RESUMO
Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX-2 cell activation, we performed RNA-seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum-induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA-494-3p, a microRNA associated with anti-liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA-494-3p in LX-2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α-SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum.
Assuntos
Fator 3 Ativador da Transcrição , Proteínas de Helminto , Células Estreladas do Fígado , Cirrose Hepática , MicroRNAs , Schistosoma japonicum , Esquistossomose Japônica , Animais , Fator 3 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/genética , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/parasitologia , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/genética , Cirrose Hepática/parasitologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Camundongos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Actinas/metabolismo , Actinas/genética , Linhagem Celular , Regulação da Expressão Gênica , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Modelos Animais de Doenças , Antígenos de HelmintosRESUMO
Background: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP's epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures. Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis. Results: Infants (0-1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were bla NDM-5 in children (58.1%) and bla KPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 bla KPC-2 and ST15 bla OXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing bla NDM-5 and bla OXA-181 in the NICU. Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.
RESUMO
Robot path planning is an important component of ensuring the robots complete work tasks effectively. Nowadays, most maps used for robot path planning obtain relevant coordinate information through sensor measurement, establish a map model based on coordinate information, and then carry out path planning for the robot, which is time-consuming and labor-intensive. To solve this problem, a method of robot path planning based on ant colony algorithms after the standardized design of non-standard map grids such as photos was studied. This method combines the robot grid map modeling with image processing, bringing in calibration objects. By converting non-standard actual environment maps into standard grid maps, this method was made suitable for robot motion path planning on non-standard maps of different types and sizes. After obtaining the planned path and pose, the robot motion path planning map under the non-standard map was obtained by combining the planned path and pose with the non-standard real environment map. The experimental results showed that this method has a high adaptability to robot non-standard map motion planning, can realize robot path planning under non-standard real environment maps, and can make the obtained robot motion path display more intuitive and convenient.
