Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition.

Ischemic stroke (IS) has become a cerebrovascular disease which seriously threatens the elderly people. It has been reported that circRNAs participate in multiple diseases, including IS. However, the role of circHECTD1 in IS remains largely unknown. To mimic IS in vitro, human cerebral microvascular endothelial cells (HCMECs) were treated with oxygen glucose deprivation/reperfusion (OGD/R). Meanwhile, MCAO mouse model was established to detect the expression of circHECTD1 in IS. qRT-PCR and western blot were used to test gene and protein expressions, respectively. CCK-8 assay was used to investigate the cell viability. Moreover, cell migration and tube formation were assessed by transwell and tube formation assays. In addition, RIP and luciferase assay were performed to explore the association among circHECTD1, miR-335 and NOTCH2. CircHECTD1 was significantly upregulated in IS. OGD/R significantly induced EndoMT in HCMECs, while knockdown of circHECTD1 notably reversed this phenomenon. In addition, silencing of circHECTD1 remarkably reversed OGD/R-induced promotion of HCMEC tube formation and migration. Meanwhile, circHECTD1 upregulated the level of NOTCH2 through binding with miR-335. Furthermore, miR-335 inhibited the process of EndoMT in IS via targeting NOTCH2. In summary, circHECTD1 knockdown significantly alleviated EndoMT process in HCMECs via mediation of miR-335/NOTCH2 axis. Thus, circHECTD1 might act as a potential target against IS.

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse.

PURPOSE: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP. EXPERIMENTAL DESIGN: Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ analysis followed by ingenuity pathway analysis (IPA) of DEPs. DEPs are validated using Western blot analysis. RESULTS: A total of 1789 unique protein sequences are identified in the uterosacral ligament connective tissues. The expression levels of 88 proteins are significantly different between prolapse and control groups (≥1.2-fold, p < 0.05). IPA demonstrates the association of 14 DEPs with "Connective Tissue Function." Among them, fibromodulin, collagen alpha-1 (XIV) chain, calponin-1, tenascin, and galectin-1 appear most likely to play a role in the etiology of POP. CONCLUSIONS AND CLINICAL RELEVANCE: At least six proteins not previously associated with the pathogenesis of POP with biologic functions that suggest a plausible relationship to the disorder are identified. These results may be helpful for furthering the understanding of the pathophysiological mechanisms of POP.

[Histological changes of the prostate and acute urinary retention in patients with benign prostatic hyperplasia].

OBJECTIVE: To investigate the roles of prostatic infarction, prostatic inflammation and the type of prostatic hyperplasia in acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH). METHODS: We retrospectively analyzed 102 cases of BPH, 49 complicated by AUR and the other 53 without AUR. We compared the incidences of prostatic infarction and prostatic inflammation, the types of prostatic hyperplasia, the patients' age, the level of prostate specific antigen (PSA), the prostate volume, and international prostate symptom score (IPSS) between the AUR and non-AUR groups. RESULTS: The PSA level was significantly increased in the AUR group as compared with the non-AUR group (P < 0.05). There were no statistically significant differences between the two groups in the mean age, prostate volume and IPSS (P > 0.05). The type of prostatic hyperplasia showed no correlation with AUR. The incidence rate of AUR was 5.620 and 2.326 times higher in the BPH patients with prostatic infarction and prostatic inflammation respectively than in those without (P < 0.05). CONCLUSION: Prostatic infarction and prostatic inflammation are important risk factors of AUR in BPH patients.

Metabolomic profiles delineate potential roles for gadolinium chloride in the proliferation or inhibition of Hela cells.

Lanthanides (Lns) compounds have been reported to possess contrary effects on cell activity, i.e., promoting cell cycle progression and cell growth by lower concentration treatment, but suppressing cell proliferation and inducing cell apoptosis at higher dosing. However, the cellular processes during the intervention and the possible underlying mechanisms are still not well clarified. Using a combination of high-throughput liquid chromatography (LC) with mass spectrometry (MS), we have investigated the metabolomic profiles of Hela cells following gadolinium chloride (GdCl(3)) treatment in time- and concentration- dependent manners. A total of 48 metabolites released by Hela cells are identified to be differentially expressed (P < 0.05) in different states. Metabolic pathways analyses reveal that the differential metabolites are mainly characterized by increased lipid and amino acid metabolisms and by decreased lipid, amino acid, and carbohydrate metabolisms for cells treated with GdCl(3) at lower and higher concentrations, respectively. Notably, in the higher level GdCl(3) case, the down-expressions of metabolites are predominantly in the glycolytic and the redox pathways. The above results, obtained by using a metabolomic strategy for the first time, disclose that different cell signaling pathways are activated by GdCl(3) treatment with different concentrations, leading to inhibitory or promotional effect on Hela cells.

[Effect of bisphenol A on semen quality of exposed workers: a pilot study].

OBJECTIVE: To explore the semen quality of the workers exposed to the xenoestrogen bisphenol A (BPA) was explored. METHODS: A cross-sectional study of 20 BPA exposed and 16 control workers with similar age, physical activities was performed. Tests included quantifying BPA in blood samples and investigating the quantity and quality of semen. Semen parameters were determined with the method recommended by WHO. RESULTS: 94.4% exposed workers were found BPA in blood, and the median was 101.94 microg/L. However, only 18.8% control subjects were found BPA in blood, and the median level was 0 microg/L. The sperm density of exposed workers [(68.65 +/- 44.00) x 10(6)/ml] was significantly lower than that of control [(118.56 +/- 98.36) x 10(6)/ml]. Relationship analysis showed the positive relationships (r = 0.44, P < 0.01) between the sperm with quick forward progression and BPA level in blood, negative relationships between the percentage of normal sperm and BPA level in blood (r = -0.62, P = 0.01). CONCLUSION: BPA could affect the sperm density, and may influence the semen quality. More research should be performed on the effect and the mechanism of BPA on man.