Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. ...Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 μg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser
-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.
There are few studies on the clinical profile of Chinese patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The purpose of this study was to describe the clinical ...characteristics of ARVD/C patients from China, particularly to define the features of electrocardiograph and treatment outcomes.
Thirty-nine patients hospitalized in Fu Wai Cardiovascular Hospital from 1998 to 2006 were included. The data were obtained from the medical archive and the follow-up records.
Of these patients 33 were male and 6 female (age at the first presentation was (34.9 +/- 9.8) years). The most common symptoms were palpitation (62%) and syncope (44%). Right precordial QRSd >or= 110 ms was detected in 69% of the patients, epsilon wave in 59%, and a ratio of QRSd in V(1) + V(2) + V(3)/V(4) + V(5) + V(6) >or= 1.2 in 82%. The most frequent features of electrocardiogram in patients without right bundle-branch block were T-wave inversions and S-wave upstroke in V(1)-V(3) >or= 55 ms (96% and 90% of 28 patients, respectively). Radiofrequency catheter ablation (RFCA) for ventricular tachycardia (VT) was successful in 15 (68%) of 22 patients. The recurrence rate of VT was 46% (7/15) during the follow-up of (16.7 +/- 11.2) months. Seven patients had cardioverter/defibrillator (ICD) implanted plus drug therapy and 17 patients took antiarrhythmic drugs alone. During the follow-up of (35.6 +/- 19.0) months, all patients with ICD implanted received at least one appropriate ICD shock. One patient died of ventricular fibrillation suddenly and one patient underwent heart transplantation for progressive biventricular heart failure during the drug therapy alone.
This study demonstrated the clinical and ECG features of the 39 ARVD/C Chinese patients. ICD provided life-saving protection by effectively terminating malignant arrhythmias, and the high recurrence of VT was the major problem of RFCA therapy.
The Chinese white wax scale insect, Ericerus pela, is an important resource insect in China. The rapid response of E. pela to decreasing temperatures plays key roles in the population distribution. ...In this study, we analyzed the gene expression of E. pela treated with low temperature using transcriptome analyses and weighted gene coexpression network analysis (WGCNA). The results showed that the cold resistance of E. pela involved changes in the expression of many genes. The genes were mainly involved in alcohol formation activity, lipid metabolism, membrane and structure, and oxidoreductase activity. According to the WGCNA results, some pathways related to cold resistance were found in the genes in the modules, such as cytoskeleton proteins, cytoskeleton protein pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, ether lipid metabolism, and thermogenesis. Some of the hub genes were nonspecific lipid‐transfer proteins, DnaJ homolog subfamily C member 13, paramyosin, tropomodulin, and tubulin beta chain. In particular, the hub genes of the tan module included the heat shock protein (hsp) 10, hsp 60, hsp 70, and hsp 90 genes. Thirty‐five antifreeze protein (afp) genes were identified according to the annotation results. Three afp genes were further identified among the hub genes. Six of these genes were selected for heterogeneous protein expression. One of them was expressed successfully. The thermal hysteresis activity (THA) analyses showed that the THA was 1.73°C. These results showed that the cytoskeleton, lipid metabolism, thermogenesis, HSPs and AFPs may play important roles in the cold resistance of E. pela.
Differential scanning calorimeter scanning result for the heterologously expressed AFP.
Research Highlights
The changed genes during cold resistance were mainly involved in alcohol formation activity, lipid metabolism, membrane, and structure.
The antifreeze protein has thermal hysteresis activity of 1.73°C.
Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated ...mechanisms of its suppression of long-term potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CA1 synapses but increased the GABA A receptor-mediated synaptic currents in CA1 pyramidal cells via a presynaptic mechanism. Inhibition of GABA A receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LTP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4 -/- mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre;ErbB4 -/- hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4 -/- mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LTP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LTP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia.
Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in ...predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.
