BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it redu...BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and regulated on activation,normal T-cell expressed and secreted(RANTES)levels in serum and ileal tissue in animal studies.The histopathological changes of the ileal mucosa in different groups were observed under a microscope.Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide(LPS)-induced decrease in permeability.Immunofluorescence and Western blot assays were used to detect the levels of RANTES,inhibitor of nuclear factor kappa-B kinaseβ(IKKβ),phosphorylated IKKβ(p-IKKβ),inhibitor of nuclear factor kappa-B kinaseα(IκBα),p65,and p-p65 proteins in different groups in vitro.RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol,magnolol inhibited the expression of proinflammatory cytokines,IL-1β,IL-6,and TNF-αin a dose-dependent manner.In addition,magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats.Moreover,in vitro studies suggested that magnolol inhibited the increase of p65 nucleation,thereby markedly downregulating the production of the phosphorylated form of IKKβin LPS-treated Caco2 cells.Specifically,magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B(NF-κB)from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways,thereby suppressing IL-1β,IL-6,and TNF-αexpression to alleviate the mucosal barrier dysfunction in sepsis.展开更多
Electrochemical reduction of CO_(2)(CO_(2)RR)to high value-added chemicals is an effective way to remove excess CO_(2) from the atmosphere.Due to the unique propensity of Cu for valuable hydrocarbons,Cu-based electroc...Electrochemical reduction of CO_(2)(CO_(2)RR)to high value-added chemicals is an effective way to remove excess CO_(2) from the atmosphere.Due to the unique propensity of Cu for valuable hydrocarbons,Cu-based electrocatalysts are the most potential catalysts that allow the conversion of CO_(2) into a variety of C_(2) products such as ethylene and ethanol.Rational design of Cu-based catalysts can improve their directional selectivity to C_(2) products.Hence,in this review,we summarize the recent progress in the mechanistic studies of Cu-based catalysts on reducing CO_(2) to C_(2) products.We focus on three key strategies for efficiently enhancing electrocatalytic performance of Cu-based catalysts,including tuning electronic structure,surface structure,and coordination environment.The correlation between the structural characteristics of Cu-based catalysts and their activity and selectivity to C_(2) products is discussed.Finally,we discuss the challenges in the field of CO_(2) electroreduction to C_(2) products and provide the perspectives to design efficient Cu-based catalysts in the future.展开更多
Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation ...Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.展开更多
Mitochondria serve as the powerhouse of cells,respond to cellular demands and stressors,and play an essential role in cell signaling,differentiation,and survival.Aberrant mitochondria function has been linked to diver...Mitochondria serve as the powerhouse of cells,respond to cellular demands and stressors,and play an essential role in cell signaling,differentiation,and survival.Aberrant mitochondria function has been linked to diverse and complex human diseases such as neurodegenerative diseases,cancers,myopathies,premature aging,and metabolic syndromes(Nunnari and Suomalainen,2012).展开更多
This study examined the role of regulated upon activation normal T cell expressed and secreted(RANTES) and its receptor C-C chemokine receptor type 5(CCR5) in gastric cancer metastasis and the associated mechanism...This study examined the role of regulated upon activation normal T cell expressed and secreted(RANTES) and its receptor C-C chemokine receptor type 5(CCR5) in gastric cancer metastasis and the associated mechanism.The expression of RANTES and CCR5 was detected by using immunohistochemical staining and Western blotting in the gastric cancer tissues obtained from 60 gastric cancer patients with or without lymph node metastasis(n=30 in each).The results showed that the expression levels of RANTES and CCR5 were higher in gastric cancer with lymph node metastasis than in that without metastasis(P0.05).The expression levels of RANTES in 30 lymph nodes with cancerous invasion were higher than in 30 normal lymph nodes(P0.05).Chemotactic test revealed that the number of migrating gastric cancer cells(n=295.0±54.6) induced by the protein of cancer-invading lymph nodes was greater than that by the protein mixture from cancer-invading lymph nodes and RANTES antibody(n=42.5±11.6)(P0.05).RT-PCR showed that the expression levels of the main Th1 cytokines(IL-2,γ-IFN) were lower in gastric cancer with lymph node metastasis(2.22±0.90,3.26±1.15 respectively) than in that without metastasis(3.07±1.67,4.77±1.52 respectively)(P0.05),but the expression level of the main Th 2 cytokine(IL-10) was higher in gastric cancer with lymph nodes metastasis(6.06±2.04) than in that without metastasis(4.88±1.87)(P0.05).It was concluded that RANTES and its receptor CCR5 may contribute to gastric cancer metastasis through influencing the balance of Th1/Th2.RANTES and CCR5 may become a marker of gastric cancer metastasis.展开更多
