IS257-mediated amplification of tet(L) variant as a novel mechanism of enhanced tigecycline resistance in Staphylococcus cohnii.

The mechanism of enhanced tigecycline MIC in Staphylococcus cohnii after in vitro tigecycline exposure was investigated. S. cohnii 11-B-312 was exposed to incremental concentrations of tigecycline (2-32 mg/L) and the mutants growing at 8, 16 and 32 mg/L were determined by AST and WGS. Copy number and relative transcription level of the tet(L) gene were determined by quantitative PCR. The fitness cost was evaluated by growth kinetics and competition assays. The results revealed that enhanced tigecycline MIC was identified in S. cohnii mutants. Copy number and relative transcription level of tet(L) in the mutants increased 8-, 20-, and 23-fold and 20-, 34-, and 39-fold in the presence of 8, 16, and 32 mg/L tigecycline, respectively. The read-mapping depth ratio analysis indicated that a multidrug resistance region carrying the tet(L) variant has a gradually increased copy number, correlating with the tigecycline selection pressure. S. cohnii strain 11-B-312_32 had a fitness cost, and enhanced tigecycline MIC can revert to the initial level in the absence of tigecycline. In summary, enhanced tigecycline MIC develops with extensive amplification of an IS257-flanked tet(L)-carrying segment in S. cohnii. IS257 seems to play a vital role in the gain and loss of the amplification product.

PUB30-mediated downregulation of the HB24-SWEET11 module is involved in root growth inhibition under salt stress by attenuating sucrose supply in Arabidopsis.

One of the strategies that plants adopt to cope with an unfavorable environment is to sacrifice their growth for tolerance. Although moderate salt stress can induce root growth inhibition, the molecular mechanisms regulating this process have yet to be elucidated. Here, we found that overexpression of a zinc finger-homeodomain family transcription factor, HOMEOBOX PROTEIN 24 (HB24), led to longer primary roots than in the wild-type in the presence of 125 mM NaCl, whereas this phenotype was reversed for the hb24 loss-of-function mutant, indicating a negative impact of HB24 on salt-induced root growth inhibition. We then found that salt stress triggered the degradation of HB24 via the ubiquitin-proteasome pathway, as mediated by a plant U-box type E3 ubiquitin ligase 30 (PUB30) that directly targets HB24. We verified that HB24 is able to directly bind to the promoters of Sugars Will Eventually be Exported Transporter 11/12 (SWEET11/12) to regulate their expression in roots. Through genetic and biochemical assays, we further demonstrated that the HB24-SWEET11 module plays a negative role in salt-induced root growth inhibition. Therefore, we propose that under salt stress, PUB30 mediates HB24's degradation, thereby downregulating the expression of SWEET11, resulting in reduced sucrose supply and root growth inhibition.

σ-Aromaticity in an unsaturated ring: osmapentalene derivatives containing a metallacyclopropene unit.

In general, aromaticity can be clarified as π- and σ-aromaticity according to the type of electrons with major contributions. The traditional π-aromaticity generally describes the π-conjugation in fully unsaturated rings whereas σ-aromaticity may stabilize fully saturated rings with delocalization caused by σ-electron conjugation. Reported herein is an example of σ-aromaticity in an unsaturated three-membered ring (3 MR), which is supported by experimental observations and theoretical calculations. Specifically, when the 3 MR in cyclopropaosmapentalene is cleaved by ethane through two isodesmic reactions, both of them are highly endothermic (+29.7 and +35.0 kcal mol(-1)). These positive values are in sharp contrast to the expected exothermicity, thus indicating aromaticity in the 3 MR. Further nucleus-independent chemical shift and anisotropy of the current-induced density calculations reveal the nature of σ-aromaticity in the unsaturated 3 MR.

A sialic acid-targeted near-infrared theranostic for signal activation based intraoperative tumor ablation.

Agents enabling tumor staging are valuable for cancer surgery. Herein, a targetable sialic acid-armed near-infrared profluorophore (SA-pNIR) is reported for fluorescence guided tumor detection. SA-pNIR consists of a sialic acid entity effective for in vivo tumor targeting and a profluorophore which undergoes lysosomal acidity-triggered fluorogenic isomerization. SA-pNIR displays a number of advantageous biomedical properties in mice, e.g. high tumor-to-normal tissue signal contrast, long-term retention in tumors and low systemic toxicity. In addition, SA-pNIR effectively converts NIR light into cytotoxic heat in cells, suggesting tumor-activatable photothermal therapy. With high performance tumor illumination and lysosome-activatable photothermal properties, SA-pNIR is a promising agent for detection and photothermal ablation of surgically exposed tumors.

Two-phase construction of multilayer perceptrons using information theory.

This brief presents a two-phase construction approach for pruning both input and hidden units of multilayer perceptrons (MLPs) based on mutual information (MI). First, all features of input vectors are ranked according to their relevance to target outputs through a forward strategy. The salient input units of an MLP are thus determined according to the order of the ranking result and by considering their contributions to the network's performance. Then, the irrelevant features of input vectors can be identified and eliminated. Second, the redundant hidden units are removed from the trained MLP one after another according to a novel relevance measure. Compared with its related work, the proposed strategy exhibits better performance. Moreover, experimental results show that the proposed method is comparable or even superior to support vector machine (SVM) and support vector regression (SVR). Finally, the advantages of the MI-based method are investigated in comparison with the sensitivity analysis (SA)-based method.