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Abstract Interleukin-18, a member of the interleukin − 1 family of cytokines, is upregulated in glioma. However, its effects on glioma remain unclear. This study aimed to explore the role and underlying mechanisms of interleukin-18 expression in glioma. Here, we demonstrated that interleukin-18 enhanced resistance to temozolomide by increasing proliferation and inhibiting apoptosis in cultured glioma cells. Further in vivo studies revealed that interleukin-18 promoted temozolomide resistance in BALB/c nude mice bearing tumor. Mechanical exploration indicated that interleukin-18 stimulation could activate the PI3K/AKT signaling pathway in glioma cells, and PI3K inhibition could reduce the temozolomide resistance promoted by interleukin-18. We found that interleukin-18 upregulated CD274 expression in glioma, revealing its potential effects on the microenvironment. Furthermore, we established a tumor xenograft model and explored the therapeutic efficacy of anti-interleukin-18 monoclonal antibody. Targeting interleukin-18 prolonged survival and attenuated CD274 expression in the mice bearing tumor. Combined treatment with anti-interleukin-18 and anti-PD-1 monoclonal antibody showed better efficacy in suppressing tumor growth than either treatment alone in mice bearing tumor. Collectively, these data present that interleukin-18 promotes temozolomide chemoresistance in glioma cells via PI3K/Akt activation and establishes an immunosuppressive milieu by modulating CD274. This study highlights the therapeutic value of interleukin-18 in glioma.

Cobweb disease in white button mushroom (Agaricus bisporus) is a newly identified disease caused by Cladobotryum mycophilum in China. Currently, there are few highly effective and safe fungicides for controlling this disease in the field. This study assessed the fungicidal effect of prochloraz–manganese chloride complex and seboctylamine acetate against C. mycophilum, as well as their ability to control cobweb disease. Additionally, the residues of these fungicides in the mycelium and the mushroom were evaluated. The extent of the fungicidal effect against the pathogen was determined based on the efficiency of crop production. The results revealed that, in addition to the potent inhibitory effect of prochloraz–manganese chloride complex on the hyphae of C. mycophilum, the domestically developed seboctylamine acetate exhibited high toxicity, inhibiting both mycelial growth and spore germination of C. mycophilum, with EC50 values of 0.990 mg/L and 0.652 mg/L, respectively. Furthermore, the application of the two chemical agents had no adverse effects on the mycelial growth and fruiting body growth of A. bisporus, and the residual amount of chemical agent was lower than the maximum residue limit standard. The field application results showed that 400 mg/L of prochloraz–manganese chloride complex and 6 mg/L of seboctylamine acetate resulted in 61.38% and 81.17% disease control respectively. This study presents efficient and safe fungicides for controlling cobweb disease in white button mushroom. Additionally, a residue determination analysis of the fungicide seboctylamine acetate in mushroom crops is described.

Abstract Temozolomide (TMZ) resistance remains the major obstacle in the treatment of glioblastoma (GBM). Lactylation is a novel post‐translational modification that is involved in various tumors. However, whether lactylation plays a role in GBM TMZ resistance remains unclear. Here it is found that histone H3K9 lactylation (H3K9la) confers TMZ resistance in GBM via LUC7L2‐mediated intron 7 retention of MLH1. Mechanistically, lactylation is upregulated in recurrent GBM tissues and TMZ‐resistant cells, and is mainly concentrated in histone H3K9. Combined multi‐omics analysis, including CUT&Tag, SLAM‐seq, and RNA‐seq, reveals that H3K9 lactylation is significantly enriched in the LUC7L2 promoter and activates LUC7L2 transcription to promote its expression. LUC7L2 mediates intron 7 retention of MLH1 to reduce MLH1 expression, and thereby inhibit mismatch repair (MMR), ultimately leading to GBM TMZ resistance. Of note, it is identified that a clinical anti‐epileptic drug, stiripentol, which can cross the blood–brain barrier and inhibit lactate dehydrogenase A/B (LDHA/B) activity, acts as a lactylation inhibitor and renders GBM cells more sensitive to TMZ in vitro and in vivo. These findings not only shed light on the mechanism of lactylation in GBM TMZ resistance but also provide a potential combined therapeutic strategy for clinical GBM treatment.

Fungal diseases not only reduce the yield of edible mushrooms but also pose potential threats to the preservation and quality of harvested mushrooms. Cobweb disease, caused primarily by fungal pathogens from the Hypocreaceae family, is one of the most significant diseases affecting edible mushrooms. Deciphering the genomes of these pathogens will help unravel the molecular basis of their evolution and identify genes responsible for pathogenicity. Here, we present high-quality genome sequences of three cobweb disease fungi: Hypomyces aurantius Cb-Fv, Cladobotryum mycophilum CB-Ab, and Cladobotryum protrusum CB-Mi, isolated from Flammulina velutipes, Agaricus bisporus, and Morchella importuna, respectively. The assembled genomes of H. aurantius, C. mycophilum, and C. protrusum are 33.19 Mb, 39.83 Mb, and 38.10 Mb, respectively. This is the first report of the genome of H. aurantius. Phylogenetic analysis revealed that cobweb disease pathogens are closely related and diverged approximately 17.51 million years ago. CAZymes (mainly chitinases, glucan endo-1,3-beta-glucosidases, and secondary metabolite synthases), proteases, KP3 killer proteins, lipases, and hydrophobins were found to be conserved and strongly associated with pathogenicity, virulence, and adaptation in the three cobweb pathogens. This study provides insights into the genome structure, genome organization, and pathogenicity of these three cobweb disease fungi, which will be a valuable resource for comparative genomics studies of cobweb pathogens and will help control this disease, thereby enhancing mushroom quality.