The title compound,(1S,4R)-4,7,7-trimethyl-6-oxabicyclo [3.2.1] octane-1,4-diol(C(10)H(18)O3), has been synthesized from terpinolene via one-step catalytic synthetic method and structurally characterized by me...The title compound,(1S,4R)-4,7,7-trimethyl-6-oxabicyclo [3.2.1] octane-1,4-diol(C(10)H(18)O3), has been synthesized from terpinolene via one-step catalytic synthetic method and structurally characterized by means of HRMS, IR, 1H-NMR, (13)C-NMR and single-crystal X-ray diffraction. The compound crystallizes in trigonal, space group R-3, with a = 27.892(9), b = 27.892(9), c = 6.720(2) A, γ = 120°, Z = 18, V = 4527(3) A3, Dc = 1.230 g/cm3, Mr = 186.24, λ(Mo Kα) = 0.71073?, μ = 0.09 mm(-1), F(000) = 1836, the final R = 0.051 and wR = 0.161. The title compound molecule contained a 6-oxabicyclo[3.2.1]octane skeleton and two hydroxyl groups, which were connected through intermolecular O–H…O hydrogen bonds to generate a two-dimensional network. Especially, the preliminary bioassay showed that the title compound can promote the root growth and shoot elongation of rape(Brassica campestris) at low concentration(0.62570 mmol·L^-1) and inhibit them at high concentration(〉 70 mmol·L^-1).展开更多
The cleavage reactions of Ser-His and its N-terminal phosphorylated form - N-(O,O-diisopropyl) phosphoryl seryl-histidine (DIPP-Ser-His) were studied on DNA. It was found that the phosphorylation of Ser-His caused the...The cleavage reactions of Ser-His and its N-terminal phosphorylated form - N-(O,O-diisopropyl) phosphoryl seryl-histidine (DIPP-Ser-His) were studied on DNA. It was found that the phosphorylation of Ser-His caused the lost of the cleavage activity on DNA. The result might give some clue on the regulation of the activity of protein by phosphorylation.展开更多
As a common clinical disease,insomnia was usually treated with anti-psychotic or sedativehypnotic drugs in Western medicine,which showed a fast efficacy,as well as easy drug tolerance and side effects.In traditional C...As a common clinical disease,insomnia was usually treated with anti-psychotic or sedativehypnotic drugs in Western medicine,which showed a fast efficacy,as well as easy drug tolerance and side effects.In traditional Chinese medicine,the basic and key pathogenesis of insomnia are believed to be“the restlessness of the mind”,as well as“the absence of the mind”;and the treatment mainly focus on“regulating mental activities and smoothing the liver”.By combining the theoretical basis and characteristics of Fang’s scalp acupuncture,this paper aims to explain the advantages of Fang’s scalp acupuncture in the treatment of insomnia,and provide new ideas and methods for its clinical treatment.展开更多
As a new generation of artificial enzymes,nanozymes show outstanding advantages such as high stability,low cost,and facile synthesis,which endow them with promising applications in biomedical and environmental fields....As a new generation of artificial enzymes,nanozymes show outstanding advantages such as high stability,low cost,and facile synthesis,which endow them with promising applications in biomedical and environmental fields.Among the various reported nanozymes,metal-organic frameworks(MOFs)could mimic the active center of natural enzymes and provide a hydrophobic environment,which makes MOFs attractive alternatives to natural enzymes.Owing to the highly structural diversity and tailorability of MOFs,rational design will contribute to improve the activity of MOF-based nanozymes and promote their potential applications in both biomedical and environmental fields.Therefore,a comprehensiye suminary of activity regulatory strategies of MOF-based nanozymes is urgently needed.Firstly,we summarized the activity regulatory strategies of MOFs with intrinsic enzyme-like activities via modulation of metal nodes,ligands,structures and morphologies.Then the applications of MOF-based nanozymes in biosensing,hazardous degradation,antibacterial,and cancer therapy were also introduced.Finally,the current challenges and future perspectives were discussed in depth.It is highly expected that this review will provide a better understanding on the rational design of novel high-performance MOF-based nanozymes.展开更多
