Insights from the neural guidance factor Netrin-1 into neurodegeneration and other diseases.

Netrin-1 was initially discovered as a neuronal growth cue for axonal guidance, and its functions have later been identified in inflammation, tumorigenesis, neurodegeneration, and other disorders. We have recently found its alterations in the brains with Alzheimer's disease, which might provide important clues to the mechanisms of some unique pathologies. To provide better understanding of this promising molecule, we here summarize research progresses in genetics, pathology, biochemistry, cell biology and other studies of Netrin-1 about its mechanistic roles and biomarker potentials with an emphasis on clinical neurodegenerative disorders in order to expand understanding of this promising molecular player in human diseases.

Application of pectin hydrolyzing bacteria in tobacco to improve flue-cured tobacco quality.

To study the relationship between the diversity of the surface microbial community and tobacco flavor, and to improve tobacco quality using microorganisms. The microbial community composition and diversity of 14 samples of flue-cured tobacco from tobacco-producing areas in Yunnan with varying grades were analyzed by high-throughput sequencing. PICRUSt was used for predicting microbial functions. A strain of Bacillus amyloliquefaciens W6-2 with the ability to degrade pectin was screened from the surface of flued-cured tobacco leaves from Yunnan reroasted tobacco leave. The enzyme preparation was prepared through fermentation and then applied for treating flue-cured tobacco. The improvement effect was evaluated by measuring the content of macromolecule and the changes in volatile components, combined with sensory evaluations. The bacterial communities on the surface of flue-cured tobacco exhibited functional diversity, consisting primarily of Variovorax, Pseudomonas, Sphingomonas, Burkholderia, and Bacillus. These bacterial strains played a role in the aging process of flue-cured tobacco leaves by participating in amino acid metabolism and carbohydrate metabolism. These metabolic activity converted complex macromolecules into smaller molecular compounds, ultimately influence the smoking quality and burning characteristics of flue-cured tobacco. The pectinase preparation produced through fermentation using W6-2 has been found to enhance the aroma and sweetness of flue-cured tobacco, leading to improved aroma, reduced impurities, and enhanced smoothness. Additionally, the levels of pectin, cellulose, and hemicellulose decreased, while the levels of water-soluble sugar and reducing sugar increased, and the contents of esters, ketones, and aldehydes increased, and the contents of benzoic acid decreased. The study revealed the correlation between surface microorganisms and volatile components of Yunnan tobacco leaves, and the enzyme produced by the pectin-degrading bacteria W6-2 effectively improved the quality of flue-cured tobacco.

Metabolomics-based study of chemical compositions in cellulase additives derived from a tobacco-origin Bacillus subtilis and their impact on tobacco sensory attributes.

To enhance the quality of tobacco leaves and optimize the smoking experience, diverse strains of functional bacteria and their associated metabolites have been used in tobacco aging. Exogenous cellulase additives are frequently employed to facilitate the degradation of cellulose and other macromolecular matrices and enhance the quality of the tobacco product. However, little is known about how microbial metabolites present in exogenous enzyme additives affect tobacco quality. In this study, crude cellulase solutions, produced by a tobacco-originating bacterium Bacillus subtilis FX-1 were employed on flue-cured tobacco. The incorporation of cellulase solutions resulted in the reduction of cellulose crystallinity in tobacco and the enhancement of the overall sensory quality of tobacco. Notably, tobacco treated with cellulase obtained from laboratory flask fermentation demonstrated superior scent and flavor attributes in comparison to tobacco treated with enzymes derived from industrial bioreactor fermentation. The targeted and untargeted metabolomic analysis revealed the presence of diverse flavor-related precursors and components in the cellulase additives, encompassing sugars, alcohols, amino acids, organic acids, and others. The majority of these metabolites exhibited significantly higher levels in the flask group compared to the bioreactor group, probably contributing to a pronounced enhancement in the sensory quality of tobacco. Our findings suggest that the utilization of metabolic products derived from B. subtilis FX-1 as additives in flue-cured tobacco holds promise as a viable approach for enhancing sensory attributes, establishing a solid theoretical foundation for the potential development of innovative tobacco aging additives.

