Dependence of the formation kinetics of carbon dioxide hydrate on clay aging for solid carbon dioxide storage.

Clay-based marine sediments have great potential for safe and effective carbon dioxide (CO2) encapsulation by storing enormous amounts of CO2 in solid gas hydrate form. However, the aging of clay with time changes the surface properties of clay and complicates the CO2 hydrate formation behaviors in sediments. Due to the long clay aging period, it is difficult to identify the role of clay aging in the formation of CO2 hydrate in marine sediments. Here, we used ultrasonication and plasma treatment to simulate the breakage and oxidation of clay nanoflakes in aging and investigated the influence of clay aging on CO2 hydrate formation kinetics. We found that the breakage and oxidation of clay nanoflakes would disrupt the siloxane rings and graft hydroxyl on the clay nanoflakes. This decreased the negative charge density of clay nanoflakes and weakened the interfacial interaction of clay nanoflakes with the surrounding water. Therefore, the small clay nanoflakes enriched in hydroxyl would disrupt the surrounding tetrahedral water structure analogous to the CO2 hydrate, resulting in the prolongation of CO2 hydrate nucleation. These results revealed the influence of the structure-function relationship of clay nanoflakes with CO2 hydrate formation and are favorable for the development of hydrate-based CO2 storage.

Hyphal editing of the conserved premature stop codon in CHE1 is stimulated by oxidative stress in Fusarium graminearum.

Although genome-wide A-to-I editing mediated by adenosine-deaminase-acting-on-tRNA (ADAT) occurs during sexual reproduction in the presence of stage-specific cofactors, RNA editing is not known to occur during vegetative growth in filamentous fungi. Here we identified 33 A-to-I RNA editing events in vegetative hyphae of Fusarium graminearum and functionally characterized one conserved hyphal-editing site. Similar to ADAT-mediated editing during sexual reproduction, majority of hyphal-editing sites are in coding sequences and nonsynonymous, and have strong preference for U at -1 position and hairpin loops. Editing at TA437G, one of the hyphal-specific editing sites, is a premature stop codon correction (PSC) event that enables CHE1 gene to encode a full-length zinc fingertranscription factor. Manual annotations showed that this PSC site is conserved in CHE1 orthologs from closely-related Fusarium species. Whereas the che1 deletion and CHE1TAA (G438 to A) mutants had no detectable phenotype, the CHE1TGG (A437 to G) mutant was defective in hyphal growth, conidiation, sexual reproduction, and plant infection. However, the CHE1TGG mutant was increased in tolerance against oxidative stress and editing of TA437G in CHE1 was stimulated by H2O2 treatment in F. graminearum. These results indicate that fixation of the premature stop codon in CHE1 has a fitness cost on normal hyphal growth and reproduction but provides a benefit to tolerance against oxidative stress. Taken together, A-to-I editing events, although rare (not genome-wide), occur during vegetative growth and editing in CHE1 plays a role in response to oxidative stress in F. graminearum and likely in other fungal pathogens.

High-quality genome assembly and annotation of Clonostachys chloroleuca strain Cc878 using Oxford Nanopore long-read sequencing.

As a noteworthy biocontrol fungus, Clonostachys chloroleuca currently lacks a high-quality reference genome. Here, we present the first high-quality genome assembly of C. chloroleuca strain Cc878 achieved through Oxford Nanopore Long-Read sequencing. The nuclear genome of Cc878 was assembled into four contigs, totaling 59.38 Mb.

Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi.

A-to-I mRNA editing in animals is mediated by ADARs, but the mechanism underlying sexual stage-specific A-to-I mRNA editing in fungi remains unknown. Here, we show that the eukaryotic tRNA-specific heterodimeric deaminase FgTad2-FgTad3 is responsible for A-to-I mRNA editing in Fusarium graminearum. This editing capacity relies on the interaction between FgTad3 and a sexual stage-specific protein called Ame1. Although Ame1 orthologs are widely distributed in fungi, the interaction originates in Sordariomycetes. We have identified key residues responsible for the FgTad3-Ame1 interaction. The expression and activity of FgTad2-FgTad3 are regulated through alternative promoters, alternative translation initiation, and post-translational modifications. Our study demonstrates that the FgTad2-FgTad3-Ame1 complex can efficiently edit mRNA in yeasts, bacteria, and human cells, with important implications for the development of base editors in therapy and agriculture. Overall, this study uncovers mechanisms, regulation, and evolution of RNA editing in fungi, highlighting the role of protein-protein interactions in modulating deaminase function.

Regulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum.

Deoxynivalenol (DON) is the most frequently detected mycotoxin in cereal grains and processed food or feed. Two transcription factors, Tri6 and Tri10, are essential for DON biosynthesis in Fusarium graminearum. In this study we conduct stranded RNA-seq analysis with tri6 and tri10 mutants and show that Tri10 acts as a master regulator controlling the expression of sense and antisense transcripts of TRI6 and over 450 genes with diverse functions. TRI6 is more specific for regulating TRI genes although it negatively regulates TRI10. Two other TRI genes, including TRI5 that encodes a key enzyme for DON biosynthesis, also have antisense transcripts. Both Tri6 and Tri10 are essential for TRI5 expression and for suppression of antisense-TRI5. Furthermore, we identify a long non-coding RNA (named RNA5P) that is transcribed from the TRI5 promoter region and is also regulated by Tri6 and Tri10. Deletion of RNA5P by replacing the promoter region of TRI5 with that of TRI12 increases TRI5 expression and DON biosynthesis, indicating that RNA5P suppresses TRI5 expression. However, ectopic constitutive overexpression of RNA5P has no effect on DON biosynthesis and TRI5 expression. Nevertheless, elevated expression of RNA5P in situ reduces TRI5 expression and DON production. Our results indicate that TRI10 and TRI6 regulate each other's expression, and both are important for suppressing the expression of RNA5P, a long non-coding RNA with cis-acting inhibitory effects on TRI5 expression and DON biosynthesis in F. graminearum.

Adaptive advantages of restorative RNA editing in fungi for resolving survival-reproduction trade-offs.

RNA editing in various organisms commonly restores RNA sequences to their ancestral state, but its adaptive advantages are debated. In fungi, restorative editing corrects premature stop codons in pseudogenes specifically during sexual reproduction. We characterized 71 pseudogenes and their restorative editing in Fusarium graminearum, demonstrating that restorative editing of 16 pseudogenes is crucial for germ tissue development in fruiting bodies. Our results also revealed that the emergence of premature stop codons is facilitated by restorative editing and that premature stop codons corrected by restorative editing are selectively favored over ancestral amino acid codons. Furthermore, we found that ancestral versions of pseudogenes have antagonistic effects on reproduction and survival. Restorative editing eliminates the survival costs of reproduction caused by antagonistic pleiotropy and provides a selective advantage in fungi. Our findings highlight the importance of restorative editing in the evolution of fungal complex multicellularity and provide empirical evidence that restorative editing serves as an adaptive mechanism enabling the resolution of genetic trade-offs.

FgSdhC Paralog Confers Natural Resistance toward SDHI Fungicides in Fusarium graminearum.

Fusarium graminearum exhibited natural resistance to a majority of succinate dehydrogenase inhibitor fungicides (SDHIs) and the molecular mechanisms responsible for the natural resistance were still unknown. Succinate dehydrogenase subunit C (SdhC) is an essential gene for maintaining succinate-ubiquinone oxidoreductase (SQR) function in fungi. In F. graminearum, a paralog of FgSdhC named as FgSdhC1 was identified. Based on RNA-Seq and qRT-PCR assay, we found that the expression level of FgSdhC1 was very low but upregulated by SDHIs treatment. Based on reverse genetics, we demonstrated that FgSdhC1 was an inessential gene in normal growth but was sufficient for maintaining SQR function and conferred natural resistance or reduced sensitivity toward SDHIs. Additionally, we found that the standard F. graminearum isolate PH-1 had high sensitivity to a majority of SDHIs. A single nucleotide variation (C to T) in the FgSdhC1 of isolate PH-1, resulting in a premature termination codon (TAA) replacing the fourth amino acid glutamine (Q), led to the failure of FgSdhC1 to perform functions of conferring nature resistance. These results established that a dispensable paralogous gene determined SDHIs resistance in natural populations of F. graminearum.

A non-pheromone GPCR is essential for meiosis and ascosporogenesis in the wheat scab fungus.

