Relationships between structure and antioxidant capacity and activity of glycosylated flavonols

The antioxidant capacity (AC) and antioxidant activity (AA) of three flavonols (FLV), aglycones and their glycosylated derivatives were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays in various solvents. Findings confirmed that the glycosylation at the 3-position (3-glycosylation) always decreased the AC under most conditions due to substitution of the 3-position hydroxyl group and glycoside disruption in the molecular planarity. The 7-glycosylated derivatives did not have the above effects, thus generally exhibited ACs similar to their aglycones. Glycosylation decreased the AA of kaempferol and isorhamnetin for both assays in methanol, 3-glycosylation inhibited quercetin AA in the ABTS assay. In the DPPH assay, the AA of 3-glycosylated quercetin was significantly higher than quercetin. Using LC–MS/MS analysis, we found that quercetin and quercetin-7-glucoside underwent dimerization during the antioxidant reaction, potentially leading to a decline in AAs. However, 3-glycoside substitution may have hindered dimer formation, thereby allowing the FLVs to retain strong free radical scavenging abilities.National Key Research and Development Program of China | Ref. 2019YFC160670

Personalized connectivity-based network targeting model of transcranial magnetic stimulation for treatment of psychiatric disorders: computational feasibility and reproducibility

Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating psychiatric disorders; however, the variability in treatment efficacy among individuals underscores the need for further improvement. Growing evidence has shown that TMS induces a broad network modulatory effect, and its effectiveness may rely on accurate modulation of the pathological network specific to each disorder. Therefore, determining the optimal TMS coil setting that will engage the functional pathway delivering the stimulation is crucial. Compared to group-averaged functional connectivity (FC), individual FC provides specific information about a person’s brain functional architecture, offering the potential for more accurate network targeting for personalized TMS. However, the low signal-to-noise ratio (SNR) of FC poses a challenge when utilizing individual resting-state FC. To overcome this challenge, the proposed solutions include increasing the scan duration and employing the cluster method to enhance the stability of FC. This study aimed to evaluate the stability of a personalized FC-based network targeting model in individuals with major depressive disorder or schizophrenia with auditory verbal hallucinations. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, we assessed the model’s stability. We employed longer scan durations and cluster methodologies to improve the precision in identifying optimal individual sites. Our findings demonstrate that a scan duration of 28 minutes and the utilization of the cluster method achieved stable identification of individual sites, as evidenced by the intraindividual distance falling below the ~1cm spatial resolution of TMS. The current model provides a feasible approach to obtaining stable personalized TMS targets from the scalp, offering a more accurate method of TMS targeting in clinical applications

Protective effects of green tea polyphenols against benzo[a]pyrene-induced reproductive and trans-generational toxic effects in Japanese Medaka (Oryzias latipes)

In order to investigate the protective effect of green tea polyphenols (GTP) on benzo[a]pyrene (BaP)-induced reproductive and trans-generational toxicity, Japanese Medaka was injected intraperitoneally with BaP alone and co-injected with both BaP and GTP of different concentrations, respectively. Exposure to BaP alone significantly suppressed fecundity, fertilization success, and egg diameter/protein content and markedly induced deformation ratio in F1 generation. However, GTP could help recover reproductive functions, egg quality suppressed by BaP and reduced deformation ratio. VTG-1, a molecular marker of reproductive toxicity, was significantly down-regulated in females exposed to BaP, but a dose-dependent increase was observed in co-exposed groups. Up-regulation of GSH-Px, dose-dependent decrease of CYP1A1, and the GST expression inhibited by BaP was recovered and even markedly up-regulated in the co-exposure groups. These findings show promising protective effects of GTP against BaP-induced reproductive and trans-generational toxicity

DataSheet_1_Personalized connectivity-based network targeting model of transcranial magnetic stimulation for treatment of psychiatric disorders: computational feasibility and reproducibility.docx

Repetitive transcranial magnetic stimulation (rTMS) holds promise for treating psychiatric disorders; however, the variability in treatment efficacy among individuals underscores the need for further improvement. Growing evidence has shown that TMS induces a broad network modulatory effect, and its effectiveness may rely on accurate modulation of the pathological network specific to each disorder. Therefore, determining the optimal TMS coil setting that will engage the functional pathway delivering the stimulation is crucial. Compared to group-averaged functional connectivity (FC), individual FC provides specific information about a person’s brain functional architecture, offering the potential for more accurate network targeting for personalized TMS. However, the low signal-to-noise ratio (SNR) of FC poses a challenge when utilizing individual resting-state FC. To overcome this challenge, the proposed solutions include increasing the scan duration and employing the cluster method to enhance the stability of FC. This study aimed to evaluate the stability of a personalized FC-based network targeting model in individuals with major depressive disorder or schizophrenia with auditory verbal hallucinations. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, we assessed the model’s stability. We employed longer scan durations and cluster methodologies to improve the precision in identifying optimal individual sites. Our findings demonstrate that a scan duration of 28 minutes and the utilization of the cluster method achieved stable identification of individual sites, as evidenced by the intraindividual distance falling below the ~1cm spatial resolution of TMS. The current model provides a feasible approach to obtaining stable personalized TMS targets from the scalp, offering a more accurate method of TMS targeting in clinical applications.</p

Data_Sheet_1_Targeting the pathological network: Feasibility of network-based optimization of transcranial magnetic stimulation coil placement for treatment of psychiatric disorders.docx

It has been recognized that the efficacy of TMS-based modulation may depend on the network profile of the stimulated regions throughout the brain. However, what profile of this stimulation network optimally benefits treatment outcomes is yet to be addressed. The answer to the question is crucial for informing network-based optimization of stimulation parameters, such as coil placement, in TMS treatments. In this study, we aimed to investigate the feasibility of taking a disease-specific network as the target of stimulation network for guiding individualized coil placement in TMS treatments. We present here a novel network-based model for TMS targeting of the pathological network. First, combining E-field modeling and resting-state functional connectivity, stimulation networks were modeled from locations and orientations of the TMS coil. Second, the spatial anti-correlation between the stimulation network and the pathological network of a given disease was hypothesized to predict the treatment outcome. The proposed model was validated to predict treatment efficacy from the position and orientation of TMS coils in two depression cohorts and one schizophrenia cohort with auditory verbal hallucinations. We further demonstrate the utility of the proposed model in guiding individualized TMS treatment for psychiatric disorders. In this proof-of-concept study, we demonstrated the feasibility of the novel network-based targeting strategy that uses the whole-brain, system-level abnormity of a specific psychiatric disease as a target. Results based on empirical data suggest that the strategy may potentially be utilized to identify individualized coil parameters for maximal therapeutic effects.</p