[Efficacy and safety analysis of P-GemDOx regimen and stratified prognosis in patients with early extranodal NK/T cell lymphoma].

Objective: To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . Methods: A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. Results: After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (P<0.001) between the POD<24 group (n=14) and the POD≥24 group (n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion: This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

DNA methylation promotes the expression of PPARγ transcript 1 at least in part by preventing NRF1 binding to the promoter P1 of chicken PPARγ gene.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of adipogenesis. Our previous study revealed that chicken PPARγ has 3 alternative promoters named as P1, P2, and P3, and the DNA methylation of promoter P3 was negatively associated with PPARγ mRNA expression in abdominal adipose tissue (AAT). However, the methylation status of promoters P1 and P2 is unclear. Here we assessed promoter P1 methylation status in AAT of Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF). The results showed that promoter P1 methylation differed in AAT between the lean and fat lines of NEAUHLF at 7 wk of age (p < 0.05), and AAT expression of PPARγ transcript 1 (PPARγ1), which was derived from the promoter P1, was greatly higher in fat line than in lean line at 2 and 7 wk of age. The results of the correlation analysis showed that P1 methylation was positively correlated with PPARγ1 expression at 7 wk of age (Pearson's r = 0.356, p = 0.0242), suggesting P1 methylation promotes PPARγ1 expression. To explore the underlying molecular mechanism of P1 methylation on PPARγ1 expression, bioinformatics analysis, dual-luciferase reporter assay, pyrosequencing, and electrophoresis mobility shift assay (EMSA) were performed. The results showed that transcription factor NRF1 repressed the promoter activity of the unmethylated P1, but not the methylated P1. Of all the 4 CpGs (CpG48, CpG49, CpG50, and CpG51), which reside within or nearby the NRF1 binding sites of the P1, only CpG49 methylation in AAT was remarkably higher in the fat line than in lean line at 7 wk of age (3.18 to 0.57, p < 0.05), and CpG49 methylation was positively correlated with PPARγ1 expression (Pearson's r = 0.3716, p = 0.0432). Furthermore, EMSA showed that CpG49 methylation reduced the binding of NRF1 to the P1. Taken together, our findings illustrate that P1 methylation promotes PPARγ1 expression at least in part by preventing NRF1 from binding to the promoter P1.

[Association between HBV viral load and severity of liver inflammation in patients with chronic hepatitis B virus infection].

Objective: To explore the relationship and dynamic changes between virological markers and hepatic pathological damage due to host anti-hepatitis B virus (HBV) immunity in the natural course of disease in chronic HBV infected patients. Methods: Two hundred and thirty-eight adult chronic HBV-infected patients who underwent liver biopsy from January 2016 to June 2022 in Taizhou Hospital, Zhejiang Province, were retrospectively selected. General clinical data such as age, gender, platelets, ALT, AST, albumin, HBV DNA, qHBsAg, HBeAg, and liver pathology diagnostic indexes such as the grade of liver necroinflammation and liver fibrotic stages of the patients were collected. The patients were grouped according to HBeAg status, and subgrouped according to different grades of liver necroinflammation and different HBV DNA loads. Statistical analyses were performed to compare the differences in HBV virologic marker levels between the groups, and the correlation between them and the indicators of hepatic inflammatory injury, such as ALT,AST, and the grade of liver necroinflammation in the patients. Results: The levels of HBV virological markers in HBeAg-positive patients with moderate or higher liver necroinflammatory grade (G≥2) were significantly lower than those with mild (no) liver necroinflammatory grade (G < 2) (P < 0.01); whereas the opposite trend was observed in HBeAg-negative patients, with the levels of HBV DNA, and qHBsAg in the G≥2 subgroup being significantly higher than those in the G < 2 subgroup (P < 0.01). Correspondingly, HBV DNA level and qHBsAg showed weak to moderately strong negative correlation with liver necroinflammatory grade and AST which was an indicator of hepatic inflammatory injury in HBeAg-positive patients (P < 0.05); whereas in HBeAg-negative patients, they showed weak to moderately strong positive correlation with hepatic inflammatory activity and ALT, AST (P < 0.001), in which qHBsAg showed only a weak positive correlation with patients' liver necroinflammatory grade (P = 0.003). Further subgroup analyses of HBeAg-positive patients according to whether the HBV DNA level was > 2×10(6) IU/ml showed weak to moderate negative correlations between HBV virological markers and liver necroinflammatory grade as well as ALT and AST in the subgroup of patients with HBV DNA > 2×10(6) IU/ml (P < 0.05); however, the negative correlation disappeared in patients who were still HBeAg positive and had HBV DNA ≤ 2×10(6) IU/ml. Moreover, HBV DNA and ALT, HBeAg and AST showed moderate positive correlation (P < 0.05). Conclusion: We speculate that the activation of host anti-HBV immunity can efficiently inhibit HBV replication by targeting the infected hepatocytes, but only in the early phase of disease progression in HBeAg positive patients with HBV DNA high (> 2×10(6) IU/ml).