Meiosis is essential for generating genetic diversity and sexual spores, but the regulation of meiosis and ascosporogenesis is not clear in filamentous fungi, in which dikaryotic and diploid cells formed inside fruiting bodies are not free living and independent of pheromones or pheromone receptors. In this study, Gia1, a non-pheromone GPCR (G protein-coupled receptor) with sexual-specific expression in Fusarium graminearum, is found to be essential for ascosporogenesis. The gia1 mutant was normal in perithecium development, crozier formation, and karyogamy but failed to undergo meiosis, which could be partially rescued by a dominant active mutation in GPA1 and activation of the Gpmk1 pathway. GIA1 orthologs have conserved functions in regulating meiosis and ascosporogenesis in Sordariomycetes. GIA1 has a paralog, GIP1, in F. graminearum and other Hypocreales species which is essential for perithecium formation. GIP1 differed from GIA1 in expression profiles and downstream signaling during sexual reproduction. Whereas the C-terminal tail and IR3 were important for intracellular signaling, the N-terminal region and EL3 of Gia1 were responsible for recognizing its ligand, which is likely a protein enriched in developing perithecia, particularly in the gia1 mutant. Taken together, these results showed that GIA1 encodes a non-pheromone GPCR that regulates the entry into meiosis and ascosporogenesis via the downstream Gpmk1 MAP kinase pathway in F. graminearum and other filamentous ascomycetes.

Wheat adaptation to environmental stresses under climate change: Molecular basis and genetic improvement.

Wheat (Triticum aestivum) is a staple food for about 40% of the world's population. As the global population has grown and living standards improved, high yield and improved nutritional quality have become the main targets for wheat breeding. However, wheat production has been compromised by global warming through the more frequent occurrence of extreme temperature events, which have increased water scarcity, aggravated soil salinization, caused plants to be more vulnerable to diseases, and directly reduced plant fertility and suppressed yield. One promising option to address these challenges is the genetic improvement of wheat for enhanced resistance to environmental stress. Several decades of progress in genomics and genetic engineering has tremendously advanced our understanding of the molecular and genetic mechanisms underlying abiotic and biotic stress responses in wheat. These advances have heralded what might be considered a "golden age" of functional genomics for the genetic improvement of wheat. Here, we summarize the current knowledge on the molecular and genetic basis of wheat resistance to abiotic and biotic stresses, including the QTLs/genes involved, their functional and regulatory mechanisms, and strategies for genetic modification of wheat for improved stress resistance. In addition, we also provide perspectives on some key challenges that need to be addressed.

The evolution of mini-chromosomes in the fungal genus Colletotrichum.

Anthracnose diseases caused by Colletotrichum species are among the most common fungal diseases. These symptoms typically manifest as dark, sunken lesions on leaves, stems, and fruit. In China, mango anthracnose seriously affects fruit yield and quality. Genome sequencing of several species shows the presence of mini-chromosomes. These are thought to contribute to virulence, but their formation and activity remain to be fully elucidated. Here, we assembled 17 Colletotrichum genomes (16 isolated from mango plus one from persimmon) through PacBio long-read sequencing. Half of the assembled scaffolds had telomeric repeats at both ends indicating full-length chromosomes. Based on comparative genomics analysis at interspecies and intraspecies levels, we identified extensive chromosomal rearrangements events. We analyzed mini-chromosomes of Colletotrichum spp. and found large variation among close relatives. In C. fructicola, homology between core chromosomes and mini-chromosomes suggested that some mini-chromosomes were generated by recombination of core chromosomes. In C. musae GZ23-3, we found 26 horizontally transferred genes arranged in clusters on mini-chromosomes. In C. asianum FJ11-1, several potential pathogenesis-related genes on mini-chromosomes were upregulated, especially in strains with highly pathogenic phenotypes. Mutants of these upregulated genes showed obvious defects in virulence. Our findings provide insights into the evolution and potential relationships to virulence associated with mini-chromosomes. IMPORTANCE Colletotrichum is a cosmopolitan fungal genus that seriously affects fruit yield and quality of many plant species. Mini-chromosomes have been found to be related to virulence in Colletotrichum. Further examination of mini-chromosomes can help us elucidate some pathogenic mechanisms of Colletotrichum. In this study, we generated novel assemblies of several Colletotrichum strains. Comparative genomic analyses within and between Colletotrichum species were conducted. We then identified mini-chromosomes in our sequenced strains systematically. The characteristics and generation of mini-chromosomes were investigated. Transcriptome analysis and gene knockout revealed pathogenesis-related genes located on mini-chromosomes of C. asianum FJ11-1. This study represents the most comprehensive investigation of chromosome evolution and potential pathogenicity of mini-chromosomes in the Colletotrichum genus.

