Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China.

OBJECTIVES: We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. METHODS: Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. RESULTS: Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1-29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2-8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. CONCLUSIONS: This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles.

Synthesis and biological evaluation of novel isothiazoloquinoline quinone analogues.

Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.

Advanced non-noble materials in bifunctional catalysts for ORR and OER toward aqueous metal-air batteries.

The catalyst in the oxygen electrode is the core component of the aqueous metal-air battery, which plays a vital role in the determination of the open circuit potential, energy density, and cycle life of the battery. For rechargeable aqueous metal-air batteries, the catalyst should have both good oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic performance. Compared with precious metal catalysts, non-precious metal materials have more advantages in terms of abundant resource reserves and low prices. Over the past few years, great efforts have been made in the development of non-precious metal bifunctional catalysts. This review selectively evaluates the advantages, disadvantages and development status of recent advanced materials including pure carbon materials, carbon-based metal materials and carbon-free materials as bifunctional oxygen catalysts. Preliminary improvement strategies are formulated to make up for the deficiency of each material. The development prospects and challenges facing bifunctional catalysts in the future are also discussed.

[Homology of Staphylococcus aureus isolated from skin lesions and nose of patients with impetigo].

OBJECTIVE: To investigate the homology of Staphylococcus aureus (SA) strains isolated from nose and skin lesions of impetigo children. METHODS: Totally 263 outpatients aged 3 months to 14 years who were seen by the Department of Dermatology of Beijing Children's Hospital between August 2005 and March 2006 were enrolled in this study. The isolations from nose and skin lesions of 58 impetigo children who were randomly selected from these 263 children with spa sequence were typed. The sequence results of SA were analyzed using special websites. RESULTS: There were 106 impetigo patients in these 263 children. The isolation rate of SA was 78.3% in the nose of 106 impetigo patients and was 21.0% in that of the rest 157 patients (P < 0.01). The age of all nasal carriers was concentrated in 1-6 years. Among the 106 impetigo patients, 30 patients had their primary lesions on the face (including 28 cases of SA nose isolates) and 76 patients had their primary lesions on the other parts of body (including 56 cases of SA nose isolates) (P < 0.01). The spa typing showed that 26 of the 30 impetigo patients had the same type pairs of nose and skin. CONCLUSIONS: SA isolated from the skin lesions and nose of impetigo patients has remarkably homology. Nasal carriage of SA may be closely relevant with the occurrence of impetigo.

Isobaric tag for relative and absolute quantitation-based comparative proteomic analysis of human pathogenic Prototheca zopfii genotype 2 and environmental genotype 1 strains.

BACKGROUND/PURPOSE: Prototheca species are ubiquitous achlorophyllic microalgae belonging to the family Chlorellaceae, which can cause a wide range of infections in humans and animals. Mainly in individuals with immunologic defects or trauma, Prototheca spp. can cause even lethal diseases. However, the exact pathogenic mechanism of Prototheca in causing disease remains largely unknown. To investigate the differences between pathogenic and nonpathogenic Prototheca spp. genotypes on proteome level, a nonpathogenic Prototheca zopfii genotype 1 strain, isolated from cow manure, and a human pathogenic P. zopfii genotype 2, isolated from human granulomatous lymphadenitis, were studied. METHODS: Differentially expressed proteins between the two genotypes were quantified by isobaric tag for relative and absolute quantitation-based quantitative proteomics, using liquid chromatography-tandem mass spectrometry. RESULTS: A total of 245 proteins were identified from the proteomic analysis after data filtering to eliminate low-scoring spectra. Among these, 35 proteins that displayed a significant (p<0.05) 1.5-fold change were considered as differentially expressed proteins. CONCLUSION: The differentially expressed proteins were associated with suppressed energy production and conversion, carbohydrate transport and metabolism, and enhanced translation in the genotype 2 strain, and are thus potentially relevant in the pathogenic mechanism of P. zopfii genotype 2, but need further investigation.

[Clinical application of extracorporeal shock wave to repair and reconstruct osseous tissue framework in the treatment of avascular necrosis of the femoral head (ANFH)].

OBJECTIVE: To investigate the application value of extracorporeal shock wave to repair and reconstruct osseous tissue for the treatment of avascular necrosis of the femoral head (ANFH). METHODS: A total of 42 hips of 36 patients with ANFH were treated with extracorporeal shock waves included 29 males and 7 females,aged from 21 to 66 during March 2006 to March 2008. The course of disease was 6 months to 3 years (means 1.3 years). According to Ficat classification 8 hips were in stages I, 25 were in stage II, and 9 were in stage III. The energy density of ESWT was from 0.18 to 0.25 mJ/mm2. The treatment focusing points of avascular necrosis of the femoral on the surface projection were marked with X-ray fluoroscopy, and 1 to 2 points were selected for one treatment with 400 to 500 pulses in each point. Generally 3 to 5 treatments were performed, once per 7 days. The CR, CT or MRI and the hip Harris score were obtained to investigate the clinical effects of extracorporeal shock wave for repair and reconstruct osseous tissue framework and improve the hip function before treatment and at 3, 12 months after treatment. RESULTS: The X-ray,CT or MR were performed of 42 hips,35 hips were treated successfully after extracorporeal shock wave therapy, cure occurred in 6 cases, marked effect in 13 cases, effectiveness in 16 cases and ineffectiveness in 7 case. After one years of followed-up, no relapse was found, the femoral head further collapse did not occur. The Harris hip score of stage I, II, III ere respectivey (90.1 +/- .4), (81.2 +/- .5), (66.9 +/- .6) at 3 months and (91.6 +/- .4), (91.1 +/- .5), (79.0 +/- .1) at 12 months after treatment. The scores after treatment were increased significantly than that of before treatment (P < 0.01). CONCLUSION: Extracorporeal shock wave therapy has obviously therapeutic effect in the repairing and reconstructing osseous tissue and improve the hip Harris score and improve the hip function. It is a effect significantly, non-invasion, less complications, simple-accurate therapy method for ischemic necrosis of the femoral head.