Understanding the constraints that shape the evolution of antibiotic resistance is critical for predicting and controlling drug resistance. Despite its importance, however, a systematic investigation of evolutionary constraints is lacking. Here, we perform a high-throughput laboratory evolution of Escherichia coli under the addition of 95 antibacterial chemicals and quantified the transcriptome, resistance, and genomic profiles for the evolved strains. Utilizing machine learning techniques, we analyze the phenotype–genotype data and identified low dimensional phenotypic states among the evolved strains. Further analysis reveals the underlying biological processes responsible for these distinct states, leading to the identification of trade-off relationships associated with drug resistance. We also report a decelerated evolution of β-lactam resistance, a phenomenon experienced by certain strains under various stresses resulting in higher acquired resistance to β-lactams compared to strains directly selected by β-lactams. These findings bridge the genotypic, gene expression, and drug resistance gap, while contributing to a better understanding of evolutionary constraints for antibiotic resistance.

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Bivalent molecules of bis-Imidacloprid with 2-10 alkylene tethers as well as tethers containing an ethenylene, ethynylene, phenylene and oxide joint were prepared. These dimeric chloronicotinyl molecules were highly Insecticidal against American cockroaches on injection at 2-30 nanomolar doses. The minimum lethal dose of the most potent hexamethylene derivative was close to that of imidacloprid, and the potency was augmented up to about thirty-five-fold following pretreatment with metabolic inhibitors, while the binding affinity to [3H] imidacloprid-binding sites on the nicotinic acetylcholine receptor was weaker than that of imidacloprid by a factor of 160. The hexamethylene derivative elicited impulses in cockroach central nerves with an initial excitation and subsequent block at a potency comparable to imidacloprid.

A 2-month-old girl with incontinentia pigmenti presented with acute-onset right-handed focalized seizures and subsequent seizure generalization. Computed tomography, magnetic resonance imaging and single photon emission computed tomography results indicated that she had multiple cerebral infarctions. These findings suggest that incontinentia pigmenti should be included among the neurocutaneous syndromes associated with ischemic strokes in childhood. This is the first report of a case with incontinentia pigmenti associated with cerebral infarction evaluated by single photon emission computed tomography.

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