Polysaccharides from Fuzhuan brick tea(FBTPS),one of most important bioactive components in tea,showed various health-promoting functions.Our previous work demonstrated that the crude FBTPS(CFBTPS)could modulate the g...Polysaccharides from Fuzhuan brick tea(FBTPS),one of most important bioactive components in tea,showed various health-promoting functions.Our previous work demonstrated that the crude FBTPS(CFBTPS)could modulate the gut microbiota.However,which purified fraction in CFBTPS contributing to the modulation of gut microbiota remains unclear.Thus,the fermentation characteristics and probiotic activity of a purified fraction(FBTPS-2-1)of CFBTPS were evaluated in this work.The results showed that gut microbiota could utilize FBTPS-2-1 to produce short-chain fatty acids including acetic,propionic,n-butyric and n-valeric acids.FBTPS-2-1 could modulate the structure and metabolic pathways of gut microbiota.FBTPS-2-1 could increase the health-promoting gut microbiota such as Prevotellaceae and Bifidobacteriaceae,and decreased the harmful bacteria such as Enterobacteriaceae and Fusobacteriaceae.The results of metagenomics showed that Prevotella copri and Megamonas funiformis were the dominant bacteria after fermentation of FBTPS-2-1.Furthermore,FBTPS-2-1 could regulate the biosynthesis and metabolism pathways of gut microbiota.Thus,the enrichment of food with FBTPS-2-1 is expected as a potential strategy for promoting human health due to modulation of gut microbiota.展开更多
Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of ant...Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.展开更多
The release of the generative pre-trained transformer(GPT)series has brought artificial general intelligence(AGI)to the forefront of the artificial intelligence(AI)field once again.However,the questions of how to defi...The release of the generative pre-trained transformer(GPT)series has brought artificial general intelligence(AGI)to the forefront of the artificial intelligence(AI)field once again.However,the questions of how to define and evaluate AGI remain unclear.This perspective article proposes that the evaluation of AGI should be rooted in dynamic embodied physical and social interactions(DEPSI).More specifically,we propose five critical characteristics to be considered as AGI benchmarks and suggest the Tong test as an AGI evaluation system.The Tong test describes a value-and ability-oriented testing system that delineates five levels of AGI milestones through a virtual environment with DEPSI,allowing for infinite task generation.We contrast the Tong test with classical AI testing systems in terms of various aspects and propose a systematic evaluation system to promote standardized,quantitative,and objective benchmarks and evaluation of AGI.展开更多
Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairmen...Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.展开更多
The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,w...The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.展开更多
With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks...With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks that encompass a wide range of ability dimensions and difficulty levels.However,although many benchmarks exist,the field still lacks a quantification system to assess ability decompositions or difficulty levels.Here,we took the visual domain as a starting point and proposed an explainable system for task ability decomposition and difficulty level quantification of vision(TADDL-V).Using large language models,TADDL-V decomposed the visual abilities required for a given task and leveraged statistical data to map between ability sets and task difficulty levels.The estimated ability masses align with human intuition,and TADDL-V's task difficulty estimates are empirically validated against aggregated human comparisons of task difficulty.Furthermore,we proposed an AGI visual evaluation task set,AGI-V70,comprising 70 composite visual tasks that incorporate visual abilities across a broad spectrum of task difficulties.Together,TADDL-V serves as a prototype for ability decomposition and task difficulty level quantification,which are essential for future AGI evaluations.展开更多
