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In order to investigate the nonvolatile taste-active components in crayfish, free amino acids, nucleotides, organic acids, soluble sugars and alkaloids in cooked crayfish muscle were qualitatively and quantitatively analyzed by 1H nuclear magnetic resonance (1H NMR). Their taste activity values (TAVs) and equivalent umami concentration (EUC) were calculated to evaluate the key taste-active compounds and umami attributes, respectively. The results suggested that a total of 33 taste-active compounds were detected, among which arginine, histidine, glutamic acid, alanine, lysine, glycine, adenosine 5’-monophosphate (AMP), inosine 5’-mononucleotide (IMP), succinic acid and lactic acid were the key taste-active compounds with TAVs greater than 1.0, and they played an important role in the taste of crayfish. The EUC of crayfish was 9.1 g monosodium glutamate (MSG)/100 g, indicating very intense umami taste.

Pulmonary arterial hypertension (PAH) is an incurable disease with high mortality. Chemerin has been found to be associated with pulmonary hypertension (PH). However, the specific role of chemerin in mediating PH development remains unclear. This study aimed to elucidate the regulatory effects and the underlying mechanism of chemerin on PH and to investigate the expression levels of chemerin protein in plasma in PAH patients. In vivo , two animal models of PH were established in rats by monocrotaline (MCT) injection and hypoxia. We found that the expression levels of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), were significantly upregulated in the lungs of PH rats. Primary cultured pulmonary arterial smooth muscle cells [(PASMCs) (isolated from pulmonary arteries of normal healthy rats)] were exposed to hypoxia or treated with recombinant human chemerin, we found that CMKLR1 expression was upregulated in PASMCs in response to hypoxia or chemerin stimulation, whereas the exogenous chemerin significantly promoted the migration and proliferation of PASMCs. Notably, the regulatory effects of chemerin on PASMCs were blunted by PD98059 (a selective ERK1/2 inhibitor). Using enzyme linked immunosorbent assay (ELISA), we found that the protein level of chemerin was also markedly increased in plasma from idiopathic pulmonary arterial hypertension (IPAH) patients compared to that from healthy controls. Moreover, the diagnostic value of chemerin expression in IPAH patients was determined through receiver operating characteristic (ROC) curve analysis and the result revealed that area under ROC curve (AUC) for plasma chemerin was 0.949. Taken together, these results suggest that chemerin exacerbates PH progression by promoting the proliferation and migration of PASMCs via the ERK1/2 signaling pathway, and chemerin is associated with pulmonary hypertension. [ABSTRACT FROM AUTHOR]

To research structural performance of extra-large-span cable-stayed bridge under different section forms, with the engineering background of a 800m main-span cable-stayed bridge with steel truss girder, the cable-stayed bridge with steel box girder is designed according to the current bridge regulations when two bridges are designed in an ultimate state of the carrying capacity, so the maximum stress and minimum stress of the stress envelope diagram are substantially the same. A comprehensive comparison is given to two types of bridge on the aspect of static force, natural vibration frequency, stability, economic performance and so on. Analysis results provide future reference for the large-span cable-stayed bridge to select between the steel truss girder and the steel box girder.

Purpose: Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment. Patients and Methods: We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea, while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of C–C chemokine receptor 2 (CCR2) on monocytes and plasma levels of CC-chemokine ligand 2 (CCL2), high mobility group box-1 (HMGB-1), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were measured in HC and rosacea patients before and after treatment. Results: The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythematotelangiectatic rosacea (ETR) and ETR-papulopustular rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phymatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1β and TNF-α in patients than in HC, which all significantly decreased after treatment. Conclusion: Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea. [ABSTRACT FROM AUTHOR]

