Exploration and validation of m7G-related genes as signatures in the immune microenvironment and prognostic indicators in low-grade glioma.

OBJECTIVES: Currently, an increasing number of studies are focusing on the impact of m7G modification in cancer. This study aims to investigate the prognostic value of m7G-related genes in low-grade glioma (LGG). METHODS: LGG samples were obtained from the CGGA database, and normal samples were obtained from GTEx. Differentially expressed m7G-related genes were identified, and genes highly associated with macrophage M2 in LGG patients were identified by immuno-infiltration and WGCNA analysis. The intersection of differentially expressed m7G-related genes and macrophage M2-associated genes yielded candidate genes, and hub genes were identified using 5 algorithms in CytoHubba. Enrichment analysis verified the relevant pathways of hub genes, and their performance in tumor classification was evaluated. RESULTS: A total of 3329 differentially expressed m7G-related genes were identified. 1289 genes were highly associated with macrophage M2 in LGG patients. The intersection of m7G-related genes and results in WGCNA yielded 840 candidate genes, and six hub genes (STXBP1, CPLX1, PAB3A, APBA1, RIMS1, and GRIN2B) were identified. Hub genes were enriched in synaptic transmission-related pathways and showed good performance for tumor classification. There were significant differences in survival levels between clusters. CONCLUSIONS: The identified m7G-related genes may provide new insight into the treatment and prognosis of LGG.

Integrative analysis of CBR1 as a prognostic factor associated with IDH-mutant glioblastoma in the Chinese population.

BACKGROUND: Glioblastoma multiforme (GBM) is a common primary intracranial tumor with poor prognosis. Common indicators in the clinical diagnosis of glioma include MGMT promoter methylation, isocitrate dehydrogenase (IDH) mutation, 1p/19q codeletion, and TERT mutation. Among these, IDH mutation is extremely important for GBM diagnosis and treatment. METHODS: The Chinese Glioma Population Database (CGGA) and Gene Expression Omnibus (GEO) data (GSE131273) related to glioma in the Chinese population were used for differential analysis (DGA) and weighted gene coexpression network analysis (WGCNA). The expression levels of hub genes between the IDH1 wild-type and mutant GBM cell lines were detected by RT-qPCR. Kaplan-Meier (KM) plotter was used to analyze hub gene expression levels and prognostic values. RESULTS: Eight hub genes were identified by WGCNA and different expression genes (DEG) analysis, namely, one upregulated gene (CRYAB) and seven downregulated genes (EFEMP2, RBP1, TAGLN2, CBR1, MSN, ALDH7A1, and MT1M). Four of these genes (ALDH7A1, MSN, CBR1, and MTM1) showed significant differences between IDH-wild-type and IDH-mutant GBM, verified at the cellular level. Moreover, the high expression of CBR1 was significantly correlated with poor overall survival (OS) in patients with IDH-mutant GBM, and we finally identified CBR1 as a specific prognostic factor in IDH-mutant GBM. CONCLUSION: Results revealed different gene expressions between IDH-wild-type and IDH-mutant GBM. These genes may help monitor the occurrence and development of glioma. CBR1 can be used as a prognostic marker to identify IDH-mutant glioblastoma patients.

Bioaccessibility and bioavailability adjusted dietary exposure of cadmium for local residents from a high-level environmental cadmium region.

The critical health risks caused by cadmium (Cd) via dietary exposure are commonly assessed by detecting Cd concentrations in foods. Differently, in this study, the bioaccessibility and bioavailability of Cd in major local harvests were introduced to assess the dietary exposure of local residents from a high-level environmental Cd region. The results indicated that certain Cd was released into the digestive juice after in vitro digestion with a bioaccessibility of 20-63% for rice and 3-32% for leafy vegetables, and the released portion was partially absorbed by Caco-2 cells with a bioavailability of 2-21% for rice and 0.2-13% for leafy vegetables. The results obtained from the toxicokinetic model revealed that the predicted urinary Cd values from the estimated daily intake (EDI) of Cd, which accounted for bioaccessibility and bioavailability, were consistent with the actual measured values, and the EDIs were considerably lower than the acceptable daily intake. This suggests that the bioaccessibility and bioavailability adjusted dietary Cd exposure should be more precise. The key issues addressed in our study implores that a potential health risk cannot be neglected in people with high consumption of rice from high-level zone.