Imiquimod is an imidazoquinoline derivative. Some studies have shown that imiquimod modulates the Th1/Th2 response by inducing the production of Th1 cytokines IFN-γ and interleukin (IL)-12. and by inhibiting Th2 cy...Imiquimod is an imidazoquinoline derivative. Some studies have shown that imiquimod modulates the Th1/Th2 response by inducing the production of Th1 cytokines IFN-γ and interleukin (IL)-12. and by inhibiting Th2 cytokines IL-4 and IL-5. These data suggest that imiquimod has therapeutic appli . cations in atopic diseases such as allergic asthma that are associated with overexpression of Th2 cytokines.展开更多
Nanozymes are nanomaterials with enzymatic properties that address the shortcomings of natural enzymes.Among them,many nanozymes could absorb near-infrared(NIR)light and respond to NIR light stimulation,providing us w...Nanozymes are nanomaterials with enzymatic properties that address the shortcomings of natural enzymes.Among them,many nanozymes could absorb near-infrared(NIR)light and respond to NIR light stimulation,providing us with a new perspective to regulate their catalytic performance.During the past several years,the use of NIR light as an external stimulus has made considerable progress,which has given a powerful shove-ahead to their applications in biomedical fields.This review highlights recent advances in the application of NIR light-responsive nanozyme-based systems.First,we will discuss the mechanisms of such NIR light-regulated nanozymes.Then,various strategies are summarized to construct effective NIR light-responsive nanozymes.After that,this remote-controlled catalytic system covers multiple applications,from bactericidal to tumor therapeutics.Finally,the challenges faced by NIR light-responsive nanozymes are outlined and future directions for advancing NIR light-responsive nanozyme research are proposed.We anticipate that this review will guide and inspire researchers to synthesize effective NIR-activated nanozymes and may promote breakthroughs in this field.展开更多
The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in...The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear.Here,we have constructed a series of IONPs with different magneto-thermal conversion abilities,and systematically study the effect of magnetic field stimulation on the peroxidase(POD)activity of IONPs.The results show that POD activity is effectively amplified via an in situ alternating magnetic field(AMF)stimulation with no solution temperature rise,and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs,confirming the origin of activity enhancement arises from the local magnetothermal effect.As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate(SAR),this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.展开更多
The atomically dispersed Fe^(3+)sites of Fe-N-C single-site catalysts(SSCs)are demonstrated as the active sites for CO_(2)electroreduction(CO_(2)RR)to CO but suffer from the reduction to Fe^(2+)at~−0.5 V,accompanied b...The atomically dispersed Fe^(3+)sites of Fe-N-C single-site catalysts(SSCs)are demonstrated as the active sites for CO_(2)electroreduction(CO_(2)RR)to CO but suffer from the reduction to Fe^(2+)at~−0.5 V,accompanied by the drop of CO faradaic efficiency(FECO)and deterioration of partial current(JCO).Herein,we report the construction of F-doped Fe-N-C SSCs and the electron-withdrawing character of fluorine could stabilize Fe3+sites,which promotes the FECO from the volcano-like highest value(88.2%@−0.40 V)to the high plateau(>88.5%@−0.40-−0.60 V),with a much-increased JCO(from 3.24 to 11.23 mA·cm^(−2)).The enhancement is ascribed to the thermodynamically facilitated CO_(2)RR and suppressed competing hydrogen evolution reaction,as well as the kinetically increased electroactive surface area and improved charge transfer,due to the stabilized Fe^(3+)sites and enriched defects by fluorine doping.This finding provides an efficient strategy to enhance the CO_(2)RR performance of Fe-N-C SSCs by stabilizing Fe^(3+).展开更多
N-acyl-homoserine lactones(AHLs) serve as quorum-sensing signals, which control a number of bacterial processes in many proteobacteria. Here we report the effects of exogenous short-chain AHL on the denitrifying pro...N-acyl-homoserine lactones(AHLs) serve as quorum-sensing signals, which control a number of bacterial processes in many proteobacteria. Here we report the effects of exogenous short-chain AHL on the denitrifying process of Paracoccus denitrificans, which are capable of aerobic and anaerobic growth by utilizing nitrate. The denitrification activity of these cells was monitored by measuring denitrification products(including nitrate, nitrite,and nitrous oxide), and the individual messenger ribonucleic acid(m RNA) levels of nitrate,nitrite, nitric oxide and nitrous oxide reductases. The results indicated that 2 μmol/L C6-homoserine lactone(HSL) has little effect on cell density under either anaerobic or aerobic culture conditions, and the nitrate reduction activity appeared slightly affected by N-hexanoyl-DL-homoserine lactone(C6-HSL). However, exogenous C6-HSL significantly affected the transcription of nitrite reductase and nitric oxide reductase genes in P.denitrificans regardless of the presence of oxygen, and N2O accumulation activity in P. denitrificans was suppressed by C6-HSL under aerobic condition. In contrast, exogenous C6-HSL stimulated the production of N2O under anaerobic condition, suggesting that the regulation of denitrification by quorum sensing may be important in N2O release.展开更多