Sialylated immunoglobulin G(IgG)is a kind of glycoproteins in breast milk with the property of anti-inflammation.Our previous work showed that sialylated IgG could significantly promote the growth of Bifidobacterium i...Sialylated immunoglobulin G(IgG)is a kind of glycoproteins in breast milk with the property of anti-inflammation.Our previous work showed that sialylated IgG could significantly promote the growth of Bifidobacterium in the gut microbiota of healthy volunteers.Nevertheless,whether sialylated IgG can benefit patients with inflammatory bowel disease(IBD)as prebiotics remains unclear.Therefore,its prebiotic effect on the gut microbiota of IBD patients was investigated by in vitro fermentation in this study.The results showed that sialylated IgG could significantly enhance the diversity,richness and composition of gut microbiota in IBD samples compared with non-sialylated IgG.In detail,sialylated IgG not only improved the growth of three common genera(Romboutsia,Prevotella and Akkermansia)with low relative abundance in IBD samples but also increased the genera(Bifidobacterium,Actinomyces,Atopobium and Citrobacter)with low relative abundance both in healthy and IBD fecal samples.Correspondingly,the contents of short-chain fatty acids for fermentation group of fecal sample from IBD patients with sialylated IgG as the carbon source were higher than those for fermentation group of fecal sample from IBD patients with non-sialylated IgG as the carbon source.In addition,the metabolic pathway results confirmed that sialylated IgG upregulated the functional genes related to hydrolysis,absorption and utilization of carbohydrates.The transcriptome sequencing results further showed that sialylated IgG could induce particular gene expression of Bifidobacterium bifidum to modulate the gut microbiota of IBD patients.Thus,as a kind of natural dietary component,sialylated IgG has potential applications in treating IBD.展开更多
Antibody–drug conjugates(ADCs)take the advantage of monoclonal antibodies to selectively deliver highly potent cytotoxic drugs to tumor cells,which have become a powerful measure for cancer treatment in recent years....Antibody–drug conjugates(ADCs)take the advantage of monoclonal antibodies to selectively deliver highly potent cytotoxic drugs to tumor cells,which have become a powerful measure for cancer treatment in recent years.To develop a more effective therapy for human epidermal growth factor receptor 2(HER2)-positive cancer,we explored a novel ADCs composed of anti-HER2 scFv–HSA fusion antibodies conjugates with a potent cytotoxic drug DM1.The resulting ADCs,T-SA1–DM1 and T-SA2–DM1(drug-to-antibody ratio in the range of 3.2–3.5)displayed efficient inhibition in the growth of HER2-positive tumor cell lines and the half-maximal inhibitory concentration on SKBR-3 and SKOV3 cells were both at the nanomolar levels in vitro.In HER2-positive human ovarian cancer xenograft models,T-SA1–DM1 and T-SA2–DM1 also showed remarkable antitumor activity.Importantly,three out of six mice exhibited complete remission without regrowth in the high-dose group of T-SA1–DM1.On the basis of the analysis of luminescence imaging,anti-HER2 scFv–HSA fusion antibodies,especially T-SA1,showed strong and rapid tumor tissue penetrability and distribution compared with trastuzumab.Collectively,the novel type of ADCs is effective and selective targeting to HER2-positive cancer,and may be a promising antitumor drug candidate for further studies.展开更多
基金supported by the National Natural Science Foundation of China(No.32001645 and No.31972025)the National Key Research and Development Program of China(2018YFC1604404)the Fundamental Research Funds for the Central Universities(KJQN202154)。
文摘Polysaccharides from Fuzhuan brick tea(FBTPS),one of most important bioactive components in tea,showed various health-promoting functions.Our previous work demonstrated that the crude FBTPS(CFBTPS)could modulate the gut microbiota.However,which purified fraction in CFBTPS contributing to the modulation of gut microbiota remains unclear.Thus,the fermentation characteristics and probiotic activity of a purified fraction(FBTPS-2-1)of CFBTPS were evaluated in this work.The results showed that gut microbiota could utilize FBTPS-2-1 to produce short-chain fatty acids including acetic,propionic,n-butyric and n-valeric acids.FBTPS-2-1 could modulate the structure and metabolic pathways of gut microbiota.FBTPS-2-1 could increase the health-promoting gut microbiota such as Prevotellaceae and Bifidobacteriaceae,and decreased the harmful bacteria such as Enterobacteriaceae and Fusobacteriaceae.The results of metagenomics showed that Prevotella copri and Megamonas funiformis were the dominant bacteria after fermentation of FBTPS-2-1.Furthermore,FBTPS-2-1 could regulate the biosynthesis and metabolism pathways of gut microbiota.Thus,the enrichment of food with FBTPS-2-1 is expected as a potential strategy for promoting human health due to modulation of gut microbiota.
