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As a famous prescription in China, AnGong NiuHuang (AGNH) pill exerts good neuroprotection for ischaemic stroke (IS), but its mechanism is still unclear. In this study, the neuroprotection of AGNH was evaluated in the rat IS model which were established with the surgery of middle cerebral artery occlusion (MCAO), and the potential mechanism was elucidated by transcriptomic analysis and metabolomic analysis. AGNH treatment obviously decreased the infarct volume and Zea-Longa 5-point neurological deficit scores, improved the survival percentage of rats, regional cerebral blood flow (rCBF), and rat activity distance and activity time. Transcriptomics showed that AGNH exerted its anti-inflammatory effects by affecting the regulatory network including Tyrobp, Syk, Tlr2, Myd88 and Ccl2 as the core. Integrating transcriptomics and metabolomics identified 8 key metabolites regulated by AGNH, including L-histidine, L-serine, L-alanine, fumaric acid, malic acid, and N-(L-arginino) succinate, 1-pyrroline-4-hydroxy-2-carboxylate and 1-methylhistamine in the rats with IS. Additionally, AGNH obviously reduced Tyrobp, Syk, Tlr2, Myd88 and Ccl2 at both the mRNA and protein levels, decreased IL-1β, KC-GRO, IL-13, TNF-α, cleaved caspase 3 and p65 nucleus translocation, but increased IκBα expression. Network pharmacology analysis showed that quercetin, beta-sitosterol, baicalein, naringenin, acacetin, berberine and palmatine may play an important role in protecting against IS. Taken together, this study reveals that AGNH reduced neuroinflammation and protected against IS by inhibiting Tyrobp/Syk and Tlr2/Myd88, as well as NF-κB signalling pathway and regulating multiple metabolites. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a common lung disease that can lead to restricted airflow and respiratory problems, causing a significant health, economic, and social burden. Detecting the COPD stage can provide a timely warning for prompt intervention in COPD patients. However, existing methods based on inspiratory (IN) and expiratory (EX) chest CT images are not sufficiently accurate and efficient in COPD stage detection. The lung region images are autonomously segmented from IN and EX chest CT images to extract the 1 , 781 × 2 lung radiomics and 13 , 824 × 2 3D CNN features. Furthermore, a strategy for concatenating and selecting features was employed in COPD stage detection based on radiomics and 3D CNN features. Finally, we combine all the radiomics, 3D CNN features, and factor risks (age, gender, and smoking history) to detect the COPD stage based on the Auto-Metric Graph Neural Network (AMGNN). The AMGNN with radiomics and 3D CNN features achieves the best performance at 89.7 % of accuracy, 90.9 % of precision, 89.5 % of F1-score, and 95.8 % of AUC compared to six classic machine learning (ML) classifiers. Our proposed approach demonstrates high accuracy in detecting the stage of COPD using both IN and EX chest CT images. This method can potentially establish an efficient diagnostic tool for patients with COPD. Additionally, we have identified radiomics and 3D CNN as more appropriate biomarkers than Parametric Response Mapping (PRM). Moreover, our findings indicate that expiration yields better results than inspiration in detecting the stage of COPD. The workflow of this study. (a) The IN and EX lung region is segmented using a well trained U Net (R231). (b) Radiomics features are obtained through the PyRadiomics tool, and 3D CNN features are extracted using the frozen encoder in the pre trained Med3D model. (c) The IN+EX radiomics and IN+EX 3D CNN features are concatenated, and the Lasso algorithm is subsequently applied to screen for useful data. (d) The selected features and ri sk factors are sent to the AMGNN, resulting in COPD multi classification outcomes. [ABSTRACT FROM AUTHOR]

