Antidepressant Activity of Euparin: Involvement of Monoaminergic Neurotransmitters and SAT1/NMDAR2B/BDNF Signal Pathway.

Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.

CPR++: Object Localization via Single Coarse Point Supervision.

Point-based object localization (POL), which pursues high-performance object sensing under low-cost data annotation, has attracted increased attention. However, the point annotation mode inevitably introduces semantic variance due to the inconsistency of annotated points. Existing POL heavily rely on strict annotation rules, which are difficult to define and apply, to handle the problem. In this study, we propose coarse point refinement (CPR), which to our best knowledge is the first attempt to alleviate semantic variance from an algorithmic perspective. CPR reduces the semantic variance by selecting a semantic centre point in a neighbourhood region to replace the initial annotated point. Furthermore, We design a sampling region estimation module to dynamically compute a sampling region for each object and use a cascaded structure to achieve end-to-end optimization. We further integrate a variance regularization into the structure to concentrate the predicted scores, yielding CPR++. We observe that CPR++ can obtain scale information and further reduce the semantic variance in a global region, thus guaranteeing high-performance object localization. Extensive experiments on four challenging datasets validate the effectiveness of both CPR and CPR++. We hope our work can inspire more research on designing algorithms rather than annotation rules to address the semantic variance problem in POL.

Rethinking Sampling Strategies for Unsupervised Person Re-Identification.

Unsupervised person re-identification (re-ID) remains a challenging task. While extensive research has focused on the framework design and loss function, this paper shows that sampling strategy plays an equally important role. We analyze the reasons for the performance differences between various sampling strategies under the same framework and loss function. We suggest that deteriorated over-fitting is an important factor causing poor performance, and enhancing statistical stability can rectify this problem. Inspired by that, a simple yet effective approach is proposed, termed group sampling, which gathers samples from the same class into groups. The model is thereby trained using normalized group samples, which helps alleviate the negative impact of individual samples. Group sampling updates the pipeline of pseudo-label generation by guaranteeing that samples are more efficiently classified into the correct classes. It regulates the representation learning process, enhancing statistical stability for feature representation in a progressive fashion. Extensive experiments on Market-1501, DukeMTMC-reID and MSMT17 show that group sampling achieves performance comparable to state-of-the-art methods and outperforms the current techniques under purely camera-agnostic settings. Code has been available at https://github.com/ucas-vg/GroupSampling.

Downregulation of miR-128 Ameliorates Ang II-Induced Cardiac Remodeling via SIRT1/PIK3R1 Multiple Targets.

Recent studies reported that miR-128 was differentially expressed in cardiomyocytes in response to pathologic stress. However, its function and mechanism remain to be fully elucidated. The aim of the present study was to investigate the role of miR-128 in chronic angiotensin II (Ang II) infusion-induced cardiac remodeling and its underlying mechanism. The cardiac remodeling and heart failure in vivo were established in C57BL/6 mice by chronic subcutaneous Ang II delivery. Knocking down miR-128 was conducted in the hearts of the mice by intravenous injection of HBAAV2/9-miR-128-GFP sponge (miR-128 inhibitor). In vitro experiments of cardiac hypertrophy, apoptosis, and aberrant autophagy were performed in cultured cells after Ang II treatment or transfection of miR-128 antagomir. Our results showed that chronic Ang II delivery for 28 days induced cardiac dysfunction, hypertrophy, fibrosis, apoptosis, and oxidative stress in the mice, while the miR-128 expression was notably enhanced in the left ventricle. Silencing miR-128 in the hearts of mice ameliorated Ang II-induced cardiac dysfunction, hypertrophy, fibrosis apoptosis, and oxidative stress injury. Moreover, Ang II induced excessive autophagy in the mouse hearts, which was suppressed by miR-128 knockdown. In cultured cells, Ang II treatment induced a marked elevation in the miR-128 expression. Downregulation of miR-128 in the cells by transfection with miR-128 antagomir attenuated Ang II-induced apoptosis and oxidative injury probably via directly targeting on the SIRT1/p53 pathway. Intriguingly, we found that miR-128 inhibition activated PIK3R1/Akt/mTOR pathway and thereby significantly damped Ang II-stimulated pathological autophagy in cardiomyocytes, which consequently mitigated cell oxidative stress and apoptosis. In conclusion, downregulation of miR-128 ameliorates Ang II-provoked cardiac oxidative stress, hypertrophy, fibrosis, apoptosis, and dysfunction in mice, likely through targeting on PIK3R1/Akt/mTORC1 and/or SIRT1/p53 pathways. These results indicate that miR-128 inhibition might be a potent therapeutic strategy for maladaptive cardiac remodeling and heart failure.