The combined impact of xylo-oligosaccharides and gamma-irradiated astragalus polysaccharides on the immune response, antioxidant capacity, and intestinal microbiota composition of broilers.

The present study investigated the individual and combined effects of xylo-oligosaccharides (XOS) and gamma-irradiated astragalus polysaccharides (IAPS) on the immune response, antioxidant capacity and intestinal microbiota composition of broiler chickens. A total of 240 newly hatched Ross 308 chicks were randomly allocated into 5 dietary treatments including the basal diet (control), or the basal diet supplemented with 50 mg/kg chlortetracycline (CTC), 100 mg/kg XOS (XOS), 600 mg/kg IAPS (IAPS), and 100 mg/kg XOS + 600 mg/kg IAPS (XOS + IAPS) respectively. The results showed that birds in the control group had lower the thymus index and serum lysozyme activity than those in the other 4 groups (P < 0.05). Moreover, there was an interaction between XOS and IAPS treatments on increasing the serum lysozyme activity (P < 0.05). Birds in the CTC and XOS + IAPS groups had lower serum malondialdehyde concentration and higher serum total antioxidant capacity activity and mucosal interleukin 2 mRNA expression of jejunum than those in the control group (P < 0.05). In addition, birds in the control groups had lower duodenal and jejunal IgA-producing cells number than these in other 4 groups (P < 0.05). As compared with the CTC group, dietary individual XOS or IAPS administration increased duodenal IgA-producing cells number (P < 0.05). Meanwhile, there was an interaction between XOS and IAPS treatments on increasing duodenal and jejunal IgA-Producing cells numbers (P < 0.05). Dietary CTC administration increased the proportion of Bacteroides, and decreased the proportion of Negativibacillus (P < 0.05). However, dietary XOS + IAPS administration increased Firmicutes to Bacteroidetes ratio, the proportion of Ruminococcaceae, as well as decreased the proportion of Barnesiella and Negativibacillus (P < 0.05). In conclusion, the XOS and IAPS combination could improve intestinal mucosal immunity and barrier function of broilers by enhancing cytokine gene expression, IgA-producing cell production and modulates cecal microbiota, and the combination effect of XOS and IAPS is better than that of individual effect of CTC, XOS, or IAPS in the current study.

Creatine nitrate supplementation strengthens energy status and delays glycolysis of broiler muscle via inhibition of LKB1/AMPK pathway.