Complete genome sequence analysis of Bacillus velezensis A5, a promising biocontrol agent from the Pacific Ocean.

Tobacco bacterial wilt (TBW) caused by Ralstonia solanacearum is a serious soil-borne disease, which seriously damages the growth of tobacco crops. Bacillus velezensis A5 was isolated from 3000 m deep-sea sediments of the Pacific Ocean, and was found to be antagonistic to TBW. Here, we report the complete genome sequence of strain A5, which has a 4,000,699-bp single circular chromosome with 3827 genes and a G + C content of 46.44%, 87 tRNAs, and 27 rRNAs. A total of 12 gene clusters were identified in the genome of strain A5, which were responsible for the biosynthesis of antibacterial compounds, including surfactin, bacillaene, fengycin, difficidin, bacillibactin, and bacilysin. Additionally, strain A5 was found to contain a series of genes related to the biosynthesis of carbohydrate-active enzymes and secreted proteins. Our results indicate that strain A5 can be considered a promising biocontrol agent against TBW in agricultural fields.

Intraoperative blood pressure and cardiac complications after aneurysmal subarachnoid hemorrhage: a retrospective cohort study.

BACKGROUND: Previous studies report that intraoperative hypotension worsens outcomes after aneurysmal subarachnoid hemorrhage (aSAH). However, the hypotensive harm threshold for major adverse cardiovascular events (MACE) remains unclear. METHODS: The authors included aSAH patients who had general anesthesia for aneurysmal clipping/coiling. MACE were defined by a composite of acute myocardial injury, acute myocardial infarction, and other cardiovascular complications identified by electrocardiogram and echocardiography. The authors initially used logistic regression and change-point analysis based on the second derivative to identify mean arterial pressure (MAP) of 75 mmHg as the harm threshold. Thereafter, our major exposure was MAP below 75 mmHg characterized by area, duration, and time-weighted average. The area below 75 mmHg represents the severity and duration of exposure and was defined as the sum of all areas below a specified threshold using the trapezoid rule. Time-weighted average MAP was derived by dividing area below the threshold by the duration of anesthesia. All analyses were adjusted for baseline risk factors including age greater than 70 years, female sex, severity of intracerebral hemorrhage, history of cardiovascular disease, and preoperative elevated myocardial enzymes. RESULTS: Among 1029 patients enrolled, 254 (25%) developed postoperative MACE. Patients who experienced MACE were slightly older (59±11 vs. 54±11 years), were slightly more often women (69 vs. 58%), and had a higher prevalence of cardiovascular history (65 vs. 47%). Adjusted cardiovascular risk increased nearly linearly over the entire range of observed MAP. However, there was a slight inflexion at MAP of 75 mmHg. MACE was significantly associated with area [adjusted odds ratios (aOR) 1.004 per 10 mmHg.min, 95% CI: 1.001-1.007, P =0.002), duration (aOR 1.031 per 10 min, 95% CI: 1.009-1.054, P =0.006), and time-weighted average (aOR 3.516 per 10 mmHg, 95% CI: 1.818-6.801, P <0.001) of MAP less than 75 mmHg. CONCLUSIONS: Lower blood pressures were associated with cardiovascular complications over the entire observed range, but worsened when MAP was less than 75 mmHg. Pending trial data to establish causality, it may be prudent to keep MAP above 75 mmHg in patients having surgical aSAH repairs to reduce the risk of MACE.

CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.

BACKGROUND AND AIMS: Although the benefits of vertical sleeve gastrectomy (VSG) surgery are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine the role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG. APPROACH AND RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, short hairpin RNA-mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation from wild type-VSG mice (vs. fecal microbiota transplantation from wild-type-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received fecal microbiota transplantation from knockout-sham and knockout-VSG mice. CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and gut microbiota profile by targeting CYP8B1 may provide novel insight into the development of therapies that noninvasively mimic bariatric surgery to treat obesity and its complications.

Complete genome sequence of Bacillus cereus Z4, a biocontrol agent against tobacco black shank, isolated from the Western Pacific Ocean.

