MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1

Introduction. Sepsis-induced acute lung injury (ALI) is an inflammatory process involved with simultaneous production of inflammatory cytokines and chemokines. In this study, we investigated the regulatory role of miR-539-5p in sepsis-induced ALI using a mouse model of cecal ligation puncture (CLP) and an in vitro model of primary murine pulmonary microvascular endothelial cells (MPVECs). Material and methods. Adult male C57BL/6 mice were intravenously injected with or without miR-539-5p agomir or scrambled control one week before CLP operation. MPVECs were transfected with miR-539-5p mimics or control mimics, followed by lipopolysaccharide (LPS) stimulation. ROCK1 was predicted and confirmed as a direct target of miR-539-5p using dual-luciferase reporter assay. In rescue experiment, MPVECs were co-transfected with lentiviral vector expressing ROCK1 (or empty vector) and miR-539-5p mimics 24 h before LPS treatment. The transcriptional activity of caspase-3, the apoptosis ratio, the levels of miR-539-5p, interleukin-1b (IL-1b), interleukin-6 (IL-6), and ROCK1 were assessed. Results. Compared to sham group, mice following CLP showed pulmonary morphological abnormalities, elevated production of IL-1b and IL-6, and increased caspase-3 activity and apoptosis ratio in the lung. In MPVECs, LPS stimulation resulted in a significant induction of inflammatory cytokine levels and apoptosis compared to untreated cells. The overexpression of miR-539-5p in septic mice alleviated sepsis-induced pulmonary injury, apoptosis, and inflammation. MiR-539-5p also demonstrated anti-apoptotic and anti-inflammatory effect in LPS-treated MPVECs. The upregulation of ROCK1 in MPVECs recovered miR-539-5p-suppressed caspase-3 activity and proinflammatory cytokine production. Conclusion. In conclusion, miR-539-5p alleviated sepsis-induced ALI via suppressing its downstream target ROCK1, suggesting a therapeutic potential of miR-539-5p for the management of sepsis-induced ALI

A secure cross-domain interaction scheme for blockchain-based intelligent transportation systems

Si, H., Li, W., Wang, Q., Cao, H., Bação, F., & Sun, C. (2023). A secure cross-domain interaction scheme for blockchain-based intelligent transportation systems. PeerJ Computer Science, (November 2023), 1-36. https://doi.org/10.7717/peerj-cs.1678, https://doi.org/10.7717/peerj-cs.1678/supp-1, https://doi.org/10.7717/peerj-cs.1678/supp-2---This work was supported by the Henan Province Key Science-technology Research Project under Grant No. 232102520006 and 232102210122, the Key Research Project of Henan Provincial Higher Education Institution under Grant No. 23A520005, and the Henan Province Major Public Welfare Projects under Grant No. 201300210300. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.In the intelligent transportation system (ITS), secure and efficient data communication among vehicles, road testing equipment, computing nodes, and transportation agencies is important for building a smart city-integrated transportation system. However, the traditional centralized processing approach may face threats in terms of data leakage and trust. The use of distributed, tamper-proof blockchain technology can improve the decentralized storage and security of data in the ITS network. However, the cross-trust domain devices, terminals, and transportation agencies in the heterogeneous blockchain network of the ITS still face great challenges in trusted data communication and interoperability. In this article, we propose a heterogeneous cross-chain interaction mechanism based on relay nodes and identity encryption to solve the problem of data cross-domain interaction between devices and agencies in the ITS. First, we propose the ITS cross-chain communication framework and improve the cross-chain interaction model. The relay nodes are interconnected through libP2P to form a relay node chain, which is used for cross-chain information verification and transmission. Secondly, we propose a relay node secure access scheme based on identity-based encryption to provide reliable identity authentication for relay nodes. Finally, we build a standard cross-chain communication protocol and cross-chain transaction lifecycle for this mechanism. We use Hyperledger Fabric and FISCO BCOS blockchain to design and implement this solution, and verify the feasibility of this cross-chain interaction mechanism. The experimental results show that the mechanism can achieve a stable data cross-chain read throughput of 2,000 transactions per second, which can meet the requirements of secure and efficient cross-chain communication and interaction among heterogeneous blockchains in the ITS, and has high application value.publishersversionpublishe

Regulatory and functional divergence among members of Ibβfruct2, a sweet potato vacuolar invertase gene controlling starch and glucose content