The Chinese medicine formula Pien Tze Huang (PZH) has been applied to the treatment of various diseases, the reported anti-tumor mechanisms included regulation of inflammation-associated cytokine secretion and cancer growth pathways. However, the potential influence of PZH on tumor metabolism remains unclear. This study aimed to investigate the global effect of PZH on hepatocellular carcinoma (HCC) compared with the anti-tumor agent sorafenib based on tandem mass tag (TMT) label proteomic and phosphoproteomic analysis in addition to parallel reaction monitoring (PRM) verification. It was observed that PZH could inhibit tumor weight by 59–69% in different concentrations. TMT proteomic studies indicated that fructose/mannose metabolism and glucagon signaling pathway in PZH group, and arachidonic acid metabolism and PPAR signaling pathway in sorafenib group, were significantly enriched, while glycolysis/gluconeogenesis pathway was found to be enriched remarkably both in PZH and sorafenib groups in TMT phosphoproteomic study. PRM verification further indicated that both PZH and sorafenib could down-regulate phosphorylations of the glycolytic enzymes phosphofructokinases 1, fructose-bisphosphate Aldolase A, phosphoglycerate mutase 2 and lactate dehydrogenase A chain, while phosphorylations of long chain fatty acid CoA ligase in fatty acid activation and acetyl-coenzyme A synthetase in glycolysis were significantly inhibited by PZH and sorafenib, respectively. This study proposed that PZH shared a similar anti-tumor mechanism of metabolic regulation to sorafenib, but differed in the regulation of some metabolic nodes. This is the first time to uncover the relationship between the anti-tumor effect of PZH and metabolic related enzymes, which distinguished from the known mechanisms of PZH. These data provided the potential molecular basis for PZH acting as a therapeutic drug for HCC, and offered cues of manipulation on Warburg effect under the treatment of PZH. [ABSTRACT FROM AUTHOR]

The phenomenon of brain recovery after long-term abstinence has been reported in substance use disorders. However, few longitudinal studies have been conducted to observe the potential recovery in heroin users, and little is known about the neural mechanism underlying the decreased craving after prolonged abstinence. The 8-month longitudinal study was carried out in 29 heroin users and 30 healthy controls. By choosing the L_DLPFC, which was activated by the heroin cue as the seeding region, different brain connection patterns were compared between healthy controls and heroin users by using Granger causality analysis (GCA) at baseline. Then, a paired t test was employed to detect the potential recovery of L_DLPFC circuits after prolonged abstinence. The visual analog scale (VAS) and trail-making test-A (TMT-A) were adopted to investigate craving and cognitive control impairment, respectively. The neuroimaging changes were then correlated with behavioral improvements. Similar analyses were applied for the mirrored right DLPFC to verify the lateralization hypothesis of the DLPFC in addiction. In the longitudinal study, enhanced GCA coefficients were observed in the L_DLPFC-R_insula circuit of heroin users after long-term abstinence and were associated with craving score changes. At baseline, decreased GCA coefficients from the left DLPFC to the bilateral SMA and right putamen, together with the reduced GCA strength from the bilateral OFC to the left DLPFC, were found between HUs and HCs. Our findings extended the brain recovery phenomenon into the field of heroin and suggested that the increased regulation of the L_DLPFC over the insula after prolonged abstinence was important for craving inhibition. [ABSTRACT FROM AUTHOR]

To date, our understanding of the role of abnormal hippocampal volume in imaging studies of insomnia disorders (ID) has remained in apparent contradiction. Given that hippocampal function can be mapped to anatomically defined substructures, the hippocampal substructure volume can be examined in detail at present. In this study, we examined the volumes of hippocampal substructures between IDs and healthy controls (HC) to accurately find hippocampal markers of ID. First, we used the automated hippocampal substructure module in FreeSurfer6.0 to inspect T1-weighted magnetic resonance images between 22 IDs and 30 HC. Then, 12 hippocampal substructures were computed. Volumetric assessment was performed at the hippocampal substructure level between groups. Our study revealed significant reduced volume of the bilateral fimbria in IDs compared with HC (p < 0.05/12, Bonferroni corrected), although there was no difference in the total volume of hippocampus. In addition, the correlation analysis showed that the total hippocampal volume of the left hemisphere was negatively correlated with Pittsburgh Sleep Quality Index (PSQI) scores. With regard to hippocampal substructure results, negative correlations were detected between bilateral fimbria volume and clinical variables (i.e., PSQI, SDS, and SAS) in all subjects. Taken together, we revealed marked differences in the volume of the hippocampal substructure between IDs and HC, which provided a more accurate structural imaging marker for the pathological of ID. [ABSTRACT FROM AUTHOR]