Strip Adjustment of Airborne LiDAR Data in Urban Scenes Using Planar Features by the Minimum Hausdorff Distance.

In Airborne Light Detection and Ranging (LiDAR) data acquisition practice, discrepancies exist between adjacent strips even though careful system calibrations have been performed. A strip adjustment method using planar features acquired by the Minimum Hausdorff Distance (MHD) is proposed to eliminate these discrepancies. First, semi-suppressed fuzzy C-means and restricted region growing algorithms are used to extract buildings. Second, a binary image is generated from the minimum bounding rectangle that covers overlapping regions. Then, connected components labeling algorithm is applied to process the binary image to extract individual buildings. After that, building matching is performed based on MHD. Third, a coarse-to-fine approach is used to segment building roof planes. Then, plane matching is conducted under the constraints of MHD and normal vectors similarity. The last step is the calculation of the parameters based on Euclidean distance minimization between matched planes. Two different types of datasets, one of which was acquired by a dual-channel LiDAR system Trimble AX80, were selected to verify the proposed method. Experimental results show that the corresponding planar features that meet adjustment requirements can be successfully detected without any manual operations or auxiliary data or transformation of raw data, while the discrepancies between strips can be effectively eliminated. Although adjustment results of the proposed method slightly outperform the comparison alternative, the proposed method also has the advantage of processing the adjustment in a more automatic manner than the comparison method.

Understanding the effect of anthocyanins extracted from purple sweet potatoes on alcohol-induced liver injury in mice.

Anthocyanins as antioxidants are potential to protect liver from alcoholic damage, but might be pro-oxidants under certain conditions. In this study, twelve purple sweet potatoes anthocyanins (PSPA) were isolated and their effects on alcohol-induced liver injury were studied. These PSPA were rich in cyanidin derivatives and fed to male C57BL/6 mice as colorants in alcoholic drink with low, median, or high dosages PSPA i.e. 50, 100, or 300 mg/kg·BW·d. Compared to the alcohol group, the median-dose PSPA showed a clear improvement in the liver indexes/histology, serum ALT level, oxidative stress status, and even a recovery to the normal level, however the high dose PSPA promoted the liver injury via a pro-oxidant effect, as reflected by increased malondialdehyde (MDA) content and decreased GSH level. The results suggested that cyanidin derivatives with an ortho-hydroxyl structure on B-ring might promote the oxidative stress of alcohol-induced liver injury at high doses as a pro-oxidant.

Design, synthesis, and SAR study of 3-(benzo[d][1,3]dioxol-5-yl)-N-benzylpropanamide as novel potent synergists against fluconazole-resistant Candida albicans.

Based on our previous discovery and SAR study on the lead compounds 7d, 5 and berberine which can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, a series of 3-(benzo[d][1,3]dioxol-5-yl)-N-(substituted benzyl)propanamides were designed, synthesized, and evaluated for their in vitro synergistic activity in combination with fluconazole. The series 2a-f were designed by replacing the amide moiety of the lead compound 7d with retro-amide moiety, and compounds 2a and 2b showed more activity than the lead 7d. Furthermore, introducing biphenyl moiety into series 2d-f afforded series 3a-r, most of which exhibited significantly superior activity to the series 2d-f. Especially, compound 3e, at a concentration of 1.0µg/ml, can enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans from 128.0µg/ml to 0.125-0.25µg/ml. A clear SAR of the compounds is discussed.

Design, synthesis, and in vitro evaluation of novel antifungal triazoles.

Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Most of the compounds exhibited potent in vitro antifungal activities against 8 fungal isolates. Especially, compounds a10, a13, and a14 exhibited superior or comparable antifungal activity to ravuconazole against all the tested fungi. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole moiety of ravuconazole with fluorophenylisoxazole resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum.

Synthesis and Biological Evaluation of Novel 2-Aminonicotinamide Derivatives as Antifungal Agents.

