Effects of Age on Compounds, Metabolites and Meat Quality in Beijing-You Chicken Breast Meat.

The physical properties, free amino acids, and metabolites of Beijing-You chicken (BYC) breast meat aged 90, 120, and 150 days were analyzed to investigate the flavor changes with age. The shear force and intramuscular fat increased from 90 to 120 days significantly. The contents of total free amino acids and essential amino acids decreased from 90 to 120 days significantly. No significant differences were detected between 120 and 150 days. The contents of sweet amino acids, bitter amino acids, and umami amino acids showed no significant differences between different ages. In addition, GC-MS and LC-MS were integrated for metabolite detection in breast meat. A total of 128, 142, and 88 differential metabolites were identified in the comparison groups of 120 d vs. 90 d, 150 d vs. 90 d, and 150 d vs. 120 d. Amino acids and lipids were the main differential metabolites. The pathway analysis showed that arginine biosynthesis, histidine metabolism, purine metabolism, and cysteine and methionine metabolism were the main pathways involved in flavor formation during BYC development. It was also found that the metabolites associated with flavor, such as methionine, cysteine, glucose, anserine, arachidonic acid, and glycerol 1-phosphate, were significantly affected by age.

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.

Proteomic Profiling of Thigh Meat at Different Ages of Chicken for Meat Quality and Development.

Chicken age contributes to the meat characteristics; however, knowledge regarding the pathways and proteins associated with meat quality and muscle development are still scarce, especially in chicken thigh meat. Hence, the objective of this study was to elucidate the intricate relationship between these traits by liquid chromatography mass spectrometry at three different ages. A total of 341 differential expressed proteins (DEPs) were screened out (fold change ≥ 1.50 or ≤0.67 and p < 0.05) among 45 thigh meat samples (15 samples per age) of Beijing-You chicken (BYC), collected at the age of 150, 300, or 450 days (D150, D300, and D450), respectively. Subsequently, based on the protein interaction network and Markov cluster algorithm (MCL) analyses, 91 DEPs were divided into 26 MCL clusters, which were associated with pathways of lipid transporter activity, nutrient reservoir activity, signaling pathways of PPAR and MAPK, focal adhesion, ECM-receptor interaction, the cell cycle, oocyte meiosis, ribosomes, taurine and hypotaurine metabolism, glutathione metabolism, muscle contraction, calcium signaling, nucleic acid binding, and spliceosomes. Overall, our data suggest that the thigh meat of BYC at D450 presents the most desirable nutritional value in the term of free amino acids (FAAs) and intramuscular fat (IMF), and a series of proteins and pathways associated with meat quality and development were identified. These findings also provide comprehensive insight regarding these traits across a wide age spectrum.

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.

Integration of GC-MS and LC-MS for metabolite characteristics of thigh meat between fast- and slow-growing broilers at marketable age.

Thigh meat from Cobb 500 broiler (Cobb) and Beijing-You chicken (BYC) at marketable age were compared to explore the impact of growth rate on meat quality. BYC had a higher water capacity, as well as lower shear forces and IMF content than Cobb, indicating that the growth rate has a significant influence on meat quality. Additionally, 144 upregulated and 44 downregulated differential metabolites were identified using gas chromatography mass spectroscopy (GC-MS) and liquid chromatography mass spectrometer (LC-MS). Moreover, we found a significant difference between the dominant expression of metabolites in the two genotypes. The highly expressed metabolites in Cobb were amino acids and their derivatives, including l-citrulline, dimethylglycine, 1,4-butanediamine, alanine, and creatine. In contrast, BYC deposited more bioactive compounds, such as, α-linolenic acid, linoleic acid, eicosapentaenoic acid, anserine, and taurine. These results indicate that meat quality and metabolite profiles differ greatly between fast- and slow-growing chickens.

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.

Development and application of arachnomelia syndrome genetic detection in four Chinese dual-purpose cattle populations.