基金supported by the Key Technology R&D Program of Jiangsu Province(BE2020341)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Theasinensin A(TSA),a dimer of epigallocatechin gallate,has been preliminarily demonstrated to have hypoglycemia and anti-inflammatory effects.However,little information is available on its potential mechanisms of anti-diabetes.Therefore,the present study aimed to investigate the influence of TSA on glucose and lipid metabolism and gut microbiota in high-fat-diet/streptozotocin-induced diabetic mice.As result,TSA improved polydipsia,polyphagia and impaired glucose tolerance of diabetic mice,declined the fasting blood glucose and hepatic triglyceride level,and enhanced the expression at mRNA level of insulin receptor substrate,phosphoinositide 3-kinase,protein kinase B and glucagon-like peptide 1 receptor(GLP-1R)in the diabetic liver.Moreover,TSA could restore the disorder of gut microbiota of diabetic mice.High-dose(100 mg/kg)TSA showed better benefi cial effects from the blood biochemical parameters,hepatic function and gut microbiota.In general,high-dose TSA significantly modulated gut microbiota by increasing the relative abundance of Akkermansia and decreasing the relative abundances of Acetatifactor,Anaerotruncus,Pseudofl avonifactor,Oscillibacter and Clostridium clusters.The results indicated that TSA could exert an anti-diabetes effect in diabetic mice through restoring glucose homeostasis,declining hepatic steatosis,activating insulin and GLP-1 signaling pathways,and ameliorating gut microbiota dysbiosis.
基金supported by the National Key Research and Development Program of China (2022ZD0114900).
文摘The release of the generative pre-trained transformer(GPT)series has brought artificial general intelligence(AGI)to the forefront of the artificial intelligence(AI)field once again.However,the questions of how to define and evaluate AGI remain unclear.This perspective article proposes that the evaluation of AGI should be rooted in dynamic embodied physical and social interactions(DEPSI).More specifically,we propose five critical characteristics to be considered as AGI benchmarks and suggest the Tong test as an AGI evaluation system.The Tong test describes a value-and ability-oriented testing system that delineates five levels of AGI milestones through a virtual environment with DEPSI,allowing for infinite task generation.We contrast the Tong test with classical AI testing systems in terms of various aspects and propose a systematic evaluation system to promote standardized,quantitative,and objective benchmarks and evaluation of AGI.
基金the financial support from the Key Research and Development Program of Ningxia Hui Autonomous Region of China(2021BEF02008)the National Natural Science Foundation of China(32272330)the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.
基金funded by the National Science and Technology Major Project for Major New Drug Innovation and Development(2017ZX09302010).
文摘The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.
基金supported by the National Science and Technology Major Project(Grant No.2022ZD0114900)the National Natural Science Foundation of China(Grant Nos.32471151,32200854)the Young Elite Scientists Sponsorship Program(Grant No.2021QNRC00)to Yujia PENG。
文摘With the rapid development of multi-modal foundation models and the pursuit of artificial general intelligence(AGI),there is a growing need for corresponding evaluation systems.Systematic AGI evaluation requires tasks that encompass a wide range of ability dimensions and difficulty levels.However,although many benchmarks exist,the field still lacks a quantification system to assess ability decompositions or difficulty levels.Here,we took the visual domain as a starting point and proposed an explainable system for task ability decomposition and difficulty level quantification of vision(TADDL-V).Using large language models,TADDL-V decomposed the visual abilities required for a given task and leveraged statistical data to map between ability sets and task difficulty levels.The estimated ability masses align with human intuition,and TADDL-V's task difficulty estimates are empirically validated against aggregated human comparisons of task difficulty.Furthermore,we proposed an AGI visual evaluation task set,AGI-V70,comprising 70 composite visual tasks that incorporate visual abilities across a broad spectrum of task difficulties.Together,TADDL-V serves as a prototype for ability decomposition and task difficulty level quantification,which are essential for future AGI evaluations.