Based on the structures of the reported compounds G884 [N-(3-(pentan-2-yloxy)phenyl)nicotinamide], E1210 [3-(3-(4-((pyridin-2-yloxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-amine], and 10 b [2-amino-N-((5-(3-fluorophenoxy)thiophen-2-yl)methyl)nicotinamide], which inhibit the biosynthesis of glycosylphosphatidylinositol (GPI)-anchored proteins in fungi, a series of novel 2-aminonicotinamide derivatives were designed, synthesized, and evaluated for in vitro antifungal activity. Most of these compounds were found to exhibit potent in vitro antifungal activity against Candida albicans, with MIC80 values ranging from 0.0313 to 4.0 µg mL-1 . In particular, compounds 11 g [2-amino-N-((5-(((2-fluorophenyl)amino)methyl)thiophen-2-yl)methyl)nicotinamide] and 11 h [2-amino-N-((5-(((3-fluorophenyl)amino)methyl)thiophen-2-yl)methyl)nicotinamide] displayed excellent activity against C. albicans, with MIC80 values of 0.0313 µg mL-1 , and exhibited broad-spectrum antifungal activity against fluconazole-resistant C. albicans, C. parapsilosis, C. glabrata, and Cryptococcus neoformans, with a MIC80 range of 0.0313-2.0 µg mL-1 . Further studies by electron microscopy and laser confocal microscopy indicated that compound 11 g targets the cell wall and decreases GPI anchor content on the cell surface of C. albicans.

Conventional, ultrasound-assisted, and accelerated-solvent extractions of anthocyanins from purple sweet potatoes.

Purple sweet potatoes (PSPs) are rich in anthocyanins. In this study, we investigated the extraction efficiency of anthocyanins from PSPs using conventional extraction (CE), ultrasound-assisted extraction (UAE), and accelerated-solvent extraction (ASE). Additionally, the effects of these extraction methods on antioxidant activity and anthocyanin composition of PSP extracts were evaluated. In order of decreasing extraction efficiency, the extraction methods were ASE>UAE>CE for anthocyanins (218-244 mg/100 g DW) and CE>UAE>ASE for total phenolics (631-955 mg/100 g DW) and flavonoids (28-40 mg/100 g DW). Antioxidant activities of PSP extracts were CE≈UAE>ASE for ORAC (766-1091 mg TE/100 g DW) and ASE>CE≈UAE for FRAP (1299-1705 mg TE/100 g DW). Twelve anthocyanins were identified. ASE extracts contained more diacyl anthocyanins and less nonacyl and monoacyl anthocyanins than CE and ASE extracts (P<0.05).

Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 µg/ml, decreased the MIC80 of fluconazole from 128.0 µg/ml to 1.0-0.5 µg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

Berberine inhibits fluphenazine-induced up-regulation of CDR1 in Candida albicans.

Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.

[Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans].

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

Structural optimization of berberine as a synergist to restore antifungal activity of fluconazole against drug-resistant Candida albicans.

We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. A structure-activity relationship study of 95 analogues led us to identify the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a-l, which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound 7 d (N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(2-fluorophenyl)acetamide) significantly decreased the MIC80 values of fluconazole from 128.0 µg mL⁻¹ to 0.5 µg mL⁻¹ against fluconazole-resistant C. albicans and exhibited much lower levels of cytotoxicity than berberine toward human umbilical vein endothelial cells.

Removal of off-flavours from radish (Raphanus sativus L.) anthocyanin-rich pigments using chitosan and its mechanism(s).

In this paper, we examined the role of chitosan in the removal of off-flavours from radish anthocyanin-rich pigments and studied the mechanisms of the process. Four radish glucosinolates (glucoraphenin, dehydroerucin, glucobrassicin, and glucoerucin) were identified by LC-MSn from root extracts and dehydroerucin was found to be the major glucosinolate in red radish roots. Application of chitosan with 76%, 83% or 89% deacetylation in radish extracts attributed to 26%, 35% or 43% adsorption rate for glucosinolates, and 28%, 26% or 22% for anthocyanins, respectively. HS-SPME/GC-MS analysis demonstrated that the concentration of volatile compounds decreased by 70%, resulting in the loss of odorous compounds. The changes in chitosan spectra before/after adsorption and after desorption at 1590 and 3360cm(-1) and at broad bands from 2600 to 2000cm(-1) suggest that the dominant adsorption mechanisms of glucosinolates on chitosan may be electrostatic attractions, including hydrogen bonds and charge neutralisation.