Proteins play a central role in all domains of life,and precise regulation of their activity is essential for understanding the related biological processes and therapeutic functions.Nucleic acid aptamers,the molecula...Proteins play a central role in all domains of life,and precise regulation of their activity is essential for understanding the related biological processes and therapeutic functions.Nucleic acid aptamers,the molecular recognition components derived from systematic evolution of ligands by exponential enrichment(SELEX),can specifically identify proteins with antibody-like recognition characteristics and help to regulate their activity.This minireview covers the SELEX-based selection of protein-binding aptamers,membrane protein analytical techniques based on aptamer-mediated target recognition,aptamer-mediated functional regulation of proteins,including membrane receptors and non-membrane proteins(thrombin as a model),as well as the potential challenges and prospects regarding aptamer-mediated protein manipulation,aiming to supply some useful information for researchers in this field.展开更多
p38 regulated/activated protein kinase(PRAK)plays a key role in cell senescence and tumor suppression.The aim of this study was to investigate if PRAK had effect on cell proliferation.The growth of PRAK+/+and PRAK^(–...p38 regulated/activated protein kinase(PRAK)plays a key role in cell senescence and tumor suppression.The aim of this study was to investigate if PRAK had effect on cell proliferation.The growth of PRAK+/+and PRAK^(–/–)mouse embryonicfibroblast(MEF)cells was measured by methylthiazoletetrazolium(MTT)colorimetric assay,and the proportion of the cell number in different phases of the cell cycle was analyzed byflow cytometry.The growth curves showed that the growth rate was notably decreased,and cell double time was elongated in PRAK^(–/–)cells;moreover,the number of PRAK^(–/–)cells was decreased by 44.5%compared with that of PRAK+/+cells cultured for 96 h,suggesting that G2/M transition is inhibited in PRAK^(–/–)cells.Meanwhile,G1/S transition was also inhibited in PRAK^(–/–)cells,observed withflow cytometry analysis.The ratios of G0/G1,G2/M,and S phases of PRAK+/+cells were 44.9%,12.2%,and 42.9%,respec-tively,while those of PRAK^(–/–)cells were 55.3%,7.3%,and 37.4%,respectively.There were 23.1%increase and 12.7%decrease of the number of PRAK^(–/–)cells in G1 and S phases in comparison with that of PRAK+/+cells,respectively.Taken together,PRAK gene knockout in MEF cells leads to cell cycle arrest and proliferation inhibition.展开更多
The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans(Ong and Corces,2014).The nuclear architectural proteins are known to facilitate the formation...The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans(Ong and Corces,2014).The nuclear architectural proteins are known to facilitate the formation of topological domains within the genome through mediating inter-and intra-chromosomal interactions.In vertebrate,CCCTC-binding factor(CTCF)is the main architectural protein that mediates long-range chromosomal interactions among its DNA binding sites through a process that is stabilized by cohesin (Parelho et al., 2008; Wendt et al., 2008).展开更多
Ⅰ Current status of Chinese auto standardization "Standardization Law of Peo-ples’ Republic of China" promulgat-ed in Dec. 1988 and enforced in April 1989 stipulates that Chinese standards are divided into...Ⅰ Current status of Chinese auto standardization "Standardization Law of Peo-ples’ Republic of China" promulgat-ed in Dec. 1988 and enforced in April 1989 stipulates that Chinese standards are divided into national standard and occupation standard by levels, and mandatory standard and recommended standard in attri-展开更多
In this paper new heterocyclic compounds 5-[(1,l-dimethyl)ethyl]-3-aryl-(1H-1,2,3-traizol-1-yl)-5-isoxazolidinols were obtained by the reaction of vinyl triazole derivatives with hydroxylamine hydrochloride under the ...In this paper new heterocyclic compounds 5-[(1,l-dimethyl)ethyl]-3-aryl-(1H-1,2,3-traizol-1-yl)-5-isoxazolidinols were obtained by the reaction of vinyl triazole derivatives with hydroxylamine hydrochloride under the action of sodium carbonate. The biological tests indicate that they had plant-growth regulating activity.展开更多
基金Basic Public Welfare Research Foundation of Zhejiang Province,China,No.GD21H290001and Traditional Chinese Medicine Science and Technology Project Foundation of Zhejiang Province,China,No.2020ZB072.