This study aimed to evaluate the effects of dietary creatine nitrate (CrN) on growth performance, meat quality, energy status, glycolysis, and related gene expression of liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway in Pectoralis major (PM) muscle of broilers. A total of 240 male Arbor Acres broilers (28-day-old) were randomly allocated to one of 5 dietary treatments: the basal diet (control group), and the basal diets supplemented with 600 mg/kg guanidinoacetic acid (GAA), 300, 600, or 900 mg/kg CrN (identified as GAA600, CrN300, CrN600, or CrN900, respectively). We found that dietary GAA and CrN supplementation for 14 d from d 28 to 42 did not affect broiler growth performance, carcass traits, and textural characteristics of breast muscle. GAA600, CrN600, and CrN900 treatments increased pH24h and decreased drip loss of PM muscle compared with the control (P < 0.05). The PM muscles of CrN600 and CrN900 groups showed higher glycogen concentration and lower lactic acid concentration accompanied by lower activities of phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) (P < 0.05). Simultaneously, GAA600 and all CrN treatments increased concentration of muscle creatine, phosphocreatine (PCr) and ATP, and decreased AMP concentration and AMP/ATP ratio (P < 0.05). Meanwhile, the concentrations of muscle creatine, PCr, and ATP were increased linearly, while muscle AMP concentration and AMP/ATP ratio were decreased linearly and quadratic as the dose of CrN increased (P < 0.05). GAA600, CrN600, and CrN900 treatments upregulated mRNA expression of CreaT in PM muscle, and CrN600 and CrN900 treatments downregulated GAMT expression in liver and PM muscle compared with the control or GAA600 groups (P < 0.05). The mRNA expression of muscle LKB1, AMPKα1, and AMPKα2 was downregulated linearly in response to the increasing CrN level (P < 0.05). Overall, CrN showed better efficacy on strengthening muscle energy status and improve meat quality than GAA at the some dose. These results indicate that CrN may be a potential replacement for GAA as a new creatine supplement.

The combined impact of xylo-oligosaccharides and gamma-irradiated Astragalus polysaccharides on growth performance and intestinal mucosal barrier function of broilers.

This study was conducted to investigate the individual and combined effects of xylo-oligosaccharides (XOS) and gamma-irradiated Astragalus polysaccharides (IAPS) on the growth performance and intestinal mucosal barrier function of broiler chickens. A total of 240 1-day-old Ross-308 chicks were allocated into 5 groups for 21 d: control group (basal diet), antibiotic growth promoter (AGP) group (basal diet supplemented with 50 mg/kg chlortetracycline), XOS group (basal diet supplemented with 100 mg/kg XOS), IAPS group (basal diet supplemented with 600 mg/kg IAPS), and XOS + IAPS group (basal diet supplemented with 100 mg/kg XOS and 600 mg/kg IAPS). The results showed that birds in the XOS + IAPS group showed higher ADG and lower feed-to-gain ratio than those in the control group (P < 0.05). The XOS, IAPS, and XOS + IASP treatments significantly increased villus height (VH) of all intestine segments, jejunal goblet cell numbers, and VH-to-crypt depth ratio (VH/CD) of broilers than those of the control group (P < 0.05). Birds in the XOS + IAPS group had higher jejunal VH/CD ratio and goblet cell numbers than those from the XOS or IAPS groups (P < 0.05). In addition, there was a synergy effect between XOS and IAPS on increasing duodenal goblet cell numbers and improving ileal morphology (higher VH and VH/CD ratio) (P < 0.05). The XOS, IAPS and XOS + IAPS treatments increased the mRNA expression of zonula occludens-1 and occludin of the jejunum as compared with the control group (P < 0.05). Simultaneously, birds in the XOS + IAPS group showed lower plasma D-lactic acid concentration and higher mRNA expression of claudin-1, claudin-3, and occludin in the jejunum than those in the control or IAPS groups (P < 0.05). Moreover, there was no significant difference in growth performance, intestinal morphology, and intestinal barrier function of broilers between the AGP and XOS + IAPS groups. In conclusion, the combination of XOS and IAPS had a better potential as chlortetracycline substitute for improving the growth performance, intestinal morphology, and intestinal barrier function of broilers.

Enhanced transforming growth factor-beta signaling and fibrosis in the pectoralis major muscle of broiler chickens affected by wooden breast myopathy.

