94 research outputs found

    Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways

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    Objective(s): Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin’s function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients’ serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway

    Lignosulfonic Acid Exhibits Broadly Anti-HIV-1 Activity – Potential as a Microbicide Candidate for the Prevention of HIV-1 Sexual Transmission

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    Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide

    Age-specific reference values for low psoas muscle index at the L3 vertebra level in healthy populations: A multicenter study

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    Background and aimsThe progressive and generalized loss of skeletal muscle mass, strength and physical function is defined as sarcopenia. Sarcopenia is closely related to the prognosis of patients. Accurate diagnosis and adequate management of sarcopenia are crucial. The psoas muscle mass index taken at the third lumbar vertebra (L3-PMI, cm2/m2) is one of the established methods for evaluating skeletal muscle mass. However, the cutoff values of L3-PMI for diagnosis of sarcopenia are not yet to be clarified in Asian populations. We attempted to establish reference values for low L3-PMI that would be suitable for defining sarcopenia in the Northern Chinese population.MethodsThis was a retrospective, multicenter cross-sectional study. A search of abdominal CT imaging reports was conducted in four representative cities in northern China. Transverse CT images were measured using the analysis software Slice-O-Matic. Low psoas muscle index was defined as the 5th percentile or mean-2SD of the study group.Results1,787 healthy individuals in the study were grouped by age. The sex and number of people in each group were similar. L3-PMI had a negative linear correlation with age, and a strong correlation with the skeletal muscle index taken at the third lumbar vertebrae (L3-SMI, cm2/m2). The L3-PMI reference values in males were 5.41 cm2/m2 for 20–29 years, 4.71 cm2/m2 for 30–39 years, 4.65 cm2/m2 for 40–49 years, 4.10 cm2/m2 for 50–59 years and 3.68 cm2/m2 for over 60 years by using 5th percentile threshold. Similarly, the reference values in females were 3.32, 3.40, 3.18, 2.91, and 2.62 cm2/m2. When using mean-2SD as the reference, the values for each age group were 4.57, 4.16, 4.03, 3.37, and 2.87 cm2/m2 for males and 2.79, 2.70, 2.50, 2.30, and 2.26 cm2/m2 for females, respectively.ConclusionWe defined the reference values of age-specific low skeletal muscle mass when simply evaluated by L3-PMI. Further studies about the association of sarcopenia using these reference values with certain clinical outcomes or diseases are needed

    Complement and the Alternative Pathway Play an Important Role in LPS/D-GalN-Induced Fulminant Hepatic Failure

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    Fulminant hepatic failure (FHF) is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb) or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway), and C3 deficient mice (C3−/− mice). The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR) and C5a receptor (C5aR) expression was also upregulated. Compared with wild-type mice, C3−/− mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D-GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure

    Upper ocean biogeochemistry of the oligotrophic North Pacific Subtropical Gyre : from nutrient sources to carbon export

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    Subtropical gyres cover 26–29% of the world’s surface ocean and are conventionally regarded as ocean deserts due to their permanent stratification, depleted surface nutrients, and low biological productivity. Despite tremendous advances over the past three decades, particularly through the Hawaii Ocean Time-series and the Bermuda Atlantic Time-series Study, which have revolutionized our understanding of the biogeochemistry in oligotrophic marine ecosystems, the gyres remain understudied. We review current understanding of upper ocean biogeochemistry in the North Pacific Subtropical Gyre, considering other subtropical gyres for comparison. We focus our synthesis on spatial variability, which shows larger than expected dynamic ranges of properties such as nutrient concentrations, rates of N2 fixation, and biological production. This review provides new insights into how nutrient sources drive community structure and export in upper subtropical gyres. We examine the euphotic zone in subtropical gyres as a two-layered vertically structured system: a nutrient-depleted layer above the top of the nutricline in the well-lit upper ocean and a nutrient-replete layer below in the dimly lit waters. These layers vary in nutrient supply and stoichiometries and physical forcing, promoting differences in community structure and food webs, with direct impacts on the magnitude and composition of export production. We evaluate long-term variations in key biogeochemical parameters in both of these euphotic zone layers. Finally, we identify major knowledge gaps and research challenges in these vast and unique systems that offer opportunities for future studies

    Mitochondrial genome characterization and phylogeny of Wallacea dactyliferae Maulik 1919 (Coleoptera: Chrysomelidae) from China

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    Wallacea dactyliferae Maulik (Coleoptera: Chrysomelidae) has been reported as a new invasive palm pest in Asia recently. So far, a total of 29 species have been reported in Wallacea. In the present study, the whole mitochondrial genome of W. dactyliferae was identified for the first time (also for the first species of Wallacea) by using high throughput sequencing systems. The entire genome is 16,243 bp in length (ACCN: OK513040) consisting of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and an A + T-rich region. Phylogenetic analysis revealed that insects from the same subfamily were clustered together, with W. dactyliferae being clustered together with other Cassidinae species. This study can provide essential DNA molecular data for further phylogenetic and evolutionary analyses for Chrysomelidae family of the Coleoptera order

    Rapid and cyclic dust accumulation during MIS 2 in Central Asia inferred from loess OSL dating and grain-size analysis

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    Due to lack of reliable proxies from the Westerlies-dominant region, the strength change of Northern Hemisphere Westerlies remains poorly understood. The aim of this study is to provide a reliable paleoclimatic proxy about the Northern Hemisphere Westerlies change. Here we report a 30.7 m thick loess section from the Ili basin directly controlled by the Westerlies. Based on optically stimulated luminescence (OSL) and high resolution grain-size records, we reconstruct the change history of the Westerlies strength during the last glacial period (mainly Marine Isotope Stages 2, MIS2), being similar with the Westerlies index recorded in the Qinghai Lake sediments. Within error limits, all ages are in stratigraphic order. We further compare the climatic records among the Ili loess, Qinghai Lake and the NGRIP, their similarity shows a good climatic coupling relationship among the Central Asia, East Asia and the North Atlantic, and the Westerlies plays a critical influence in transporting the North Atlantic signal to Central and East Asia

    The Size Effect and Microstructure Changes of Granite after Heat Treatment

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    High temperature can change the mechanical properties of granite, with significant nonlinear characteristics, and at the same time change its microstructure. Therefore, two kinds of granites are used in this paper: one is normal temperature granite and the other is granite treated at 600°C, and a detailed comparative study is made. The fracture toughness of two kinds of rocks was tested by fracture tests, and the results were analyzed by a nonlinear fracture mechanics model (SEL). At the same time, in order to understand the influence of high temperature on the mineral composition and microstructure of granite, XRD, optical microscope, and SEM were used to observe the mineral composition, microcracks, and fracture morphology of granite. The results show the following: (1) high temperature significantly changes the fracture mechanics parameters of granite. The fracture toughness of granite treated at 600°C is significantly lower than that of untreated granite, which is reduced by more than 60%. (2) No obvious size effect was found in the untreated granite, while the size effect of the granite after treatment at 600°C was significant. (3) The granite after high-temperature treatment showed strong nonlinear characteristics, and the SEL can reasonably describe and explain its nonlinear fracture characteristics. (4) The brittleness of the granite treated at 600°C decreased and the ductility increased. The microscopic morphology of the fracture was rough, with obvious steps and rivers. The microcracks and porosity had increased significantly, but the main components did not change significantly
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