Sweet potato [Ipomoea batatas (L.) Lam.] is an important food and industrial crop. Its storage root is rich in starch, which is present in the form of granules and represents the principal storage carbohydrate in plants. Starch content is an important trait of sweet potato controlling the quality and yield of industrial products. Vacuolar invertase encoding gene Ibβfruct2 was supposed to be a key regulator of starch content in sweet potato, but its function and regulation were unclear. In this study, three Ibβfruct2 gene members were detected. Their promoters displayed differences in sequence, activity, and cis-regulatory elements and might interact with different transcription factors, indicating that the three Ibβfruct2 family members are governed by different regulatory mechanisms at the transcription level. Among them, we found that only Ibβfruct2-1 show a high expression level and promoter activity, and encodes a protein with invertase activity, and the conserved domains and three conserved motifs NDPNG, RDP, and WEC are critical to this activity. Only two and six amino acid residue variations were detected in sequences of proteins encoded by Ibβfruct2-2 and Ibβfruct2-3, respectively, compared with Ibβfruct2-1; although not within key motifs, these variations affected protein structure and affinities for the catalytic substrate, resulting in functional deficiency and low activity. Heterologous expression of Ibβfruct2-1 in Arabidopsis decreased starch content but increased glucose content in leaves, indicating Ibβfruct2-1 was a negative regulator of starch content. These findings represent an important advance in understanding the regulatory and functional divergence among duplicated genes in sweet potato, and provide critical information for functional studies and utilization of these genes in genetic improvement

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

Citrus Postharvest Green Mold: Recent Advances in Fungal Pathogenicity and Fruit Resistance

As the major postharvest disease of citrus fruit, postharvest green mold is caused by the necrotrophic fungus Penicillium digitatum (Pd), which leads to huge economic losses worldwide. Fungicides are still the main method currently used to control postharvest green mold in citrus fruit storage. Investigating molecular mechanisms of plant–pathogen interactions, including pathogenicity and plant resistance, is crucial for developing novel and safer strategies for effectively controlling plant diseases. Despite fruit–pathogen interactions remaining relatively unexplored compared with well-studied leaf–pathogen interactions, progress has occurred in the citrus fruit–Pd interaction in recent years, mainly due to their genome sequencing and establishment or optimization of their genetic transformation systems. Recent advances in Pd pathogenicity on citrus fruit and fruit resistance against Pd infection are summarized in this review

Epinephelus rankini Whitley, 1945, a valid species of grouper (Teleostei, Perciformes, Epinephelidae) from Western Australia and southeast Indonesia

The grouper Epinephelus rankini, described from the waters off Western Australia, has long been regarded as a junior synonym of Epinephelus multinotatus. However, the two species are discernible as distinct species on the basis of their morphological characteristics and genetic differences by the holotype material and non-type of specimens.In this study, Epinephelus rankini is considered as a valid species and re-described based on the examination of the holotype and additional specimens. Epinephelus rankini can be distinguished from the closely-related species E. multinotatus by the following combination of characters: body dark greyish-brown to chocolate with irregular white blotches (vs. body pale brownish-grey with irregular and small white blotches in E. multinotatus), absence of small dark brown spots (vs. numerous small dark brown spots in E. multinotatus). Furthermore, genetic differences between the two species strongly support the validity of both species based on molecular analysis (mtDNA, COI gene). In addition based on the sampling range, E. rankini was observed range from the Abrolhos Islands of Western Australia to south-eastern Indonesia, while E. multinotatus ranges from the Persian Gulf to southern Mozambique

Evolution Model and Driving Mechanism of Urban Logistics Land: Evidence from the Yangtze River Delta

Logistics land is the spatial carrier for the development of logistics enterprises. Its evolution mode and driving mechanism determine the level of high-quality development of the logistics industry, and serve as an important basis for urban planning and territorial spatial planning. This study introduced a Boston consulting group (BCG) matrix and geographically weighted regression (GWR) spatial econometric models to carry out empirical research on the Yangtze River Delta (YRD), in an effort to provide scientific information for evidence-based decision-making by governments and enterprises. The scale and ratio of logistics land (LLS and LLR) in the YRD showed significant spatial heterogeneity and autocorrelation, cities with large logistics land use converging from clusters to belts from 2000 to 2020, and agglomerations with high logistics land ratio (LLR) migrating from inland to coastal areas. Diversified models of logistics land evolution also emerged, such as high scale–high speed cities, low scale–low speed cities, high scale–low speed cities, and low scale–high speed cities. In addition, the driving mechanism of LLS and LLR was very complex, with a great difference in the intensity, nature and spatial effects of the influence of different factors. The inspiration from empirical case studies is urgent to revise the planning norms and clarify the LLS and LLR control standards for logistics land use. Meanwhile, the synergistic development target of the logistics industry in the new era is changing from the manufacturing industry to the commerce and trade industry; the establishment of planning zoning and the designing of differentiated management policies significantly improve the planning applicability

Decoding the hundred-year water level changes of the largest Saline Lake in China: A joint lake-basin modeling study based on a revised SWAT+

