Epidemiological and Genetic Characteristics of Clinical Carbapenem-Resistant Pseudomonas aeruginosa Strains in Guangdong Province, China.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a bacterial pathogen that may cause serious drug-resistant infections that are potentially fatal. To investigate the genetic characteristics of these organisms, we tested 416 P. aeruginosa strains recovered from 12 types of clinical samples collected in 29 different hospital wards in 10 hospitals in Guangdong Province, China, from 2017 to 2020. These strains were found to belong to 149 known sequence types (STs) and 72 novel STs, indicating that transmission of these strains involved multiple routes. A high rate of resistance to imipenem (89.4%) and meropenem (79.4%) and a high prevalence of pathogenic serotypes (76.4%) were observed among these strains. Six STs of global high-risk clones (HiRiCs) and a novel HiRiC strains, ST1971, which exhibited extensive drug resistance, were identified. Importantly, ST1971 HiRiC, which was unique in China, also exhibited high virulence, which alarmed the further surveillance on this highly virulent and highly resistant clone. Inactivation of the oprD gene and overexpression of efflux systems were found to be mainly responsible for carbapenem resistance in these strains; carriage of metallo-ß-lactamase (MBL)-encoding genes was less common. Interestingly, frameshift mutations (49.0%) and introduction of a stop codon (22.4%) into the oprD genes were the major mechanisms of imipenem resistance. On the other hand, expression of the MexAB-OprM efflux pump and MBL-encoding genes were mechanisms of resistance in >70% of meropenem-resistant strains. The findings presented here provide insights into the development of effective strategies for control of worldwide dissemination of CRPA. IMPORTANCE Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major concern in clinical settings worldwide, yet few genetic and epidemiological studies on CRPA strains have been performed in China. Here, we sequence and analyze the genomes of 416 P. aeruginosa strains from hospitals in China to elucidate the genetic, phenotypic, and transmission characteristics of CRPA strains and to identify the molecular signatures responsible for the observed increase in the prevalence of CRPA infections in China. These findings may provide new insight into the development of effective strategies for worldwide control of CRPA and minimize the occurrence of untreatable infections in clinical settings.

Quantitative MRI evaluation of articular cartilage in patients with meniscus tear.

Purpose: The aim of this study was to assess quantitatively articular cartilage volume, thickness, and T2 value alterations in meniscus tear patients. Materials and methods: The study included 32 patients with meniscus tears (17 females, 15 males; mean age: 40.16 ± 11.85 years) and 24 healthy controls (12 females; 12 males; mean age: 36 ± 9.14 years). All subjects were examined by 3 T magnetic resonance imaging (MRI) with 3D dual-echo steady-state (DESS) and T2 mapping images. All patients underwent diagnostic arthroscopy and treatment. Cartilage thickness, cartilage volume and T2 values of 21 subregions of knee cartilage were measured using the prototype KneeCaP software (version 2.1; Siemens Healthcare, Erlangen, Germany). Mann-Whitney-U tests were utilized to determine if there were any significant differences among subregional articular cartilage volume, thickness and T2 value between patients with meniscus tear and the control group. Results: The articular cartilage T2 values in all subregions of the femur and tibia in the meniscus tear group were significantly higher (p< 0.05) than in the healthy control group. The cartilage thickness of the femoral condyle medial, femur trochlea, femur condyle lateral central, tibia plateau medial anterior and patella facet medial inferior in the meniscus tear group were slightly higher than in the control group (p< 0.05). In the femur trochlea medial, patella facet medial inferior, tibia plateau lateral posterior and tibia plateau lateral central, there were significant differences in relative cartilage volume percentage between the meniscus tear group and the healthy control group (p< 0.05). Nineteen patients had no cartilage abnormalities (Grade 0) in the meniscus tear group, as confirmed by arthroscopic surgery, and their T2 values in most subregions were significantly higher (p< 0.05) than those of the healthy control group. Conclusion: The difference in articular cartilage indexes between patients with meniscus tears and healthy people without such tears can be detected by using quantitative MRI. Quantitative T2 values enable early and sensitive detection of early cartilage lesions.

Insight on Reaction Pathways of Photocatalytic CO2 Conversion.

Photocatalytic CO2 conversion to value-added chemicals is a promising solution to mitigate the current energy and environmental issues but is a challenging process. The main obstacles include the inertness of CO2 molecule, the sluggish multi-electron process, the unfavorable thermodynamics, and the selectivity control to preferable products. Furthermore, the lack of fundamental understanding of the reaction pathways accounts for the very moderate performance in the field. Therefore, in this Perspective, we attempt to discuss the possible reaction mechanisms toward all C1 and C2 value-added products, taking into account the experimental evidence and theoretical calculation on the surface adsorption, proton and electron transfer, and products desorption. Finally, the remaining challenges in the field, including mechanistic understanding, reactor design, economic consideration, and potential solutions, are critically discussed by us.

