Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.

Objective To evaluate the application value of three-dimensional speckle tracking imaging (3D-STI) in quantitatively evaluating the left ventricular global strain in recipients within 3 months after renal transplantation. Methods Clinical data including blood pressure, serum creatinine and tacrolimus blood concentration of 34 renal transplant recipients were collected before operation, 7 d, 1 month and 3 months after operation, respectively. Meanwhile, conventional echocardiography and 3D-STI examination were performed. Echocardiographic parameters [left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF)] and 3D-STI parameters [left ventricular global peak longitudinal strain (GPLS), global peak circumferential strain (GPCS), global peak radial strain (GPRS) and global peak area strain (GPAS)] of recipients were collected. The changes of these parameters before operation, 7 d, 1 month and 3 months after operation were statistically compared. The changing characteristic and application value of 3D-STI in quantitatively evaluating the left ventricular global strain in recipients within 3 months after renal transplantation were evaluated. Results LVEF and GPCS did not significantly differ at different time points (all P > 0.05), whereas LVEDV, LVESV, GPLS, GPAS and GPRS significantly differed at different time points from preoperative to within postoperative 3 months (all P < 0.001). GPLS, GPAS and GPRS trended to decline within postoperative 1 month, and slightly increased at 3 months after operation, which was still lower than the preoperative levels. Conclusions Application of 3D-STI may sensitively detect the changes of left ventricular global strain in recipients after renal transplantation when no significant variations are observed in postoperative LVEF. Compared with conventional echocardiography, 3D-STI may more accurately evaluate the changes of left ventricular global strain in recipients after renal transplantation.

Objective To investigate and analyze the military operation ability and influence factors of soldiers alongthe border in an extremely cold environment and to provide a scientific basis for effectively improving the combat effective -ness of the army stationed the cold regions.Methods According to relevant standards, recruits(the length of service <1month) and old soldiers(the length of service >1 year) were randomly selected to investigate their military operationfactors, physical condition, sleep condition, mental health and cognitive ability.Results Cold was the main factor whichaffected military operation capability in cold regions.According to physical standards,border troops were in poor physicalcondition.Results of SCL-90 showed that the total score, the number of positive items , the score of each factor of the 130recruits were significantly lower than those of the Chinese army model and 46 veterans (P <0.05).There was nosignificant difference in these aspects between the 46 veterans and Chinese army model.Recruits were in better sleepcondition and had better instantaneous memory(P <0.05).Birthplace had no effect on these factors .Recruits from Centraland South China were in poorer sleep condition than those from cold regions (P <0.05).Results of SCL-90 showed that thetotal score,the factors of somatization, coercion, depression and anxiety of communication veterans were significantly higherthan those of the Chinese army model (P <0.05).The sleep condition of communication veterans was poorer than that ofmotorized infantry and patrol veterans (P <0.05).Conclusion Cold is the main factorthat impacts the ability of militaryoperations in cold regions.The physical work capacity of border guards in cold regions was significantly below the militarystandard, so the level of military training should be strengthened .Research on cold-protection equipment for special tasks should be strengthened.