Study region: Qinghai Lake Basin (QLB), the largest saline lake in China and its collecting basin Study focus: Climate change has caused clear shrinkage or dramatic water level fluctuation of lakes in arid and semi-arid regions, while the underlain mechanisms remain unclear. The joint lake-basin investigations (spatial) and long-term studies (temporal) are urgently needed. This study developed SWAT+ to jointly simulate the water cycle of QLB and investigated how the hydrological regime of QLB changed at the hundred-year scale. New hydrological insights for the region: The modeling framework consisted of the revised SWAT+ , reanalysis data, and reconstructed water level based on lake gravity core performed quite well (NSE > 0.9 for lake water level) in simulating the hydrological processes of QLB at the hundred-year scale (1910 – 2018). Temporally, decadal variations of hydrological components in QLB decreased in sequence of precipitation (46.33 mm), lateral flow (26.85 mm), evapotranspiration (16.03 mm), snowmelt (10.44 mm), groundwater flow (5.66 mm), and overland flow (1.18 mm). Spatially, precipitation, water yield, lateral flow, and groundwater flow in upstream regions of QLB, where the precipitation amount was small, were most sensitive to climate change. The long-term water level decrease of Qinghai Lake during 1928 – 2003 was mainly driven by variations of river runoff and lake surface evaporation; the clear water level increase since 2004 was dominated by river runoff changes

What influences does grazing bring about to stream nutrient fluxes in alpine meadows?

Non-point source pollution is a serious environmental issue and has attracted a lot of scientific attention. Currently, the influences of grazing on the water and nutrient cycles in alpine meadows, as well as corresponding underlying mechanisms, still remain unclear. The quantitative contributions of influence variables to the nutrient loading variations in rivers and streams in alpine-meadow watersheds need to be elucidated. In the study, the Soil and Water Assessment Tool (SWAT) was applied to a typical alpine-meadow watershed (the Buha River Basin, BRB) on the Tibetan Plateau, where non-intensive grazing and farming were developed, to reproduce the water and nutrient cycles. Results showed that SWAT model performed well in simulating monthly streamflow, TN, and TP fluxes from 2016 to 2022 (NSE > 0.6). Grazing slightly increased the streamflow by 4.27% because it reduced aboveground biomass and leaf area index of vegetation, which subsequently reduced the ET of grasslands. Grazing increased the annual NH4-N fluxes by 0.50% due to livestock manure inputs to the basin; in contrast, grazing reduced the annual fluxes of TN and TP of Buha River by 3.36% and 0.48%, respectively, during 2016 – 2022, which were driven by the increased plant uptake of NO3-N/soluble P from soil layer due to grazing. As a result, non-intensive grazing was beneficial for the water management and nutrient control in the studied alpine-meadow watershed. The hydrological, water-quality, and meteorological variables accounted for 30.78%, 28.27%, and 21.23% of the variations in N fluxes in Buha River, respectively. The dissolved oxygen (10.68%), soluble phosphorus (10.51%), precipitation (6.27%), overland flow (5.60%), and water temperature (5.53%) each explained more than 5% of the N flux variations. The present study quantified the effects of grazing and farming on stream nutrient fluxes based on mathematical modeling and statistical methods, and the findings could provide scientific supports for the managements of alpine-meadow watersheds

Characteristics and Performance Evaluation of QZSS Onboard Satellite Clocks

In the Global Navigation Satellite System (GNSS) community, the Quasi-Zenith Satellite System (QZSS) is an augmentation system for users in the Asia-Pacific region. However, the characteristics and performance of four QZSS satellite clocks in a long-term scale are unknown at present. However, it is crucial to the positioning, navigation and timing (PNT) services of users, especially in Asia-Pacific region. In this study, the characteristics and performance variation of four QZSS satellite clocks, which including the phase, frequency, frequency drift, fitting residuals, frequency accuracy, periodic terms, frequency stability and short-term clock prediction, are revealed in detail for the first time based on the precise satellite clock offset products of nearly 1000 days. The important contributions are as follows: (1) It is detected that the times of phase and frequency jump are 2.25 and 1.5 for every QZSS satellite clock in one year. The magnitude of the frequency drift is about 10−18. The periodic oscillation of frequency drift of J01 and J02 satellite clocks is found. The clock offset model precision of QZSS is 0.33 ns. (2) The two main periods of QZSS satellite clock are 24 and 12 hours, which is the influence of the satellite orbit; (3) The frequency stability of 100, 1000 and 10,000 s are 1.98 × 10−13, 6.59 × 10−14 and 5.39 × 10−14 for QZSS satellite clock, respectively. The visible “bump” is found at about 400 s for J02 and J03 satellite clocks. The short-term clock prediction accuracy of is 0.12 ns. This study provides a reference for the state monitoring and performance variation of the QZSS satellite clock