IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Dietary metabolizable energy and crude protein levels affect the performance, egg quality and biochemical parameters of a dual-purpose chicken.

Effects of dietary metabolizable energy (ME) and crude protein (CP) level on performance, egg quality and biochemical parameters were studied in a dual-purpose chicken-Beijing You Chicken (BYC) at peak laying period. A 3 × 3 factorial experiment was arranged, including 3 levels of dietary ME (11.31, 11.51, 11.71 MJ/kg) and 3 levels of dietary CP (14%, 15%, 16%). The results showed that dietary CP level alone and the interaction of ME by CP affected the total feed intake (TFI) during 27-30 wks, dietary ME level affected the mortality rate of 27-34 wks of age (p = 0.018), with the highest mortality rate found in 11.31 MJ/kg group (3.10%). The albumen height (AH), Haugh unit (HU) and egg grade (EG) of 16% group was higher than those in 14% and 15% groups (p < 0.05). Serum immunoglobulin G content in 11.31 MJ/kg group was lower than in 11.51 MJ/kg and 11.71 MJ/kg groups (p = 0.037). The present study suggested that dietary levels of 11.51 MJ/kg ME and 16.0% CP are enough to maintain the performance and egg quality of BYC at peak laying period. 11.31 MJ/kg ME increased the mortality of the chicken, which may be related to the decrease of the humoral immune function and antioxidative capability.

The effect of protease inhibitors-based antiretroviral therapy on serum/plasma interleukin-6 levels among PLHIV: a systematic review and meta-analysis.

Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ2 test) and I2 statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I2 = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4+ counts < 350 cell/mm3 , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.

Transcriptional analyses provide novel insights into the transgenerational effects of Poly (I:C) on chickens.

Pathogenic microorganisms that are ubiquitous in the environment threaten human health and food safety. Polyinosinic:polycytidylic acid (Poly (I:C)) is a macromolecule with a double-stranded RNA structure, which is often used to simulate viruses. Our previous study found that Poly (I:C) maternal stimulation could affect the reproduction of laying hens and their offspring, but the underlying mechanism needed to be explored. In the present study, splenic transcriptomes were sequenced and analyzed from two groups (Poly (I:C) treatment as the challenged group and saline treatment as the control) and in three generations (maternal stimulated F0 hens, unchallenged F1 and F2 generations). The results showed that Poly (I:C) maternal stimulation affected gene expression patterns in laying hens and their offspring. A total of 27 differentially expressed genes (DEGs) with the same regulating trend were discovered in the F0 and F1 generations, indicating an influence of the intergenerational transmission effect. Functional enrichment analysis of Gene Ontology (GO) showed that lymphocyte differentiation, positive regulation of leukocyte differentiation, positive regulation of MAPK cascade, and T cell differentiation were the common biological processes between F0 and F1 generations, revealing Poly (I:C) could affect the immunity of the treated F0 hens and the unchallenged subsequent generations. Further study showed that pathways associated with growth, development, biosynthesis, and metabolism of F2 chicks were also affected by Poly (I:C) maternal stimulation. Correlation analysis between DEGs and reproductive traits revealed that PHLDA2 (pleckstrin homology-like domain family A member 2) and PODN (podocan) with inheritable effect were highly correlated with egg-laying rate and egg weight in F1 hens, suggesting their potential long-term role in regulating reproductive traits. ARHGAP40, FGB, HRH4, PHLDA2, PODN, NTSR1, and NMU were supposed to play important roles in regulating chickens' immunity and reproductive traits. This study reveals the far-reaching effect on transcriptome induced by Poly (I:C), reflecting the influence of the mother's living environment on the offspring. It is an important reference for future research into the multi-generational transmission of maternal stimulation and harmful environmental factors.

Long-lasting effects of lipopolysaccharide on the reproduction and splenic transcriptome of hens and their offspring.