文摘BACKGROUND Sepsis is a major medical challenge.Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects,but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and regulated on activation,normal T-cell expressed and secreted(RANTES)levels in serum and ileal tissue in animal studies.The histopathological changes of the ileal mucosa in different groups were observed under a microscope.Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide(LPS)-induced decrease in permeability.Immunofluorescence and Western blot assays were used to detect the levels of RANTES,inhibitor of nuclear factor kappa-B kinaseβ(IKKβ),phosphorylated IKKβ(p-IKKβ),inhibitor of nuclear factor kappa-B kinaseα(IκBα),p65,and p-p65 proteins in different groups in vitro.RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol,magnolol inhibited the expression of proinflammatory cytokines,IL-1β,IL-6,and TNF-αin a dose-dependent manner.In addition,magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats.Moreover,in vitro studies suggested that magnolol inhibited the increase of p65 nucleation,thereby markedly downregulating the production of the phosphorylated form of IKKβin LPS-treated Caco2 cells.Specifically,magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B(NF-κB)from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways,thereby suppressing IL-1β,IL-6,and TNF-αexpression to alleviate the mucosal barrier dysfunction in sepsis.
基金the supports sponsored by the National Natural Science Foundation of China(22005215,22090031)the Hebei Province Innovation Ability Promotion Project(20544401D,20312201D)。
文摘Electrochemical reduction of CO_(2)(CO_(2)RR)to high value-added chemicals is an effective way to remove excess CO_(2) from the atmosphere.Due to the unique propensity of Cu for valuable hydrocarbons,Cu-based electrocatalysts are the most potential catalysts that allow the conversion of CO_(2) into a variety of C_(2) products such as ethylene and ethanol.Rational design of Cu-based catalysts can improve their directional selectivity to C_(2) products.Hence,in this review,we summarize the recent progress in the mechanistic studies of Cu-based catalysts on reducing CO_(2) to C_(2) products.We focus on three key strategies for efficiently enhancing electrocatalytic performance of Cu-based catalysts,including tuning electronic structure,surface structure,and coordination environment.The correlation between the structural characteristics of Cu-based catalysts and their activity and selectivity to C_(2) products is discussed.Finally,we discuss the challenges in the field of CO_(2) electroreduction to C_(2) products and provide the perspectives to design efficient Cu-based catalysts in the future.
文摘Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.
基金Supported by an endowment to JES from Cardinal Hill Rehabilitation Hospital
文摘Mitochondria serve as the powerhouse of cells,respond to cellular demands and stressors,and play an essential role in cell signaling,differentiation,and survival.Aberrant mitochondria function has been linked to diverse and complex human diseases such as neurodegenerative diseases,cancers,myopathies,premature aging,and metabolic syndromes(Nunnari and Suomalainen,2012).
基金supported by a grant from Natural Sciences Foundation of Hubei Province of China (No. 2006ABA098)
文摘This study examined the role of regulated upon activation normal T cell expressed and secreted(RANTES) and its receptor C-C chemokine receptor type 5(CCR5) in gastric cancer metastasis and the associated mechanism.The expression of RANTES and CCR5 was detected by using immunohistochemical staining and Western blotting in the gastric cancer tissues obtained from 60 gastric cancer patients with or without lymph node metastasis(n=30 in each).The results showed that the expression levels of RANTES and CCR5 were higher in gastric cancer with lymph node metastasis than in that without metastasis(P0.05).The expression levels of RANTES in 30 lymph nodes with cancerous invasion were higher than in 30 normal lymph nodes(P0.05).Chemotactic test revealed that the number of migrating gastric cancer cells(n=295.0±54.6) induced by the protein of cancer-invading lymph nodes was greater than that by the protein mixture from cancer-invading lymph nodes and RANTES antibody(n=42.5±11.6)(P0.05).RT-PCR showed that the expression levels of the main Th1 cytokines(IL-2,γ-IFN) were lower in gastric cancer with lymph node metastasis(2.22±0.90,3.26±1.15 respectively) than in that without metastasis(3.07±1.67,4.77±1.52 respectively)(P0.05),but the expression level of the main Th 2 cytokine(IL-10) was higher in gastric cancer with lymph nodes metastasis(6.06±2.04) than in that without metastasis(4.88±1.87)(P0.05).It was concluded that RANTES and its receptor CCR5 may contribute to gastric cancer metastasis through influencing the balance of Th1/Th2.RANTES and CCR5 may become a marker of gastric cancer metastasis.