Yachihe Bridge in China is a hybrid cable-stayed bridge with concrete decks at the side spans and a steel truss deck at the mid-span. The 800-m-long truss deck breaks a new record as the longest steel truss cable-stayed bridge in the world. Constrained by site terrain, poor transportation conditions and limited time, a cable crane was adopted for the erection of the 16-m-long truss deck segments, marking the first time that a cable crane has been used in the deck erection of a cable-stayed bridge. This paper primarily deals with the challenges faced and solutions formulated during the bridge construction process, and also presents field load tests for the cable crane. [ABSTRACT FROM AUTHOR]

Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. [ABSTRACT FROM AUTHOR]

The interaction between rice protein isolate (RPI) and ferulic acid (FA) was systematically investigated. The results showed that fluorescence intensity of the RPI decreased gradually upon increasing the concentration of ferulic acid, and the maximum emission shifted from 352.0 to 359.2 nm. It was proposed that a static quenching of RPI-FA complex occurred, due to the hydrophobic interactions. Moreover, CD spectra and FT-IR spectroscopy data suggested that the concentration of β-turn and α-helix decreased while those of random coil and β-sheet increased in RPI-FA complex. The decrease of intensity of the amide I band and amide II band in the RPI-FA complex implied a significant reduction of protein α-helical structure and the presence of non-polar hydrophobic interactions. In addition, SDS-PAGE results demonstrated that ferulic acid reacted with glutelin acidic subunits (34–37 KDa) as well as globulin (26 KDa), and ferulic acid might bind with aromatic amino acid residues of RPI. Furthermore, the RPI-FA complex exhibited high DPPH• scavenging ability, ABTS+• scavenging ability and ORAC value. Finally, emulsion stabilized by RPI-FA complex could decrease the concentration of hydroperoxide, TBARS, and hexanal, thereby effectively restraining fat oxidation degradation. Image 1 • Rice protein isolate and ferulic acid were interacted by hydrophobic interactions. • Ferulic acid reacted with gluten acid subunits and globulin of RPI. • RPI-FA complex could improve the oxidative stability of corn oil in emulsion. [ABSTRACT FROM AUTHOR]

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol . 00:00-00, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O 2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO 2 %) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO 2 % difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94β-His146β in nitrosyl -Hb(NO-Hb), NO-HbβCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 00:00-00, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dt max were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dt max , and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

[Figure: see text].

Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.

Enhanced interaction between vascular endothelial cells and circulating leukocytes, as a result of transcriptional activation of cell adhesion molecules (CAM), helps establish a proinflammatory milieu contributing to the pathogenesis of chronic hypoxia-induced pulmonary hypertension. The molecular switch that dictates CAM transactivation is not clearly defined. Our goal was to determine the involvement of the transcriptional modulator megakaryocytic leukemia 1 (MKL1), also known as myocardin-related transcription factor A (MRTF-A), in CAM transactivation and the underlying mechanism. We report here that compared with wild-type littermates, MKL1/MRTF-A knockout mice were more resistant to the development of hypoxia-induced pulmonary hypertension when exposed to low oxygen pressure. Notably, CAM induction in knockout mice was significantly attenuated with a concomitant reduction of leukocyte adhesion. In cultured vascular endothelial cells, overexpression of MKL1/MRTF-A enhanced, whereas depletion of MKL1/MRTF-A dampened, hypoxia-induced CAM transactivation. In response to hypoxia, MKL1/MRTF-A formed a complex with NF-κB on the CAM promoters. Of interest, MKL1/MRTF-A was responsible for recruiting a histone H3 lysine 4 methyltransferase complex to the CAM promoters. Finally, endothelial-specific silencing of ASH2 and WDR5, 2 key components of the histone H3 lysine 4 methyltransferase complex, ameliorated hypoxia-induced pulmonary hypertension in mice. In conclusion, our data suggest that MKL1/MRTF-A, by coordinating key epigenetic alterations on CAM promoters, provides a critical link to hypoxia-induced endothelial malfunction and contributes to the pathogenesis of hypoxia-induced pulmonary hypertension., (© 2015 American Heart Association, Inc.)