Lipopolysaccharide (LPS) is ubiquitous in the environment and is released after the death of gram-negative bacteria, which may be related to inflammation and immunosuppression. However, its impact on the reproduction of animals and their offspring, especially the underlying mechanism need further elucidation. Here, we used laying hens as a model organism to investigate the effects of maternal exposure to LPS (LPS maternal stimulation) on animal and their offspring's immunity and reproductive performance, as well as the regulatory role of the transcriptome. We found that the LPS maternal stimulation could reduce the egg-laying rate of hens and their offspring, especially during the early and late laying stages. The transcriptome study of the spleen in F0, F1 and F2 generations showed that the maternal stimulation of the LPS affects the patterns of gene expression in laying hens, and this change has a long-lasting effect. Further analysis of DEGs and their enrichment pathways found that the LPS maternal stimulation mainly affects the reproduction and immunity of laying hens and their offspring. The DEGs such as AVD, HPS5, CATHL2, S100A12, EXFABP, RSFR, LY86, PKD4, XCL1, FOS, TREM2 and MST1 may play an essential role in the regulation of the immunity and egg-laying rate of hens. Furthermore, the MMR1L3, C3, F13A1, LY86 and GDPD2 genes with heritable effects are highly correlated with the egg-laying rate, may have an important reference value for further research. Our study reveals the profound implications of LPS exposure on immunity and reproduction of offspring, elaborating the impact of immune alteration on the egg-laying rate, emphasizing the regulatory role of intergenerational transmission of the transcriptome, implying that the environment parents being exposed to has an important impact on offspring.

STAT1 participates in the induction of substance P expression in airway epithelial cells by respiratory syncytial virus.

PURPOSE: The regulation effect and mechanism of respiratory syncytial virus (RSV) infection on the expression of tachykinin substance P (SP) in airway epithelial cells was investigated. METHODS: The regulation of SP expression by RSV was investigated in the BEAS-2B airway epithelial cell line. RT-qPCR, immunofluorescence, and ELISA assay were used to examine the expression of the SP encoding gene TAC1, the intracellular SP protein expression, and the extracellular SP secretion. RESULTS: The mRNA expression of TAC1 and the intracellular SP protein level in BEAS-2B cells were significantly enhanced by RSV infection with multiplicity of infection (MOI) values of both 1 and 0.1 at 48 hours post infection. Heat-inactivated and UV-inactivated RSV, but not live RSV, significantly induced SP secretion in both control BEAS-2B cells and CX3CR1 receptor knockout cells without affecting the TAC1 gene expression or cell viability. RSV G protein (2-10 µg/ml) and fractalkine (10-50 ng/ml), both CX3CR1 receptor ligands, did not affect SP secretion in BEAS-2B cells. Inhibition of STAT1 phosphorylation by fludarabine (1 µM) markedly reduced the RSV-induced TAC1 gene expression and antagonized the inhibition of RSV replication by interferon-α in BEAS-2B cells. CONCLUSIONS: STAT1 participates in RSV infection-induced SP expression in airway epithelial cells.

Reducing cost and time to diagnosis and treatment of obstructive sleep apnea using ambulatory sleep study: a Singapore sleep centre experience.

