A consistently decreasing prevalence of MRSA infections in China has been reported, however, the underlying mechanism of molecular processes responsible for this decline in MRSA infections has been poorly understood. We conducted an epidemiologic investigation to determine the dynamic changes of Staphylococcus aureus infections. A total of 3695 S. aureus isolates was recovered from 2008 to 2017, and subsequently characterized by infection types, resistance profile, and clone types. The frequency of respiratory infection decreased over the study period from 76% to 52%. The proportion of MRSA remarkably decreased (from 83.5% to 54.2%, 2008-2017) ( p < .0001). The prevalence of predominant healthcare-associated MRSA (HA-MRSA) clones, ST239-t030 and ST239-t037, significantly decreased (from 20.3% to 1% and 18.4% to 0.5%, 2008-2017, respectively); both of them were replaced by the continually growing ST5-t2460 clone (from 0% to 17.3%, 2008-2017). Epidemic community-acquired MRSA (CA-MRSA) ST59 and ST398 clones also increased (from 1.0% to 5.8% and 1.8% to 10.5%, 2008-2017, respectively). These results demonstrated a significant decrease in the previously dominant HA-MRSA ST239 clones, leading to a marked decrease in the prevalence of MRSA over the past decade, and shed new light on the complex competition of S. aureus clones predominating within the health-care environment.

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Due to its evascular, aneural, and alymphatic conditions, articular cartilage shows extremely poor regenerative ability. Thus, directing chondrocyte toward a desired location and function by utilizing the mechanical cues of biomaterials is a promising approach for effective tissue regeneration. However, chondrocytes cultured on Petri dish will lose their typical phenotype which may lead to compromised results. Therefore, we fabricated polydimethylsiloxane (PDMS) materials with various stiffness as culture substrates. Cell morphology and focal adhesion of chondrocytes displayed significant changes. The cytoskeletal tension of the adherent cells observed by average myosin IIA fluorescent intensity increased as stiffness of the underlying substrates decreased, consistent with the alteration of chondrocyte phenotype in our study. Immunofluorescent images and q-PCR results revealed that chondrocyte cultured on soft substrates showed better chondrocyte functionalization by more type II collagen and aggrecan expression, related to the lowest mRNA level of Rac-1, RhoA, ROCK-1, and ROCK-2. Taken together, this work not only points out that matrix elasticity can regulate chondrocyte functionalization via RhoA/ROCK pathway, but also provides new prospect for biomechanical control of cell behavior in cell-based cartilage regeneration.

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Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 ( NTRK1, NTRK2 and NTRK3 ) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLC γ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.

Thuringiensin is a thermostable secondary metabolite inBacillus thuringiensis and has insecticidal activity against a wide range of insects. Until now, the regulatory mechanisms and genetic determinants involved in thuringiensin production have remained unclear. Here, we successfully used heterologous expression-guided screening in an Escherichia coli-Bacillus thuringiensis shuttle bacterial artificial chromosome library, to clone the intact thuringiensin synthesis (thu) cluster. Then the thu cluster was located on a 110-kb endogenous plasmid bearing insecticide crystal protein gene cry1Ba in strain CT-43. Furthermore, the plasmid, named pBMB0558, was indirectly cloned and sequenced. The gene functions on pBMB0558 were annotated by BLAST based on the GenBank TM and KEGG databases. The genes on pBMB0558 could be classified into three functional modules: a thuringiensin synthesis cluster, a type IV secretion system-like module, and mobile genetic elements. By HPLC coupling mass spectrometer, atmospheric pressure ionization with ion trap, and TOF technologies, biosynthetic intermediates of thuringiensin were detected. The thuE gene is proved to be responsible for the phosphorylation of thuringiensin at the last step by vivo and vitro activity assays. The thuringiensin biosynthesis pathway was deduced and clarified. We propose that thuringiensin is an adenine nucleoside oligosaccharide rather than an adenine nucleotide analog, as is traditionally believed, based on the predicted functions of the key enzymes, glycosyltransferase (ThuF) and exopolysaccharide polymerization protein (Thu1).

This work first introduced the protein-based l-tyrosine to thermosets, and proved that the l-tyrosine building-block can confer materials with high performance.

We developed and evaluated the specificity and sensitivity of a simple loop-mediated isothermal amplification (LAMP) method for rapid detection of P. aeruginosa strains. The optimal reaction condition was found to be 65°C for 45 min, with the detection limit as 100 fg DNA/ tube and 10 CFU/reaction. Application of LAMP assays were performed 426 clinical samples (including 252 P. aeruginosa and 174 non-P. aeruginosa isolates) using a rapid procedure and easy result confirmation. Sensitivity of LAMP and PCR assays was found to be 97.6% (246/252) and 90.5% (228/252), respectively; with a 100% specificity for both assays.