基金Supported by the National Natural Science Foundation of China(No.31460174)the Science and Research Start-Up Project for the Recruit Talent of Guangxi University for Nationalities(No.2014MDQD014)Innovation Project of Guangxi Graduate Education(gxun-chxzs2016113)
文摘The title compound,(1S,4R)-4,7,7-trimethyl-6-oxabicyclo [3.2.1] octane-1,4-diol(C(10)H(18)O3), has been synthesized from terpinolene via one-step catalytic synthetic method and structurally characterized by means of HRMS, IR, 1H-NMR, (13)C-NMR and single-crystal X-ray diffraction. The compound crystallizes in trigonal, space group R-3, with a = 27.892(9), b = 27.892(9), c = 6.720(2) A, γ = 120°, Z = 18, V = 4527(3) A3, Dc = 1.230 g/cm3, Mr = 186.24, λ(Mo Kα) = 0.71073?, μ = 0.09 mm(-1), F(000) = 1836, the final R = 0.051 and wR = 0.161. The title compound molecule contained a 6-oxabicyclo[3.2.1]octane skeleton and two hydroxyl groups, which were connected through intermolecular O–H…O hydrogen bonds to generate a two-dimensional network. Especially, the preliminary bioassay showed that the title compound can promote the root growth and shoot elongation of rape(Brassica campestris) at low concentration(0.62570 mmol·L^-1) and inhibit them at high concentration(〉 70 mmol·L^-1).
文摘The cleavage reactions of Ser-His and its N-terminal phosphorylated form - N-(O,O-diisopropyl) phosphoryl seryl-histidine (DIPP-Ser-His) were studied on DNA. It was found that the phosphorylation of Ser-His caused the lost of the cleavage activity on DNA. The result might give some clue on the regulation of the activity of protein by phosphorylation.
基金Xi’an Fang’s Scalp Acupuncture School Inheritance Studio Project{Shi Wei Ji Han[2018]No.699}Clinical study of the Treatment of motor aphasia after stroke with Fang’s scalp acupuncture combined with resuscitating acupuncture therapy(Source of scientific research:Project of Shaanxi Provincial Administration of Traditional Chinese MedicineProject No.:2019-ZZ-LC027).
文摘As a common clinical disease,insomnia was usually treated with anti-psychotic or sedativehypnotic drugs in Western medicine,which showed a fast efficacy,as well as easy drug tolerance and side effects.In traditional Chinese medicine,the basic and key pathogenesis of insomnia are believed to be“the restlessness of the mind”,as well as“the absence of the mind”;and the treatment mainly focus on“regulating mental activities and smoothing the liver”.By combining the theoretical basis and characteristics of Fang’s scalp acupuncture,this paper aims to explain the advantages of Fang’s scalp acupuncture in the treatment of insomnia,and provide new ideas and methods for its clinical treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.31901000 and 22022609)the Natural Science Foundation of Jiangsu Higher Education Institutes of China(No.19KJA610003)+1 种基金the Postdoctoral Science Foundation of Jiangsu Province(No.2019K152)the Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions。
文摘As a new generation of artificial enzymes,nanozymes show outstanding advantages such as high stability,low cost,and facile synthesis,which endow them with promising applications in biomedical and environmental fields.Among the various reported nanozymes,metal-organic frameworks(MOFs)could mimic the active center of natural enzymes and provide a hydrophobic environment,which makes MOFs attractive alternatives to natural enzymes.Owing to the highly structural diversity and tailorability of MOFs,rational design will contribute to improve the activity of MOF-based nanozymes and promote their potential applications in both biomedical and environmental fields.Therefore,a comprehensiye suminary of activity regulatory strategies of MOF-based nanozymes is urgently needed.Firstly,we summarized the activity regulatory strategies of MOFs with intrinsic enzyme-like activities via modulation of metal nodes,ligands,structures and morphologies.Then the applications of MOF-based nanozymes in biosensing,hazardous degradation,antibacterial,and cancer therapy were also introduced.Finally,the current challenges and future perspectives were discussed in depth.It is highly expected that this review will provide a better understanding on the rational design of novel high-performance MOF-based nanozymes.
