Oxidative stress in depression is a prime cause of neurotransmitter metabolism dysfunction in the brain. Acetylcholinesterase (AChE), a key hydrolase in the cholinergic system, directly determines the degradation of neurotransmitters. However, due to the complexity of the brain and lack of appropriate in situ imaging tools, the mechanism underlying the changes in AChE activity in depression remains unclear. Hence, we generated a twophoton fluorescence probe (MCYN) for real-time visualization of AChE with excellent sensitivity and selectivity. AChE can specifically recognize and cleave the carbamic acid ester bond in MCYN, and MCYN emits bright fluorescence at 560 nm by two-photon excitation at 800 nm. By utilizing MCYN to monitor AChE, we discovered a significant increase in AChE activity in the brains of mice with depression phenotypes. Notably, with the assistance of a two-photon fluorescence imaging probe of the superoxide anion radical (O 2•− ), in vivo visualization for the first time revealed the positive correlation between AChE and O 2•− levels associated with depressive behaviors. This finding suggests that oxidative stress may induce AChE overactivation, leading to depression-related behaviors. This work provides a new and rewarding perspective to elucidate the role of oxidative stress regulating AChE in the pathology of depression.

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Depression is intimately linked with oxidative stress. As one of the most reactive and oxidative reactive oxygen species that is overproduced during oxidative stress,t he hydroxyl radical (COH) can cause macromolecular damage and subsequent neurological diseases.However,due to the high reactivity and lowconcentration of COH, precise exploration of COH in brains remains ac hallenge.T he two-photon fluorescence probe MD-B was developed for in situ COH imaging in living systems.T his probe achieves exceptional selectivity towards COH through the one-electron oxidation of 3-methylpyrazolone as an ew specific recognition site.M D-B can be used to map COH in mouse brain, therebyr evealing that increased COH is positively correlated with the severity of depression phenotypes.F urthermore, COH has been shown to inactivate deacetylase SIRT1,therebyleading to the occurrence and development of depression phenotypes.T his work provides anew strategy for the future treatment of depression.Depression as one of the most common and disabling mental disorders,w ith aw orldwide prevalence of approximately 17 %. [1] However,u nderstanding of the pathophysiology of depression is still rudimentary due to its complex aetiology. [2] Previous findings suggest that oxidative stress contributes to the pathogenesis of depression. [3][4][5] Theh ydroxyl radical (COH) is one of the most reactive and oxidative reactive oxygen species (ROS) that is overproduced during oxidative stress. [6] Excess COH leads to irreparable damage to neural cells and potentially even to neurological disease. [7] Therefore,t here is an urgent need to develop an effective means for tracing COH in living brain to define the relationship between depression and COH levels.Recently,f luorescence imaging has become ar obust approach for real-time monitoring of molecular events in living cells and in vivo because of its non-destructive nature and spatiotemporal resolution. [8][9][10] Fluorescent probes have been developed to reveal the biological functions of COH in living cells,i nz ebrafish, and in the abdomens of mice. [11][12][13][14][15][16][17][18][19] Given the very high reactivity and low concentration of COH and the particularly complicated construction of the brain, two-photon (TP) fluorescence imaging is the most appropriate for brain imaging because it provides ah igher signal-tobackground ratio,d eeper tissue imaging, higher spatialtemporal resolution, and less specimen photodamage than one-photon (OP) fluorescence imaging. [20][21][22][23] Molecular fluorescent probes have some appealing performance characteristics in terms of stability,ease of crossing of the blood-brain barrier (BBB), and easy excretion, which is preferable for the TP in situ imaging of COH in the brains of living mice with depression-like behaviours.However,suitable TP fluorescent probes for brain imaging of COH with specificity,h igh sensitivity,and instantaneous response are still scarce.Inspired by the specific one-electron oxidation reaction between COH and 3-methyl-pyrazolone in the...

Random projection is widely used as a method of dimension reduction. In recent years, its combination with standard techniques of regression and classification has been explored. Here we examine its use for anomaly detection in high-dimensional settings, in conjunction with principal component analysis (PCA) and corresponding subspace detection methods. We assume a so-called spiked covariance model for the underlying data generation process and a Gaussian random projection. We adopt a hypothesis testing perspective of the anomaly detection problem, with the test statistic defined to be the magnitude of the residuals of a PCA analysis. Under the null hypothesis of no anomaly, we characterize the relative accuracy with which the mean and variance of the test statistic from compressed data approximate those of the corresponding test statistic from uncompressed data.Furthermore, under a suitable alternative hypothesis, we provide expressions that allow for a comparison of statistical power for detection. Finally, whereas these results correspond to the ideal setting in which the data covariance is known, we show that it is possible to obtain the same order of accuracy when the covariance of the compressed measurements is estimated using a sample covariance, as long as the number of measurements is of the same order of magnitude as the reduced dimensionality.

A near-infrared fluorescent probe was exploited to sensitively visualize ozone in the brains of mice with depression phenotypes in situ.