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Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer and is the second leading cause of cancer-related deaths worldwide. Unlike apoptosis, necroptosis (NCPS) triggers an immune response by releasing damage-related molecular factors. However, the clinical prognostic features of necroptosis-associated genes in HCC are still not fully explored.Methods: We analyzed the single-cell datasets GSE125449 and GSE151530 from the GEO database and performed weighted co-expression network analysis on the TCGA data to identify the necroptosis genes. A prognostic model was built using COX and Lasso regression. In addition, we performed an analysis of survival, immunity microenvironment, and mutation. Furthermore, the hub genes and pathways associated with HCC were localized within the single-cell atlas.Results: Patients with HCC in the TCGA and ICGC cohorts were classified using a necroptosis-related model with significant differences in survival times between high- and low-NCPS groups (p < 0.05). High-NCPS patients expressed more immune checkpoint-related genes, suggesting immunotherapy and some chemotherapies might prove beneficial to them. In addition, a single-cell sequencing approach was conducted to investigate the expression of hub genes and associated signaling pathways in different cell types.Conclusion: Through the analysis of single-cell and bulk multi-omics sequencing data, we constructed a prognostic model related to necroptosis and explored the relationship between high- and low-NCPS groups and immune cell infiltration in HCC. This provides a new reference for further understanding the role of necroptosis in HCC.

Abstract Background Bronchial asthma is one of the most common inflammatory airway disorders. As one of the main non-drug therapies, the Sanfu herbal patch (SHP) has been widely used to treat bronchial asthma, although the evidence for its efficacy and associated mechanism are inconclusive. The objective of this trial is to clarify the clinical efficacy and safety of the SHP in the treatment of bronchial asthma in the chronic persistent or clinical remission stage and to provide high-quality data for further research. Methods We propose a multicentre, double-blinded, parallel, randomized, placebo-controlled clinical trial involving 4 study hospitals in China. A total of 72 eligible participants will be randomized into an SHP group and a placebo group. They will receive an SHP for 3 treatment sessions. The primary outcome will be changes in forced expiratory volume in 1 s after 3 treatment sessions. Secondary outcomes will include the following: (1) the Asthma Quality of Life Questionnaire, Asthma Control Test, and Asthma Long-term Follow-up Scale; (2) levels of Metallothionein-2 and Transgelin-2 in blood and urine; and (3) levels of IL-5, IL-13, IL-23, IL-25, and thymic stromal lymphopoietin in blood. Analysis of the data will be performed at baseline, at the end of the 2nd and 3rd treatment sessions, and at the 24-week follow-up. The safety of the SHP will be evaluated at each treatment session. Discussion The aims of this trial are to determine whether the SHP is more effective than placebo in the treatment of patients with bronchial asthma, as well as whether the SHP works by reducing airway inflammation and reversing bronchoconstriction. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR1900024616. Registered on 19 July 2019.

The guarantee of cell survival under hypoxic conditions and rapid vascularization is a key in tissue engineering strategies for treating bone defects. Our study aimed to establish the protective role of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) in hypoxic conditions and realize rapid vascularization in bone defects. Resveratrol (Res), a non-flavonoid polyphenolic compound, and angiopoietin-2 (ANG2), a vascular activating factor, were applied to enhance BMSC and HUVEC survival, osteogenesis, and angiogenesis. The morphology, autophagy, viability, apoptosis, cycle, and osteogenic differentiation of BMSCs treated with Res were analyzed. The results indicated that Res could improve BMSC survival and differentiation via the autophagy pathway under hypoxic conditions. In addition, Res maintained HUVEC growth and proliferation in a hypoxic and ANG2 double-adverse environment via the autophagy pathway. To simulate a relatively hypoxic environment, small-aperture PEGDA/TCS hydrogels containing Res and ANG2 were prepared. BMSCs were cultured in the PEGDA/TCS scaffold and transplanted into a large tibial defect. CD31 immunofluorescence showed that the density and size of new blood vessels in the bone defect were significantly enhanced by ANG2 and Res at 8 weeks after surgery. H&E, Masson, and immunohistochemical staining results indicated that ANG2 combined with Res could promote new bone formation in defects. All these results suggested that Res combined with ANG2 may be a novel strategy for the targeted therapy of hypoxic bone defects with tissue engineering scaffolds.

With the development of wireless sensor network technology, the routing strategy has important significance in the Internet of Things. An efficient routing strategy is one of the fundamental technologies to ensure the correct and fast transmission of wireless sensor networks. In this paper, we study how to combine deep learning technology with routing technology to propose an efficient routing strategy to cope with network topology changes. First, we use the recurrent neural network combined with the deep deterministic policy gradient method to predict the network traffic distribution. Second, the multi-hop node state is considered as the input of a double deep Q network. Therefore, the nodes can make routing decisions according to the current state of the network. Multi-hop state-aware routing strategy based on traffic flow forecasting (MHSA-TFF) is proposed. Simulation results show that the MHSA-TFF can improve transmission delay, average routing length, and energy efficiency.