A fluorogenic-inhibitor-based probe for profiling and imaging of monoamine oxidase A in live human glioma cells and clinical tissues

Monoamine oxidase A(MAO-A)plays a critical role in the development of glioma and other neurological disorders.Specific analysis of MAO-A activities and its drug interactions in intact tissue is important for biological and pharmacological research,but highly challenging with current chemical tools.Fluorogenic-inhibitor-based probes offer improved selectivity,sensitivity,and effectiveness to image and profile endogenous targets in an activity-based manner from mammalian cells,which are however rare.Herein,we report HD1 as the first fluorogenic-inhibitor-based probe that can selectively label endogenous MAO-A from various mammalian cells and clinical tissues.The probe was delicately designed based on N-propargyl tetrahydropyridine,a small MAO-A-specific fluorogenic and inhibitory war-head,so that the probe becomes fluorescent upon in situ enzymatic oxidation and covalent labeling of MAO-A.With the excellent binding affinity(in vitro K_(i)=285 n M)and fluorogenic properties,HD1 offers a promising approach to simultaneously image endogenous MAO-A activities by super-resolution fluorescence microscopy and study its drug interactions by subsequent activity-based protein profiling,in both live cells and human glioma tissues.

Staphylococcus aureus bloodstream infection in a Chinese tertiary-care hospital:A single-center retrospective study

To the Editor:Despite major advances in medical care,the incidence and mortality of bloodstream infection(BSI)remain high,which is still a global public health challenge.BSI can be caused by various microorganisms,and the most common organisms are Escherichia coli,Klebsiella pneumoniae,and Staphylococcus aureus(S.aureus),according to the China Antimicrobial Surveillance Network(CHINET).[1]S.aureus is the third most common cause of BSI,which is associated with shortterm mortality rates of 15–30%,long-term excess mortality,and increased healthcare costs.At present,there are many studies on Gram-negative bacteremia but relatively few on S.aureus bloodstream infection(SA-BSI),especially in China.With the occurrence of new treatments and clinical conditions,such as aging and extensive antibiotic resistance,it is necessary to reanalyze the clinical characteristics and prognosis of SA-BSI.