PURPOSE: The current gold standard for diagnosis of obstructive sleep apnea (OSA) is overnight in laboratory polysomnography (PSG). However, PSGs are expensive, labor-intensive, and have long wait times. An ambulatory sleep study device, the WatchPAT, has been shown to have high correlation for sleep indices measured compared with PSG (AASM, 2016). Use of the WatchPAT could potentially lead to shorter waiting times and earlier diagnosis of OSA (Lancet Resp Med 3:310-8, 2015). Our study aimed to investigate if WatchPAT reduces time to diagnosis and treatment of OSA in a tertiary healthcare setting. A secondary aim was to investigate the cost-benefit of an ambulatory sleep study. METHODS: All patients who underwent diagnostic sleep studies in a single tertiary institution from 2014 to 2017 were retrospectively reviewed. Baseline characteristics and time from ordering of sleep study to prescription of continuous positive airway pressure were recorded. Data were categorized into two groups by type of diagnostic sleep study, PSG, and WatchPAT. The time to treatment and cost for diagnosis of OSA were compared between groups with the Paired T test/Wilcoxon signed-rank test. RESULTS: Of 1898 patients who had diagnostic sleep studies over a 4-year period, 1660 patients (88%) underwent PSG and 238 patients (12%) underwent WatchPAT. Patients in the WatchPAT group had a shorter time to diagnosis (21 days versus 79.8 days, p < 0.001) and treatment (46.3 days versus 118.4 days, p < 0.001) compared to the PSG group. Cost-benefit calculation showed that this earlier treatment led to cost-saving of US $1179.50 per patient. CONCLUSION: An ambulatory sleep study is an option for earlier access to diagnosis and treatment of OSA with the potential of considerable cost savings.

Genomic analyses and biological validation of candidate genes for rectal temperature as an indicator of heat stress in Holstein cattle.

Heat stress is a major cause of welfare issues and economic losses to the worldwide dairy cattle industry. Genetic selection for heat tolerance has a great potential to positively affect the dairy industry, as the gains are permanent and cumulative over generations. Rectal temperature (RT) is hypothesized to be a good indicator trait of heat tolerance. Therefore, this study investigated the genetic architecture of RT by estimating genetic parameters, performing genome-wide association studies, and biologically validating potential candidate genes identified to be related to RT in Holstein cattle. A total of 33,013 RT records from 7,598 cows were used in this study. In addition, 1,114 cows were genotyped using the Illumina 150K Bovine BeadChip (Illumina, San Diego, CA). Rectal temperature measurements taken in the morning (AMRT) and in the afternoon (PMRT) are moderately heritable traits, with estimates of 0.09 ± 0.02 and 0.04 ± 0.01, respectively. These 2 traits are also highly genetically correlated (r = 0.90 ± 0.08). A total of 10 SNPs (located on BTA3, BTA4, BTA8, BTA13, BTA14, and BTA29) were found to be significantly associated with AMRT and PMRT. Subsequently, gene expression analyses were performed to validate the key functional genes identified (SPAG17, FAM107B, TSNARE1, RALYL, and PHRF1). This was done through in vitro exposure of peripheral blood mononuclear cells (PBMC) to different temperatures (37°C, 39°C, and 42°C). The relative mRNA expression of 2 genes, FAM107B and PHRF1, significantly changed between the control and heat stressed PBMC. In summary, RT is heritable, and enough genetic variability exists to enable genetic improvement of heat tolerance in Holstein cattle. Important genomic regions were identified and biologically validated; FAM107B and PHRF1 are the main candidate genes identified to influence heat stress response in dairy cattle.

mTOR/NF-κB signaling pathway protects hippocampal neurons from injury induced by intermittent hypoxia in rats.

OBJECTIVE: To expound the roles of mTOR and NF-kB signaling pathway in intermittent hypoxia (IH)-induced damage of hippocampal neurons. METHODS: For rat experiments, mTOR inhibitor (Rapamycin, Rapa) and NF-κB signaling inhibitor (ammonium pyrrolidine dithiocarbamate, PDTC) were applied to inhibit mTOR and NF-κB signaling, respectively. For neuron experiments, hippocampal neurons from rat were successfully cultured. Different concentrations of Rapa and PDTC were added to the cultured hippocampal neurons. Rat or primary hippocampal neurons were exposed to normoxic or IH conditions after administration of Rapa and PDTC. The effects of Rapa and PDTC administration on learning and memory ability of rats and hippocampal injury after IH exposure were assayed by Morris water maze and H&E staining. Electron microscope was utilized to examine primary hippocampal neuron ultrastructure changes after IH exposure and Rapa or PDTC administration. The expressions of NF-κB-p65, IκBα, IKKß, BDNF, TNF-α, IL-1ß, PSD-95 and SYN in hippocampal neurons were examined. RESULTS: Compared with normal control rats or neurons, IH-treated group had elevated expression levels of NF-kB, TNF-α and IL-1ß and suppressed expression level of BDNF, PSD-95 and SYN. These results were reversed upon pre-treatment with Rapa and PDTC. Furthermore, IκBα and IKKß expressions were down-regulated in IH group. No notable difference was manifested in PDTC pre-treatment group, while a prominent increase was shown after Rapa pre-administration. CONCLUSION: The administration of PDTC and Rapa could prevent IH-induced hippocampal neuron impairment, indicating that inhibition of the mTOR and NF-κB pathway may likely act as a therapeutic target for obstructive sleep apnea.

