The Estimation of Nodal Power Supply Reliability through the Network Connectivity by Complex Network Method

The paper studies the reliability of the power system from the perspective of node loads. The reliability of the whole system can be estimated by evaluating the power supply reliability of each node. A measure, connectivity observed at load node (Ci), is proposed. Ci is calculated through a recursion equation by evaluating the generation capacity that can be transferred from the further neighbor to the nearest neighbor of load node i. IEEE-30 bus system is taken as a test system. We calculated the index of 7 load nodes at 2 different load levels with different N-1 failures. The test results show that the variation of the index and that of the percentage load shedding at selected load nodes show good consistency

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background: Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer’s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects. Methodology/Principal Findings: aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%). Conclusions/Significance: It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects

High-free Fatty Acid Treatment Induced Anti-inflammatory Changes in a Natural Killer (NK) Cell Line

Background: Natural killer (NK) cells play a role in the pathogenesis of various metabolic diseases related to obesity. While our initial findings have indicated a potential involvement of NK cells in the pathogenesis of type 2 diabetes mellitus, the precise mechanism underlying NK cell-mediated development of this form of diabetes remains inadequately comprehended.Objective: To investigate the impact and the underlying mechanism of high glucose and elevated levels of free fatty acids (FFAs) on immune and inflammatory responses and oxidative stress in NK92 cells.Methods: In this experiment, the CCK8 cytotoxicity assay was used to select the 44.4 mM and 1.5 mM concentrations of high glucose and high FFAs, respectively, to treat NK92 cells for 4 days. The concentrations of superoxide dismutase (SOD) and glutathione (GSH) were determined using a biochemical analyzer. Intracellular reactive oxygen species (ROS) levels, cytokines concentrations (TNF-α, IFN-γ, IL-6, and IL-10), and the expression levels of intracellular molecules (perforin and granzyme B) were assessed by flow cytometry.Results: The number of NK92 cell clumps was significantly reduced in the high-FFA (HF) group. In addition, the production of ROS and levels of cytokines (TNF-α, IFN-γ, IL-6, and IL-10) significantly decreased in the HF group but showed no significant change in the high-glucose (HG) group. This observation was consistent with the expression levels of perforin and granzyme B that decreased in the HF group.Conclusion: High FFAs induced morphological changes and serious damage to oxidative stress and inflammatory response in NK92 cells

Inhibition of Influenza A Virus (H1N1) Fusion by Benzenesulfonamide Derivatives Targeting Viral Hemagglutinin

Hemagglutinin (HA) of the influenza virus plays a crucial role in the early stage of the viral life cycle by binding to sialic acid on the surface of host epithelial cells and mediating fusion between virus envelope and endosome membrane for the release of viral genomes into the cytoplasm. To initiate virus fusion, endosome pH is lowered by acidification causing an irreversible conformational change of HA, which in turn results in a fusogenic HA. In this study, we describe characterization of an HA inhibitor of influenza H1N1 viruses, RO5464466. One-cycle time course study in MDCK cells showed that this compound acted at an early step of influenza virus replication. Results from HA-mediated hemolysis of chicken red blood cells and trypsin sensitivity assay of isolated HA clearly showed that RO5464466 targeted HA. In cell-based assays involving multiple rounds of virus infection and replication, RO5464466 inhibited an established influenza infection. The overall production of progeny viruses, as a result of the compound's inhibitory effect on fusion, was dramatically reduced by 8 log units when compared with a negative control. Furthermore, RO5487624, a close analogue of RO5464466, with pharmacokinetic properties suitable for in vivo efficacy studies displayed a protective effect on mice that were lethally challenged with influenza H1N1 virus. These results might benefit further characterization and development of novel anti-influenza agents by targeting viral hemagglutinin