Arachnomelia syndrome (AS) is an autosomal recessive hereditary disorder in cattle, and affected calves are usually stillborn and characterized by complex anomalies. Therefore, identification of the carrier animals based on genetic tests is important for the control and elimination of this defect. The aim of this study was to build an effective workflow to routinely screen the AS mutations in bovine MOSC1 and SUOX genes and determine individuals carrying the AS mutations in four Chinese cattle populations. By combining the fluorescence-labeled PCR and capillary electrophoresis, we established a convenient and cost-effective workflow to detect two AS casual mutations simultaneously. Sanger sequencing was further used as a validation criterion and showed that 100% of the tests (37/37) had consistent results with genotype calls determined by our established workflow. Then, 582 bulls and 1-926 cows from Chinese dual-purpose cattle populations of Simmental, Sanhe, Shuxuan, and Xinjiang Brown were subjected to AS detection. The results showed that four bulls and 11 cows in the Simmental population, and six bulls and six cows in the Sanhe population were identified as AS carriers with the MOCS1 mutation c.1224_1225delCA. However, no animal was found to carry the c.363_364insG mutation in the SUOX gene. The frequencies of AS carriers were 1.08% and 1.65% in the Simmental and Sanhe populations, respectively, with a frequency of 1.076% in four populations. The pedigree analysis found that all carriers could be traced back to a common ancestor, the German Simmental sire ROMEL. Those findings suggested that this genetic defect spread into China mainly through the wide use of ROMEL. In conclusion, the occurrence of AS has not had a wide impact on the Chinese cattle industry; however, a screening system and mating strategy should be employed to gradually eliminate this recessive gene from the Chinese dual-purpose cattle population.

IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37.

PURPOSE: Neutrophilic asthma is associated with asthma exacerbation, steroid insensitivity, and severe asthma. Interleukin (IL)-24 is overexpressed in asthma and is involved in the pathogenesis of several allergic inflammatory diseases. However, the role and specific mechanism of IL-24 in neutrophilic asthma are unclear. We aimed to elucidate the roles of IL-24 and IL-37 in neutrophilic asthma, the relationships with IL-17A and the mechanisms regulating neutrophilic asthma progression. METHODS: Purified human neutrophils were isolated from healthy volunteers, and a cell coculture system was used to evaluate the function of IL-24 in epithelium-derived IL-17A-dependent neutrophil migration. IL-37 or a small interfering RNA (siRNA) targeting IL-24 was delivered intranasally to verify the effect in a murine model of house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic asthma. RESULTS: IL-24 enhanced IL-17A production in bronchial epithelial cells via the STAT3 and ERK1/2 signaling pathways; this effect was reversed by exogenous IL-37. Anti-IL-17A monoclonal antibodies reduced neutrophil chemotaxis induced by IL-24-treated epithelial cells in vitro. Increased IL-24 and IL-17A expression in the airway epithelium was observed in HDM/LPS-induced neutrophilic asthma. IL-37 administration or IL-24 silencing attenuated neutrophilic asthma, reducing IL-17A levels and decreasing neutrophil airway infiltration, airway hyperresponsiveness, and goblet cell metaplasia. Silencing IL-24 inhibited T-helper 17 (Th17) immune responses, but not Th1 or Th2 immune responses, in the lungs of a neutrophilic asthma model. CONCLUSIONS: IL-24 aggravated neutrophilic airway inflammation by increasing epithelium-derived IL-17A production, which could be suppressed by IL-37. Targeting the IL-24/IL-17A signaling axis is a potential strategy, and IL-37 is a potential candidate agent for alleviating neutrophilic airway inflammation in asthma.

Breast Meat Fatty Acid Profiling and Proteomic Analysis of Beijing-You Chicken During the Laying Period.