Bacillus species have been considered as promising biological control agents due to their excellent antimicrobial ability. Bacillus cereus strain Z4 was isolated from 2000 m deep sea sediments of the Western Pacific Ocean, which possesses significant antifungal activity against Phytophthora nicotianae, the pathogenic fungus of tobacco black shank disease. To reveal the underlying antifungal genetic mechanisms, here, we report the complete genomic sequence of the strain Z4. The genome has one circular chromosome of 5,664,309 bp with a G + C content of 35.31%, 109 tRNAs, and 43 rRNAs. Genomic analysis identified 10 gene clusters related to the biosynthesis of biocontrol active compounds, including bacillibactin, petrobactin, fengycin, and molybdenum cofactor. Meanwhile, 6 gene clusters were responsible for the biosynthesis of metabolites with unknown functions. Strain Z4 also contains a large number of genes encoding carbohydrate-active enzymes and secreted proteins, respectively. The whole genomic analysis of Bacillus cereus Z4 may provide a valuable reference for elucidating its biocontrol mechanism against tobacco black shank.

Application of starch degrading bacteria from tobacco leaves in improving the flavor of flue-cured tobacco.

Starch is an essential factor affecting the quality of flue-cured tobacco, and high starch content can affect the sensory quality and safety. Recently, the degradation of macromolecules in tobacco raw materials by using additional microorganisms to improve their intrinsic quality and safety has become a new research hotspot in the tobacco industry. However, the technical maturity and application scale are limited. Our study analyzed the correlation between microbial community composition and volatile components on the surface of tobacco leaves from 14 different grades in Fujian tobacco-producing areas. The PICRUSt software was utilized to predict the function of the microbial community present in tobacco leaves. Furthermore, dominant strains that produced amylase were screened out, and an enzyme solution was prepared to enhance the flue-cured tobacco flavor. Changes in the content of macromolecules and volatile components were determined, and sensory evaluations were conducted to assess the overall quality of the tobacco leaves. The results showed that the dominant bacterial genera on the surface of Fujian tobacco leaves were Variovorax, Sphingomonas, Bacillus, etc. Bacillus was positively correlated with various volatile components, which contributed to the sweet and aromatic flavors of Fujian flue-cured tobacco. The main genetic functions of Fujian flue-cured tobacco surface bacteria were carbohydrate metabolism and amino acid metabolism. After treating flue-cured tobacco with an enzyme preparation prepared by the fermentation of Paenibacillus amylolyticus A17 #, the content of starch, pectin, and cellulose in flue-cured tobacco decreased significantly compared with the control group. Meanwhile, the content of total soluble sugar and reducing sugar was significantly increased, and the volatile aroma components, such as 3-hydroxy--damascone, 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-Pyran-4-one, ethyl palmitate, ethyl linolenic acid, etc., were significantly increased. The aroma quality and quantity of flue-cured tobacco were enhanced, while impurities were reduced. The smoke characteristics were improved, with increased fineness, concentration, and moderate strength. The taste characteristics were also improved, with reduced irritation and a better aftertaste. In conclusion, Bacillus, as the dominant genus in the abundance of bacterial communities on tobacco surfaces in Fujian, had an essential impact on the flavor of tobacco leaves by participating in carbohydrate metabolism and finally forming the unique flavor style of flue-cured tobacco in Fujian tobacco-producing areas. Paenibacillus amylolyticus A17 #, a target strain with amylase-producing ability, was screened from the surface of Fujian flue-cured tobacco. The enzyme preparation, produced by the fermentation of Paenibacillus amylolyticus A17 #, was utilized to reduce the content of macromolecules, increase the content of water-soluble total sugar and reducing sugar, and produce a variety of crucial volatile aroma components, which had a significant improvement on the quality of tobacco leaves.

Complete genome analysis of Bacillus subtilis TY-1 reveals its biocontrol potential against tobacco bacterial wilt.