Genome-wide analysis reveals molecular convergence underlying domestication in 7 bird and mammals.

BACKGROUND: In response to ecological niche of domestication, domesticated mammals and birds developed adaptively phenotypic homoplasy in behavior modifications like fearlessness, altered sociability, exploration and cognition, which partly or indirectly result in consequences for economic productivity. Such independent adaptations provide an excellent model to investigate molecular mechanisms and patterns of evolutionary convergence driven by artificial selection. RESULTS: First performing population genomic and brain transcriptional comparisons in 68 wild and domesticated chickens, we revealed evolutionary trajectories, genetic architectures and physiologic bases of adaptively behavioral alterations. To extensively decipher molecular convergence on behavioral changes thanks to domestication, we investigated selection signatures in hundreds of genomes and brain transcriptomes across chicken and 6 other domesticated mammals. Although no shared substitution was detected, a common enrichment of the adaptive mutations in regulatory sequences was observed, presenting significance to drive adaptations. Strong convergent pattern emerged at levels of gene, gene family, pathway and network. Genes implicated in neurotransmission, semaphorin, tectonic protein and modules regulating neuroplasticity were central focus of selection, supporting molecular repeatability of homoplastic behavior reshapes. Genes at nodal positions in trans-regulatory networks were preferably targeted. Consistent down-regulation of majority brain genes may be correlated with reduced brain size during domestication. Up-regulation of splicesome genes in chicken rather mammals highlights splicing as an efficient way to evolve since avian-specific genomic contraction of introns and intergenics. Genetic burden of domestication elicits a general hallmark. The commonly selected genes were relatively evolutionary conserved and associated with analogous neuropsychiatric disorders in human, revealing trade-off between adaption to life with human at the cost of neural changes affecting fitness in wild. CONCLUSIONS: After a comprehensive investigation on genomic diversity and evolutionary trajectories in chickens, we revealed basis, pattern and evolutionary significance of molecular convergence in domesticated bird and mammals, highlighted the genetic basis of a compromise on utmost adaptation to the lives with human at the cost of high risk of neurophysiological changes affecting animals' fitness in wild.

Genome-wide characterization of copy number variations in the host genome in genetic resistance to Marek's disease using next generation sequencing.