Fibrosis has also been recorded as a prominent pathological feature within wooden breast (WB) myopathy of broiler chickens. This study was conducted to evaluate the accumulation of fibril collagen, deposition of the extracellular matrix (ECM) components, and the underlying mechanism mediating the pathogenic fibrotic process in the pectoralis major (PM) muscle of WB-affected birds. Broiler chickens were categorized into the control and WB groups based on the evaluation of myopathic lesions. Results indicated that the total content and area of collagen in cross-sections of the PM muscle, as well as the augmented expression of collagen-I and fibronectin in the ECM, were greatly increased in birds with WB. Wooden breast myopathy upregulated expressions of transforming growth factor-beta (TGF-ß) and the phosphorylation of Smad 2 and 3, thereby activating TGF-ß-mediated Smad signaling pathway, which further enhanced the transcription of profibrotic mediators. In addition, regulators involved in collagen biosynthesis and cross-linking including prolyl 4-hydroxylase, lysyl oxidase, lysyl hydroxylase, and decorin were increased in the WB muscle. Finally, the expressions of both matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) were increased in the WB muscle, which might be related with reduced ECM remodeling. Overall, WB myopathy induces severe fibrosis by enhancing ECM deposition and collagen cross-linking in the PM muscle of broiler chickens, possibly via the activation of TGF-ß signaling and the dysregulation of the MMP and TIMP system.

Microbiota populations and short-chain fatty acids production in cecum of immunosuppressed broilers consuming diets containing γ-irradiated Astragalus polysaccharides.

This study was designed to evaluate the effects of γ-irradiated Astragalus polysaccharides (IAPS) on growth performance, cecal microbiota populations, and concentrations of cecal short-chain fatty acids of immunosuppressed broilers. A total of 144 one-day-old broiler chicks were randomly assigned into 3 groups: nontreated group (control), cyclophosphamide (CPM)-treated groups fed either a basal diet or the diets containing 900 mg/kg IAPS, respectively. On day 16, 18, and 20, broilers in the control group were intramuscularly injected with 0.5 mL sterilized saline (0.75%, wt/vol), and those in the CPM and IAPS groups were intramuscularly injected with 0.5 mL CPM (40 mg/kg of BW). The trial lasted 21 d. Compared with the control group, CPM treatment decreased the broiler average daily gain (ADG) and feed intake (P < 0.05) but did not affect the overall microbial diversity and compositions, as well as the concentrations of cecal acetate, propionate, and butyrate in cecum of broilers (P > 0.05). Dietary IAPS supplementation increased broiler ADG, Shannon index, and decreased Simpson index (P < 0.05). Specifically, broilers fed diets containing IAPS showed lower abundances of Faecalibacterium, Bacteroides, and Butyricicoccus and higher proportions of Ruminococcaceae UCG-014, Negativibacillus, Shuttleworthia, Sellimonas, and Mollicutes RF39_norank, respectively (P < 0.05). The IAPS treatment also increased butyrate concentration (P < 0.05) and tended to elevate acetate concentration (P = 0.052) in cecal digesta. The results indicated that IAPS are effective in increasing the cecal beneficial bacteria and short-chain fatty acids production, contributing to improvement in the growth performance of immunosuppressive broilers. These findings may expand our knowledge about the function of modified Astragalus polysaccharides in broiler chickens.

Dynamics and bifurcations in multistable 3-cell neural networks.

We disclose the generality of the intrinsic mechanisms underlying multistability in reciprocally inhibitory 3-cell circuits composed of simplified, low-dimensional models of oscillatory neurons, as opposed to those of a detailed Hodgkin-Huxley type [Wojcik et al., PLoS One 9, e92918 (2014)]. The computational reduction to return maps for the phase-lags between neurons reveals a rich multiplicity of rhythmic patterns in such circuits. We perform a detailed bifurcation analysis to show how such rhythms can emerge, disappear, and gain or lose stability, as the parameters of the individual cells and the synapses are varied.

Characteristics and incidence of broiler chicken wooden breast meat under commercial conditions in China.