文摘Imiquimod is an imidazoquinoline derivative. Some studies have shown that imiquimod modulates the Th1/Th2 response by inducing the production of Th1 cytokines IFN-γ and interleukin (IL)-12. and by inhibiting Th2 cytokines IL-4 and IL-5. These data suggest that imiquimod has therapeutic appli . cations in atopic diseases such as allergic asthma that are associated with overexpression of Th2 cytokines.
基金funded by the National Natural Science Foundation of China(12274356)the Fundamental Research Funds for the Central Universities(20720220022)the 111 Project(B16029)
文摘Nanozymes are nanomaterials with enzymatic properties that address the shortcomings of natural enzymes.Among them,many nanozymes could absorb near-infrared(NIR)light and respond to NIR light stimulation,providing us with a new perspective to regulate their catalytic performance.During the past several years,the use of NIR light as an external stimulus has made considerable progress,which has given a powerful shove-ahead to their applications in biomedical fields.This review highlights recent advances in the application of NIR light-responsive nanozyme-based systems.First,we will discuss the mechanisms of such NIR light-regulated nanozymes.Then,various strategies are summarized to construct effective NIR light-responsive nanozymes.After that,this remote-controlled catalytic system covers multiple applications,from bactericidal to tumor therapeutics.Finally,the challenges faced by NIR light-responsive nanozymes are outlined and future directions for advancing NIR light-responsive nanozyme research are proposed.We anticipate that this review will guide and inspire researchers to synthesize effective NIR-activated nanozymes and may promote breakthroughs in this field.
基金supported by the National Natural Science Foundation of China(81771981,82072063,and 31400663)the National Natural Science Foundation for Young Scholars of China(31901003)+2 种基金Shaanxi Province Funds for Distinguished Young Scholars(202031900097)Shaanxi Science and Technology Department(2019KW-078)the Postdoctoral Science Foundation of China(2020M673631XB)。
文摘The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear.Here,we have constructed a series of IONPs with different magneto-thermal conversion abilities,and systematically study the effect of magnetic field stimulation on the peroxidase(POD)activity of IONPs.The results show that POD activity is effectively amplified via an in situ alternating magnetic field(AMF)stimulation with no solution temperature rise,and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs,confirming the origin of activity enhancement arises from the local magnetothermal effect.As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate(SAR),this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.
基金the National Key Research and Development Program of China(Nos.2021YFA1500900,2017YFA0206500,and 2018YFA0209103)the National Natural Science Foundation of China(Nos.21832003,21972061,and 52071174)+1 种基金the Natural Science Foundation of Jiangsu Province,Major Project(No.BK20212005)Nanjing University Innovation Program for PhD candidate(No.CXYJ21-38).
文摘The atomically dispersed Fe^(3+)sites of Fe-N-C single-site catalysts(SSCs)are demonstrated as the active sites for CO_(2)electroreduction(CO_(2)RR)to CO but suffer from the reduction to Fe^(2+)at~−0.5 V,accompanied by the drop of CO faradaic efficiency(FECO)and deterioration of partial current(JCO).Herein,we report the construction of F-doped Fe-N-C SSCs and the electron-withdrawing character of fluorine could stabilize Fe3+sites,which promotes the FECO from the volcano-like highest value(88.2%@−0.40 V)to the high plateau(>88.5%@−0.40-−0.60 V),with a much-increased JCO(from 3.24 to 11.23 mA·cm^(−2)).The enhancement is ascribed to the thermodynamically facilitated CO_(2)RR and suppressed competing hydrogen evolution reaction,as well as the kinetically increased electroactive surface area and improved charge transfer,due to the stabilized Fe^(3+)sites and enriched defects by fluorine doping.This finding provides an efficient strategy to enhance the CO_(2)RR performance of Fe-N-C SSCs by stabilizing Fe^(3+).
基金supported by the National Natural Science Foundation of China(Nos.41371266,41501250,21377157)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB15030101)
文摘N-acyl-homoserine lactones(AHLs) serve as quorum-sensing signals, which control a number of bacterial processes in many proteobacteria. Here we report the effects of exogenous short-chain AHL on the denitrifying process of Paracoccus denitrificans, which are capable of aerobic and anaerobic growth by utilizing nitrate. The denitrification activity of these cells was monitored by measuring denitrification products(including nitrate, nitrite,and nitrous oxide), and the individual messenger ribonucleic acid(m RNA) levels of nitrate,nitrite, nitric oxide and nitrous oxide reductases. The results indicated that 2 μmol/L C6-homoserine lactone(HSL) has little effect on cell density under either anaerobic or aerobic culture conditions, and the nitrate reduction activity appeared slightly affected by N-hexanoyl-DL-homoserine lactone(C6-HSL). However, exogenous C6-HSL significantly affected the transcription of nitrite reductase and nitric oxide reductase genes in P.denitrificans regardless of the presence of oxygen, and N2O accumulation activity in P. denitrificans was suppressed by C6-HSL under aerobic condition. In contrast, exogenous C6-HSL stimulated the production of N2O under anaerobic condition, suggesting that the regulation of denitrification by quorum sensing may be important in N2O release.
