Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nucl...Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, harrier function and prevention of bacterial manslocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide, range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved展开更多
Farnesoid X receptor （FXR） is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metab...Farnesoid X receptor （FXR） is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is a potential drug target for a number of metabolic disorders, especially those related to the metabolic syndrome. More recently, our group and others have extended the functions of FXR to more than metabolic regulation, which include anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis. These new findings suggest that FXR has much broader roles than previously thought, and also higi.light FXR as a drug target for multiple diseases. This review summarizes the basic information of FXR but focuses on its new functions.展开更多
Understanding energy dissipation and transport in nanoscale structures is of great importance for the design of energy-efficient circuits and energy-conversion systems.This is also a rich domain for fundamental discov...Understanding energy dissipation and transport in nanoscale structures is of great importance for the design of energy-efficient circuits and energy-conversion systems.This is also a rich domain for fundamental discoveries at the intersection of electron,lattice(phonon),and optical(photon)interactions.This review presents recent progress in understanding and manipulation of energy dissipation and transport in nanoscale solid-state structures.First,the landscape of power usage from nanoscale transistors(~10^(-8) W)to massive data centers(~10^(-9) W)is surveyed.Then,focus is given to energy dissipation in nanoscale circuits,silicon transistors,carbon nanostructures,and semiconductor nanowires.Concepts of steady-state and transient thermal transport are also reviewed in the context of nanoscale devices with sub-nanosecond switching times.Finally,recent directions regarding energy transport are reviewed,including electrical and thermal conductivity of nanostructures,thermal rectification,and the role of ubiquitous material interfaces.展开更多
OBJECTIVE: To study changes in the nuclear factor-κB p65(NF-κB p65)-inducible nitric oxide synthase(i NOS)-nitric oxide(NO) signaling pathway and the effects of Xinfeng capsules(XFC) in patients with ankylosing spon...OBJECTIVE: To study changes in the nuclear factor-κB p65(NF-κB p65)-inducible nitric oxide synthase(i NOS)-nitric oxide(NO) signaling pathway and the effects of Xinfeng capsules(XFC) in patients with ankylosing spondylitis(AS)METHODS: One hundred twenty patients with AS were randomly divided into an XFC group and a Salazopyrin group. Sixty health subjects were included as a normal control group. In the two treatment groups, pulmonary functional parameters,forced vital capacity(FVC), forced expiratory volume in 1 second(FEV1), maximal voluntary ventilation(MVV), peak expiratory flow(PEF), forced expiratory flow at 25% of forced vital capacity(FEF25),forced expiratory flow at 50% of forced vital capacity(FEF50), and forced expiratory flow at 75% of forced vital capacity(FEF75) were determined. Enzyme linked immunosorbent assays were used for detection of the serum oxidative stress indexes,NF-κB p65, i NOS, NO, reactive oxygen species(ROS), reactive nitrogen species(RNS), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), total antioxidative capacity(TAOC) and interleukin-4(IL-4), IL-10, IL-1β, and tumor necrosis factor-α(TNF-α) contents. Westergren's method was used for determination of erythrocyte sedimentation rate(ESR). High-sensitivity C-reactive protein(Hs-CRP) was detected with a 7060 full-automatic biochemical analyzer(Hitachi, Japan).RESULTS: The clinical therapeutic effect in the XFC group was significantly superior to that in the Salazopyrin group(P<0.01). Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT,TAOC, IL-4, IL-10 were significantly lower, and NF-κB p65, i NOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR,and Hs-CRP significantly higher in patients with AS(P<0.01 or P<0.05). Compared with before treatment, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC,IL-4, and IL-10 were significantly increased, and NF-κB p65, i NOS, NO, ROS, RNS, MDA, IL-1β, TNF-α,ESR, CRP, visual analog scales(VAS), Bath ankylosing spondylitis disease active index, Bath ankylosing s展开更多
