the effects of MXSGD on gut flora and lung tissue microecology of mice with CsA-induced hypoimmunity were investigated.ResultsMXSGD was able to preserve lung tissue morphology and structure, reduce serum inflammatory marker expression and protect against CsA-induced lung tissue damage. Compared to the model, MXSGD increased beneficial gut bacteria: Eubacterium ventriosum group and Eubacterium nodatum group; decreased intestinal pathogens: Rikenellaceae RC9 intestinal group; reduced the abundance of Chryseobacterium and Acinetobacter, promoted the production of Lactobacillus and Streptococcus, and then promoted the lung flora to produce short-chain fatty acids. MXSGD was able to enhance the expression of serum metabolites such as Americine, 2-hydroxyhexadecanoylcarnitine, Emetine, All-trans-decaprenyl diphosphate, Biliverdin-IX-alpha, Hordatin A and N-demethyl mifepristone in the CsA-induced hypoimmunity lung injury model.ConclusionMXSGD can restore gut and lung microbiota diversity and serum metabolite changes to inhibit inflammation, ameliorate CsA-induced hypoimmunity lung injury.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Background Pathogenic bacteria are widespread in nature and can cause infections and various complications, thereby posing a severe risk to public health. Therefore, simple, rapid, sensitive, and cost-effective methods must be developed to detect pathogenic bacteria. Biosensors are prominent platforms for detecting pathogenic bacteria owing to their high sensitivity, specificity, repeatability, and stability. With the development of nanotechnology, graphene oxide (GO) has been increasingly introduced into the construction of fluorescent biosensors to enhance their performance owing to its unique physicochemical properties. Results This review systematically summarizes the development of GO-based fluorescent biosensors for the detection of pathogenic bacteria. First, we introduce the functionalization and modification of GO. The design and signal amplification strategies for GO-based fluorescent biosensors are also discussed. Finally, we explore the challenges and new perspectives associated with this field, with the aim of facilitating the development of GO-based fluorescent sensing technologies to prevent the spread of multidrug-resistant bacteria. Significance This review will aid in the development of high-performance biosensors for pathogenic bacterial assays.