Experimental evidence for the functional importance and adaptive advantage of A-to-I RNA editing in fungi.

Adenosine-to-inosine (A-to-I) editing is the most prevalent type of RNA editing in animals, and it occurs in fungi specifically during sexual reproduction. However, it is debatable whether A-to-I RNA editing is adaptive. Deciphering the functional importance of individual editing sites is essential for the mechanistic understanding of the adaptive advantages of RNA editing. Here, by performing gene deletion for 17 genes with conserved missense editing (CME) sites and engineering underedited (ue) and overedited (oe) mutants for 10 CME sites using site-specific mutagenesis at the native locus in Fusarium graminearum, we demonstrated that two CME sites in CME5 and CME11 genes are functionally important for sexual reproduction. Although the overedited mutant was normal in sexual reproduction, the underedited mutant of CME5 had severe defects in ascus and ascospore formation like the deletion mutant, suggesting that the CME site of CME5 is co-opted for sexual development. The preediting residue of Cme5 is evolutionarily conserved across diverse classes of Ascomycota, while the postediting one is rarely hardwired into the genome, implying that editing at this site leads to higher fitness than a genomic A-to-G mutation. More importantly, mutants expressing only the underedited or the overedited allele of CME11 are defective in ascosporogenesis, while those expressing both alleles displayed normal phenotypes, indicating that concurrently expressing edited and unedited versions of Cme11 is more advantageous than either. Our study provides convincing experimental evidence for the long-suspected adaptive advantages of RNA editing in fungi and likely in animals.

Clay nanoflakes and organic molecules synergistically promoting CO2 hydrate formation.

Carbon dioxide (CO2) reduction is an urgent challenge worldwide due to the dramatically increased CO2 concentration and concomitant environmental problems. Geological CO2 storage in gas hydrate in marine sediment is a promising and attractive way to mitigate CO2 emissions owning to its huge storage capability and safety. However, the sluggish kinetics and unclear enhancing mechanisms of CO2 hydrate formation limit the practical application of hydrate-based CO2 storage technologies. Here, we used vermiculite nanoflakes (VMNs) and methionine (Met) to investigate the synergistic promotion of natural clay surface and organic matter on CO2 hydrate formation kinetics. Induction time and t90 in VMNs dispersion with Met were shorter by one to two orders of magnitude than Met solution and VMNs dispersion. Besides, CO2 hydrate formation kinetics showed significant concentration-dependence on both Met and VMNs. The side chains of Met can promote CO2 hydrate formation by inducing water molecules to form a clathrate-like structure. However, when Met concentration exceeded 3.0 mg/mL, the critical amount of ammonium ions from dissociated Met distorted the ordered structure of water molecules, inhibiting CO2 hydrate formation. Negatively charged VMNs can attenuate this inhibition by adsorbing ammonium ions in VMNs dispersion. This work sheds light on the formation mechanism of CO2 hydrate in the presence of clay and organic matter which are the indispensable constituents of marine sediments, also contributes to the practical application of hydrate-based CO2 storage technologies.

Discovery and Characterization of Putative Glycoprotein-Encoding Mycoviruses in the Bunyavirales.