Bone marrow-derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3-mediated macrophage pyroptosis.

Rupture of atherosclerotic plaques constitutes the major cause of thrombosis and acute ischemic coronary syndrome. Bone marrow-derived mesenchymal stem cells microvesicles (BMSCs-MVs) are reported to promote angiogenesis. This study investigated the role of BMSCs-MVs in stabilizing atherosclerotic plaques. BMSCs-MVs in mice were isolated and identified. The mouse model of atherosclerosis was established, and mice were injected with BMSCs-MVs via the tail vein. The macrophage model with high glucose and oxidative damage was established and then incubated with BMSCs-MVs. Nod-like receptor protein 3 (NLRP3) expression, pyroptosis-related proteins, and inflammatory factors were detected. Actinomycin D was used to inhibit the secretion of BMSCs-MVs to verify the source of microRNA-223 (miR-223). The binding relationship between miR-223 and NLRP3 was predicted and verified. BMSCs-MVs with knockdown of miR-223 were cocultured with bone marrow-derived macrophages with knockdown of NLRP3, and then levels of miR-223, NLRP3, pyroptosis-related proteins, and inflammatory factors were detected. BMSCs-MVs could reduce the vulnerability index of atherosclerotic plaques and intima-media thickness in mice, and inhibit pyroptosis and inflammation. BMSCs-MVs inhibited pyroptosis and inflammatory factors in macrophages. BMSCs-MVs carried miR-223 to inhibit NLRP3 expression and reduce macrophage pyroptosis, thereby stabilizing the atherosclerotic plaques.

Long noncoding RNA HAGLROS regulates cell apoptosis and autophagy in lipopolysaccharides-induced WI-38 cells via modulating miR-100/NF-κB axis.

Pneumonia is a lower respiratory disease caused by pathogens or other factors. This study aimed to explore the roles and mechanism of long noncoding RNA HAGLROS in lipopolysaccharides (LPS)-induced inflammatory injury in pneumonia. The HAGLROS expression in serum of patients with acute stage pneumonia was detected. To induce pulmonary injury, WI-38 human lung fibroblasts were stimulated with lipopolysaccharides (LPS). The HAGLROS expressions in LPS-treated WI-38 cells and the effects of HAGLROS knockdown on the viability, apoptosis, and autophagy of LPS-induced cells were detected. Moreover, the regulatory relationship between HAGLROS and miR-100 was explored as well as the functional targets of miR-100 were identified. Furthermore, the regulatory relationship between miR-100 and PI3K/AKT/NF-κB pathway was elucidated. LncRNA HAGLROS was higher expressed in serum of patients with acute stage pneumonia compared with that in serum of healthy control. LPS caused WI-38 cell injury and increased HAGLROS levels. Downregulation of HAGLROS alleviated LPS-induced cell injury via increasing cell viability, and inhibiting apoptosis and autophagy. Moreover, there was a negative correlation between HAGLROS and miR-100, and the effects of HAGLROS downregulation on LPS-induced apoptosis and autophagy in WI-38 cells were by regulation of miR-100. Furthermore, NFΚB3 was verified as a functional target of miR-100 and effects of miR-100 inhibition on LPS-induced WI-38 cell injury were alleviated by knockdown of NFΚB3. Besides, Knockdown of HAGLROS inhibited the activation of PI3K/AKT/NF-κB pathway. Our findings reveal that downregulation of HAGLROS may alleviate LPS-induced inflammatory injury in WI-38 cells via modulating miR-100/NF-κB axis. HAGLROS/miR-100/NF-κB axis may provide a new strategy for treating acute stage of pneumonia.

Knockdown of PFTK1 Expression by RNAi Inhibits the Proliferation and Invasion of Human Non-Small Lung Adenocarcinoma Cells.

PFTK1 (PFTAIRE protein kinase 1), also named CDK14 (cyclin-dependent kinase 14), is a member of the cell division cycle 2 (CDC2)-related protein kinase family. It is highly expressed in several malignant tumors. However, the role of PFTK1 in the progression of non-small cell lung cancer (NSCLC) is still elusive. In this study, we aimed to explore the expression and function of PFTK1 in NSCLC cells. Our results showed that PFTK1 was significantly upregulated in human NSCLC cell lines. Silencing the expression of PFTK1 inhibited the proliferation of NSCLC cells. In addition, silencing the expression of PFTK1 endowed NSCLC cells with decreased migration and invasion abilities, as well as epithelial-mesenchymal transition (EMT) progress in A549 cells. A mechanistic study showed that knockdown of PFTK1 inhibited the expression of ß-catenin, cyclin D1, and c-Myc in A549 cells. In summary, we report that small interfering RNA (siRNA)-PFTK1 might inhibit the proliferation and invasion of NSCLC cells by suppressing the Wnt/ß-catenin signaling pathway. Therefore, PFTK1 may represent a novel therapeutic target for the treatment of NSCLC.