Macrophages exist in various tissues,several body cavities,and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers.Macrophages possess binary M1...Macrophages exist in various tissues,several body cavities,and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers.Macrophages possess binary M1/M2 macrophage polarization settings,which perform a central role in an array of immune tasks via intrinsic signal cascades and,therefore,must be precisely regulated.Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered.In addition,the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology.Moreover,they are an integral part of the tumor microenvironment,playing a part in the regulation of a wide variety of processes including angiogenesis,extracellular matrix transformation,cancer cell proliferation,metastasis,immunosuppression,and resistance to chemotherapeutic and checkpoint blockade immunotherapies.Herein,we discuss immune regulation in macrophage polarization and signaling,mechanical stresses and modulation,metabolic signaling pathways,mitochondrial and transcriptional,and epigenetic regulation.Furthermore,we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions.Moreover,we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis.Lastly,we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.展开更多
Obesity and its associated complications are highly related to a current public health crisis around the world.A growing body of evidence has indicated that G-protein coupled bile acid(BA) receptor TGR5(also known as ...Obesity and its associated complications are highly related to a current public health crisis around the world.A growing body of evidence has indicated that G-protein coupled bile acid(BA) receptor TGR5(also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders.We have identified notoginsenoside Ftl(Ftl) from Panax notoginseng as an agonist of TGR5 in vitro.However,the pharmacological effects of Ftl on diet-induced obese(DIO) mice and the underlying mechanisms are still elusive.Here we show that Ftl(100 mg/100 diet) increased adipose lipolysis,promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1(GLP-1) secretion in the ileum of wild type but not Tgr5^(-/-) obese mice.In addition,Ftl elevated serum free and taurineconjugated bile acids(BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose tissues.The metabolic benefits of Ftl were abolished in Cyp27 al^(-/-) mice which have much lower BA levels.These results identify Ftl as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.展开更多
Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknow...Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.展开更多
RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies...RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies,the sequencing cost is dropping dramatically with the sequencing output increasing sharply.However,the sequencing reads are still short in length and contain various sequencing errors.Moreover,the intricate transcriptome is always more complicated than we expect.These challenges proffer the urgent need of efficient bioinformatics algorithms to effectively handle the large amount of transcriptome sequencing data and carry out diverse related studies.This review summarizes a number of frequently-used applications of transcriptome sequencing and their related analyzing strategies,including short read mapping,exon-exon splice junction detection,gene or isoform expression quantification,differential expression analysis and transcriptome reconstruction.展开更多
Pretreatment of lower H2O2 doses （0.05, 0.5 and 5 mM） for 24 h was able to dose-dependently attenuate lipid peroxidation in wheat seedling leaves mediated by further oxidative damage elicited by higher dose of H2O2 ...Pretreatment of lower H2O2 doses （0.05, 0.5 and 5 mM） for 24 h was able to dose-dependently attenuate lipid peroxidation in wheat seedling leaves mediated by further oxidative damage elicited by higher dose of H2O2 （150 mM） for 6 h, with 0.5 mM H2O2 being the most effective concentrations. Further results illustrated that 0.5 mM H2O2 pretreatment triggered the biphasic production of H2O2 during a 24 h period. We also noticed that only peak Ⅰ （0.25 h） rather than peak Ⅱ （4 h） was approximately consistent with the enhancement of heme oxygenase （HO） activity, HO-1 gene expression. Meanwhile, enhanced superoxide dismutase （SOD） activity, Mn-SOD and Cu, Zn-SOD transcripts might be a potential source of peak Ⅰ of endogenous H2O2. Further results confirmed that 0.5 mM H2O2 treatment for 0.5 h was able to upregulate HO gene expression, which was detected by enzyme activity determination, semi-quantitative reverse transcription-polymerase chain reaction and western blotting. Meanwhile, the application of N,N＇-dimethylthiourea, a trap for endogenous H2O2, not only blocked the upregulation of HO, but also reversed the corresponding oxidation attenuation. Together, the above results suggest that endogenous H2O2 production （peak Ⅰ） plays a positive role in the induction of HO by enhancing its mRNA level and protein expression, thus leading to the acclimation to oxidative stress.展开更多