The disparity in fatty acids (FA) composition exhibits a significant impact on meat quality, however, the molecular regulatory mechanisms underlying this trait in chicken are far from clear. In this study, a total of 45 female Beijing-You chicken (BYC) hens, fed on the same diet, were collected at the slaughter age of 150, 300, or 450 days (D150, D300, and D450) from sexual maturation stage to culling stage (15 birds per age). Gas chromatography-mass spectrometry (GC-MS) and tandem mass tag labeling technology based on liquid chromatography mass spectrometry (TMT-LC-MS/MS) analysis strategies were applied to profile FA compositions and to compare differential expressed proteins (DEPs) between these different slaughter ages, respectively. The FA profiling showed that increasing hen ages resulted in increased contents of both saturated and unsaturated fatty acids. Proteomic analyses showed a total of 4,935 proteins in chicken breast muscle with the false discovery rate (FDR) < 1% and 664 of them were differentially expressed (fold change > 1.50 or < 0.67 and P < 0.01). There were 410 up- and 116 down-regulated proteins in D150 vs. D300 group, 32 up- and 20 down-regulated in D150 vs. D450 group, and 72 up- and 241 down-regulated in D300 vs. D450 group. A total of 57 DEPs related to FA/lipid-related metabolisms were obtained according to the enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). These DEPs were involved in 21 significantly enriched (P < 0.05) pathways, including well-known pathways for FA synthesis (metabolism, desaturation, and elongation) and the signaling pathways for lipid metabolism (PPAR, adipocytokine, calcium, VEGF, MAPK, and Wnt). In addition, there existed several representative DEPs (FABP, FABP3, apoA-I, apoA-IV, apoC-III, apoB, VTG1, and VTG2) involved in the regulation of FA/lipid transportation. The construction of the interaction networks indicated that HADH, ACAA2, HADHA, ACSL1, CD36, CPT1A, PPP3R1, and SPHK1 were the key core nodes. Finally, eight DEPs were quantified using parallel reaction monitoring (PRM) to validate the results from TMT analysis. These results expanded our understanding of how the laying age affects the FA compositions and metabolism in hen breast meat.

Blood Lead and High-Density Lipoprotein Concentrations in Relation to Human Blood Pressure: A Cross Sectional Study.

Background: While the relationship between blood pressure and blood lead has been studied more extensively, the effect of high-density lipoprotein (HDL) concentration on this relationship remains uncertain. Therefore, this study aimed to determine the effect of HDL concentration on the relationship between blood lead and blood pressure. Methods: The research used cross-sectional data from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES), which included 16,451 participants aged 20-60 years. Multivariable linear regression was used to evaluate the correlation among blood lead, systolic blood pressure (SBP), and diastolic blood pressure (DBP). HDL concentration was determined by low HDL concentration (≤ 49 mg/dl) and high HDL concentration (>49 mg/dl) stratified. The effect of HDL concentration was assessed by an interaction test between blood lead and SBP in multivariable linear regression. Results: In this cross-sectional research, we identified a positive correlation between blood lead and SBP, but not DBP. The relationship between blood lead and SBP was different in the group with low and high HDL concentrations (ß: 0.21 95% Cl:-0.05-0.46 vs. ß:0.47 95% Cl: 0.15-0.79). In addition, high HDL significantly altered the positive correlation between blood lead and SBP (P-value of interaction < 0.001). Conclusion: The study suggests an interaction between HDL and blood lead in elevating SBP, which may have important clinical implications.

SENP6 induces microglial polarization and neuroinflammation through de-SUMOylation of Annexin-A1 after cerebral ischaemia-reperfusion injury.

BACKGROUND: Previous data have reported that Sentrin/SUMO-specific protease 6 (SENP6) is involved in ischaemic brain injury and induces neuronal apoptosis after cerebral ischaemia, but the role of SENP6 in microglia-induced neuroinflammation and its underlying mechanism remain poorly understood. This research systematically explored the function and potential mechanism of SENP6 in microglia-induced neuroinflammation after ischaemic stroke. RESULTS: We first identified an increased protein level of SENP6 in microglia after cerebral ischaemia. Then, we demonstrated that SENP6 promoted detrimental microglial phenotype polarization. Specifically, SENP6-mediated de-SUMOylation of ANXA1 targeted the IκB kinase (IKK) complex and selectively inhibited the autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression. In addition, downregulation of SENP6 in microglia effectively reduced cocultured neuronal damage induced by ischaemic stroke. More importantly, we employed an AAV-based technique to specifically knockdown SENP6 in microglia/macrophages, and in vivo experiments showed that SENP6 inhibition in microglia/macrophages notably lessened brain ischaemic infarct size, decreased neurological deficit scores, and ameliorated motor and cognitive function in mice subjected to cerebral ischaemia surgery. CONCLUSION: We demonstrated a previously unidentified mechanism by which SENP6-mediated ANXA1 de-SUMOylation regulates microglial polarization and our results strongly indicated that in microglia, inhibition of SENP6 may be a crucial beneficial therapeutic strategy for ischaemic stroke.