Establishment of a Bernard-Soulier syndrome model in zebrafish

Platelets play an essential role in thrombosis and hemostasis. Abnormal hemostasis can cause spontaneous or severe post-traumatic bleeding. Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder caused by a complete quantitative deficiency in the GPIb-IX-V complex. Multiple mutations in GP9 lead to the clinical manifestations of BSS. Understanding the roles and underlying mechanisms of GP9 in thrombopoiesis and establishing a proper animal model of BSS would be valuable to understand the disease pathogenesis and to improve its medical management. Here, by using CRISPR-Cas9 technology, we created a zebrafish gp9SMU15 mutant to model human BSS. Disruption of zebrafish gp9 led to thrombocytopenia and a pronounced bleeding tendency, as well as an abnormal expansion of progenitor cells. The gp9SMU15 zebrafish can be used as a BSS animal model as the roles of GP9 in thrombocytopoiesis are highly conserved from zebrafish to mammals. Utilizing the BSS model, we verified the clinical GP9 mutations by in vivo functional assay and tested clinical drugs for their ability to increase platelets. Thus, the inherited BSS zebrafish model could be of benefit for in vivo verification of patient-derived GP9 variants of uncertain significance and for the development of potential therapeutic strategies for BSS

Influence of Chrysanthemum morifolium-maize intercropping pattern on yield, quality, soil condition, and rhizosphere soil microbial communities of C. morifolium

IntroductionChrysanthemum morifolium Ramat. is a perennial herb in the Compositae family, often employed in traditional Chinese medicine due to its medicinal value. The planting of C. morifolium faces the challenges of continuous cropping, and intercropping is able to somewhat overcome the obstacles of continuous cropping.MethodsIn our study, we designed two different C. morifolium-maize intercropping patterns, including C. morifolium-maize narrow-wide row planting (IS) and C. morifolium-maize middle row planting (IM). Compared with monoculture, the agronomic traits, yield, active ingredients, soil physicochemical properties, soil enzyme activities, and rhizosphere soil microbial communities of C. morifolium and maize were measured under the two C. morifolium-maize intercropping patterns.ResultsThe findings indicated that (1) Intercropping elevated the agronomic traits, yield, and active ingredients of C. morifolium, especially in C. morifolium-maize narrow-wide row planting pattern, which indicating that interspecific distance played an important role in intercropping system; (2) Intercropping enhanced soil physicochemical properties and enzyme activities of C. morifolium and maize; (3) Intercropping altered rhizosphere soil microbial communities of C. morifolium and maize, making microbial interrelationships more complex. (4) Intercropping could recruit a large number of beneficial microorganisms enrich in the soil, including Bacillus, Sphingomonas, Burkholderia-Caballeronia-Paraburkholderia, Chaetomium, and Ceratorhiza, which may increase the content of AN, NN, AvK, ExCa, AvCu, AvZn and other nutrients in soil and promoted the growth and quality of C. morifolium.DiscussionIn summary, intercropping with maize could promote the accumulation of beneficial microorganisms in the soil, thus improving the overall growing environment, and finally realizing the growth and improvement of C. morifolium

DaiTongXiao improves gout nephropathy by inhibiting inflammatory response through the TLR4/MyD88/NF-κB pathway

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties.Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression.Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) −18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue.Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression

Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of β-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer’s Disease

Alzheimer’s disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the β-amyloid (Aβ) aggregation process. In this study, we bilaterally injected Aβ oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Aβ plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFα and IL-6) induced by Aβ were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Aβ intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Aβ deposition and the inflammatory response in the brain

Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or Sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment

Dynamic genome evolution in a model fern

The large size and complexity of most fern genomes have hampered efforts to elucidate fundamental aspects of fern biology and land plant evolution through genome-enabled research. Here we present a chromosomal genome assembly and associated methylome, transcriptome and metabolome analyses for the model fern species Ceratopteris richardii. The assembly reveals a history of remarkably dynamic genome evolution including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago. These changes include massive gene loss, rampant tandem duplications and multiple horizontal gene transfers from bacteria, contributing to the diversification of defence-related gene families. The insertion of transposable elements into introns has led to the large size of the Ceratopteris genome and to exceptionally long genes relative to other plants. Gene family analyses indicate that genes directing seed development were co-opted from those controlling the development of fern sporangia, providing insights into seed plant evolution. Our findings and annotated genome assembly extend the utility of Ceratopteris as a model for investigating and teaching plant biology