[Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment].

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1ß), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1ß, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Lysophosphatidic Acid Signalling Regulates Human Sperm Viability via the Phosphoinositide 3-Kinase/AKT Pathway.

Lysophosphatidic acid (LPA) signalling is essential for maintaining germ cell viability during mouse spermatogenesis; however, its role in human spermatozoa is unknown. We previously demonstrated that peroxiredoxin 6 (PRDX6) calcium-independent phospholipase A2 (iPLA2) releases lysophospholipids such as LPA or arachidonic acid (AA) and that inhibiting PRDX6 iPLA2 activity impairs sperm cell viability. The exogenous addition of LPA bypassed the inhibition of PRDX6 iPLA2 activity and maintained the active phosphoinositide 3-kinase (PI3K)/AKT pathway. Here, we aimed to study PI3K/AKT pathway regulation via LPA signalling and protein kinases in maintaining sperm viability. The localization of LPARs in human spermatozoa was determined using immunocytochemistry, and P-PI3K and P-AKT substrate phosphorylations via immunoblotting. Sperm viability was determined using the hypo-osmotic swelling test. LPAR1, 3, 5 and 6 were located on the sperm plasma membrane. The inhibition of LPAR1-3 with Ki16425 promoted the impairment of sperm viability and decreased the phosphorylation of PI3K AKT substrates. Inhibitors of PKC, receptor-type PTK and PLC impaired sperm viability and the PI3K/AKT pathway. Adding 1-oleoyl-2-acetyl-snglycerol (OAG), a cell-permeable analog of diacylglycerol (DAG), prevented the loss of sperm viability and maintained the phosphorylation of PI3K. In conclusion, human sperm viability is supported by LPAR signalling and regulated by PLC, PKC and RT-PTK by maintaining phosphorylation levels of PI3K and AKT substrates.

Human activity recognition in an end-of-life consumer electronics disassembly task.

The production of electronic waste, also known as e-waste, has risen with the growing reliance on electronic products. To reduce negative environmental impact and achieve sustainable industrial processes, recovering and reusing products is crucial. Advances in AI and robotics can help in this effort by reducing workload for human workers and allowing them to stay away from hazardous materials. However, autonomous human motion/intention perception is a primary barrier in e-waste remanufacturing. To address the research gap, this study combined experimental data collection with deep learning models for accurate disassembly task recognition. Over 570,000 frames of motion data were collected from inertial measurement units (IMU) worn by 22 participants. A novel sequence-based correction (SBC) algorithm was also proposed to further improve the accuracy of the overall pipeline. Results showed that models (CNN, LSTM, and GoogLeNet) had an overall accuracy of 88-92%. The proposed SBC algorithm improved accuracy to 95%.

[Simulation and Regulation of Sustainable Utilization of Water Resources in China Based on Improved Water Resources Ecological Footprint Model].

The original ecological footprint model of water resources was improved here to explore the rational policy of water resources development and utilization. Aiming to address the problems of high complexity, weak applicability, and insufficient systematicness and dynamics of the existing water resources ecological footprint model, the grey water footprint was introduced into the model to quantify the water for decontamination. In the calculation of the water resources ecological footprint index, the rainwater collection project, seawater desalination, and water resources regeneration, unconventional water sources were considered, and when combined with the system dynamics simulation technology, the SD model of water resources sustainable utilization in China was established. We carried out research on the regulation and control of sustainable utilization of water resources in China. The results showed that the development and utilization of water resources in China remained within the ecological carrying capacity as a whole from 2000 to 2017, and the development of water resources still had potential, but the supply and demand of water resources were unbalanced. Given this, from the perspective of throttling, open-source, and pollution control, six control schemes for sustainable utilization of water resources in China were set up, including the continuation of the current situation, green throttling, pollution control, strict planning for water source development, and comprehensive treatment. Among them, the comprehensive coordination plan for 2018-2050 could properly solve the problem of water resources supply and demand under the conditions of meeting the ecological sustainability of water resources and reasonable water resources load and was the best regulation plan to realize the sustainable utilization of water resources in China. At present, the development of water resources in China lags, which does not match the growth rate of social and economic development on water resources consumption. It is necessary to further strengthen the efforts of open-source, water-saving, and pollution control based on the original policies, so as to alleviate the ecological stress of water resources.