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.

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.

Population Genomic Sequencing Delineates Global Landscape of Copy Number Variations that Drive Domestication and Breed Formation of in Chicken.

Copy number variation (CNV) is an important genetic mechanism that drives evolution and generates new phenotypic variations. To explore the impact of CNV on chicken domestication and breed shaping, the whole-genome CNVs were detected via multiple methods. Using the whole-genome sequencing data from 51 individuals, corresponding to six domestic breeds and wild red jungle fowl (RJF), we determined 19,329 duplications and 98,736 deletions, which covered 11,123 copy number variation regions (CNVRs) and 2,636 protein-coding genes. The principal component analysis (PCA) showed that these individuals could be divided into four populations according to their domestication and selection purpose. Seventy-two highly duplicated CNVRs were detected across all individuals, revealing pivotal roles of nervous system (NRG3, NCAM2), sensory (OR), and follicle development (VTG2) in chicken genome. When contrasting the CNVs of domestic breeds to those of RJFs, 235 CNVRs harboring 255 protein-coding genes, which were predominantly involved in pathways of nervous, immunity, and reproductive system development, were discovered. In breed-specific CNVRs, some valuable genes were identified, including HOXB7 for beard trait in Beijing You chicken; EDN3, SLMO2, TUBB1, and GFPT1 for melanin deposition in Silkie chicken; and SORCS2 for aggressiveness in Luxi Game fowl. Moreover, CSMD1 and NTRK3 with high duplications found exclusively in White Leghorn chicken, and POLR3H, MCM9, DOCK3, and AKR1B1L found in Recessive White Rock chicken may contribute to high egg production and fast-growing traits, respectively. The candidate genes of breed characteristics are valuable resources for further studies on phenotypic variation and the artificial breeding of chickens.

UHPLC-QTOF/MS-based comparative metabolomics in pectoralis major of fast- and slow-growing chickens at market ages.

The molecular regulatory mechanism underlying meat quality between different chicken genotypes remains elusive. This study aimed to identify the differences in metabolites and pathways in pectoralis major (breast muscle) between a commercial fast-growing chicken genotype (Cobb500) and a slow-growing Chinese native chicken genotype (Beijing-You chickens, BYC) at market ages respectively based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF/MS). Eighteen metabolites were identified as potential biomarkers between BYC and Cobb500 at market ages. Among them, L-cysteine exhibited a higher relative intensity in BYC compared with Cobb500 and was enriched into 10 potential flavor-associated KEGG pathways. In addition, the glycerophospholipid metabolism pathway was found to be associated with chicken meat flavor and the accumulation of sn-glycerol 3-phosphate and acetylcholine was more predominant in BYC than that in Cobb500, which were catalyzed by glycerophosphocholine phosphodiesterase (GPCPD1, EC:3.1.4.2), choline O-acetyltransferase (CHAT, EC:2.3.1.6), and acetylcholinesterase (ACHE, EC:3.1.1.7). Overall, the present study provided some metabolites and pathways for further investigating the roles of the differences in meat flavor quality in breast muscle between Cobb500 and BYC at market ages.

