Comprehensive analysis of advanced glycation end-products in commonly consumed foods:presenting a database for dietary AGEs and associated exposure assessment

Advanced glycation end-products(AGEs)are a group of heterogeneous compounds formed in heatprocessed foods and are proven to be detrimental to human health.Currently,there is no comprehensive database for AGEs in foods that covers the entire range of food categories,which limits the accurate risk assessment of dietary AGEs in human diseases.In this study,we first established an isotope dilution UHPLCQq Q-MS/MS-based method for simultaneous quantification of 10 major AGEs in foods.The contents of these AGEs were detected in 334 foods covering all main groups consumed in Western and Chinese populations.Nε-Carboxymethyllysine,methylglyoxal-derived hydroimidazolone isomers,and glyoxal-derived hydroimidazolone-1 are predominant AGEs found in most foodstuffs.Total amounts of AGEs were high in processed nuts,bakery products,and certain types of cereals and meats(>150 mg/kg),while low in dairy products,vegetables,fruits,and beverages(<40 mg/kg).Assessment of estimated daily intake implied that the contribution of food groups to daily AGE intake varied a lot under different eating patterns,and selection of high-AGE foods leads to up to a 2.7-fold higher intake of AGEs through daily meals.The presented AGE database allows accurate assessment of dietary exposure to these glycotoxins to explore their physiological impacts on human health.

Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases:A dangerous liaison?

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

Receptor of advanced glycation end-products axis and gallbladder cancer:A forgotten connection that we should reconsider

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications

BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.

Advanced-glycation end-products axis:A contributor to the risk of severe illness from COVID-19 in diabetes patients

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial role of the receptor for advanced-glycation end-products(RAGE)in orchestrating a plethora of proinflammatory cellular responses leading to many of the complications and end-organ damages reported in patients with diabetes mellitus(DM).During the coronavirus disease 2019(COVID-19)pandemic,many clinical reports have pointed out that DM increases the risk of COVID-19 complications,hospitalization requirements,as well as the overall severe acute respiratory syndrome coronavirus 2 case-fatality rate.In the present review,we intend to focus on how the basal activation state of the RAGE axis in common preexisting conditions in DM patients such as endothelial dysfunction and hyperglycemia-related prothrombotic phenotype,as well as the contribution of RAGE signaling in lung inflammation,may then lead to the increased mortality risk of COVID-19 in these patients.Additionally,the crosstalk between the RAGE axis with either another severe acute respiratory syndrome coronavirus 2 receptor molecule different of angiotensin-converting enzyme 2 or the renin-angiotensin system imbalance produced by viral infection,as well as the role of this multi-ligand receptor on the obesity-associated lowgrade inflammation in the higher risk for severe illness reported in diabetes patients with COVID-19,are also discussed.

Lactobacillus fermentum as a new inhibitor to control advanced glycation end-product formation during vinegar fermentation

The inhibitory activity of lactic acid bacteria(LAB)toward advanced glycation end-products(AGEs)during vinegar fermentation was studied,and its relationships with the substrate consumption,antioxidant capacity,total phenolic content,total flavonoid compounds,α-glucosidase,andα-amylase activity inhibition were evaluated.The vinegar was made from rice powder flour by liquid-state fermentation(LSF).The selected LAB strains were separately co-cultivated with Saccharomyces cerevisiae and Acetobacter pasteurianus 1.41 in alcoholic and acetic acid fermentation,respectively.Among 3 strains,Lactobacillus fermentum showed the strongest inhibitory effect on the formation of total fluorescent AGEs and carboxymethyl lysine(CML)/carboxyethyl lysine(CEL)in the fermentation process.The corresponding mechanisms included the acceleration of substrate consumtion,improvement of antioxidant activities,and inhibition ofα-glucosidase andα-amylase.In addition,the fluorescent AGEs and the CML/CEL were negatively correlated with the antioxidant activities,while theα-glucosidase andα-amylase activities were positively correlated with the total phenols and total flavonoids.Moreover,the variety of main flavor compounds increased,including esters,alcohols,phenols and acids.The results of the study support the potential use of screened LAB strains to inhibit the formation of fluorescent AGEs,CML and CEL on fermented products and in the food processing industry,without associated risks to consumers.