Bacillus subtilis TY-1 was isolated from 2000 m-deep sea sediments of the Western Pacific Ocean, which was found to exhibit strong antagonistic activity against tobacco bacterial wilt caused by Ralstonia solanacearum. Here, we present the annotated complete genomic sequence of the strain Bacillus subtilis TY-1. The genome consists of a 4,030,869-bp circular chromosome with a G + C content of 43.88%, 86 tRNAs, and 30 rRNAs. Genomic analysis identified a large number of gene clusters involved in the biosynthesis of antibacterial metabolites, including lipopeptides(surfactin, bacillibactin, and fengycin) and polyketides(bacillaene). Meanwhile, numerous genes encoding carbohydrate-active enzymes and secreted proteins were found in TY-1. These findings suggest that Bacillus subtilis TY-1 appears to be a potential biocontrol agent against tobacco bacterial wilt in agricultural fields.

Comparison of logistic regression and machine learning methods for predicting postoperative delirium in elderly patients: A retrospective study.

AIMS: To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients. METHOD: This was a retrospective study of perioperative medical data from patients undergoing non-cardiac and non-neurology surgery over 65 years old from January 2014 to August 2019. Forty-six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and precision. RESULTS: In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765-0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%. CONCLUSIONS: The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model.

Determination of Zearalenone and Its Derivatives in Feed by Gas Chromatography-Mass Spectrometry with Immunoaffinity Column Cleanup and Isotope Dilution.

In this study, a gas chromatography-mass spectrometry (GC-MS) method was established for the determination of zearalenone and its five derivatives in feed, including zearalanone, α-zearalanol, ß-zearalanol, α-zearalenol, and ß-zearalenol. An effective immunoaffinity column was prepared for sample purification, which was followed by the silane derivatization of the eluate after an immunoaffinity chromatography analysis for target compounds by GC-MS. Matrix effects were corrected by an isotope internal standard of zearalenone in this method. The six analytes had a good linear relationship in the range of 2-500 ng/mL, and the correlation coefficients were all greater than 0.99. The limits of detection (LODs) and limits of quantification (LOQs) were less than 1.5 µg/kg and 5.0 µg/kg, respectively. The average spike recoveries for the six feed matrices ranged from 89.6% to 112.3% with relative standard deviations (RSDs) less than 12.6%. Twenty actual feed samples were analyzed using the established method, and at least one target was detected. The established GC-MS method was proven to be reliable and suitable for the determination of zearalenone and its derivatives in feed.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Metagenomic insight into the microbial degradation of organic compounds in fermented plant leaves.

Microbial degradation of organic compounds is an environmentally benign and energy efficient part in product processing. Fermentation of plant leaves involves enzymatic actions of many microorganisms. However, microbes and enzymes discovered from natural degradation communities were still limited by cultural methods. In this study, we used a metagenomics sequence-guided strategy to identify the microbes and enzymes involved in compound degradation and explore the potential synergy among community members in fermented tobacco leaves. The results showed that contents of protein, starch, pectin, lignin, and cellulose varied in fermented leaves from different growing sites. The different compound contents were closely related to taxonomic composition and functional profiles of foliar microbial communities. Microbial communities showed significant correlations with protein, lignin, and cellulose. Vital species for degradations of protein (Bacillus cereus and Terribacillus aidingensis), lignin (Klebsiella pneumoniae and Pantoea ananatis) and cellulose (Pseudomonas putida and Sphingomonas sp. Leaf20) were identified and relating hydrolytic enzymes were annotated. Further, twenty-two metagenome-assembled genomes (MAGs) were assembled from metagenomes and six potential cellulolytic genomes were used to reconstruct the cellulose-degrading process, revealing the potential metabolic cooperation related to cellulose degradation. Our work should deepen the understanding of microbial roles in plant fermentation and provide a new viewpoint for applying microbial consortia to convert plant organic components to small molecules.

