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The resistance temperature characteristics and thermal stability of graphite based flexible grounding materials were studied. With the method of current heating and constant temperature protection, the resistance of grounding body at each temperature was measured by voltammetry, and the average resistance temperature coefficient was derived. With the resistance temperature characteristic parameters of the grounding body obtained from the experiment, the maximum temperature rise of the graphite based flexible grounding body under the power frequency grounding fault current and lightning impulse current was calculated iteratively, which is verified by the calculation of the thermal stability coefficient. The experimental results show that the graphite based flexible grounding body has a negative temperature coefficient. When the maximum allowable service temperature of the graphite based flexible grounding body is 450 ℃, the maximum allowable current under 0.5 s power frequency current is about 1.4 kA, which is 8/20 μs the maximum allowable passing current amplitude of graphite based flexible grounding body under the impact of high frequency lightning current is 287.9 kA.

We intended to explore whether N[H.sub.4]Cl influences the viability and regulates the expression of Wnt/[beta]-catenin pathway in hepatocytes. The Chang liver cell line was used and cultured with different concentrations of N[H.sub.4]Cl (2.5, 5,10, 20, 40, and 50 mmol/L) for 12, 24, and 48 h. The viability of hepatocytes was detected by MTT assay. The mRNA and protein expression level was analyzed with qRT-PCR and Western blotting, respectively. N[H.sub.4]Cl concentration significantly affects the viability of hepatocytes. With the increase of N[H.sub.4]Cl concentration, the viability of hepatocytes was decreased, accordingly. The mRNA and protein expression of Wntl, [beta]-catenin, and cyclin D was significantly increased after treatment with low concentrations of N[H.sub.4]Cl as compared with the control group, whereas their expression levels were decreased after treatment with high concentrations of N[H.sub.4]Cl. The mRNA and protein expression of Wntl, [beta]-catenin, and cyclin D was also significantly increased after treatment with N[H.sub.4]Cl for a short period as compared with the control group, whereas their expression levels were decreased after treatment with N[H.sub.4]Cl for a long period. In addition, we found N[H.sub.4]Cl treatment significantly reversed the results after RNA silencing of Wnt1 in hepatocytes. N[H.sub.4]Cl influences the viability of hepatocytes and affects the expression of Wnt/[beta]-catenin pathway in hepatocytes. Key words: N[H.sub.4]Cl, Wnt/[beta]-catenin pathway, hepatocytes. Nous visons a etudier si le N[H.sub.4]Cl influence la viabilite et regule l'expression de la voie de signalisation Wnt/[beta]-catenine dans les hepatocytes. Nous avons utilise la lignee Chang de cellules hepatiques que nous avons mises en culture et exposees a differentes concentrations de N[H.sub.4]Cl (2,5, 5,10, 20, 40 et 50 mmol/L) pendant 12, 24 et 48 h. Nous avons detecte la viabilite des hepatocytes a l'aide du test MTT. Nous avons etudie l'expression de l'ARNm et des proteines a l'aide des techniques de qRT-PCR et d'immunobuvardage de Western, respectivement. La concentration de N[H.sub.4]Cl modifie nettement la viabilite des hepatocytes. En effet, on fait diminuer la viabilite des hepatocytes consecutivement a l'augmentation de la concentration de N[H.sub.4]Cl. L'expression d'ARNm et de proteines pour Wnt1, la [beta]-catenine et la cycline D augmentait nettement plus apres une exposition a de faibles concentrations de N[H.sub.4]Cl que chez les temoins, alors que leur degre d'expression diminuait apres l'exposition a des concentrations elevees de N[H.sub.4]Cl. L'expression d'ARNm et de proteines pour Wnt1, la [beta]-catenine et la cycline D augmentait aussi nettement plus apres une exposition au N[H.sub.4]Cl pendant de courtes periodes que chez les temoins, alors que leur degre d'expression diminuait apres l'exposition au N[H.sub.4]Cl pendant de longues periodes. De plus, nous avons observe que l'exposition au N[H.sub.4]Cl inversait de facon notable les resultats apres la mise sous silence de l'ARN de Wnt1 dans les hepatocytes. Le N[H.sub.4]Cl a une influence sur la viabilite des hepatocytes et modifie l'expression de la voie de signalisation Wnt/[beta]-catenine dans les hepatocytes. [Traduit par la Redaction] Mots-cles : N[H.sub.4]Cl, voie de signalisation Wnt/[beta]-catenine, hepatocytes., Introduction Liver has a strong ability of regeneration after hepatic injury or resection (Jo et al. 2007) and is a quiescent organ with >90% of the cells present in the [...]

