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BACKGROUND: Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations. However, preliminary studies have documented the pathophysiological changes in certain brain regions, such as the cerebellum, highlighting a need for further research to support the current understanding of this disease. AIM: To study brain changes in depressed adolescents. METHODS: This study enrolled 34 adolescents with depression and 34 age-, sex-, and education-level-matched healthy control (HC) individuals. Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow (CBF) analysis, respectively. Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses. RESULTS: The cerebellum, superior frontal gyrus, cingulate gyrus, pallidum, middle frontal gyrus, angular gyrus, thalamus, precentral gyrus, inferior temporal gyrus, superior temporal gyrus, inferior frontal gyrus, and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals. These patients with depression further presented with a pronounced drop in CBF in the left pallidum (group = 98, and peak t = - 4.4324), together with increased CBF in the right percental gyrus (PerCG) (group = 90, and peak t = 4.5382). In addition, 17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus (r = - 0.5231, P < 0.01). CONCLUSION: The right PerCG showed structural and CBF changes, indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

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A small-molecule fluorescent probe offers unique advantages for the detection of hydrogen sulfide (H2S) and other reactive small molecules including high sensitivity, cell permeability and high spatiotemporal resolution. Generally, in order to obtain good cell permeability, fluorescent probes are liposoluble, which in turn leads to poor water solubility. Thus, it is regrettable that most of these fluorescent probes cannot be used in fully aqueous systems and hence, organic solvents are used, which may cause negative effects on living cells. Silicon nanodots (SiNDs) have been widely used in many fields due to good water solubility, benign nature, biocompatibility and low toxicity. Herein, we proposed a two-photon SiND-ANPA-N3 fluorescent probe with good water solubility, excellent biocompatibility and low toxicity; it is suitable to detect H2S in totally aqueous media and living cells. This strategy may provide a technically simple and facile approach for designing fluorescent probes with excellent solubility, benign nature, and biocompatibility for use in fully aqueous systems and in vivo.

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As a small molecule gas, formaldehyde (FA) is the simplest carbonyl active material and plays an important role in the carbon cycle of metabolism. However, due to the volatile nature of the gas, it is difficult to accurately quantify its content, which limits the study of the mechanism of action in life activities. Thus, an efficient approach to quantitative detection of FA in cells especially in single cell is urgent needed. Nevertheless, no method for quantifying FA in single cell has been reported to date. In this work, a fluorescent probe N-propyl-4-hydrazino-naphthalimide (NPHNA), which has highly desirable attributes and has been applied to living biological samples, was chosen as labeling reagent to detect endogenous FA at single cell level. After optimization of separation conditions, fast baseline separation of the FA derivative N-propyl-4-hydrazone-naphthalimide product (NPHNA-FA) and NPHNA was achieved in about 5 min by CE with LIF detection. The detection limit for FA was 5 amol (S/N ratio of 3). The developed method was validated by the measurements of intracellular levels of FA in single cell.

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BODIPY-based probes have excellent fluorescence properties. However, small Stokes shifts approximately 5-15 nm greatly affect their detection sensitivity. In this study, we compared the Stokes shifts of reported BODIPY-based probes with various of substituents, and found that the phenyl groups on the specific position of BODIPY core could expand the Stokes shift of BODIPY-based probes, and methoxy groups on these phenyl substituents could enhance such effects. Then, by quantum chemical calculations, we found that the number of methoxy groups might also have obvious effect on the Stokes shift of BODIPY. Taking nitric oxide (NO) as analyte, 4,4-difluoro-8-(3,4-diaminophenyl)-3,5-bis(2,4-dimethoxyphenyl)-4-bora-3a,4a-diaza-s-indancene (DMOPB) with diaminophenyl substituents has been designed and synthesized. Compared with monomethoxy-phenyl substituted BODIPY-based probes (MOPBs) in our previous work, Stokes shift of DMOPB was expanded by 10 nm when using dimethoxyphenyl instead of monomethoxyphenyl, which is basically consistent with the quantum chemistry calculation of 11 nm. DMOPB can react with NO in only 2 min to form the triazole DMOPB-T with a fluorescence quantum yield of 0.32. An excellent linear relationship was observed in the range of NO concentration from 0.5 µM to 4 µM and the detection limit was 1 nM. The experimental results indicate that DMOPB with high sensitivity, excellent selectivity, low toxicity and dark background can be a great candidate for imaging NO in cells and tissues. Considering the lack of practical way to increase Stokes shift of small-molecule fluorescent probes based on specific fluorophore, the proposed strategy has great potential for the designing of probes with large Stokes shift.

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Carbonyl compounds are widely distributed in organisms, and the commonly used methods for determination of them like UV/fluorescence/mass spectrometry always require derivatization reagents. However, the reported derivatization reagents have significant difference in reactivity, which is very unfavorable for developing highly reactive reagent. In this study, we theoretically investigated the factors affecting the reactivity of hydrazine-based derivatization reagents, and proposed a strategy for filtering highly reactive reagents by quantum chemical calculation. With this strategy, N-propyl-4-hydrazino-1,8-naphthalimide (NPHNA) was filtered out as a fluorescent derivatization reagent. Taking aliphatic aldehydes as representatives, we evaluated the reactivity of NPHNA for carbonyl compounds. The derivatization of NPHNA with aliphatic aldehydes could be finished at room temperature within 60 min or 35 °C within 35 min, which showed higher reactivity than the most popular UV/MS reagent, 2,4-dinitrophenylhydrazine (DNPH). We believe that the strategy we proposed in this work is of great potential to design highly reactive UV/fluorescent/MS labeling reagents for carbonyl compounds and even other analytes.

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Hydrogen sulfide (H2S) is a new endogenously generated gasotransmitter and has implicated in many physiologies and pathologies closely related to its intracellular and intercellular signaling transduction. Although many fluorescent probes have been exploited to track and quantify H2S in living systems, none of them could be used for monitoring intercellular transmission of H2S. Herein, we developed a cell surface specific H2S probe, 4-azido-6-sulfo-N-hexadecyl-1,8-naphthalimide, sodium salt (ASNHN-N3), trying to investigate the behaviors of extracellular release of H2S. ASNHN-N3 is week fluorescent and could react with H2S at 37 °C in pH 7.4 buffer solutions to form product ASNHN-NH2 with strong fluorescence (Φ = 0.22). Using ASNHN-N3 as H2S probe, excellent linear correlation versus the concentration of NaHS was obtained ranging from 0 to 10 µM and the detection limit was 0.75 µM. With the lipid anchor and the hydrophilic sulfonic group introduced into the 1,8-naphthalimide (a skeleton of two-photon fluorescent probe), the amphiphilic probe is located at the surface of living cells which can record H2S efflux from the cell diffusing across the plasma membrane in living cells and deep-tissue by using two-photon microscopy. Thus we present a new strategy for further studying the mechanism of signaling molecules in cell communication and signal pathways.

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