Organic pollutants,a pivotal factor in water pollution,have persistently menaced the aquatic ecosystem,as well as the sustainable development of human health,economy,and society.Consequently,there is an urgent need fo...Organic pollutants,a pivotal factor in water pollution,have persistently menaced the aquatic ecosystem,as well as the sustainable development of human health,economy,and society.Consequently,there is an urgent need for advanced techniques to efficiently eliminate organic micropollutants from water.Here,we present the synthesis of three nonporous cavitand-crosslinked polymers capable of adsorbing diverse organic pollutants from aqueous solutions.These polymeric adsorbents exhibit outstanding adsorptive performance towards the tested micropollutants,characterized by high apparent adsorption rate constants(kobs)and maximum adsorption capacities(qmax,e).Notably,Compound NCCP-1 demonstrated a remarkable qmax,e of 459 mg/g for bisphenol A(BPA),ranking among the highest values reported for organic polymer adsorbents.In-depth investigation of the adsorption mechanism of the nonporous polymer revealed that it involves the recognition of pollutants by the deep cavities of the cavitand moieties and the interstitial spaces between them,primarily mediated by the hydrophobic effect.Furthermore,NCCP-1 was applied in situ water purification simulations and was proven to maintain its removal efficiency over more than four cycles,highlighting its potential for practical applications in water treatment.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the c...The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.展开更多
The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve...The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.展开更多
High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholester...High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.展开更多
Chaperonins, a class of molecular chaperones, are oligomeric complexes acting as a protein-folding chamber in an ATP-dependent manner. Chaperonins have been classifed
Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive inva-sive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment...Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive inva-sive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largelyunknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifenresistance; however, very little information is available regarding the genes whose loss-of-function alternation contrib-ute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells fromthe tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifenresistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, γ-glutamyltransferase-like activity 1,slit-robo RhoGTPase-activating protein, tetraspan NET-4, HSPC194, amiloride-sensitive epithelial sodium channel gene,and Notch2, were the eight mutated genes identified in different tamoxifen resistant clones, suggesting their requirementfor tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggeststhat multiple pathways can influence tamoxifen sensitivity in breast cancer cells.展开更多
肺癌是世界上最致命的癌症类型。仅仅在美国，每年就有超过225000人被确诊为肺癌，2012年预计死于肺癌的患者大约有16万。与癌胚抗原（carcinoembryonic antigen，CEA）在结肠癌以及前列腺特异抗原（prostate specific antigen，PSA）...肺癌是世界上最致命的癌症类型。仅仅在美国，每年就有超过225000人被确诊为肺癌，2012年预计死于肺癌的患者大约有16万。与癌胚抗原（carcinoembryonic antigen，CEA）在结肠癌以及前列腺特异抗原（prostate specific antigen，PSA）在前列腺癌中的作用不同，在肺癌患者诊治过程中，肿瘤标志物的应用并不广泛。肺癌的诊断依赖于影像学检查，而不是体液中的肿瘤标志物。然而在最近的研究中，循环肿瘤细胞（circulating tumor cells，CTCs）的潜在价值被发现。基于CTCs的分析已经被视作“液相活组织检查”，它将有助于我们对恶性肿瘤进行定性和定量的分析。展开更多
基金supported by the National Natural Science Foundation of China(Nos.22322107,22101169 and 22071144)by Shanghai Scientific and Technological Committee(No.22010500300).
文摘Organic pollutants,a pivotal factor in water pollution,have persistently menaced the aquatic ecosystem,as well as the sustainable development of human health,economy,and society.Consequently,there is an urgent need for advanced techniques to efficiently eliminate organic micropollutants from water.Here,we present the synthesis of three nonporous cavitand-crosslinked polymers capable of adsorbing diverse organic pollutants from aqueous solutions.These polymeric adsorbents exhibit outstanding adsorptive performance towards the tested micropollutants,characterized by high apparent adsorption rate constants(kobs)and maximum adsorption capacities(qmax,e).Notably,Compound NCCP-1 demonstrated a remarkable qmax,e of 459 mg/g for bisphenol A(BPA),ranking among the highest values reported for organic polymer adsorbents.In-depth investigation of the adsorption mechanism of the nonporous polymer revealed that it involves the recognition of pollutants by the deep cavities of the cavitand moieties and the interstitial spaces between them,primarily mediated by the hydrophobic effect.Furthermore,NCCP-1 was applied in situ water purification simulations and was proven to maintain its removal efficiency over more than four cycles,highlighting its potential for practical applications in water treatment.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金financially supported by the National Natural Science Foundation of China(No.32172855)Fundamental Research Funds for the Central Universities(Nos.2632024ZD07,2632024TD02)the Open Project of Jiangsu Provincial Science and Technology Resources(Clinical Resources)Coordination Service Platform(No.TC2023B001)。
文摘The presence of the blood–brain barrier limits the drug concentration in the brain,while low concentrations of antibiotics make it difficult to kill infecting bacteria and tends to induce drug resistance,making the clinical treatment of bacterial meningitis challenging.Herein,a nose-to-brain delivery strategy of small-sized nanozyme has been fabricated for combating bacterial meningitis,to overcome the low drug concentration and drug resistance.This strategy was achieved by a proteinsupported Au nanozyme(ANZ).With a particle size of less than 10 nm,it possesses both glucose oxidase-like and peroxidase-like activities and can generate large amounts of reactive oxygen species through a cascade effect without the addition of external H_(2)O_(2).Benefiting from the cascade catalytic amplification effect generated by its dual enzymelike activities,ANZ shows significant broad-spectrum antibacterial activity without inducing bacterial resistance in vitro.Notably,small-sized ANZ exhibits higher brain entry efficiency and greater accumulation after intranasal administration compared to oral or intravenous administration.In a mouse model of bacterial meningitis,the mice treated with ANZ had lower bacterial loads in the brain and higher survival and clinical behavior scores compared to the classical antibiotic ceftriaxone.Additionally,the meningitis mice exhibited undamaged cognitive and behavioral abilities,indicating the excellent biocompatibility of ANZ.The above results demonstrate that nose-to-brain delivery of ANZ exhibits high intracerebral accumulation,strong antibacterial efficacy and does not lead to bacterial resistance.It holds broad prospects for the treatment of bacterial meningitis.
文摘The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.
文摘High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.
文摘Chaperonins, a class of molecular chaperones, are oligomeric complexes acting as a protein-folding chamber in an ATP-dependent manner. Chaperonins have been classifed
基金supported in part by US Army BreastCancer Research Program Idea Award No. DAMD17-01-1-0389.
文摘Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive inva-sive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largelyunknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifenresistance; however, very little information is available regarding the genes whose loss-of-function alternation contrib-ute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells fromthe tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifenresistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, γ-glutamyltransferase-like activity 1,slit-robo RhoGTPase-activating protein, tetraspan NET-4, HSPC194, amiloride-sensitive epithelial sodium channel gene,and Notch2, were the eight mutated genes identified in different tamoxifen resistant clones, suggesting their requirementfor tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggeststhat multiple pathways can influence tamoxifen sensitivity in breast cancer cells.