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the study.From 18 wk of age,the body weight and blood glucose were measured every week and 2 wk respectively.When the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was measured.The segments were fixed in 10% formalin,embedded in paraffin and five micron sections were cut.The layer thickness was measured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis software.RESULTS:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the experiment.The wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial cells.The AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs 22.45 ± 1.26,P < 0.01 for mucosa).No visible difference was found for RAGE distribution between the two groups.In the intestine AGE and RAGE distributed in epithelial cells of villi and crypt.RAGE was also found in neurons in the myenteric and submucosal plexus.The intensity of AGE staining in mucosa of all segments and RAGE staining in neurons in all segments were strongest in the diabetes group.Significant difference for AGE was found in the epithelial cells of villi and crypt in duodenum(immunopositive area/total measuring area %:13.37 ± 3.51 vs 37.48 ± 8.43,P < 0.05 for villi; 0.38 ± 0.12 vs 1.87 ± 0.53,P < 0.05 for crypt) and for RAGE in neurons of all segments(e.g.,for jejunum:no staining neurons% 0 vs 0,mild 36.0 ± 5.2 vs 28.7 ± 3.5,moderate 53.2 ± 4.8 vs 55.8 ± 5.4,strong 10.7 ± 1.1 vs 15.4 ± 2.0,P < 0.05).In the colon,RAGE was primarily found in neurons in the myenteric and submucosal plexus.It was stronger in the diabetes group than in the normal group(no staining neurons% 6.2 ± 0.2 vs 0.3 ± 0.04,mild 14.9 ± 2.1 vs 17.6 ± 1.5,moderate 53.1 ± 4.6 vs 44.7 ± 4.4,strong 25.6 ± 18 vs 43.6 ± 4.0,P < 0.05).In the rectum,RAGE was primarily found in the mucosa epithelial cells.CONCLUSION:The AGE and RAGE expression was upregulated in the GI tract of GK diabetic rats and may contribute to GI dysfunction in type 2 diabetic patients.

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

Rosiglitazone inhibits expression of acyl-coenzyme A:cholesterol acyltransferase-1 in THP-1 macrophages induced by advanced glycation end-products

Objective:To investigate the effects of rosiglitazone,a synthetic ligand of peroxisome proliferators-activated receptor gamma(PPARγ),on the expression of acyl-coenzyme A:cholesterol acyltransferase-1(ACAT-1) in phorbol myristate acetate(PMA)-pretreated THP-1 cells after the inducement of advanced glycation end products(AGEs).Methods:After THP-1 cells were cultured in the presence of 0.1 μmol/L PMA for 72 h to induce phagocytic differentiation,the obtained THP-1 macrophages were treated with rosiglitazone for 4 h at different concentrations(1,5 or 10 μmol/L) and then exposed to AGEs-modified bovine serum albumin(AGEs-BSA) for 24 h at a concentration of 200 mg/L.Reverse transcription polymerase chain reaction(RT-PCR) and Western blot analysis were performed to detect the mRNA and protein expressions of ACAT-1 respectively.Results:Administration of AGEs-BSA(200 mg/L) into the THP-1 macrophages resulted in up-regulation of ACAT-1 at mRNA and protein levels when compared with the expressions in macrophages incubated with serum-free RPMI1640.Pretreatment of rosiglitazone inhibited significantly the increased expression of ACAT-1 induced by AGEs-BSA in a concentration-dependent manner.Conclusion:PPARγ activation by rosiglitazone down-regulates ACAT-1 expression induced by AGEs in THP-1 macrophages,which might provide a new way for treating atherogenesis in diabetic patients.

Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion

AIM To determine the possibility that diabetes mellitus promotes pancreatic ductal adenocarcinoma via glyceraldehyde(GA)-derived advanced glycation-end products(GA-AGEs).METHODS PANC-1,a human pancreatic cancer cell line,was treated with 1-4 mmol/L GA for 24 h. The cell viability and intracellular GA-AGEs were measured by WST-8 assay and slot blotting. Moreover,immunostaining of PANC-1 cells with an anti-GA-AGE antibody was performed. Western blotting(WB) was used to analyze the molecular weight of GA-AGEs. Heat shock proteins 90α,90β,70,27 and cleaved caspase-3 were analyzed by WB. In addition,PANC-1 cells were treated with GA-AGEs-bovine serum albumin(GA-AGEs-BSA),as a model of extracellular GA-AGEs,and proliferation of PANC-1 cells was measured.RESULTS In PANC-1 cells,GA induced the production of GA-AGEs and cell death in a dose-dependent manner. PANC-1 cell viability was approximately 40% with a 2 mmol/L GA treatment and decreased to almost 0% with a 4 mmol/L GA treatment(each significant difference was P < 0.01). Cells treated with 2 and 4 mmol/L GA produced 6.4 and 21.2 μg/mg protein of GA-AGEs,respectively(P <0.05 and P < 0.01). The dose-dependent production of some high-molecular-weight(HMW) complexes of HSP90β,HSP70,and HSP27 was observed following administration of GA. We considered HMW complexes to be dimers and trimers with GA-AGEs-mediated aggregation. Cleaved caspase-3 could not be detected with WB. Furthermore,10 and 20 μg/m L GA-AGEs-BSA was 27% and 34% greater than that of control cells,respectively(P < 0.05 and P < 0.01).CONCLUSION Although intracellular GA-AGEs induce pancreatic cancer cell death,their secretion and release may promote the proliferation of other pancreatic cancer cells.