BACKGROUND: Marek's disease (MD) is a highly neoplastic disease primarily affecting chickens, and remains as a chronic infectious disease that threatens the poultry industry. Copy number variation (CNV) has been examined in many species and is recognized as a major source of genetic variation that directly contributes to phenotypic variation such as resistance to infectious diseases. Two highly inbred chicken lines, 63 (MD-resistant) and 72 (MD-susceptible), as well as their F1 generation and six recombinant congenic strains (RCSs) with varied susceptibility to MD, are considered as ideal models to identify the complex mechanisms of genetic and molecular resistance to MD. RESULTS: In the present study, to unravel the potential genetic mechanisms underlying resistance to MD, we performed a genome-wide CNV detection using next generation sequencing on the inbred chicken lines with the assistance of CNVnator. As a result, a total of 1649 CNV regions (CNVRs) were successfully identified after merging all the nine datasets, of which 90 CNVRs were overlapped across all the chicken lines. Within these shared regions, 1360 harbored genes were identified. In addition, 55 and 44 CNVRs with 62 and 57 harbored genes were specifically identified in line 63 and 72, respectively. Bioinformatics analysis showed that the nearby genes were significantly enriched in 36 GO terms and 6 KEGG pathways including JAK/STAT signaling pathway. Ten CNVRs (nine deletions and one duplication) involved in 10 disease-related genes were selected for validation by using quantitative real-time PCR (qPCR), all of which were successfully confirmed. Finally, qPCR was also used to validate two deletion events in line 72 that were definitely normal in line 63. One high-confidence gene, IRF2 was identified as the most promising candidate gene underlying resistance and susceptibility to MD in view of its function and overlaps with data from previous study. CONCLUSIONS: Our findings provide valuable insights for understanding the genetic mechanism of resistance to MD and the identified gene and pathway could be considered as the subject of further functional characterization.

Cardioprotective effects of timosaponin B-II isolated from Anemarrhena rhizome in a zebrafish model.

Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.

Marek's Disease Virus Infection Induced Mitochondria Changes in Chickens.

Mitochondria are crucial cellular organelles in eukaryotes and participate in many cell processes including immune response, growth development, and tumorigenesis. Marek's disease (MD), caused by an avian alpha-herpesvirus Marek's disease virus (MDV), is characterized with lymphomas and immunosuppression. In this research, we hypothesize that mitochondria may play roles in response to MDV infection. To test it, mitochondrial DNA (mtDNA) abundance and gene expression in immune organs were examined in two well-defined and highly inbred lines of chickens, the MD-susceptible line 72 and the MD-resistant line 63. We found that mitochondrial DNA contents decreased significantly at the transformation phase in spleen of the MD-susceptible line 72 birds in contrast to the MD-resistant line 63. The mtDNA-genes and the nucleus-genes relevant to mtDNA maintenance and transcription, however, were significantly up-regulated. Interestingly, we found that POLG2 might play a potential role that led to the imbalance of mtDNA copy number and gene expression alteration. MDV infection induced imbalance of mitochondrial contents and gene expression, demonstrating the indispensability of mitochondria in virus-induced cell transformation and subsequent lymphoma formation, such as MD development in chicken. This is the first report on relationship between virus infection and mitochondria in chicken, which provides important insights into the understanding on pathogenesis and tumorigenesis due to viral infection.

Metabolomic profiling of rat urine after oral administration of the prescription antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS.

Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on traditional Chinese medicine. Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis. As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. Fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkage t", variable importance in projection and partial least-squares discriminant analysis. N-Acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies.

Comparison of temporary abdominal aortic occlusion with internal iliac artery occlusion for patients with placenta accreta - a non-randomised prospective study.

BACKGROUND: To compare the efficacy of temporary abdominal aortic occlusion with internal iliac artery occlusion for the management of placenta accreta. PATIENTS AND METHODS: 105 patients with placenta accreta were selected for treatment with temporary abdominal aortic occlusion (n = 57, group A) or bilateral iliac artery occlusion (n = 48, group B). Temporary abdominal aortic and internal iliac artery balloon occlusions were performed during caesarean sections. Data regarding the clinical success, blood loss, blood transfusion, balloon insertion time, fluoroscopy time, balloon occlusion time, foetal radiation dose, and complications were collected. RESULTS: Temporary abdominal aortic occlusion and bilateral internal iliac artery occlusion were technically successful in all patients. The amount of blood loss (P < 0.001), amount of blood transfusion (P < 0.001), balloon insertion time (P < 0.001), foetal radiation dose (P < 0.001) and fluoroscopy time (P < 0.01) in group A were significantly lower than those of patients in group B. No marked differences were found between these 2 groups with respect to age, mean postoperative hospital stay, balloon occlusion time, and Apgar score (p > 0.05). CONCLUSIONS: Temporary abdominal aortic balloon occlusion resulted in better clinical outcomes with less blood loss, blood transfusion, balloon insertion time, fluoroscopy time and foetal radiation dose than those in bilateral internal iliac balloon occlusion.
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Highly stereoselective construction of novel dispirooxindole-imidazolidines via self-1,3-dipolar cyclization of ketimines.

