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Theoretically, a deep neuron network with nonlinear activation is able to approximate any function, while empirically the performance of the model with different activations varies widely. In this work, we investigate the expressivity of the network from an activation perspective. In particular, we introduce a generalized activation region/pattern to describe the functional relationship of the model with an arbitrary activation function and illustrate its fundamental properties. We then propose a metric named pattern similarity to evaluate the practical expressivity of neuron networks regarding datasets based on the neuron level reaction toward the input. We find an undocumented dying neuron issue that the post-activation value of most neurons remain in the same region for data with different labels, implying that the expressivity of the network with certain activations is greatly constrained. For instance, around 80% of post-activation values of a well-trained Sigmoid net or Tanh net are clustered in the same region given any test sample. This means most of the neurons fail to provide any useful information in distinguishing the data with different labels, suggesting that the practical expressivity of those networks are far below the theoretical. By evaluating our metrics and the test accuracy of the model, we show that the seriousness of the dying neuron issue is highly related to the model performance. At last, we also discussed the cause of the dying neuron issue, providing an explanation of the model performance gap caused by choice of activation.

Chitosan and its derivatives are bioactive molecules that have recently been used in various fields, especially in the medical field. The antibacterial, antitumor, and immunomodulatory properties of chitosan have been extensively studied. Chitosan can be used as a drug-delivery carrier in the form of hydrogels, sponges, microspheres, nanoparticles, and thin films to treat diseases, especially those of the skin and soft tissue such as injuries and lesions of the skin, muscles, blood vessels, and nerves. Chitosan can prevent and also treat soft tissue diseases by exerting diverse biological effects such as antibacterial, antitumor, antioxidant, and tissue regeneration effects. Owing to its antitumor properties, chitosan can be used as a targeted therapy to treat soft tissue tumors. Moreover, owing to its antibacterial and antioxidant properties, chitosan can be used in the prevention and treatment of soft tissue infections. Chitosan can stop the bleeding of open wounds by promoting platelet agglutination. It can also promote the regeneration of soft tissues such as the skin, muscles, and nerves. Drug-delivery carriers containing chitosan can be used as wound dressings to promote wound healing. This review summarizes the structure and biological characteristics of chitosan and its derivatives. The recent breakthroughs and future trends of chitosan and its derivatives in therapeutic effects and drug delivery functions including anti-infection, promotion of wound healing, tissue regeneration and anticancer on soft tissue diseases are elaborated.

Supplemental material, sj-docx-1-npx-10.1177_1934578X221123698 for Tanshinone IIA Inhibits Liver Fibrosis by Regulating COL1A1 Expression Through H19/let-7a in Mice by Chao Lin, Jianming Xing, Ziping Jiang, Liqun Sun, Yongjian Gao, Shuo Yang, Dongxu Wang and Ning Yin in Natural Product Communications

Xiaowei Zhong,1,* Dianfeng Liu,1,* Ziping Jiang,2 Chengshun Li,1 Lin Chen,1 Yidan Xia,2 Da Liu,3 Qunyan Yao,4 Dongxu Wang1 1Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, People’s Republic of China; 2Department of Hand Surgery, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qunyan Yao; Dongxu Wang Email yao.qunyan@zs-hospital.sh.cn; wang_dong_xu@jlu.edu.cnObjective: Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells.MaterialsandMethods: Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo.Results: qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo.Conclusion: This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.Keywords: Chrysin, TET1, 5hmC, cell apoptosis, cell invasion