基金The study was supported by the National Key Research and Development Program of China(2017YFD0400600)the National Natural Science Foundation of China(No.31901617)+5 种基金the Top Talent Project of Department of Education of Anhui Province(gxyqZD2021125)the Excellent Talent project of Anhui Science and Technology University(XJYXRC202101)the Stable Talent Personnel Project of Anhui Science and Technology University(SPWD202101)the Graduate Innovation and Entrepreneurship Training Program of Anhui Province(2022cxcysj199)the Natural Science Research Foundation of Department of Education of Anhui Province(2022AH040236)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Sialylated immunoglobulin G(IgG)is a kind of glycoproteins in breast milk with the property of anti-inflammation.Our previous work showed that sialylated IgG could significantly promote the growth of Bifidobacterium in the gut microbiota of healthy volunteers.Nevertheless,whether sialylated IgG can benefit patients with inflammatory bowel disease(IBD)as prebiotics remains unclear.Therefore,its prebiotic effect on the gut microbiota of IBD patients was investigated by in vitro fermentation in this study.The results showed that sialylated IgG could significantly enhance the diversity,richness and composition of gut microbiota in IBD samples compared with non-sialylated IgG.In detail,sialylated IgG not only improved the growth of three common genera(Romboutsia,Prevotella and Akkermansia)with low relative abundance in IBD samples but also increased the genera(Bifidobacterium,Actinomyces,Atopobium and Citrobacter)with low relative abundance both in healthy and IBD fecal samples.Correspondingly,the contents of short-chain fatty acids for fermentation group of fecal sample from IBD patients with sialylated IgG as the carbon source were higher than those for fermentation group of fecal sample from IBD patients with non-sialylated IgG as the carbon source.In addition,the metabolic pathway results confirmed that sialylated IgG upregulated the functional genes related to hydrolysis,absorption and utilization of carbohydrates.The transcriptome sequencing results further showed that sialylated IgG could induce particular gene expression of Bifidobacterium bifidum to modulate the gut microbiota of IBD patients.Thus,as a kind of natural dietary component,sialylated IgG has potential applications in treating IBD.
基金financially supported by the National Science Foundation of China(nos 81372822,81402564 and 81572995)National High Technology Research and Development Program of China(no.2015AA020904)Guangdong Innovative Research Team Program(no.2011Y073).
文摘Antibody–drug conjugates(ADCs)take the advantage of monoclonal antibodies to selectively deliver highly potent cytotoxic drugs to tumor cells,which have become a powerful measure for cancer treatment in recent years.To develop a more effective therapy for human epidermal growth factor receptor 2(HER2)-positive cancer,we explored a novel ADCs composed of anti-HER2 scFv–HSA fusion antibodies conjugates with a potent cytotoxic drug DM1.The resulting ADCs,T-SA1–DM1 and T-SA2–DM1(drug-to-antibody ratio in the range of 3.2–3.5)displayed efficient inhibition in the growth of HER2-positive tumor cell lines and the half-maximal inhibitory concentration on SKBR-3 and SKOV3 cells were both at the nanomolar levels in vitro.In HER2-positive human ovarian cancer xenograft models,T-SA1–DM1 and T-SA2–DM1 also showed remarkable antitumor activity.Importantly,three out of six mice exhibited complete remission without regrowth in the high-dose group of T-SA1–DM1.On the basis of the analysis of luminescence imaging,anti-HER2 scFv–HSA fusion antibodies,especially T-SA1,showed strong and rapid tumor tissue penetrability and distribution compared with trastuzumab.Collectively,the novel type of ADCs is effective and selective targeting to HER2-positive cancer,and may be a promising antitumor drug candidate for further studies.