基金supported by the National Natural Science Foundation of China(No.21904046).
文摘Proteins play a central role in all domains of life,and precise regulation of their activity is essential for understanding the related biological processes and therapeutic functions.Nucleic acid aptamers,the molecular recognition components derived from systematic evolution of ligands by exponential enrichment(SELEX),can specifically identify proteins with antibody-like recognition characteristics and help to regulate their activity.This minireview covers the SELEX-based selection of protein-binding aptamers,membrane protein analytical techniques based on aptamer-mediated target recognition,aptamer-mediated functional regulation of proteins,including membrane receptors and non-membrane proteins(thrombin as a model),as well as the potential challenges and prospects regarding aptamer-mediated protein manipulation,aiming to supply some useful information for researchers in this field.
基金supported by grants from the National Key Basic Research Program(973 Program)of China(No.2002CB513005)Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,No.IRT0731)+4 种基金National Natural Science Foundation of China(No.30670828No.30572151,No.30700291)Joint Fund of NSFC with the Guangdong Provincial Government(No.U0632004)Project of Science and Technology Program of Guangdong Province(No.A1090202)Project of Science and Technology Program of Guangzhou City(No.2007J1-C0301).
文摘p38 regulated/activated protein kinase(PRAK)plays a key role in cell senescence and tumor suppression.The aim of this study was to investigate if PRAK had effect on cell proliferation.The growth of PRAK+/+and PRAK^(–/–)mouse embryonicfibroblast(MEF)cells was measured by methylthiazoletetrazolium(MTT)colorimetric assay,and the proportion of the cell number in different phases of the cell cycle was analyzed byflow cytometry.The growth curves showed that the growth rate was notably decreased,and cell double time was elongated in PRAK^(–/–)cells;moreover,the number of PRAK^(–/–)cells was decreased by 44.5%compared with that of PRAK+/+cells cultured for 96 h,suggesting that G2/M transition is inhibited in PRAK^(–/–)cells.Meanwhile,G1/S transition was also inhibited in PRAK^(–/–)cells,observed withflow cytometry analysis.The ratios of G0/G1,G2/M,and S phases of PRAK+/+cells were 44.9%,12.2%,and 42.9%,respec-tively,while those of PRAK^(–/–)cells were 55.3%,7.3%,and 37.4%,respectively.There were 23.1%increase and 12.7%decrease of the number of PRAK^(–/–)cells in G1 and S phases in comparison with that of PRAK+/+cells,respectively.Taken together,PRAK gene knockout in MEF cells leads to cell cycle arrest and proliferation inhibition.
基金Additional support for EIPC was provided by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454supported by the core funding from Temasek Life Sciences Laboratory,Singapore
文摘The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans(Ong and Corces,2014).The nuclear architectural proteins are known to facilitate the formation of topological domains within the genome through mediating inter-and intra-chromosomal interactions.In vertebrate,CCCTC-binding factor(CTCF)is the main architectural protein that mediates long-range chromosomal interactions among its DNA binding sites through a process that is stabilized by cohesin (Parelho et al., 2008; Wendt et al., 2008).
文摘Ⅰ Current status of Chinese auto standardization "Standardization Law of Peo-ples’ Republic of China" promulgat-ed in Dec. 1988 and enforced in April 1989 stipulates that Chinese standards are divided into national standard and occupation standard by levels, and mandatory standard and recommended standard in attri-
基金Project supported by the the National Natural Science Youth Foundation of Chinathe Natural Science Youth Foundation of Tianjin
文摘In this paper new heterocyclic compounds 5-[(1,l-dimethyl)ethyl]-3-aryl-(1H-1,2,3-traizol-1-yl)-5-isoxazolidinols were obtained by the reaction of vinyl triazole derivatives with hydroxylamine hydrochloride under the action of sodium carbonate. The biological tests indicate that they had plant-growth regulating activity.