The Myc proto-oncogene family consists of three members,C-MYC,MYCN,and MYCL,which encodes the transcription factor c-Myc(hereafter Myc),N-Myc,and L-Myc,respectively.Myc protein orchestrates diverse physiological proce...The Myc proto-oncogene family consists of three members,C-MYC,MYCN,and MYCL,which encodes the transcription factor c-Myc(hereafter Myc),N-Myc,and L-Myc,respectively.Myc protein orchestrates diverse physiological processes,including cell proliferation,differentiation,survival,and apoptosis.Myc modulates about 15%of the global transcriptome,and its deregulation rewires the cellular signaling modules inside tumor cells,thereby acquiring selective advantages.The deregulation of Myc occurs in>70%of human cancers,and is related to poor prognosis;hence,hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades.Nevertheless,no specific drug is currently available to directly target Myc,mainly because of its"undruggable"properties:lack of enzymatic pocket for conventional small molecules to bind;inaccessibility for antibody due to the predominant nucleus localization of Myc.Although the topic of targeting Myc has actively been reviewed in the past decades,exciting new progresses in this field keep emerging.In this review,after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer,we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.展开更多
The role of fatty acid metabolism,including both anabolic and catabolic reactions in cancer has gained increas-ing attention in recent years.Many studies have shown that aberrant expression of the genes involved in fa...The role of fatty acid metabolism,including both anabolic and catabolic reactions in cancer has gained increas-ing attention in recent years.Many studies have shown that aberrant expression of the genes involved in fatty acid synthesis or fatty acid oxidation correlate with malignant phenotypes including metastasis,therapeutic resistance and relapse.Such phenotypes are also strongly associated with the presence of a small percentage of unique cells among the total tumor cell population.This distinct group of cells may have the ability to self-renew and propagate or may be able to develop resistance to cancer therapies independent of genetic alterations.Therefore,these cells are referred to as cancer stem cells/tumor-initiating cells/drug-tolerant persisters,which are often refractory to cancer treatment and difficult to target.Moreover,interconversion between cancer cells and cancer stem cells/tumor-initiating cells/drug-tolerant persisters may occur and makes treatment even more challenging.This review highlights recent findings on the relationship between fatty acid metabolism,cancer stemness and therapeutic resistance and prompts discussion about the potential mechanisms by which fatty acid metabolism regulates the fate of cancer cells and therapeutic resistance.展开更多
Ultrathin,lightweight,and flexible aligned single-walled carbon nanotube(SWCNT)films are fabricated by a facile,environmentally friendly,and scalable printing methodology.The aligned pattern and outstanding intrinsic ...Ultrathin,lightweight,and flexible aligned single-walled carbon nanotube(SWCNT)films are fabricated by a facile,environmentally friendly,and scalable printing methodology.The aligned pattern and outstanding intrinsic properties render“metal-like”thermal conductivity of the SWCNT films,as well as excellent mechanical strength,flexibility,and hydrophobicity.Further,the aligned cellular microstructure promotes the electromagnetic interference(EMI)shielding ability of the SWCNTs,leading to excellent shielding effectiveness(SE)of~39 to 90 dB despite a density of only~0.6 g cm^(−3) at thicknesses of merely 1.5-24μm,respectively.An ultrahigh thickness-specific SE of 25693 dB mm^(−1) and an unprecedented normalized specific SE of 428222 dB cm^(2)g^(−1) are accomplished by the freestanding SWCNT films,significantly surpassing previously reported shielding materials.In addition to an EMI SE greater than 54 dB in an ultra-broadband frequency range of around 400 GHz,the films demonstrate excellent EMI shielding stability and reliability when subjected to mechanical deformation,chemical(acid/alkali/organic solvent)corrosion,and high-/low-temperature environments.The novel printed SWCNT films offer significant potential for practical applications in the aerospace,defense,precision components,and smart wearable electronics industries.展开更多
基金supported by National Cancer Institute of United States (No.1R01-CA139158,to Wendong Huang)National Natural Science Foundation of China (Nos.81303186 and ZYX-NSFC-016)China Postdoctoral Science Foundation (No.2013M531202)
文摘Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, harrier function and prevention of bacterial manslocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide, range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved
文摘Farnesoid X receptor （FXR） is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is a potential drug target for a number of metabolic disorders, especially those related to the metabolic syndrome. More recently, our group and others have extended the functions of FXR to more than metabolic regulation, which include anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis. These new findings suggest that FXR has much broader roles than previously thought, and also higi.light FXR as a drug target for multiple diseases. This review summarizes the basic information of FXR but focuses on its new functions.