There is an urgent need to develop effective therapies for ischemic stroke, but the complicated pathological processes after ischemia make doing so difficult. In the current study, we identified a ...novel diaryl acylhydrazone derivative, A11, which has multiple neuroprotective properties in ischemic stroke models. First, A11 was demonstrated to induce neuroprotection against ischemic injury in a dose-dependent manner (from 0.3 to 3 μM) in three in vitro experimental ischemic stroke models: oxygen glucose deprivation (OGD), hydrogen peroxide, and glutamate-stimulated neuronal cell injury models. Moreover, A11 was able to potently alleviate three critical pathological changes, apoptosis, oxidative stress, and mitochondrial dysfunction, following ischemic insult in neuronal cells. Further analysis revealed that A11 upregulated the phosphorylation levels of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in OGD-exposed neuronal cells, suggesting joint activation of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MEK)/ERK pathways. In rats with middle cerebral artery occlusion, single-dose administration of A11 (3 mg/kg per day, i.v.) at the onset of reperfusion significantly reduced the infarct volumes and ameliorated neurological deficits. Our study, for the first time, reports the anti-ischemic effect of diaryl acylhydrazone chemical entities, especially A11, which acts on multiple ischemia-associated pathological processes. Our results may provide new clues for the development of an effective therapeutic agent for ischemic stroke.
Studies on insect olfaction have increased our understanding of insect's chemosensory system and chemical ecology, and have improved pest control strategies based on insect behavior. In this study, ...we assembled the antennal transcriptomes of the lychee giant stink bug, Tessaratoma papillosa, by using next generation sequencing to identify the major olfaction gene families in this species. In total, 59 odorant receptors, 14 ionotropic receptors (8 antennal IRs), and 33 odorant binding proteins (28 classic OBPs and 5 plus-C OBPs) were identified from the male and female antennal transcriptomes. Analyses of tissue expression profiles revealed that all 59 OR transcripts, 2 of the 8 antennal IRs, and 6 of the 33 OBPs were primarily expressed in the antennae, suggesting their putative role in olfaction. The sex-biased expression patterns of these antenna-predominant genes suggested that they may have important functions in the reproductive behavior of these insects. This is the first report that provides a comprehensive resource to future studies on olfaction in the lychee giant stink bug.
Mining is among the human activities with widest environmental impacts, and mining-impacted environments are characterized by high levels of metals that can co-select for antibiotic resistance genes ...(ARGs) in microorganisms. However, ARGs in mining-impacted environments are still poorly understood. Here, we conducted a comprehensive study of ARGs in such environments worldwide, taking advantage of 272 metagenomes generated from a global-scale data collection and two national sampling efforts in China. The average total abundance of the ARGs in globally distributed studied mine sites was 1572 times per gigabase, being rivaling that of urban sewage but much higher than that of freshwater sediments. Multidrug resistance genes accounted for 40% of the total ARG abundance, tended to co-occur with multimetal resistance genes, and were highly mobile (e.g. on average 16% occurring on plasmids). Among the 1848 high-quality metagenome-assembled genomes (MAGs), 85% carried at least one multidrug resistance gene plus one multimetal resistance gene. These high-quality ARG-carrying MAGs considerably expanded the phylogenetic diversity of ARG hosts, providing the first representatives of ARG-carrying MAGs for the Archaea domain and three bacterial phyla. Moreover, 54 high-quality ARG-carrying MAGs were identified as potential pathogens. Our findings suggest that mining-impacted environments worldwide are underexplored hotspots of multidrug resistance genes.
We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for ...replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined = 1.48 × 10−48, OR = 1.90; rs9468925, Pcombined = 2.21 × 10−33, OR = 0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined = 9.72 × 10−17, OR = 1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.
•High pressure decreased the angle of α-1,4 glycosidic linkage.•High pressure increased the dihedral angles of α-1,4 glycosidic linkage.•High pressure made amylose helix be more ‘stout’.•High ...pressure made amylose polymers be more stable.•High pressure decreased intramolecular H-bonds and increased solvent-amylose H-bonds.
For more effective using of HHP (high hydrostatic pressure) in starch processing, in this study, molecular dynamics simulation was used to explore the effects of pressure on amylose molecular conformation at the atomic level. The results shown that, firstly, high pressure decreased the intramolecular hydrogen bonds and increased the amylose-solvent hydrogen bonds, which is consistent with the process of high pressure starch gelatinization. Secondly, high pressure made amylose polymers more “stout”. Meanwhile, high pressure decreased the angle of α-1,4 glycosidic linkage and increased the dihedral angles of α-1,4 glycosidic linkage, which indicates that pressure has obvious effects on amylose molecular conformation. Thirdly, high pressure made amylose polymers more stable. Moreover, in view of the results of energies, HHP may have an opposite gelatinization mechanism to heating. The results may be complementary to the existing experimental phenomena and provide theoretical guidance value for the using of HHP in starch processing.
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