Wooden breast (WB) has emerged as a dramatically increasing myopathy in the poultry industry over the past few years. The objective of this study was to investigate the incidence of WB in a Chinese commercial broiler processing plant, and the consequences on quality attributes, textural properties, and sensory traits. A total of 1,135 breast fillets were collected at the deboning line and assigned to normal, mild, moderate, and severe WB categories by tactile evaluation. The proportion affected by WB was approximately 61.9%. WB fillets appeared heavier and thicker than normal fillets. The degree of WB myopathy was highly correlated with fillet weight and thickness. The meat quality characteristics of cooking loss and purge loss increased along with increasing severity of WB myopathy. Compression tests of raw meat revealed higher cutting strength and shear values for WB. In cooked meat, only severe WB fillets exhibited elevated hardness and chewiness. Finally, moderate and severe WB fillets affected the sensory evaluation by consumers owing to their impaired general appearance, texture, and drip loss. The results suggested that a high proportion of WB broiler fillets would cause detrimental losses to the poultry meat retailing and processing industry.

Glucose and lipid metabolism of broiler chickens fed diets with graded levels of corn resistant starch.

1. The aim of this study was to investigate the effects of graded levels of dietary corn resistant starch (RS) on glucose and lipid metabolism of broilers. 2. A total of 320 male broiler chicks (Arbor Acres, one-day-old) were randomly allocated to five dietary treatments, including a corn-soybean control diet, a corn-soybean based diet containing 20% corn starch, and three diets containing 4%, 8% and 12% RS by replacing corn starch with 6.67%, 13.33% and 20% Hi-Maize® 260 (identified as control, RS1, RS2, RS3 and RS4, respectively). Each treatment contained eight replicates with eight birds, and the experiment lasted 42 days. 3. Birds fed RS diets showed lower (P < 0.05) concentrations of serum low-density lipoprotein cholesterol and non-esterified fatty acid (NEFA) at d 21 and 42 of age, compared to the control. Lower (P < 0.05) hepatic apolipoprotein B concentration and citrate synthase (CS) activity, as well as a higher (P < 0.05) glycogen synthase (GS) concentration were observed in birds fed RS diets than those in the control group at d 21 of age. Consuming RS diets linearly increased (P < 0.01) serum glucose concentration, and linearly decreased (P < 0.01) NEFA concentrations in broilers at d 21 and 42 of age. Liver GS concentration and activities of hexokinase, pyruvate and CS were linearly increased (P < 0.01) in broilers at d 21 of age, but were linearly decreased (P < 0.05) in birds at d 42 of age in response to the increase of dietary RS levels. Feeding RS diets linearly decreased (P < 0.05) mRNA expressions of PC, PPARα and CPT-1 at d 21 of age and the mRNA expressions of SREBP-1 c, ChREBP, ACC and FAS at d 42 of age, and linearly increased (P < 0.05) the mRNA expressions of PEPCK, PC, LKB1, AMPKα1, PPARα, CPT-1 and L-FABP at d 42 of age. 4. Feeding broilers with diets containing higher concentration of RS promoted hepatic lipolysis and gluconeogenesis through activated AMPK signalling pathway and accelerated whole-body energy expenditures in the grower phase.

Growth performance, carcass traits and digestive function of broiler chickens fed diets with graded levels of corn resistant starch.

1. This study was conducted to assess the effects of graded levels of dietary corn resistant starch (RS) on growth performance, carcass traits, nutrient retention, digestive organ index, intestinal morphology, digestive enzyme activities, and mRNA expression of certain nutrient transporters in broiler chickens.2. A total of 320, 1-d-old Arbor Acres broiler chickens were randomly assigned to five dietary treatments, with eight replicates of eight birds in each. These treatments included one corn-soybean control diet, a corn-soybean based diet containing 20% corn starch, and three diets supplemented with 4%, 8% and 12% RS by replacing corn starch with 6.67%, 13.33% and 20% of Hi-Maize 260® (identified as control, RS1, RS2, RS3 and RS4, respectively). The feeding period lasted 42 days.3. Performance parameters including feed consumption, feed conversion, body weight gain and percentage of abdominal fat at d 42 of age, nutrient retention (including dry matter, fat, total starch and nitrogen free extract), and apparent metabolisable energy was measured from d 18 to 20 and d 39 to 41 and showed negative linear responses to increasing dietary RS level (P < 0.05). Birds fed the RS3 and RS4 diets showed higher relative weight of duodenum, jejunum and ileum, as well as lower villus height and villus height/crypt depth compared to the control (P < 0.05). The activity of pancreatic trypsin of birds at d 21 and 42 of age decreased linearly in response to the increase of dietary RS level (P < 0.01). There were linear changes in up-regulated mRNA expression of SGLT-1 and down-regulated mRNA expression of GLUT-2 with increasing proportion of RS at d 21 and 42 of age (P < 0.05), respectively.4. It was concluded that feeding broilers with diets containing higher concentrations of RS impaired the development of small intestine, which resulted in lower apparent total tract retention of nutrients and poorer body weight gain, feed efficiency and carcass traits of broiler chickens.

