The clinic-based predictive modeling for prognosis of patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM. METHODS: The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted. RESULTS: A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome. CONCLUSIONS: Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention.

Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution.

More and more attention has been paid to the role of synonymous substitution in evolution, in which codon usage preference can affect gene expression distribution and protein structure and function. Vesicular glutamate transporter (VGLUT) consists of three isoforms, among which VGLUT3 is significantly different from other VGLUTs in functional importance, expression level, and distribution range, whose reason is still unclear. This study sought to analyze the role of codon preference in VGLUT differentiation. To conduct an evolutionary analysis of the three VGLUTs, this paper uses bioinformatics research methods to analyze the coding sequences of the three VGLUTs in different species and compare the codon usage patterns. Furthermore, the differences among the three VGLUTs were analyzed by combining functional importance, expression level, distribution range, gene structure, protein relationship network, expression at specific developmental stages, and phylogenetic tree, and the influence of codon usage pattern was explored. The results showed that the VGLUT with greater codon preference had less functional importance, lower expression levels, more peripheral distribution away from the CNS, smaller exon density of gene, less conserved and farther away from the CDS region miRNA regulatory sites, simpler and less tight protein interaction networks, delayed developmental expression, and more distant evolutionary relationships. Codon usage preference is a potential factor affecting VGLUT developmental expression and protein evolution.

Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE.

Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis.

An Ultrasensitive Lateral Flow Immunoassay Based on Metal-Organic Framework-Decorated Polydopamine for Multiple Sulfonylureas Adulteration in Functional Foods.

Herein, an ultrasensitive lateral flow immunoassay (LFIA), based on metal-organic framework-decorated polydopamine (PCN-224@PDA) was first established to detect multiple sulfonylureas (SUs) in functional foods. The PCN-224@PDA was synthesized using the one-pot hydrothermal method and covalently coupled with SUs antibodies, and the coupling rate was up to 91.8%. The detection limits of the developed PCN-224@PDA-LFIA for multiple SUs in functional teas and capsules were 0.22-3.72 µg/kg and 0.40-3.71 µg/kg, and quantification limits were 0.75-8.19 µg/kg and 1.03-9.08 µg/kg, respectively. The analytical sensitivity was 128-fold higher than that of similar methods reported so far. The recovery rates ranged from 83.8 to 119.0%, with coefficients of variation of 7.6-14.4%. The parallel analysis of 20 real samples by LC-MS/MS confirmed the reliability of the proposed method. Therefore, our work offers novel, ultrasensitive, and rapid technical support for on-site monitoring of SUs in functional foods.

Facile immunochromatographic assay based on metal-organic framework-decorated polydopamine for the determination of hydrochlorothiazide adulteration in functional foods.

Herein, a novel immunochromatographic assay (ICA) based on metal-organic framework-decorated polydopamine (MOF@PDA) was firstly developed for the determination of hydrochlorothiazide (HCTZ) adulteration in functional foods. The coupling rate of MOF@PDA carrier to HCTZ antibody was as high as 91.7 %. The detection limits of the developed MOF@PDA-ICA in functional tablets and capsules were 5.93 and 4.72 µg/kg, the linear ranges were 11.2-91.91 µg/kg and 9.11-86.78 µg/kg, respectively. The sensitivity was 27-fold higher than that of the reported ICA. The recovery was 82.5-116.6 %, and coefficient of variation was 6.9-14.2 %. The results can be achieved and analyzed in 8 min with the smartphone-based detection device. The parallel tests of 23 commercial functional tablets and capsules showed that the results of the MOF@PDA-ICA were consistent with that of the LC-MS/MS (R2 > 0.99). Therefore, our method is facile, sensitive, portable, and can provide a reliable technical mean for the detection of HCTZ adulteration in functional foods.

An enhanced immunochromatography assay based on colloidal gold-decorated polydopamine for rapid and sensitive determination of gentamicin in animal-derived food.

In this study, an enhancing immunochromatography assay (ICA) based on colloidal gold-decorated polydopamine (CG@PDA) was firstly developed for gentamicin in milk, muscle, liver and kidney simultaneously. CG@PDA was synthesized by one-pot method with better signal intensity, colloidal stability, and antibody coupling efficiency than traditional colloidal gold. The detection limit of the developed ICA was about 1.50 µg/kg for the four animal-derived food, which was up to 92-fold more sensitive than the reported ICA based on colloidal gold. The recovery rates were ranged from 86.0% to 114.0% with coefficient of variation between 1.6% and 13.1%. Parallel analysis of 40 samples by commercial ELISA kits was confirmed the reliability. Our research indicated that polydopamine decorated can chemically modify the surface of colloidal gold and can thus remarkably improve the detection performances of ICA.

Rainbow latex microspheres lateral flow immunoassay with smartphone-based device for simultaneous detection of three mycotoxins in cereals.

The coexistent pollution of multiple mycotoxins displays a synergistic toxicity effect that significantly threatens human health. Therefore, it is essential to establish a rapid detection method for multi-mycotoxins in food. In this study, red, green, and blue latex microspheres (LMs) were applied as the aflatoxin B1 (AFB1), T-2 toxins (T-2), and zearalenone (ZEN) antibodies labeled tracer, respectively. Based on the principle of spatial resolution, a rainbow "traffic light" pattern latex microspheres lateral flow immunoassay (LMs-LFIA) integrated with a portable and user-friendly smartphone-based device was first developed to detect three kinds of mycotoxins simultaneously. The cut-off values of the method for AFB1/T-2/ZEN in cereals were 1/15/40 µg kg-1, the limits of detection were 0.04/0.40/1.21 µg kg-1, respectively. The recoveries ranged from 82.1% to 107.5%, with the coefficient of variation from 3.0% to 8.1%. A parallel analysis in 26 naturally contaminated cereal samples was confirmed by commercial ELISA kits; the results showed a good correlation (R2＞0.99), indicating the practical reliability of the rainbow LMs-LFIA. This method provided a visually enjoyable, portable, and sensitive detection mode for multi-target detection of mycotoxins or other small molecule hazard factors in food.