Insulin reverses impaired alveolar fluid clearance in ARDS by inhibiting LPS-induced autophagy and inflammatory

Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1β activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS

A novel edge server selection method based on combined genetic algorithm and simulated annealing algorithm

Mobile edge computing is a new paradigm which provides cloud computing capabilities at the edge of pervasive radio access networks in close proximity to users. The problem of edge server selection in mobile edge environment in terms of user’s overhead is investigated in this paper. Due to the limited resources of edge server, we firstly study the task completion probability of edge servers. Secondly, we formally model the problem of edge server selection in terms of time latency and energy consumption. More especially, the computation overhead method for completing the task in cases of both service migration and non-migration is investigated. Then, a new optimized edge server selection algorithm, called combined Genetic algorithm and simulated Annealing algorithm for edge Server Selection (GASS) is designed. Finally, a series of experiments on a real-word data-trace are conducted to evaluate the performance of GASS. The results show that GASS can effectively minimize the overhead of the user and outperform traditional heuristic algorithms

TIDE: adjuvant tislelizumab plus donafenib combined with transarterial chemoembolization for high-risk hepatocellular carcinoma after surgery: protocol for a prospective, single-arm, phase II trial

BackgroundThe high recurrence rate of hepatocellular carcinoma (HCC) after surgery negatively affects the prognosis of patients. There is currently no widely accepted adjuvant therapy strategy for patients with HCC. A clinical study of effective adjuvant therapy is still needed.MethodsIn this prospective, single-arm, phase II clinical trial, an adjuvant regimen of donafenib plus tislelizumab combined with transarterial chemoembolization (TACE) will be used to treat enrolled HCC patients after surgery. Briefly, patients newly diagnosed with HCC by pathological examination who underwent curative resection and had a single tumor more than 5 cm in diameter with microvascular invasion as detected by pathological examination are eligible. The primary endpoint of the study is the recurrence-free survival (RFS) rate at 3 years, and secondary endpoints are the overall survival (OS) rate and the incidence of adverse events (AEs). The planned sample size, 32 patients, was calculated to permit the accumulation of sufficient RFS events in 3 years to achieve 90% power for the RFS primary endpoint.DiscussionVascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways regulate the relevant immunosuppressive mechanisms of HCC recurrence. Our trial will evaluate the clinical benefit of adding donafenib plus tislelizumab to TACE in patients with early-stage HCC and a high risk of recurrence.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200063003

Comprehensive Evaluation of Wild \u3cem\u3eElymus\u3c/em\u3e L. Germplasm in Inner Mongolia

Grassland degradation is increasing in severity and is an important global issue in the 21st century. Increasing research is being conducted on how to solve these problems (Niu and Jiang 2004). Restoration and revegetation of degraded grassland and the establishment of artificial pastures are important in addressing degradation. Successful restoration requires the identification of species and seed sources that are adapted to the ecological conditions of the restoration site. Elymus L. is a large genus that contains about 150 species distributed across a wide range of ecological sites across temperate and subtropical regions of the world (Dewey 1984; Love 1984). There are at least 12 species in China (Guo 1987). Elymus includes many economically important forage grasses as well as species that possess useful genes for disease resistance, stress tolerance and adaptation, which can potentially be transferred to cereal crops through gene introgression. Species within Elymus have the potential for playing an important role in artificial pasture construction, grassland and animal husbandry development and ecological restoration. However, research is lacking on Chinese Elymus species, which can provide critical information for selecting suitable Elymus varieties and extending their use in China

Weighted Fusion Robust Steady-State Kalman Filters for Multisensor System with Uncertain Noise Variances

A direct approach of designing weighted fusion robust steady-state Kalman filters with uncertain noise variances is presented. Based on the steady-state Kalman filtering theory, using the minimax robust estimation principle and the unbiased linear minimum variance (ULMV) optimal estimation rule, the six robust weighted fusion steady-state Kalman filters are designed based on the worst-case conservative system with the conservative upper bounds of noise variances. The actual filtering error variances of each fuser are guaranteed to have a minimal upper bound for all admissible uncertainties of noise variances. A Lyapunov equation method for robustness analysis is proposed. Their robust accuracy relations are proved. A simulation example verifies their robustness and accuracy relations

The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

Preparation and Stability Evaluation of Black Rice Anthocyanin Microcapsules

The stability of black rice anthocyanin microcapsules at high temperature, light and pH, and their release in simulated gastroenteric fluid were studied by emulsification and gelation of black rice anthocyanin microcapsules with calcium alginate as wall material. The stability of black rice anthocyanin in microcapsules prepared under the process parameters of sodium alginate concentration of 15 g/L, water oil volume ratio of 1∶3, wall to core ratio M (C3G)∶M (NaAlg) of 2∶1, and solution pH of 4.5 was significantly higher than that of uncoated free black ones under different pH, temperature, and light conditions. The microencapsulated anthocyanin could be kept for 4 hours in simulated gastric fluid, and the wall material was slowly decomposed and released in simulated intestinal fluid. The microencapsulation technology based on emulsified gel can improve the stability of anthocyanins, and achieve their intestinal delivery and sustained release in vivo

The use of comparative genomic hybridization to characterize genome dynamics and diversity among the serotypes of Shigella

<p>Abstract</p> <p>Background</p> <p>Compelling evidence indicates that <it>Shigella </it>species, the etiologic agents of bacillary dysentery, as well as <it>enteroinvasive Escherichia coli</it>, are derived from multiple origins of <it>Escherichia coli </it>and form a single pathovar. To further understand the genome diversity and virulence evolution of <it>Shigella</it>, comparative genomic hybridization microarray analysis was employed to compare the gene content of <it>E. coli </it>K-12 with those of 43 <it>Shigella </it>strains from all lineages.</p> <p>Results</p> <p>For the 43 strains subjected to CGH microarray analyses, the common backbone of the <it>Shigella </it>genome was estimated to contain more than 1,900 open reading frames (ORFs), with a mean number of 726 undetectable ORFs. The mosaic distribution of absent regions indicated that insertions and/or deletions have led to the highly diversified genomes of pathogenic strains.</p> <p>Conclusion</p> <p>These results support the hypothesis that by gain and loss of functions, <it>Shigella </it>species became successful human pathogens through convergent evolution from diverse genomic backgrounds. Moreover, we also found many specific differences between different lineages, providing a window into understanding bacterial speciation and taxonomic relationships.</p