Although segmented negative-sense RNA viruses (SNSRVs) have been frequently discovered in various fungi, most SNSRVs reported only the large segments. In this study, we investigated the diversity of the mycoviruses in the phytopathogenic fungus Fusarium asiaticum using the metatranscriptomic technique. We identified 17 fungal single-stranded RNA (ssRNA) viruses including nine viruses within Mitoviridae, one each in Narnaviridae, Botourmiaviridae, Hypoviridae, Fusariviridae, and Narliviridae, two in Mymonaviridae, and one trisegmented virus temporarily named Fusarium asiaticum mycobunyavirus 1 (FaMBV1). The FaMBV1 genome comprises three RNA segments, large (L), medium (M), and small (S) with 6,468, 2,639, and 1,420 nucleotides, respectively. These L, M, and S segments putatively encode the L protein, glycoprotein, and nucleocapsid, respectively. Phylogenetic analysis based on the L protein showed that FaMBV1 is phylogenetically clustered with Alternaria tenuissima negative-stranded RNA virus 2 (AtNSRV2) and Sclerotinia sclerotiorum negative-stranded RNA virus 5 (SsNSRV5) but distantly related to the members of the family Phenuiviridae. FaMBV1 could be vertically transmitted by asexual spores with lower efficiency (16.7%, 2/42). Comparison between FaMBV1-free and -infected fungal strains revealed that FaMBV1 has little effect on hyphal growth, pathogenicity, and conidium production, and its M segment is dispensable for viral replication and lost during subculture and asexual conidiation. The M and S segments of AtNSRV2 and SsNSRV5 were found using bioinformatics methods, indicating that the two fungal NSRVs harbor trisegmented genomes. Our results provide a new example of the existence and evolution of the segmented negative-sense RNA viruses in fungi. IMPORTANCE Fungal segmented negative-sense RNA viruses (SNSRVs) have been frequently found. Only the large segment encoding RNA-dependent RNA polymerase (RdRp) has been reported in most fungal SNSRVs, except for a few fungal SNSRVs reported to encode nucleocapsids, nonstructural proteins, or movement proteins. Virome analysis of the Fusarium spp. that cause Fusarium head blight discovered a novel virus, Fusarium asiaticum mycobunyavirus 1 (FaMBV1), representing a novel lineage of the family Phenuiviridae. FaMBV1 harbors a trisegmented genome that putatively encodes RdRp, glycoproteins, and nucleocapsids. The putative glycoprotein was first described in fungal SNSRVs and shared homology with glycoprotein of animal phenuivirus but was dispensable for its replication in F. asiaticum. Two other trisegmented fungal SNSRVs that also encode glycoproteins were discovered, implying that three-segment bunyavirus infections may be common in fungi. These findings provide new insights into the ecology and evolution of SNSRVs, particularly those infecting fungi.

Cachexia is associated with depression, anxiety and quality of life in cancer patients.

OBJECTIVES: This study aimed to compare depression, anxiety and quality of life (QoL) between cachexia and non-cachexia patients, and explore the relationship between cachexia and depression, anxiety and QoL in patients with cancer. METHODS: A total of 528 patients from cancer centres of four hospitals were enrolled in this cross-sectional study. All patients were divided into cachexia and non-cachexia according to international consensus definition of cachexia. Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Quality of Life Questionnaire-Cancer 30 (QLQ-C30) were used to evaluate depression, anxiety and QoL. RESULTS: 285 patients (53.98%) were classified as cachexia. The prevalence of depression, anxiety, severe depression and severe anxiety in cachexia was 30.2%, 18.6%, 6.7% and 8.4%, respectively, which were significantly higher than in non-cachexia (all p<0.01). Patients with cachexia obviously acquired poorer physical function (PF), role function (RF), cognitive function (CF), emotional function (EF), social function (SF) and overall QoL than non-cachexia patients (all p<0.01). Cachexia was positively associated with depression (unstandardised coefficient (B)=2.123, p<0.001) and anxiety (B=1.123, p=0.024), and had a negative relationship with PF, CF, EF, SF and overall QoL (all B<0, all p<0.05). CONCLUSIONS: Cachexia was associated with greater depression and anxiety and poorer QoL in patients with cancer, which emphasised the importance of timely identification and management of cachexia to improve the psychological problems and QoL among patients with cancer.

High-Quality Genome Resource of Fusarium pseudograminearum Isolate Fp22-2 by Oxford Nanopore Long-Read Sequencing.

Fusarium crown rot (FCR), caused by Fusarium pseudograminearum, results in severe yield and quality losses of cereal crops in many arid and semiarid areas of the world. Limited information about the genome of F. pseudograminearum restricts the pathogenesis research and breeding of disease-resistant wheat varieties. In this study, a high-quality genome assembly of F. pseudograminearum isolate Fp22-2 was generated using Oxford Nanopore long-read sequencing technology. The assembled nuclear genome of Fp22-2 is 37.33 Mb with a repeat content of 3.69% and is divided into four contigs with a k-mer completeness score of 97.2% and a base quality accuracy of >99.99%. A total of 14,475 protein-coding genes (BUSCO completeness score, 99.9%) were predicted and functionally annotated. Moreover, genes encoding pathogenic proteins, including effector proteins and carbohydrate-active enzymes, and secondary metabolic gene clusters were identified. Overall, the high-quality genome assembly and gene annotation provided here will allow further investigation of the biology of F. pseudograminearum and lead to the development of new control options for FCR.

