Isocitrate dehydrogenase (IDH) is a key enzyme at the critical junction between the tricarboxylic acid cycle and the glyoxylate cycle. Most bacteria have only one IDH, while a few contain two IDH isozymes. The coexistence of two different type IDHs in one organism was little known. Xylella fastidiosa is a nutritionally fastidious plant pathogen that contains two structurally different IDHs, an NAD -dependent homodimeric IDH (diXfIDH) and an NADP -dependent monomeric IDH (monoXfIDH). Kinetic characterization showed that diXfIDH displayed 206-fold preferences for NAD over NADP , while monoXfIDH showed 13,800-fold preferences for NADP over NAD . The putative coenzyme crucial amino acids (Asp-268, Ile-269, and Ala-275 in diXfIDH, and Lys-589, His-590, and Arg-601 in monoXfIDH) were studied by site-directed mutagenesis. The coenzyme specificities of the three diXfIDH mutants (D268K, D268K/I269Y, and D268K/I269Y/A275V) were switched successfully from NAD to NADP . Meanwhile, the mutant monoXfIDHs (H590L/R601L and K589T/H590L/R601L) greatly reduced the affinity for NADP , but failed to improve the ability to use NAD and had similar affinity to NADP and NAD . The biochemical properties of diXfIDH and monoXfIDH were investigated in detail. This study gives a further insight into the determinants of the coenzyme specificity in both monomeric and dimeric forms of IDHs.

N1-methyladenosine (m1A) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 m1A modification-related patterns based on m1A regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an m1A-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of m1A in glioma.

Aberrant expression of methyltransferases and demethylases may augment tumor initiation, proliferation and metastasis through RNA modification, such as m6A and m5C. However, activity of pseudouridine (Ψ) modification of RNA remains unknown in glioma, the most common malignant intracranial tumor. In this study, we explored the expression profiles of the Ψ synthase genes in glioma and constructed an efficient prediction model for glioma prognosis based on the CGGA and TCGA datasets. In addition, the risk-score signature was positively associated with malignancy of gliomas and the abundance of tumor-infiltrating immune cells such as macrophages M0 and regulatory T cells (Tregs), but negatively associated with the abundance of monocytes, NK cell activation and T cell CD4+ naive. In terms of mechanism, the risk-score signature was positively associated with the expression of inflammatory molecules such as S100A11 and CASP4 in glioma. Overall, this study provided evidence for the activity of RNA Ψ modification in glioma malignancy and local immunity.

Objective: This study aimed to systematically evaluate the effects of mind–body exercise on global cognitive function, depression, sleep disorders, fatigue level, and quality of life (QOL) in a Parkinson’s disease (PD) population.Methods: Total six English and Chinese databases were searched for articles published up to May 2021. Randomized controlled trials (RCTs) evaluating mind–body excises on non-motor symptoms of PD were included. The Cochrane risk of bias tool was used to assess the methodological quality, and we defined high-quality studies as having a low risk of bias in four or more domains. Global cognitive function was considered the primary outcome and was assessed using the Montreal Cognitive Assessment (MoCA). The secondary outcomes included QOL, fatigue, depression, and sleep quality, which were measured using the Parkinson’s Disease Questionnaire (PDQ-39), 16-item Parkinson’s Disease Fatigue Scale (PFS-16), Beck Depression Inventory (BDI), and revised Parkinson’s Disease Sleep Scale (PDSS-2), respectively. Subgroup analyses were conducted for global cognitive function and QOL to assess the optimal treatment measure across the various mind–body exercises.Results: Fourteen RCTs with 404 patients were finally included in the meta-analysis. Eight (57.14%) studies were of high quality. The pooled results showed that mind–body exercises generally had a significant advantage over the control intervention in improving global cognitive function (MD = 1.68; P = 0.0008). The dose subgroup analysis revealed that the low dose (60–120 min per week) and moderate dose (120–200 min per week) significantly increased MoCA scores compared with the control group (MD = 2.11, P = 0.01; MD = 1.27, P = 0.02, respectively). The duration subgroup analysis indicated a significant difference in the effect of the duration (6–10 and >15 weeks) on increasing MoCA scores compared with the control group (MD = 3.74, P < 0.00001; MD = 1.45, P = 0.01, respectively).Conclusion: Mind–body exercise may improve global cognitive function, sleep quality, and QOL in the PD population. In addition, low to moderate doses and appropriate durations significantly improved global cognitive function.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021275522].

Background: To alleviate anxiety before surgery is a significant concern for the pediatric anesthesiologist.Midazolam has been generally used as a premedication, and compelling data regarding effective dose to mitigate anxiety is lacking. The current trial addressed the comparable efficacy of intravenous midazolam with different doses regarding the anxiety state, ease of child-parental separation, and mask compliance as premedication in pediatric patients undergoing tonsillectomy.Methods: Three hundred and twelve children aged 2-8 years were randomly assigned, 104 per group, to receive intravenous 0.03 mg/kg midazolam (group A), 0.05 mg/kg midazolam (group B), or saline control (group C), 40 minutes before surgery. We assessed the anxiety state every 10 min after premedication with modified Yale preoperative anxiety scale (mYPAS), evaluated the emotional state during separation with parental separation anxiety scale (PSAS), and compared their compliance to mask oxygen supply with mask acceptance score (MAS).Results: Children premedicated with 0.05 mg/kg midazolam achieved a sedated state more rapidly than those who received 0.03 mg/kg midazolam (5.9±2.3 vs. 7.0±3.9, P=0.02). The proportion of satisfactory parental separation and compliance to mask ventilation was not different between midazolam groups, which was superior to saline control. The children receiving 0.05 mg/kg midazolam stayed longer in postoperative care unit than those receiving 0.03 mg/kg midazolam and saline. The incidence of postoperative adverse events was rare and comparable among groups.Conclusions: Intravenous administration of a single dose of midazolam 0.05 and 0.03 mg/kg produces similar effects on sedation status, parental separation, and mask induction acceptance, except for rapid-onset and long sedation duration in pediatric patients premedicated with 0.05 mg/kg midazolam.Trial Registration: ClinicalTrials.gov NCT04266340.