Colistin is the last line of defense for the treatment of multidrug-resistant gram-negative bacterial infections. However, colistin resistance is gradually increasing worldwide, with resistance commonly regulated by two-component system and mcr gene. Thus, this study aimed to investigate molecular epidemiology and colistin-resistant mechanism of mcr -positive and mcr -negative Escherichia coli isolates from animal in Sichuan Province, China. In this study, a total of 101 colistin-resistant E. coli strains were isolated from 300 fecal samples in six farms in Sichuan Province. PCR was used to detect mcr gene (mcr-1 to mcr-9). The prevalence of mcr-1 in colistin-resistant E. coli was 53.47% (54/101), and the prevalence of mcr-3 in colistin-resistant E. coli was 10.89% (11/101). The colistin-resistant E. coli and mcr-1 –positive E. coli showed extensive antimicrobial resistance profiles. For follow-up experiments, we used 30 mcr -negative and 30 mcr-1 –positive colistin-resistant E. coli isolates and E. coli K-12 MG1655 model strain. Multi-locus sequence typing (MLST) of 30 strains carrying mcr-1 as detected by PCR identified revealed six strains (20%) of ST10 and three strains (10%) of each ST206, ST48, and ST155 and either two (for ST542 and 2539) or just one for all other types. The conjugation experiment and plasmid replicon type analysis suggest that mcr-1 was more likely to be horizontally transferred and primarily localized on IncX4-type and IncI2-type plasmid. The ST diversity of the mcr-1 indicated a scattered and non-clonal spreading in mcr-1 –positive E. coli. Twenty-eight mcr -negative colistin-resistant E. coli isolates carried diverse amino acid alterations in PmrA, PmrB, PhoP, PhoQ, and MgrB, whereas no mutation was found in the remaining isolates. The finding showed the high prevalence of colistin resistance in livestock farm environments in Sichuan Province, China. Our study demonstrates that colistin resistance is related to chromosomal point mutations including the two-component systems PhoP/PhoQ, PmrA/PmrB, and their regulators MgrB. These point mutations may confer colistin resistance in mcr -negative E. coli. These findings help in gaining insight of chromosomal-encoded colistin resistance in E. coli. [ABSTRACT FROM AUTHOR]

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Antimicrobial resistance is rapidly increasing worldwide, highlighting the urgent need for pharmaceutical and nonpharmaceutical interventions to tackle different-to-treat bacterial infections. Tigecycline, a semi-synthesis glycylcycline for parenteral administration, is widely recognized as one of the few effective therapies available against pan-drug resistant Gram-negative pathogens. Regrettably, the efficacy of multiple drugs, including tigecycline, is currently being undermined due to the emergence of a recently discovered mobilized resistance-nodulation-division-type efflux pump gene cluster tmexCD1-toprJ1 . Herein, by employing untargeted metabolomic approaches, we reveal that the expression of tmexCD1-toprJ1 disrupts bacterial purine metabolism, with inosine being identified as a crucial biomarker. Notably, the supplementation of inosine effectively reverses tigecycline resistance in tmexCD1-toprJ1 -positive bacteria. Mechanistically, exogenous inosine enhanced bacterial proton motive force, which promotes the uptake of tigecycline. Furthermore, inosine enhances succinate biosynthesis by stimulating the tricarboxylic acid cycle. Succinate interacts with the two-component system EnvZ/OmpR and upregulates OmpK 36, thereby promoting the influx of tigecycline. These actions collectively lead to the increased intracellular accumulation of tigecycline. Overall, our study offers a distinct combinational strategy to manage infections caused by tmexCD-toprJ -positive bacteria., Importance: TMexCD1-TOprJ1, a mobilized resistance-nodulation-division-type efflux pump, confers phenotypic resistance to multiple classes of antibiotics. Nowadays, tmexCD-toprJ has disseminated among diverse species of clinical pathogens, exacerbating the need for novel anti-infective strategies. In this study, we report that tmexCD1-toprJ1 -negative and -positive bacteria exhibit significantly different metabolic flux and characteristics, especially in purine metabolism. Intriguingly, the addition of inosine, a purine metabolite, effectively restores the antibacterial activity of tigecycline by promoting antibiotic uptake. Our findings highlight the correlation between bacterial mechanism and antibiotic resistance, and offer a distinct approach to overcome tmexCD-toprJ -mediated multidrug resistance., Competing Interests: The authors declare no conflict of interest.