Dietary taurine supplementation enhances antioxidative capacity and improves breast meat quality of broiler chickens.

1. The aim of this study was to determine the effect of dietary taurine supplementation on growth performance, meat quality and antioxidant responses in breast muscle of broiler chickens.2. A total of 72 Arbor Acres broiler chickens (28-day-old) with similar body weight were randomly allocated into two groups, and fed either 0 g/kg (control; C) or 5 g/kg taurine-supplemented diets (TS) for 14 days.3. The results showed that TS had no effect on growth performance or chemical composition of breast muscle in broilers. The drip and cooking losses were significantly decreased (P < 0.05), and the pH24h of breast muscle were increased (P < 0.05) in the TS group. Meanwhile, broilers in the TS group exhibited significantly higher (P < 0.05) scavenging activities of superoxide and 2,2-diphenyl-1-picrylhydrazyl radicals, and lower (P < 0.05) contents of carbonyl, malondialdehyde, and 4-hydroxynonenal. TS increased (P < 0.05) total antioxidant capacity and superoxide dismutase activities. Moreover, TS significantly upregulated (P < 0.05) the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, superoxide dismutase, catalase, and glutathione peroxidase.4. These findings suggested that TS enhanced antioxidative capacity and improved breast meat quality of broilers via activating the Nrf2 pathway.

Spatial association between outdoor air pollution and lung cancer incidence in China.

BACKGROUND: Lung cancer is the most common cancer in China. Previous studies have indicated that lung cancer incidence exhibits remarkable spatial heterogeneity, and lung cancer is related to outdoor air pollution. However, the non-linear spatial association between outdoor air pollution and lung cancer incidence in China remains unclear. METHODS: In this study, the relationships between the lung cancer incidence of males and females from 207 counties in China in 2013 with annual concentrations of PM2.5, PM10, SO2, NO2, CO and O3 were analysed. GeoDetector q statistic was used for examining the non-linear spatial association between outdoor air pollution and incidence of lung cancer. RESULTS: An apparent spatial and population gender heterogeneity was found in the spatial association between outdoor air pollution and lung cancer incidence. Among the six selected pollutants, SO2 has the greatest influence on lung cancer (q = 0.154 in females) in north China. In the south, each selected pollutant has a significant impact on males or females, and the mean q value in the south is 0.181, which is bigger than that in the north (q = 0.154). In addition, the pollutants have evident non-linear interaction effects on lung cancer. In north China, the interaction between SO2 and PM2.5 is the dominant interaction, with q values of 0.207 in males and 0.334 in females. In the south, the dominant interactive factors are between SO2 and O3 in males and between SO2 and CO in females, with q values of 0.45, 0.232 respectively. Smoking is a substantial contributor to lung cancer among men, either in South or North China, with q value of 0.143 and 0.129 respectively, and the interaction between smoking and air pollutants increases this risk. CONCLUSIONS: This study implies that the influence of SO2 and PM2.5 on lung cancer should be focused on in north China, and in the south, the impact of O3 and CO as well as their interaction with SO2 need to be paid more attention. Smoking, particularly in men, remains a significant risk factor for lung cancer in both North and South China.

Protective effects of γ-irradiated Astragalus polysaccharides on intestinal development and mucosal immune function of immunosuppressed broilers.