基金This review was in part supported by the Nanoelectronics Research Initiative(NRI)the DARPA Young Faculty Award(No.HR0011-08-1-0035)+2 种基金the Office of Naval Research(No.N00014-09-1-0180)the National Science Foundation(No.CCF 08-29907)Intel Corp.,and Northrop Grumman.
文摘Understanding energy dissipation and transport in nanoscale structures is of great importance for the design of energy-efficient circuits and energy-conversion systems.This is also a rich domain for fundamental discoveries at the intersection of electron,lattice(phonon),and optical(photon)interactions.This review presents recent progress in understanding and manipulation of energy dissipation and transport in nanoscale solid-state structures.First,the landscape of power usage from nanoscale transistors(~10^(-8) W)to massive data centers(~10^(-9) W)is surveyed.Then,focus is given to energy dissipation in nanoscale circuits,silicon transistors,carbon nanostructures,and semiconductor nanowires.Concepts of steady-state and transient thermal transport are also reviewed in the context of nanoscale devices with sub-nanosecond switching times.Finally,recent directions regarding energy transport are reviewed,including electrical and thermal conductivity of nanostructures,thermal rectification,and the role of ubiquitous material interfaces.
基金the Twelfth Five-Year Support Project of the Ministry of Science and Technology for Clinical Studies Investigating Xin'an Medicine in the Treatment of Complicated Ascites Diseases(No.2012BAI26B02)Technology Planning Project of Anhui Science and Technology Department(No.11010402170)State Key Discipline Construction Project of TCM:Chinese Medical Arthralgia Syndrome Subject [No.(2009)30]
文摘OBJECTIVE: To study changes in the nuclear factor-κB p65(NF-κB p65)-inducible nitric oxide synthase(i NOS)-nitric oxide(NO) signaling pathway and the effects of Xinfeng capsules(XFC) in patients with ankylosing spondylitis(AS)METHODS: One hundred twenty patients with AS were randomly divided into an XFC group and a Salazopyrin group. Sixty health subjects were included as a normal control group. In the two treatment groups, pulmonary functional parameters,forced vital capacity(FVC), forced expiratory volume in 1 second(FEV1), maximal voluntary ventilation(MVV), peak expiratory flow(PEF), forced expiratory flow at 25% of forced vital capacity(FEF25),forced expiratory flow at 50% of forced vital capacity(FEF50), and forced expiratory flow at 75% of forced vital capacity(FEF75) were determined. Enzyme linked immunosorbent assays were used for detection of the serum oxidative stress indexes,NF-κB p65, i NOS, NO, reactive oxygen species(ROS), reactive nitrogen species(RNS), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), total antioxidative capacity(TAOC) and interleukin-4(IL-4), IL-10, IL-1β, and tumor necrosis factor-α(TNF-α) contents. Westergren's method was used for determination of erythrocyte sedimentation rate(ESR). High-sensitivity C-reactive protein(Hs-CRP) was detected with a 7060 full-automatic biochemical analyzer(Hitachi, Japan).RESULTS: The clinical therapeutic effect in the XFC group was significantly superior to that in the Salazopyrin group(P<0.01). Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT,TAOC, IL-4, IL-10 were significantly lower, and NF-κB p65, i NOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR,and Hs-CRP significantly higher in patients with AS(P<0.01 or P<0.05). Compared with before treatment, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC,IL-4, and IL-10 were significantly increased, and NF-κB p65, i NOS, NO, ROS, RNS, MDA, IL-1β, TNF-α,ESR, CRP, visual analog scales(VAS), Bath ankylosing spondylitis disease active index, Bath ankylosing s