Longitudinal genomic alternations and clonal dynamics analysis of primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus (PMME) is a rare gastrointestinal melanoma with a high rate of recurrence and metastasis. The standard of care for PMME has not been established yet due to a lack of understanding of its clinical and molecular pathogenesis. Thus, we performed genomic profiling on a recurrent PMME case to seek novel opportunities for the management of this rare disease. Between 2013 and 2016, 6 tissue samples including 3 from the primary tumors, 2 from the relapsed tumors, and 1 from a normal control were collected from a patient diagnosed with PMME and were subjected to whole-exome sequencing to track the dynamic genetic changes. Additionally, we also analyzed a cohort of 398 samples obtained from the TCGA skin cutanesous melanoma (TCGA-SKCM) dataset to assess the frequency and determine the clinical implications of genomic events found in the presented study. ARHGAP35 (p.L1022M) was the only mutation shared across temporal PMME lesions. The PMME samples showed higher levels of genetic instability and intra-tumor heterogeneity. They also shared several concordant copy number variations (CNV). All lesions were concordant with the evolution trajectory, and shrinkage of the founding clone caused the subclonal population to become dominant in PT1c, which was likely the reason behind metastatic seeding. ARHGAP35 mutations were found in 6% of the TCGA-SKCM cohort samples. The presence of the mutations was associated with poor progression-free survival (PFS) by both univariate and multivariate Cox regression analyses. Our study showed that the primary tumor clone disseminates earlier in PMME. This highlights the need to understand the mechanism involved in the early PMME recurrence to optimize treatment.

Combined Developmental Toxicity of the Pesticides Difenoconazole and Dimethomorph on Embryonic Zebrafish.

Difenoconazole (DIF) and dimethomorph (DIM) are widely used pesticides frequently detected together in environmental samples, so the deleterious effects of combined exposure warrant detailed examination. In this study, the individual and combined effects of DIM and DIF on conventional developmental parameters (hatching rate, deformity rate, lethality) and gene expression were measured in embryonic zebrafish. Both DIF and DIM interfered with normal zebrafish embryo development, and the most sensitive toxicity index for both was 96 h post-fertilization (hpf) deformity rate (BMDL10 values of 0.30 and 1.10 mg/L, respectively). The combination of DIF and DIM had mainly synergistic deleterious effects on 96 hpf deformity and mortality rates. Transcriptome analysis showed that these compounds markedly downregulated expression of mcm family genes, cdk1, and cdc20, thereby potentially disrupting DNA replication and cell cycle progression. Enhanced surveillance for this pesticide combination is recommended as simultaneous environmental exposure may be substantially more harmful than exposure to either compound alone.

Individual and synergistic toxic effects of carbendazim and chlorpyrifos on zebrafish embryonic development.

The fungicide carbendazim and the insecticide chlorpyrifos are frequently used together to protect various fruit and vegetable crops in China. At high doses, carbendazim is a known carcinogen while chlorpyrifos has neurotoxic potential, but the combined toxicity of these two compounds has not been systematically investigated. In this study, we examined the separate and combined effects of these compounds on zebrafish embryonic development. The LC50 values for carbendazim and chlorpyrifos at 96 h post-fertilization (hpf) were 0.89 mg/L and 3.83 mg/L, respectively. Carbendazim dose-dependently increased the spontaneous tail-wagging frequency of 24 hpf embryos, the hatching rate of 48 hpf embryos, and the mortality and deformity rate of 96 hpf embryos, while chlorpyrifos increased the heart rate of 48 hpf embryos as well as the mortality and deformity rate of 96 hpf embryos. Mixed exposure at an equipotent concentration ratio (Mix1) and at the ratio of maximum residue limits for typical fruits (apples) (Mix2) revealed significant synergistic effects on lethality at 96 hpf within the 0%-90% effect levels range. In contrast, there was an antagonistic effect of the equipotent concentration ratio on lethality in the 90%-100% concentration range, while the ratio at the maximum residue limits still showed a synergistic effect. Mix1 exhibited antagonism on hatching rate in the 0%-35% range and synergy in the 40%-100% range, while Mix2 had a synergistic effect on hatching rate in the 0%-35% range, an additive effect at 40%, and an antagonistic effect at >40%. Both mixtures had a synergistic effect on deformity rate over all concentration ranges. Carbendazim and chlorpyrifos demonstrate synergistic developmental toxicity, indicating that health and environmental risk assessments should be conducted for various combinations of these agents.