Recognition of glycoside hydrolase 12 proteins by the immune receptor RXEG1 confers Fusarium head blight resistance in wheat.

Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease in wheat (Triticum aestivum) that results in substantial yield losses and mycotoxin contamination. Reliable genetic resources for FHB resistance in wheat are lacking. In this study, we characterized glycoside hydrolase 12 (GH12) family proteins secreted by F. graminearum. We established that two GH12 proteins, Fg05851 and Fg11037, have functionally redundant roles in F. graminearum colonization of wheat. Furthermore, we determined that the GH12 proteins Fg05851 and Fg11037 are recognized by the leucine-rich-repeat receptor-like protein RXEG1 in the dicot Nicotiana benthamiana. Heterologous expression of RXEG1 conferred wheat responsiveness to Fg05851 and Fg11037, enhanced wheat resistance to F. graminearum and reduced levels of the mycotoxin deoxynivalenol in wheat grains in an Fg05851/Fg11037-dependent manner. In the RXEG1 transgenic lines, genes related to pattern-triggered plant immunity, salicylic acid, jasmonic acid, and anti-oxidative homeostasis signalling pathways were upregulated during F. graminearum infection. However, the expression of these genes was not significantly changed during infection by the deletion mutant ΔFg05851/Fg11037, suggesting that the recognition of Fg05851/Fg11037 by RXEG1 triggered plant resistance against FHB. Moreover, introducing RXEG1 into three other different wheat cultivars via crossing also conferred resistance to F. graminearum. Expression of RXEG1 did not have obvious deleterious effects on plant growth and development in wheat. Our study reveals that N. benthamiana RXEG1 remains effective when transferred into wheat, a monocot, which in turn suggests that engineering wheat with interfamily plant immune receptor transgenes is a viable strategy for increasing resistance to FHB.

High cerebrospinal fluid lactate concentration at 48 h of hospital admission predicts poor outcomes in patients with tuberculous meningitis: A multicenter retrospective cohort study.

Objective: This study aimed to analyze the cerebrospinal fluid (CSF) parameters affecting the outcomes of patients with tuberculous meningitis (TBM). Methods: This is a multi-center, retrospective, cohort study involving 81 patients who were diagnosed with TBM and treated in Haihe Clinical College of Tianjin Medical University, Tianjin Medical University General Hospital, and General Hospital of Air Force PLA from January 2016 to December 2019. Baseline data, Glasgow Coma Scale (GCS) score, and clinical presentations of all patients were collected at admission. CSF samples were collected at 48 h, 1, 2, and 3 weeks after admission. CSF lactate, adenosine deaminase, chloride, protein, glucose levels and intracranial pressure were measured. After a follow-up of 16.14 ± 3.03 months, all patients were assessed using the modified Rankin Scale (mRS) and divided into good (mRS scores of 0-2 points) and poor outcome groups (mRS scores of 3-6 points). The differences in patients' baseline data, GCS score, clinical presentations, and levels of CSF parameters detected at 48 h, 1, 2, and 3 weeks after admission between two groups were compared. Statistically significant variables were added to the binary logistic regression model to identify the factors impacting the outcomes of patients with TBM. Receiver operating characteristic (ROC) curve was used to assess the predictive ability of the model. Results: The CSF lactate level exhibited a decreasing trend within 3 weeks of admission in the two groups. For the within-group comparison, statistically significant differences in the lactate level was found in both groups between four different time points. A binary logistic regression model revealed that CSF lactate level at 48 h after admission, age, and GSC score on admission were independently associated with the outcomes of patients with TBM. ROC curve analysis showed that the area under the ROC curve (AUC) was 0.786 for the CSF lactate level (48 h), 0.814 for GCS score, and 0.764 for age. Conclusion: High CSF lactate level at 48 h after admission is one of the important factors for poor outcomes in patients with TBM.