The prognostic significance of pretransplantation evaluation of IPSS-R and WPSS in patients with myelodysplastic syndrome undergoing allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: This study aimed to explore the prognostic value of the revised international prognostic scoring system (IPSS-R) and the WHO prognostic scoring system (WPSS) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The clinical data of 184 patients with MDS who received allo-HSCT from July 2016 to June 2019 were retrospectively analyzed. IPSS-R and WPSS were performed at diagnosis and before transplantation. The prognostic values of IPSS-R and WPSS and potential risk factors were explored. Results: With a median follow-up of 21.9 (0.5-47.5) months, the two-year overall survival (OS) and progression-free survival (PFS) rates were (75.1±3.4)% and (71.6±3.6)% , respectively. The two-year cumulative relapse rate and nonrelapse mortality rate were (11.9±0.1)% and (16.5±0.1)% , respectively. There were no significant differences in OS and PFS between the IPSS-R ≤3.5 and >3.5 groups at diagnosis (P=0.409; P=0.724). No significant differences in OS and PFS between the WPSS ≤2 and >2 groups (P=0.426; P=0.726) were observed as well. When the patients were reevaluated before transplantation, the OS and PFS of the IPSS-R ≤3.5 group were significantly better than >3.5 group [OS: (88.6±4.1)% vs (65.8±5.3)% , P=0.003; PFS: (87.6±4.2)% vs (60.5±5.8)% , P=0.002]. However, there were no significant differences in OS and PFS among the WPSS ≤2 and >2 groups (P=0.584; P=0.565). In addition, the OS and PFS of the improved group based on IPSS-R were significantly better than those of the unimproved group before transplantation [OS: (83.8±4.6)% vs (69.3±5.8)% , P=0.027; PFS: (82.8±4.4)% vs. (64.0±7.2)% , P=0.006]. Multivariate analysis indicated that a pretransplant IPSS-R of >3.5 (P=0.021, HR=2.510, 95% CI 1.151-5.476) and TP53 mutation (P=0.047, HR=2.460, 95% CI 1.014-5.971) were independent risk factors for OS, whereas a pretransplant IPSS-R of >3.5 (P=0.017, HR=2.457, 95% CI 1.175-5.141) and pretransplant cytogenetic poor and very poor (P=0.008, HR=2.765, 95% CI 1.305-5.856) were independent risk factors for PFS. Conclusion: A pretransplantation evaluation of IPSS-R could help determine the prognosis of patients with MDS undergoing allo-HSCT. In addition, patients with improved IPSS-R scores before undergoing allo-HSCT had a better prognosis.

Cough Inhibition Activity of Schisandra chinensis in Guinea Pigs.

Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. (S. chinensis), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis, EE was divided into four fractions according to the polarity: petroleum ether extract (PEE), ethyl acetate extract (ECE), n-butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1, 3, 9, 10, 17 were evaluated on citric acid induced acute cough guinea pigs. The results showed that the antitussive activity of EE was almost all contained in PEE and ECE. The 16 major peaks in PEE were identified as 15 lignans (1-12 and 14-16) and 1 triterpene (compound 13), and 3 major peaks (1, 17, and 18) in ECE were also identified as lignans. Three doses of five compounds brought about a significant decrease in number of cough efforts (P < .01), and the cough inhibition rates were between 40.9% and 85.1%. Therefore, lignans are the antitussive ingredients of S. chinensis.

Comprehensive Proteomic Characterization of the Pectoralis Major at Three Chronological Ages in Beijing-You Chicken.

Chronological age is one of the important factors influencing muscle development and meat quality in chickens. To evaluate the protein expression profiles during skeletal muscle development, we performed a tandem mass tag (TMT)-based quantitative proteomic strategy in pectoralis major (breast muscle) of Beijing-You chicken (BYC) at the chronological age of 90, 120, and 150 days. Each chronological age contained 3 pooling samples or 15 birds (five birds per pooling sample). A total of 1,413 proteins were identified in chicken breast muscle with FDR < 1% and 197 of them were differentially expressed (fold change ≥1.2 or ≤0.83 and p < 0.05). There were 110 up- and 71 down-regulated proteins in 120 d vs 90 d group, 13 up- and 10 down-regulated proteins in 150 d vs 120 d group. The proteomic profiles of BYC at 120 d were very similar to those at 150 d and highly different from those at 90 d, suggesting that 120 d might be an important chronological age for BYC. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these differentially expressed proteins were mainly involved in the pathway of glycolysis/gluconeogenesis, adrenergic signaling in cardiomyocytes, focal adhesion, oocyte meiosis and phagosome. Furthermore, some DEPs were quantified using parallel reaction monitoring (PRM) to validate the results from TMT analysis. In summary, these results provided some candidate protein-coding genes for further functional validation and contribute to a comprehensive understanding of muscle development and age-dependent meat quality regulation by proteins in chickens.

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.