This study was aimed to assess the protective effects of γ-irradiated Astragalus polysaccharides (IAPS) on the development of small intestine and intestinal mucosal immunity of immunosuppressed broilers induced by cyclophosphamide (CPM). A total of 384 one-day-old broiler chicks with similar initial weight were randomly assigned into 6 groups: non-treated group (control), and CPM-treated groups fed either a basal diet or the diets containing 900 mg/kg APS, or 900, 600, 300 mg/kg IAPS, respectively. On days 16, 18, and 20, all broilers except for control group were intramuscularly injected with 0.5 mL CPM (40 mg/kg of BW). Broilers in the control group were intramuscularly injected with 0.5 mL sterilized saline (0.75%, wt/vol). This trial was lasted for 21 d. The results revealed that both APS and IAPS treatment elevated the duodenal IgA-producing cells number and the jejunal mRNA expression of interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon γ of CPM-injected broilers (P < 0.05). The decreased jejunal villus height (VH), the ratio of VH to crypt depth (V/C), as well as the intestinal intraepithelial lymphocytes (IELs) and goblet cells number in CPM-injected broilers were elevated by dietary supplementation with 900 mg/kg APS or 900, 600 mg/kg IAPS (P < 0.05). The CPM-induced decrease in jejunum index, the duodenal VH and the jejunal IgA-producing cells number were only improved in the 900 mg/kg IAPS group (P < 0.05). Furthermore, the number of IELs and IgA-producing cells in duodenum, VH, V/C, the number of goblet cells, and mRNA expression of IL-2 and IL-10 in jejunum were higher in the 900 mg/kg IAPS group than those in the 900 mg/kg APS group (P < 0.05). In summary, IAPS possessed stronger immunomodulatory effect than APS at the same supplementation level. Therefore, gamma irradiation can be used as an alternative treatment to enhance the immunomodulatory activity of APS.

Tyrosinase-doped bioink for 3D bioprinting of living skin constructs.

Three-dimensional bioprinting is an emerging technology for fabricating living 3D constructs, and it has shown great promise in tissue engineering. Bioinks are scaffold materials mixed with cells used by 3D bioprinting to form a required cell-laden structure. In this paper, a novel bioink made of gelatin methacrylamide (GelMA) and collagen (Col) doped with tyrosinase (Ty) is presented for the 3D bioprinting of living skin tissues. Ty has the dual function of being an essential bioactive compound in the skin regeneration process and also as an enzyme to facilitate the crosslink of Col and GelMA. Further, enzyme crosslinking together with photocrosslinking can enhance the mechanical strength of the bioink. The experimental results show that the bioink is able to form stable 3D living constructs using the 3D bioprinting process. The cell culture shows that three major cell lines: human melanocytes (HEM), human keratinocytes (HaCat) and human dermal fibroblasts (HDF) exhibit high cell viabilities. The viability of these three cell lines is above 90%. The proliferation and scratching test show that Ty can enhance the proliferation of HEM, inhibit the growth and migration of HDF and not affect HaCat significantly. Animal tests show that the doped bioinks for 3D bioprinting can help form an epidermis and dermis, and thus have high potential as a skin bioink.

Different oxidative status and expression of calcium channel components in stress-induced dysfunctional chicken muscle.

The objective of this study was to assess the effects of transport stress at high ambient temperatures on the oxidation status and the expression of essential elements responsible for the Ca transport (sarco- (endo-) plasmic reticulum Ca-ATPase (SERCA1) and the ryanodine receptor (RyR) in (PM) muscles of broilers. Briefly, Arbor Acres broiler chickens ( = 112) were randomly categorized into 2 treatments: unstressed control (C) and 0.5 h transport (T). Each treatment consisted of 8 replicates of 7 birds each. Birds were transported according to a designed protocol. PM muscle samples in T group were collected and classified as normal (T-NOR) or pale, soft, and exudative-like (T-PSE) using meat quality parameters. The results indicated that production of corticosterone (CORT) and reactive oxygen species (ROS) increased significantly after transportation ( < 0.05). Thiobarbituric acid reactive substance values and carbonyl contents increased significantly in the T group ( < 0.05). Moreover, the extent of lipid peroxidation and protein oxidation was more severe in the T-PSE group compared to the T-NOR group ( < 0.05). The mRNA and protein expression of SERCA1 and αRyR increased in the T-NOR group but decreased significantly in the T-PSE group compared to the CON group ( < 0.05). The mRNA expression of ßRyR was found to be enhanced in the T-NOR group compared to the CON group, whereas there was no difference in the T-PSE group ( < 0.05). The results indicate that short-distance transport of broilers affects their physiological responses and biochemical changes which may lead to different oxidative states and, importantly, to different expressions of SERCA and RyR. These induced changes in abnormal sarcoplasmic Ca homeostasis have significant implications for the development of PSE-like meat.