肉制品中晚期糖基化终末产物研究进展

肉类富含蛋白质和脂质,有利于晚期糖基化终末产物(AGEs)的生成。研究表明,AGEs会对人体产生多种危害,应尽量减少其在加工过程中的生成量。本文对近年来食品中尤其是肉制品中AGEs的形成、危害、检测进行介绍,并综述影响肉制品中AGEs生成量的因素,以期为探究减少肉制品加工过程中AGEs生成量的新方法提供思路。

CML、sRAGE、esRAGE对冠心病动脉粥样硬化的诊断价值

目的探讨ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)、内源性可溶性晚期糖基化终产物受体(esRAGE)对冠心病动脉粥样硬化的诊断价值。方法2020年6月至2022年12月,于新疆维吾尔自治区人民医院选取冠心病患者100例作为观察组。同时选取100例在我院体检的正常人作为对照组。比较两组ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)和内源性分泌性晚期糖基化终产物受体(esRAGE)水平。应用受试者操作者特征(ROC)曲线评价CML、sRAGE、esRAGE的诊断水平,并联合检测冠心病动脉粥样硬化。结果与对照组相比,观察组血清CML及sRAGE水平明显升高,而esRAGE水平呈下降趋势。血清CML、sRAGE和esRAGE可准确诊断冠心病动脉粥样硬化,联合检测灵敏度(90.91%)、特异性(68.66%)、准确性(76.00%)、阳性预测值(58.82%)、阴性预测值(93.88%)、ROC曲线下面积(AUC)(0.922)较高。结论CML、sRAGE、esRAGE与冠心病动脉粥样硬化有关,有利于临床诊断和治疗。

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

气象应用业务融入气象大数据云平台的设计

针对现有气象应用不能直接融入气象大数据平台的现状,该文采用“云+端”融入的方法,对气象应用的数据存储、产品加工、业务监控、应用接口以及应用端进行改造设计,使现有气象应用业务能够快速接入气象大数据云平台。该设计在湖北气象业务进行应用,避免了因气象业务智能化建设而造成的重复建设和资源浪费,有利于推动气象业务智能化发展,为今后气象应用改造提供了参考。

结肠癌病人血清S100钙结合蛋白A12、可溶性晚期糖基化终产物受体水平与肠道菌群失调及化疗效果的关系

目的探讨结肠癌病人血清S100钙结合蛋白A12(S100A12)、可溶性晚期糖基化终产物受体(sRAGE)水平与肠道菌群失调及化疗效果的相关性。方法选择2020年12月至2021年12月黄河水利委员会黄河中心医院收治的116例中、晚期结肠癌病人作为结肠癌组,另选取在该院同期健康体检人员120例作为对照组。采用酶联免疫吸附测定(ELISA)检测血清S100A12、sRAGE水平,检测病人肠道菌群,并对病人化疗后进行随访,Pearson法分析结肠癌病人血清S100A12、sRAGE水平与菌群失调相关性,受试者操作特征曲线(ROC曲线)分析化疗前血清S100A12、sRAGE水平对结肠癌化疗效果的诊断价值。结果与对照组比较,结肠癌组病人化疗前血清S100A12、sRAGE水平显著升高(P<0.05)。与化疗前菌群正常组[(265.34±45.78)μg/L、(381.54±36.75)ng/L]比较,菌群失调Ⅰ度组[(301.52±56.95)μg/L、(440.63±48.71)ng/L]、菌群失调Ⅱ度组[(339.29±52.35)μg/L、(432.75±49.20)ng/L]病人血清S100A12、sRAGE水平显著升高(P<0.05);与菌群失调Ⅰ度组比较,菌群失调Ⅱ度组病人血清S100A12、sRAGE水平显著升高(P<0.05)。相关性分析显示,结肠癌病人血清S100A12、sRAGE水平与大肠杆菌、粪肠球菌数量呈正相关(P<0.05),与双歧杆菌、乳酸杆菌数量呈负相关(P<0.05)。与化疗前比较,结肠癌病人化疗后血清S100A12、sRAGE水平显著降低(P<0.05);与化疗缓解组[(272.33±55.36)μg/L、(403.24±40.54)ng/L]比较,化疗无效组[(330.09±42.64)μg/L、(482.85±43.61)ng/L]病人化疗前血清S100A12、sRAGE水平显著较高(P<0.05)。血清S100A12、sRAGE联合诊断结肠癌化疗无效的曲线下面积(AUC)为0.91[95%CI:(0.84,0.96),P<0.001],灵敏度为86.05%,特异度为80.82%。结论结肠癌病人血清S100A12、sRAGE升高,与肠道菌群失调及化疗效果有关,对化疗疗效评估与预后评价有一定指导意义。