Dysfunction of the sleep-wake transition is considered to be associated with the pathology of patients with primary insomnia (PI). Previous animal study had reported that brain circuits between the striatum and cortex can regulate sleep-wake transitions. So far, few studies have systematically explored the structural connectivity of the striatum-centered circuits and their potential roles in patients with PI. In this study, we chosen the striatum as the seed and 10 priori target regions as masks to assess the structural connectivity by using seed-based classification with a diffusion tensor imaging (DTI) probabilistic tractography method. Track strengths of the striatum-centered circuits were compared between 22 patients with PI (41.27 ± 9.21 years) and 30 healthy controls (HC) (35.2 ± 8.14 years). Pittsburgh Sleep Quality Index (PSQI) was used to measure the sleep quality in all participants. Lower track strengths (left striatum- anterior cingulate cortex (ACC), left striatum- dorsal anterior cingulate cortex (dACC), left striatum-Hippocampus, and right striatum-Hippocampus) were observed in patients with PI compared to HC. Additionally, the lower track strengths of brain circuits mentioned above were negatively correlated with PSQI. Taken together, our findings revealed the lower tract strength of frontostriatal circuits in patients with PI and HC, which provided the implications of the system-level structural connections of frontostriatal circuits in the pathology of PI. We suggested that the track strengths of the frontostriatal circuits calculated from DTI can be the potential neuroimaging biomarkers of the sleep quality in patients with PI. [ABSTRACT FROM AUTHOR]

High levels of impulsivity are a risk factor for the initiation of heroin use and a core behavioral characteristic of heroin dependence. Impulsivity also contributes to the maintenance of drug use and hinders effective therapy. Here we sought to identify neuroimaging markers of impulsivity in heroin-dependent individuals (HDI), with a focus on the nucleus accumbens (NAc), a key region implicated in impulsivity and drug addiction generally. Volume and resting-state functional connectivity (RSFC) differences of the bilateral NAc were investigated between 21 HDI and 21 age-, gender-, nicotine-, alcohol-matched healthy controls (HC). The neuroimaging results were then correlated with the Barratt Impulsivity Scales (BIS-11). Higher motor impulsivity (t = 2.347, p = 0.0253) and larger right NAc volume (F (1,38) = 4.719, p = 0.036) was observed in HDI. The right NAc volume was positively correlated with BIS total (r = 0.6196, p = 0.0239) /motor (r = 0.5921, p = 0.0330) scores in HC and BIS motor (r = 0.5145, p = 0.0170) score in HDI. A negative correlation was found between RSFC of the right NAc-bilateral superior frontal gyrus (SFG) and motor impulsivity in HDI (left: r=-0.6537, p = 0.0013; right: r=-0.6167, p = 0.0029) and HC (left: r=-0.6490,p = 0.0164; right: r=-0.6993, p = 0.0078). We aimed to reveal novel multimodality neuroimaging biomarkers of the higher impulsivity in HDI by focusing on the NAc and corresponding functional circuits. Higher motor impulsivity was observed in HDI. Furthermore, the volume of the right NAc and the RSFC strength of right NAc-SFG could be neuroimaging biomarkers for the severity of impulsivity in HDI. These potential biomarkers could be a target for novel treatments in HDI. [ABSTRACT FROM AUTHOR]

To analyze the distribution pattern concerning multi-nozzle interference spray particle granularity between hydraulic supports, the present study conducts atomization interference experimental characterization for three types of nozzles used in coal mines based on a Doppler laser interference spray dust suppression simulation experimental system. The results indicate that for single-nozzle atomization, the impact of spray pressure on spray droplet size is gradually subdued, and a spray pressure of 8 MPa yields the best result; compared with single-nozzle spray, the multi-nozzle atomization interference effect can downsize the spray field overlapping zone, leading to an improved uniformity of overall spray particle distribution. As the spray field overlapping coefficient k increases, the particle size of the interference spray field decreases first and then increases. As the spray field overlapping coefficient reaches 0.4, the distribution of spray droplet size is most concentrated, corresponding to the optimal atomized dust suppression effect. Practical testing indicates that the optimal spray field overlapping coefficient measured at a fully mechanized mining face agrees well with the experimental result. Under the optimal parameters, the average total dust and respirable dust suppression rates measured at various measuring points on the downwind side during support relocation reach 78.93% and 80.53%, respectively. [ABSTRACT FROM AUTHOR]

A correction to the article "RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking. " in the December 2, 2014 issue is presented which discusses the role of Rab-interacting lysosomal protein (RILP) on the formation of endosomal membranes.