Tris(1,10-phenanthroline-κ(2)N,N')iron(II) bis-(1,1-dicyano-2-eth-oxy-2-oxoethanide).

The title compound, [Fe(C(12)H(8)N(2))(3)](C(6)H(5)N(2)O(2))(2), consists of one [Fe(phen)(3)](2+) cation (phen = 1,10-phenanthroline) and two 1,1-dicyano-2-eth-oxy-2-oxoethanide anions. Five atoms of the anion are disordered over two positions [site occupancy = 0.521 (13) for the major component]. In the complex cation, the Fe(II) atom is coordinated by six N atoms from three phen ligands in a distorted octa-hedral geometry. Two intra-molecular C-H⋯N hydrogen bonds occur in the complex cation. The crystal structure is mainly stabilized by Coulombic inter-actions. Weak intermolecular C-H⋯N inter-actions are also observed.

Water-soluble phosphate prodrugs of pleuromutilin analogues with potent in vivo antibacterial activity against Gram-positive pathogens.

A phosphate prodrug strategy was investigated to address the problem of poor aqueous solubility of pleuromutilin analogues. Water-soluble phosphate prodrugs 6a, 6b and 6c of pleuromutilin analogues were designed and synthesized. Three compounds all exhibited excellent aqueous solubility (>50mg/mL) at near-neutral pH and sufficient stability in buffer solution. In particular, the phenol pleuromutilin prodrug 6c displayed favourable pharmacokinetic profiles and comparable potency with vancomycin against MSSA and MRSA strains in vivo.

[Nonlinear regression analysis of cardiac enzyme kinetic model with modified simplex method and DUD method using SAS software].

OBJECTIVE: To compare the efficacy of modified simplex method and DUD method using SAS software for nonlinear regression analysis of cardiac enzyme kinetic model. METHOD: By using cardiac enzyme kinetic one-compartment mathematical model, nonlinear regression results obtained from DUD methods using SAS software and modified simplex method were compared with the same starting values to fit the creatine kinase curves in 22 patients with acute myocardial infarction. RESULTS: The parameters calculated by DUD method and modified simplex method were the same in 4 cases, and smaller least square was resulted from DUD method in 4 cases. In the other 14 cases, modified simplex method yielded smaller least square. The mean value of the least square calculated by modified simplex method was less than that by DUD method (867 747 vs 6 712 989, P=0.013). CONCLUSION: Modified simplex method appears to be more adequate than DUD method in estimating circulatory parameters of the one-compartment model.

[Analysis for clinical effect of a rinse containing cetylpyridinium chloride in treatment of gingivitis and periodontitis].

OBJECTIVE: To investigate the clinical effect of a 0.1% cetylpyridinium chloride(CPC) rinse on the treatment of gingivitis and periodontitis. METHODS: A multicenter, randomized, parallel group trial was conducted. The eligible patients were divided randomly into two groups. Subjects were assessed at the beginning and the end of a two-week period during which they rinsed with 0.1% CPC or complex hibitane in addition to their usual oral hygiene procedures. The variation of PLI, SBI, GI, PD, pain, halitosis and adverse effects were observed before and after investigation. RESULTS: After 14 days of treatment, in the CPC group, the decreasing rate of PLI was 63.0%, the effective rate for gingivitis and periodontitis were 83.3%, 36.7% respectively, while those periodontal indices of control group were 49.5%, 50% and 16.7%. After statistical analysis, the CPC group had significantly higher effective rates on gingivitis than the hibitane group (P < 0.01), at the same time, the effective rate was significantly different between two groups on periodontitis (P < 0.05). CONCLUSION: The use of 0.1% CPC rinse is effective in treating periodontal diseases.