Expression of heat shock protein 70 in transport-stressed broiler pectoralis major muscle and its relationship with meat quality.

Omics research has indicated that heat shock protein 70 (HSP70) is a potential biomarker of meat quality. However, the specific changes and the potential role of HSP70 in postmortem meat quality development need to be further defined. In this study, Arbor Acres broiler chickens (n=126) were randomly categorized into three treatment groups of unstressed control (C), 0.5-h transport (T) and subsequent water shower spray following transport (T/W). Each treatment consisted of six replicates with seven birds each. The birds were transported according to a designed protocol. The pectoralis major (PM) muscles of the transport-stressed broilers were categorized as normal and pale, soft and exudative (PSE)-like muscle samples according to L* and pH24 h values to test the expression and location of HSP70. Results revealed that the activities of plasma creatine kinase and lactate dehydrogenase increased significantly (P<0.05) in normal and PSE-like muscle samples after transportation. The mRNA expression of HSP70 in normal muscle samples increased significantly (P<0.05) compared with that in the controls after stress. The protein expression of HSP70 increased significantly in normal muscle samples and decreased significantly (P<0.05) in PSE-like muscles. Immuno-fluorescence showed that HSP70 was present in the cytoplasm and on surface membranes of PM muscle cells in the normal samples following stress. Meanwhile, HSP70 was present on the surface membranes and extracellular matrix but was barely visible in the cytoplasm of the PSE-like samples. Principal component analysis showed high correlations between HSP70 and meat quality and stress indicators. In conclusion, this research suggests that the variation in HSP70 expression may provide a novel insight into the pathways underlying meat quality development.

Precipitation and ultimate pH effect on chemical and gelation properties of protein prepared by isoelectric solubilization/precipitation process from pale, soft, exudative (PSE)-like chicken breast meat1.

Pale, soft, exudative (PSE)-like chicken breast is considered deteriorated raw material in the poultry meat industry that has inferior processing ability. The chemical and gelation properties of PSE-like chicken breast meat paste were studied. These pastes were prepared by the pH adjustment method and protein isolation using the isoelectric solubilization/precipitation (ISP) process from PSE-like chicken meat. The ISP-isolated samples were solubilized at pH 11.0 and recovered at pH 5.5 and 6.2. The ultimate pH of the ISP-isolated protein and meat paste was adjusted to 6.2 and 7.0. The ultimate pH in this article referred to the final pH of the extracted protein and meat paste. Higher reactive sulfhydryl content and surface hydrophobicity were found in the precipitation at pH 6.2 than at pH 5.5. However, various ultimate pH values showed no significant influence on the surface hydrophobicity. The hardness of gel, as measured by textural profile analysis, was improved using 6.2 as the precipitation pH compared with pH 5.5. The viscoelastic modulus (G΄) of gel pastes prior to the thermal gelation was higher with ISP treatment. However, lower G΄ was seen after thermal gelation compared with the control. Dynamic rheological measurement demonstrated a different gel-forming mechanism for protein precipitated at pH values of 5.5 and 6.2 compared with the meat paste. The cooking loss showed that the recovered protein failed to form a gel with good water-retention capacity unless the ultimate pH was adjusted to 7.0. Gels made from protein extracted by the ISP method had higher yellowness and lower redness values, probably due to protein denaturation. Precipitation at pH 6.2 formed a harder gel with lower water-retention ability than that at pH 5.5, and this result was possibly due to higher surface hydrophobicity and S-S bridge formation. Overall, network characteristics of ISP-treated protein gels were strongly dependent on precipitation pH and ultimate pH.