基金supported by the National Natural Science Foundation of China(Nos:81803183,82272779,82003036,82273236)National Key R&D Program of China(2022YFF0710800,2022YFF0710802)+4 种基金Natural Science Foundation of Sichuan province,China(No.2019YFS0230)Science and Technology Innovation Commission of Shenzhen(Nos:JCYJ20220530141608020,JCYJ20220530141609021)Natural Science Foundation of Guangdong province,China(Nos:2214050008970,2019A1515012079)Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515030182)Science and Technology Innovation Commission of Shenzhen(No.JCYJ20220530141608020)BioRender was used to create the figures.
文摘Macrophages exist in various tissues,several body cavities,and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers.Macrophages possess binary M1/M2 macrophage polarization settings,which perform a central role in an array of immune tasks via intrinsic signal cascades and,therefore,must be precisely regulated.Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered.In addition,the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology.Moreover,they are an integral part of the tumor microenvironment,playing a part in the regulation of a wide variety of processes including angiogenesis,extracellular matrix transformation,cancer cell proliferation,metastasis,immunosuppression,and resistance to chemotherapeutic and checkpoint blockade immunotherapies.Herein,we discuss immune regulation in macrophage polarization and signaling,mechanical stresses and modulation,metabolic signaling pathways,mitochondrial and transcriptional,and epigenetic regulation.Furthermore,we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions.Moreover,we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis.Lastly,we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.
基金financially sponsored by Shanghai Pujiang Program(17PJ1408800,China)the Natural Science Foundations of China to Lili Ding(81773961)+6 种基金Zhengtao Wang(81920108033)Yingbo Yang(81703682)financially supported by the National S&T Major Special Projects of China(No.2017ZX09309006)to Li YangInterdisciplinary Program of Shanghai Jiao Tong University to Qiaoling Yang(YG2019QNA03,China)partially supported by R01DK124627George Schaeffer fundJohn Hench fund(USA)to Wendong Huang。
文摘Obesity and its associated complications are highly related to a current public health crisis around the world.A growing body of evidence has indicated that G-protein coupled bile acid(BA) receptor TGR5(also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders.We have identified notoginsenoside Ftl(Ftl) from Panax notoginseng as an agonist of TGR5 in vitro.However,the pharmacological effects of Ftl on diet-induced obese(DIO) mice and the underlying mechanisms are still elusive.Here we show that Ftl(100 mg/100 diet) increased adipose lipolysis,promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1(GLP-1) secretion in the ileum of wild type but not Tgr5^(-/-) obese mice.In addition,Ftl elevated serum free and taurineconjugated bile acids(BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose tissues.The metabolic benefits of Ftl were abolished in Cyp27 al^(-/-) mice which have much lower BA levels.These results identify Ftl as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.