Analysis of ethoxyquin and its oxidation products in swine tissues by gas chromatography-tandem mass spectrometry for evaluating the feed-to-animal tissue transfer of ethoxyquin and its metabolites.

BACKGROUND: Ethoxyquin (EQ) is a common antioxidant which is widely used in animal feed. But the supplement of EQ in animal feed may lead to the residues of EQ and its major oxidation products: ethoxyquin quinone imine (EQI) and ethoxyquin dimer (EQDM) in animal tissue. Thus, it would pose potential health hazards to consumers. However, the method for the simultaneous determination of EQ, EQI and EQDM in animal tissues is currently not available, and the accumulation extend of these chemicals in animal tissues after EQ administration remains to be evaluated. RESULTS: A gas chromatography-tandem mass spectrometry method was successfully developed for the simultaneous determination of EQ, EQI and EQDM in swine tissues. The quantitative limits of EQ, EQI and EQDM can achieve to 0.5, 5.0 and 5.0 µg/kg in swine tissues, respectively. The spiked-recovery ratios of the three analytes (5-2000 µg/kg) were in the range of 64.7%-100.7% with relative standard deviations below 11.6%. Moreover, the utilization of this method for the analysis of actual swine tissue samples revealed that the application of commercial EQ additive in swine diet would produce the residues of all the three chemicals (EQ, EQI and EQDM) in fat, kidney, liver and muscle. CONCLUSIONS: The assay accuracy and precision of this GC-MS/MS method can meet the requirement of quantitative analysis. Meanwhile, the safety of EQ as a feed additive should be seriously considered with regard to food safety concerns since the oxidation product of EQ may have potential carcinogenicity.

Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells.

Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot. Results revealed that after pretreatment with curcumin for 3 h, copper-induced toxicity and apoptosis show a significant decline. Further experiments showed that curcumin not only decreased the production of ROS and MDA but also increased the activities of the ROS scavenging enzymes SOD and CAT. Moreover, curcumin treatment alleviated the decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c induced by copper. The protein levels of pro-caspase 3, pro-caspase 9, and PARP1 were up-regulated and the Bax/Bcl-2 ratio was down-regulated in the presence of curcumin. Taken together, our study demonstrates that curcumin has neuroprotective properties against copper in SH-SY5Y cells and the potential mechanisms might be related to oxidative stress and mitochondrial apoptosis.

Effects of organic chromium sources on growth performance, lipid metabolism, antioxidant status, breast amino acid and fatty acid profiles in broilers.

BACKGROUND: Trivalent chromium (Cr) is involved in carbohydrate, lipid, protein and nucleic acid metabolism in animals. This study evaluated the effects of different organic Cr forms with Cr methionine (CrMet), Cr picolinate (CrPic), Cr nicotinate (CrNic), and Cr yeast (Cr-yeast) at the level of 400 µg kg-1 Cr, on growth performance, lipid metabolism, antioxidant status, breast amino acid and fatty acid profiles of broilers. In total, 540 one-day-old Arbor Acres male broilers were randomly assigned to five treatments with six replicates (18 broilers per replicate) until day 42. RESULTS: The results showed growth performance was not affected by Cr sources. The Cr-yeast group had lower serum cortisol levels than the CrNic group (P < 0.05). Besides, Cr-yeast increased methionine and cysteine content in breast compared with the control group. Liver malondialdehyde content was lower in the CrMet group than the CrPic group on day 42 (P < 0.05). The n-3 polyunsaturated fatty acid (PUFA) values were increased, but the n-6/n-3 PUFA ratio was decreased in both CrMet and CrNic groups (P < 0.05). There were no significant effects on broilers' serum antioxidant status and breast total essential amino acid content among all treatments. CONCLUSIONS: Diets supplemented with organic Cr could regulate lipid metabolism, and improve amino acid and fatty acid profiles in broiler breast. Moreover, Cr-yeast was the most effective source in improving methionine and cysteine content, whereas CrMet was more effective than CrNic in increasing n-3 PUFA value and decreasing n-6/n-3 PUFA ratio in breast meat and effectively strengthened liver antioxidant ability than CrPic. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.