Aflatoxins B1(AFB1)contamination in agro-food holds great threaten to human and animal health.Conventional test strips for rapid AFB1 visualized monitoring remains challenged by improvement of sensitivity and matrix i...Aflatoxins B1(AFB1)contamination in agro-food holds great threaten to human and animal health.Conventional test strips for rapid AFB1 visualized monitoring remains challenged by improvement of sensitivity and matrix interference resistance.In this case,we developed a portable electrochemiluminescence(ECL)imaging test strip with dual-signal outputs for AFB1 quantification in corn samples.RuPEI@SiO_(2)@Au nanospheres were synthesized for bonding with anti-AFB1 antibody and then colorimetrical signal-reported on test line through the capillary flow at strips.Meanwhile,ECL imaging signal of the constructed carbon-ink-based working electrode on polyvinyl chloride substrate of strips was exported under an applied potential of 1.25 V.The whole ECL test strips not only endowed convenient colorimetric responses but guaranteed quick-witted ECL image distinguishment even at extremely low AFB1 content.The detection limit of this ECL imaging-integrated mode was 10-fold lower than that of only colorimetric mode.Furthermore,satisfactory selectivity,reliability and practicability of the as-proposed ECL test strips were demonstrated.This work offered a promising platform for on-site,accurate and sensitive detection of pollutants in foods.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
文摘目的探究肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)分子亚型特异性,为不同MIBC分子亚型患者的治疗提供指导。方法基于MIBC分子分型方法中的UNC分型法,应用转录组测序数据,将48例MIBC患者分为2种分子亚型即Basal型和Luminal型,并进行差异表达分析以探究MIBC特异性的lncRNAs,并进一步探讨其分子特征和临床意义。结合单细胞质谱流式细胞术(single-cell mass cytometry,CyTOF)和镜像质谱流式细胞术(imaging mass cytometry,IMC)分析MBNL1-AS1高表达组和低表达组Basal型MIBC患者的免疫微环境异质性。结果基于分子分型法筛选发现了在MIBC特异性表达的lncRNA MBNL1-AS1,其低表达与Basal型MIBC患者的不良预后密切相关(P=0.022)。且进一步分析转录组测序数据后发现,在Basal型MIBC中,MBNL1-AS1低表达组具有去分化(P=0.008)、高干性(P=0.020)和高增殖(P=0.010)的特征。MBNL1-AS1低表达组的Basal型MIBC患者的免疫评分与NK CD56bright细胞和Treg细胞的评分呈负相关(P<0.05),而MBNL1-AS1高表达组的B细胞和CD8+T细胞相关基因的表达水平较高。高维度单细胞蛋白质组学分析结果显示,MBNL1-AS1低表达的Basal型MIBC患者表现出较高的Treg细胞亚群丰度(P=0.016)。结论MBNL1-AS1低表达组的Basal型MIBC患者具有去分化、高干性、高增殖和免疫抑制的特点。MBNL1-AS1具有作为Basal型MIBC免疫响应生物标志物的潜能。
基金financially supported by China Postdoctoral Science Foundation(No.2022T150708)National Key Research and Development Program of China(No.2023YFF1104600)National Natural Science Foundation of China(Nos.32072305,32102089)。
文摘Aflatoxins B1(AFB1)contamination in agro-food holds great threaten to human and animal health.Conventional test strips for rapid AFB1 visualized monitoring remains challenged by improvement of sensitivity and matrix interference resistance.In this case,we developed a portable electrochemiluminescence(ECL)imaging test strip with dual-signal outputs for AFB1 quantification in corn samples.RuPEI@SiO_(2)@Au nanospheres were synthesized for bonding with anti-AFB1 antibody and then colorimetrical signal-reported on test line through the capillary flow at strips.Meanwhile,ECL imaging signal of the constructed carbon-ink-based working electrode on polyvinyl chloride substrate of strips was exported under an applied potential of 1.25 V.The whole ECL test strips not only endowed convenient colorimetric responses but guaranteed quick-witted ECL image distinguishment even at extremely low AFB1 content.The detection limit of this ECL imaging-integrated mode was 10-fold lower than that of only colorimetric mode.Furthermore,satisfactory selectivity,reliability and practicability of the as-proposed ECL test strips were demonstrated.This work offered a promising platform for on-site,accurate and sensitive detection of pollutants in foods.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