An acid-promoted self-1,3-dipolar cycloaddition of ketimines derived from isatins and benzylamines was successfully developed to assemble unprecedented dispirooxindole-imidazolidine ring systems. Generally, excellent diastereoselectivities (only a single stereoisomer formed) and good yields (up to 94%) were obtained. Consequently, this self-1,3-dipolar cycloaddition protocol offers facile access to a novel dispiroheterocyclic skeleton.

Direct sequencing of DNA pooling for screening highly informative SNPs in dairy cattle.

In this study, 139 bovine single nuclear polymorphisms (SNPs) were firstly selected and then directly sequenced using DNA pooling. Based on the ratio of two signal peak values, 92 SNPs with the ratio over 1/2 were considered as potential highly informative markers. To further verify the reliability of screening system, 59 SNP markers were genotyped in 122 Holstein cattle using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) method. The results showed that 56 SNPs had a call rate higher than 85%. The minor allele frequency (MAF) of these 56 markers ranged from 0.27 to 0.5, with an average of 0.41; and in which 54 markers had a MAF over 0.3, covering 96.4% of this group of markers (54/56). Our findings indicate that direct sequencing of DNA pooling is a useful and efficient tool for identifying highly informative SNPs.

Hydrogen sulfide attenuates surgical trauma-induced inflammatory response and cognitive deficits in mice.

BACKGROUND: It has been increasingly reported that peripheral surgical trauma triggers neuroinflammatory processes associated with postoperative cognitive dysfunction, and that mitigating the neuroinflammatory effects of surgery prevents surgery-induced cognitive dysfunction. Endogenously produced hydrogen sulfide (H2S) has multiple functions in the brain, and an increasing number of studies have demonstrated its anti-inflammatory effects. The present study was designed to investigate the effects of sodium hydrosulfide (NaHS), an H2S donor, on the cognitive impairment of mice as they experience neuroinflammatory changes induced by surgery. METHODS: Each mouse received 5 mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection once daily, 3 d before surgery, on the day of surgery, and for 3 d afterward. We assessed cognitive function using a Morris water maze and evaluated expression of proinflammatory cytokines tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in the serum and hippocampus. We performed each test 1, 3, and 7 d after surgery. RESULTS: Hippocampal-dependent memory impairment in mice after surgery was associated with increased serum proinflammatory cytokines, as well as proinflammatory cytokine expression in the hippocampus. Presurgery treatment with NaHS, an H2S donor, significantly attenuated surgery-induced memory impairment and expression of proinflammatory cytokines in the serum and hippocampus. CONCLUSIONS: These findings suggest that intraperitoneal injections of NaHS could significantly mitigate surgery-induced memory impairment in mice, which is strongly associated with reduced levels of serum and hippocampal proinflammatory cytokines.

The detection and elimination of flavin-containing monooxygenase 3 gene T329S mutation in the Beijing You chicken.

In this study, using a newly developed TaqMan-based real-time PCR method for the T329S mutation in the flavin-containing monooxygenase 3 (FMO3) gene, a marker-assisted selective breeding program against the unfavorable T allele was implemented in the Beijing You chicken breeding stock from 2010 to 2012. A total of 2,359 breeder candidate chickens were detected. After 1-generation culling in both males and females and 2-generation culling only in males, genotyping results in 2013 showed that there still remained a low unfavorable allele frequency of 0.022 in this population. The results indicated that to ensure a complete eradication of the defective tainting mutation in FMO3 out of the Beijing You population, more strict breeding and management schemes should be carried out in the future.