基金The present work was supported by the National Nature Science Foundation of China(No.81972221,81730102,81920108026,81871964,and 81902422)Emerging Cutting-Edge Technology Joint Research projects of Shanghai(SHDC12017112)+8 种基金the National Ten Thousand Plan Young Top Talents(for Dr.Yanlei Ma)the Shanghai Young Top Talents(for Dr.Yanlei Ma.No.QNBJ1701)the Shanghai Science and Technology Development Fund(No.19410713300,No.20XD1421200)the CSCO-Roche Tumor Research Fund(No.Y-2019Roche-079)the Fudan University Excellence 2025 Talent Cultivation Plan(for Dr.Yanlei Ma)Tongji University Subject Pilot Program(1501141201)Special Construction of Integrated Traditional Chinese Medicine and Western Medicine in Shanghai General Hospital(ZHYY-ZXYJHZX-1-201704)Program of Jiangsu Commission of Health(No.M2020024)Social Development Program of Yangzhou Science and Technology Bureau(No.YZ2020078).
文摘Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
基金supported by the National Basic Research Program of China (Grant Nos. 2010CB945401, 2007CB108800)National Natural Science Foundation of China (Grant Nos. 30870575,31071162,31000590)Science and Technology Commission of Shanghai Municipality (Grant No. 11DZ2260300)
文摘RNA-Seq technology is becoming widely used in various transcriptomics studies;however,analyzing and interpreting the RNA-Seq data face serious challenges.With the development of high-throughput sequencing technologies,the sequencing cost is dropping dramatically with the sequencing output increasing sharply.However,the sequencing reads are still short in length and contain various sequencing errors.Moreover,the intricate transcriptome is always more complicated than we expect.These challenges proffer the urgent need of efficient bioinformatics algorithms to effectively handle the large amount of transcriptome sequencing data and carry out diverse related studies.This review summarizes a number of frequently-used applications of transcriptome sequencing and their related analyzing strategies,including short read mapping,exon-exon splice junction detection,gene or isoform expression quantification,differential expression analysis and transcriptome reconstruction.
基金Supported by the fund for Creative Experimental Project of Undergraduate Students in Jiangsu Province of China (96)the program for New Century Excellent Talents in University (NCET-07-0441)+1 种基金the Natural Science Foundation of China (30671248)the grant obtained from the 111 Project of China (B07030)
文摘Pretreatment of lower H2O2 doses （0.05, 0.5 and 5 mM） for 24 h was able to dose-dependently attenuate lipid peroxidation in wheat seedling leaves mediated by further oxidative damage elicited by higher dose of H2O2 （150 mM） for 6 h, with 0.5 mM H2O2 being the most effective concentrations. Further results illustrated that 0.5 mM H2O2 pretreatment triggered the biphasic production of H2O2 during a 24 h period. We also noticed that only peak Ⅰ （0.25 h） rather than peak Ⅱ （4 h） was approximately consistent with the enhancement of heme oxygenase （HO） activity, HO-1 gene expression. Meanwhile, enhanced superoxide dismutase （SOD） activity, Mn-SOD and Cu, Zn-SOD transcripts might be a potential source of peak Ⅰ of endogenous H2O2. Further results confirmed that 0.5 mM H2O2 treatment for 0.5 h was able to upregulate HO gene expression, which was detected by enzyme activity determination, semi-quantitative reverse transcription-polymerase chain reaction and western blotting. Meanwhile, the application of N,N＇-dimethylthiourea, a trap for endogenous H2O2, not only blocked the upregulation of HO, but also reversed the corresponding oxidation attenuation. Together, the above results suggest that endogenous H2O2 production （peak Ⅰ） plays a positive role in the induction of HO by enhancing its mRNA level and protein expression, thus leading to the acclimation to oxidative stress.
基金This work is supported by National Cancer Institute 2R01CA139158Lymphoma SPORE Career Enhancement and Development Research Program Grants(W.H.)+2 种基金National Natural Science Foundation of China 31970555(Y.G.)Fundamental Research Funds for the Central Universities 2020FZZX001-09National Natural Science Foundation of China 32070630(J.Z.).