高端装备制造业贸易强度如何影响出口技术复杂度?——基于中国-东盟样本数据的分析

文章基于2010-2020年中国与东盟国家高端装备制造业贸易网络,运用高维固定效应模型考察高端装备制造行业贸易强度对出口技术复杂度的影响。研究结果显示:中国与东盟国家间的贸易强度对一国高端装备制造业出口技术复杂度的提升具有显著的正向影响,且贸易开放、技术创新是重要的作用机制。相较于轨道交通装备行业,贸易强度对航空装备、卫星及应用等其他领域的高端装备出口技术复杂度的提升效果更为显著。由此提出合理布局区域贸易网络、深化贸易开放和重视技术创新等对策建议,为推动我国高端装备制造业技术升级提供思路借鉴。

国有企业技术并购对企业模糊前端创新绩效的影响

基于多维邻近理论,探索技术并购对企业模糊前端创新绩效的影响,以及并购双方地理距离与收购方生产链位置的调节作用。利用2009—2019年国有企业并购数据进行实证检验,结果表明:并购双方技术相似性对企业模糊前端创新绩效具有显著负向影响,技术互补性对企业模糊前端创新绩效具有显著正向影响;并购双方地理距离、收购方所处生产链位置正向调节技术相似性与企业模糊前端创新绩效的关系以及技术互补性与企业模糊前端创新绩效的关系。采用工具变量法、替换样本研究区间和GMM估计法进行内生性与稳健性检验发现,上述结论依然成立。结论有助于深化对国有企业技术并购与模糊前端创新关系的认识,从而为企业通过技术并购实现模糊前端创新提供实践启示。

不同烟熏时间鸡腿肉香气化合物与危害物及相关前体物研究

为探究不同熏制时间下熏鸡风味成分和危害物的变化及其与前体物的关系,利用色谱质谱等技术对香气化合物、杂环胺(HAs)、晚期糖基化终末产物(AGEs)、多环芳烃(PAHs)、还原糖、游离氨基酸与脂肪酸等进行定性定量分析。结果表明,在熏鸡腿中共鉴定出67种香气化合物,气味活性值(OAVs)>1的香气化合物有24种,以愈创木酚贡献率最大。随着熏制时间增加,酚类化合物、HAs、AGEs和4种多环芳烃(PAH4)含量显著升高(P<0.05),而水分、肌酐和葡萄糖则逐渐减少。9H-吡啶并[3,4-b]吲哚(Norharman)、羧甲基赖氨酸(CML)、羧乙基赖氨酸(CEL)和?(Chr)是熏鸡中主要潜在危害物,熏制12 h后的含量分别为37.38 ng·g^(-1)、123.94μg·g^(-1)、180.13μg·g^(-1)和41.10μg·kg^(-1)。最佳熏制时间为6 h,长时间熏制不利于熏鸡香气化合物的保持且伴生大量危害物。相关性分析表明,壬醛、1-辛烯-3-醇、2,5-二甲基吡嗪等关键香气化合物含量与还原糖、部分游离氨基酸和不饱和脂肪酸含量显著负相关;Norharman、CEL和PAH4等含量与多种游离氨基酸、水分等含量显著或极显著负相关;苯丙氨酸、甲硫氨酸、酪氨酸和色氨酸等含量同时与香气化合物和危害物含量显著(P<0.05)或极显著正/负相关(P<0.01)。本研究揭示了熏鸡熏制过程中香气化合物与危害物协同伴生关系,可为熏鸡风味保持和危害物消减提供数据基础。