Genome plasticity resulting from frequent rearrangement of the bacterial genome is a fascinating but poorly understood phenomenon. First reported in Salmonella typhi, it has been observed only in a small number of Salmonella serovars, although the over 2,500 known Salmonella serovars are all very closely related. To gain insights into this phenomenon and elucidate its roles in bacterial evolution, especially those involved in the formation of particular pathogens, we systematically analyzed the genomes of 127 wild-type S. typhi strains isolated from many places of the world and compared them with the two sequenced strains, Ty2 and CT18, attempting to find possible associations between genome rearrangement and other significant genomic features. Like other host-adapted Salmonella serovars, S. typhi contained large genome insertions, including the 134 kb Salmonella pathogenicity island, SPI7. Our analyses showed that SPI7 disrupted the physical balance of the bacterial genome between the replication origin (ori) and terminus (ter) when this DNA segment was inserted into the genome, and rearrangement in individual strains further changed the genome balance status, with a general tendency toward a better balanced genome structure. In a given S. typhi strain, genome diversification occurred and resulted in different structures among cells in the culture. Under a stressed condition, bacterial cells with better balanced genome structures were selected to greatly increase in proportion; in such cases, bacteria with better balanced genomes formed larger colonies and grew with shorter generation times. Our results support the hypothesis that genome plasticity as a result of frequent rearrangement provides the opportunity for the bacterial genome to adopt a better balanced structure and thus eventually stabilizes the genome during evolution.

In recent years, the advances in terahertz applications have stimulated interest in the biological effects associated with this frequency range. We study the gene expression profile in three types of cells exposed to terahertz radiation, i.e., human ARPE-19 retinal pigment epithelial cells, simian virus 40-transformed human corneal epithelial cells, and human MIO-M1 Müller cells. We find that the gene expression in response to heat shock is unaffected, indicating that the minimum temperature increases under controlled environment. The transcriptome sequencing survey demonstrates that 6-hour irradiation with a broadband terahertz source results in specific change in gene expression and also the biological functions that are closely related to these genes. Our results imply that the effect of terahertz radiation on gene expression can last over 15 hours and depends on the type of cell.

In this study, we propose and demonstrate a broadband polarization-independent terahertz modulator based on graphene/silicon hybrid structure through a combination of continuous wave optical illumination and electrical gating. Under a pump power of 400 mW and the voltages ranging from –1.8 V to 1.4 V, modulation depths in a range of –23%–62% are achieved in a frequency range from 0.25 THz to 0.65 THz. The modulator is also found to have a transition from unidirectional modulation to bidirectional modulation with the increase of pump power. Combining the Raman spectra and Schottky current–voltage characteristics of the device, it is found that the large amplitude modulation is ascribed to the electric-field controlled carrier concentration in silicon with assistance of the graphene electrode and Schottky junction.

GPR84 is a proinflammatory G protein-coupled receptor that mediates myeloid immune cell functions. Blocking GPR84 with antagonists is a promising approach for treating inflammatory and fibrotic diseases. Previously, a GPR84 antagonist 604c, with a symmetrical phosphodiester structure, has displayed promising efficacy in a mouse model of ulcerative colitis. However, the low blood exposure resulting from physicochemical properties prevented its uses in other inflammatory diseases. In this study, a series of unsymmetrical phosphodiesters with lower lipophilicity were designed and tested. The representative compound 37 exhibited a 100-fold increase in mouse blood exposure compared to 604c while maintaining in vitro activity. In a mouse model of acute lung injury, 37 (30 mg/kg, po) significantly reduced the infiltration of proinflammatory cells and the release of inflammatory cytokines and ameliorated pathological changes equally or more effectively than N-acetylcysteine (100 mg/kg, po). These findings suggest that 37 is a promising candidate for treating lung inflammation.