文摘The Myc proto-oncogene family consists of three members,C-MYC,MYCN,and MYCL,which encodes the transcription factor c-Myc(hereafter Myc),N-Myc,and L-Myc,respectively.Myc protein orchestrates diverse physiological processes,including cell proliferation,differentiation,survival,and apoptosis.Myc modulates about 15%of the global transcriptome,and its deregulation rewires the cellular signaling modules inside tumor cells,thereby acquiring selective advantages.The deregulation of Myc occurs in>70%of human cancers,and is related to poor prognosis;hence,hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades.Nevertheless,no specific drug is currently available to directly target Myc,mainly because of its"undruggable"properties:lack of enzymatic pocket for conventional small molecules to bind;inaccessibility for antibody due to the predominant nucleus localization of Myc.Although the topic of targeting Myc has actively been reviewed in the past decades,exciting new progresses in this field keep emerging.In this review,after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer,we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.
基金supported in part by funds from the National Institutes of Health R01DE026304 and R01CA220693(to D.K.A.)Ministry of Science and Technology,R.O.C,Special Talents Award(to C.-Y.K).
文摘The role of fatty acid metabolism,including both anabolic and catabolic reactions in cancer has gained increas-ing attention in recent years.Many studies have shown that aberrant expression of the genes involved in fatty acid synthesis or fatty acid oxidation correlate with malignant phenotypes including metastasis,therapeutic resistance and relapse.Such phenotypes are also strongly associated with the presence of a small percentage of unique cells among the total tumor cell population.This distinct group of cells may have the ability to self-renew and propagate or may be able to develop resistance to cancer therapies independent of genetic alterations.Therefore,these cells are referred to as cancer stem cells/tumor-initiating cells/drug-tolerant persisters,which are often refractory to cancer treatment and difficult to target.Moreover,interconversion between cancer cells and cancer stem cells/tumor-initiating cells/drug-tolerant persisters may occur and makes treatment even more challenging.This review highlights recent findings on the relationship between fatty acid metabolism,cancer stemness and therapeutic resistance and prompts discussion about the potential mechanisms by which fatty acid metabolism regulates the fate of cancer cells and therapeutic resistance.
基金support of National Key R&D Program of China (2021YFB3502500)Provincial Key Research and Development Program of Shandong (2019JZZY010312, 2021ZLGX01)+4 种基金Natural Science Foundation of Shandong Province (2022HYYQ-014)New 20 Funded Programs for Universities of Jinan (2021GXRC036)Qilu Young Scholar Program of Shandong University (31370082163127)the assistance of Shandong University Testing and Manufacturing Center for Advanced Materialssupport from the National Science Foundation Engineering Research Center for Power Optimization of Electro Thermal Systems (POETS) under Grant No. EEC 1449548.
文摘Ultrathin,lightweight,and flexible aligned single-walled carbon nanotube(SWCNT)films are fabricated by a facile,environmentally friendly,and scalable printing methodology.The aligned pattern and outstanding intrinsic properties render“metal-like”thermal conductivity of the SWCNT films,as well as excellent mechanical strength,flexibility,and hydrophobicity.Further,the aligned cellular microstructure promotes the electromagnetic interference(EMI)shielding ability of the SWCNTs,leading to excellent shielding effectiveness(SE)of~39 to 90 dB despite a density of only~0.6 g cm^(−3) at thicknesses of merely 1.5-24μm,respectively.An ultrahigh thickness-specific SE of 25693 dB mm^(−1) and an unprecedented normalized specific SE of 428222 dB cm^(2)g^(−1) are accomplished by the freestanding SWCNT films,significantly surpassing previously reported shielding materials.In addition to an EMI SE greater than 54 dB in an ultra-broadband frequency range of around 400 GHz,the films demonstrate excellent EMI shielding stability and reliability when subjected to mechanical deformation,chemical(acid/alkali/organic solvent)corrosion,and high-/low-temperature environments.The novel printed SWCNT films offer significant potential for practical applications in the aerospace,defense,precision components,and smart wearable electronics industries.
