Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte an...Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte antigen(CTLA)-4/B7 interaction(using CTLA-4Ig) and the CD40/CD40 L interaction(using anti-CD40 L antibodies) prevents T cell mediated autoimmune diseases, transplant rejection and graft vs host disease in experimental models. Moreover, CTLA-4Ig is in clinical use to treat rheumatoid arthritis(abatacept) and to prevent rejection of renal transplants(belatacept). Under certain experimental conditions, this treatment can even result in tolerance. Surprisingly, the underlying mechanisms of immune modulation are still not completely understood. We here discuss the evidence that costimulation blockade differentially affects effector T cells(Teff) and regulatory T cells(Treg). The latter are required to control inappropriate and unwanted immune responses, and their activity often contributes to tolerance induction and maintenance. Unfortunately, our knowledge on the costimulatory requirements of Treg cells is very limited. We therefore summarize the current understanding ofthe costimulatory requirements of Treg cells, and elaborate on the effect of anti-CD40 L antibody and CTLA-4Ig treatment on Treg cell activity. In this context, we point out that the outcome of a treatment aiming at blocking the CD28/CTLA-4/B7 costimulatory interaction can vary with dosing, timing and underlying immunopathology.展开更多
A black hole is essentially a relativistic as well as a quantum object. Therefore the information paradox of black holes is a consequence of the clash between these two most fundamental theories of modern physics. It ...A black hole is essentially a relativistic as well as a quantum object. Therefore the information paradox of black holes is a consequence of the clash between these two most fundamental theories of modern physics. It is logical to conclude that a resolution of the problem requires some form of a quantum gravity theory. The present work proposes such a resolution using set theory and pointless spacetime geometry.展开更多
Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY ...Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 μM genistein), a rote- none group (treated with 50 μM rotenone), and a rotenone + genistein group (incubated with 20 μM genistein and then treated with 50μM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.展开更多
Marigold(Tagetes erecta L., African marigold) is a widely grown ornamental plant and a main source of the carotenoid lutein for the industrial production of pharmaceuticals, food coloring, and feed additives. To gain ...Marigold(Tagetes erecta L., African marigold) is a widely grown ornamental plant and a main source of the carotenoid lutein for the industrial production of pharmaceuticals, food coloring, and feed additives. To gain a deeper understanding of the genetic mechanism of lutein in marigold, a chromosome-scale assembly of the marigold(T. erecta V-01) genome was completed based on Illumina, PacBio, and Hi-C reads. The707.21-Mb assembled genome consisted of 35 834 annotated protein-coding genes, with 97.7% genomic integrity. We anchored 87.8% of the contigs(covering 621.20 Mb) to 12 pseudochromosomes, bringing the scaffold N50 length to 54.15 Mb. Phylogenetic analysis showed that marigold was closely related to the Asteraceae species bitter vine(Mikania micrantha) and sunflower(Helianthus annuus), all three of which originated in the Americas. Marigold diverged from the sunflower clade 23.57 million years ago(MYA) and from M. micrantha 19.59 MYA.Marigold has undergone three whole-genome duplication events, as well as a recent whole-genome duplication event(WGD-2) common to H.annuus and M. micrantha. Marigold gene families were significantly less expanded than those of M. micrantha or H. annuus, and the marigold genome contained significantly fewer interspersed repeats, which might account for its smaller genome. In addition, a range of candidate genes involved in the lutein biosynthetic pathway were identified. The high-quality reference genome obtained in this study provided a valuable genomic resource for studying the evolution of the Asteraceae family and for improving marigold breeding strategies.展开更多
In order to develop and utilize the tropical medicinal resource Amomum(A.)longiligulare T.L.Wu more reasonably and effectively,this paper summarizes the research progress in chemical constituents and pharmacological a...In order to develop and utilize the tropical medicinal resource Amomum(A.)longiligulare T.L.Wu more reasonably and effectively,this paper summarizes the research progress in chemical constituents and pharmacological activities of A.longiligulare by consulting the literatures,so as to provide a certain theoretical basis for exploring its material basis.The chemical constituents of A.longiligulare mainly include volatile oil,diphenylheptane and flavonoids,which have good efficacy in anti-peptic ulcer,as well as antioxidant,analgesic and other pharmacological activities.This paper briefly discusses the reasons for the differences in the composition of volatile oil studied by different scholars.By summarizing its pharmacological activities,it is found that its various pharmacological activities may be the basis of its anti-peptic ulcer.展开更多
Medicinal plants are facing threats due to loss of habitat and overexploitation of knows species. Therefore the present work shows utilization of essential oil from discarded leaves of Psidium guajava Linn. against hu...Medicinal plants are facing threats due to loss of habitat and overexploitation of knows species. Therefore the present work shows utilization of essential oil from discarded leaves of Psidium guajava Linn. against human dermatophytic fungi Trichophyton rubrum, T. mentagrophytes, Trichophyton violaceum, Trichophyton tonsurans, Epidermophyton floccosum, Microsporum gypseum and Microsporum canis. The oil was found to be fungicidal at 3.0 μl/ml and it tolerated heavy inoculum of pathogens at fungicidal concentrations. The fungicidal activity of the oil was thermostable, up to 70°C and shelf life was found to be six months, which was maximum the time taken into consideration. The oil having cineole, caryophyllane, copaene, azulene and eucalyptol as main constituents, exhibited broad fungicidal activity. The oil did not show any adverse effect on mammalian skin upto 5% concentration. Phylogeny of the dermatophytes with respect to toxicity of the oil has also been discussed using molecular data. The cost effective formulation from waste leaves can be exploited after undergoing double blind successful multicentral topical testing.展开更多
Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overl...Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.展开更多
L( s, t)-labeling is a variation of graph coloring which is motivated by a special kind of the channel assignment problem. Let s and t be any two nonnegative integers. An L (s, t)-labeling of a graph G is an assig...L( s, t)-labeling is a variation of graph coloring which is motivated by a special kind of the channel assignment problem. Let s and t be any two nonnegative integers. An L (s, t)-labeling of a graph G is an assignment of integers to the vertices of G such that adjacent vertices receive integers which differ by at least s, and vertices that are at distance of two receive integers which differ by at least t. Given an L(s, t) -labeling f of a graph G, the L(s, t) edge span of f, βst ( G, f) = max { |f(u) -f(v)|: ( u, v) ∈ E(G) } is defined. The L( s, t) edge span of G, βst(G), is minβst(G,f), where the minimum runs over all L(s, t)-labelings f of G. Let T be any tree with a maximum degree of △≥2. It is proved that if 2s≥t≥0, then βst(T) =( [△/2 ] - 1)t +s; if 0≤2s 〈 t and △ is even, then βst(T) = [ (△ - 1) t/2 ] ; and if 0 ≤2s 〈 t and △ is odd, then βst(T) = (△ - 1) t/2 + s. Thus, the L(s, t) edge spans of the Cartesian product of two paths and of the square lattice are completely determined.展开更多
Spinach (Spinacia oleracea L.) develops leaf rosettes under short-day conditions, and starts reproductive growth including bolting and flowering under long-day conditions. Japanese people prefer Oriental spinach that ...Spinach (Spinacia oleracea L.) develops leaf rosettes under short-day conditions, and starts reproductive growth including bolting and flowering under long-day conditions. Japanese people prefer Oriental spinach that bolts easily with a shorter photoperiod than European spinach. This is one of the main reasons that Oriental spinach is difficult to grow year-round. In order to understand spinach flowering mechanisms and obtain knowledge for spinach breeding, we isolated one CONSTANS-like (COL) and two FLOWERING LOCUS T (FT) homologs, which are key components of photoperiodic regulation of flowering time, from a Japanese cultivar. The expression of SoCOL1 showed diurnal rhythm with the highest expression at the end of the dark cycle. This diurnal rhythm is similar to the expression of BvCOL1 from sugar beet (Beta vulgaris), whose flower-promoting effect was observed when overexpressed in Arabidopsis. Phylogenetic analysis showed that SoCOL1 is the closest homolog of BvCOL1, suggesting that SoCOL1 is an ortholog of BvCOL1. SoFT1 and SoFT2 are closely related to BvFT1 and BvFT2, respectively. The expression of SoFT1 and SoFT2 were induced in advance of flower bud formation after changing the photoperiod, but the expression level of SoFT1 was much lower than SoFT2. Currently, we are speculating that SoFT2 is a flower-promoting factor of spinach, and that SoFT1 has a role in light signaling because the expression of SoFT1 showed a diurnal rhythm.展开更多
[Objectives]To study the effects of Fruticosa potentilla L.on the expression of key enzymes and hormones related to glucose and lipid metabolism in T2DM rats.[Methods]The ethyl acetate fraction of 95%methanol extract ...[Objectives]To study the effects of Fruticosa potentilla L.on the expression of key enzymes and hormones related to glucose and lipid metabolism in T2DM rats.[Methods]The ethyl acetate fraction of 95%methanol extract of F.potentilla(MEE)was administered orally to the T2DM rats,and the level of glucose and expression of insulin,resistin,leptin,glucokinase(GK)and glucose-6-phosphatase(G-6-Pase)in the rats were measured and detected.[Results]In the T2DM rats administered with MEE,the postprandial blood glucose level decreased,the expression levels of resistin,leptin and G-6-Pase were down-regulated,and the expression levels of insulin and GK were up-regulated(P<0.05,P<0.01).[Conclusions]F.potentilla can reduce effectively postprandial blood glucose level,regulate the expression of a variety of enzymes and hormones related to glucose and lipid metabolism and recover partially the insulin level in T2DM rats to achieve resistance to T2DM.展开更多
文摘Costimulatory signals are crucial for T cell activation. Attempts to block costimulatory pathways have been effective in preventing unwanted immune reactions. In particular, blocking the CD28/cytotoxic T lymphocyte antigen(CTLA)-4/B7 interaction(using CTLA-4Ig) and the CD40/CD40 L interaction(using anti-CD40 L antibodies) prevents T cell mediated autoimmune diseases, transplant rejection and graft vs host disease in experimental models. Moreover, CTLA-4Ig is in clinical use to treat rheumatoid arthritis(abatacept) and to prevent rejection of renal transplants(belatacept). Under certain experimental conditions, this treatment can even result in tolerance. Surprisingly, the underlying mechanisms of immune modulation are still not completely understood. We here discuss the evidence that costimulation blockade differentially affects effector T cells(Teff) and regulatory T cells(Treg). The latter are required to control inappropriate and unwanted immune responses, and their activity often contributes to tolerance induction and maintenance. Unfortunately, our knowledge on the costimulatory requirements of Treg cells is very limited. We therefore summarize the current understanding ofthe costimulatory requirements of Treg cells, and elaborate on the effect of anti-CD40 L antibody and CTLA-4Ig treatment on Treg cell activity. In this context, we point out that the outcome of a treatment aiming at blocking the CD28/CTLA-4/B7 costimulatory interaction can vary with dosing, timing and underlying immunopathology.
文摘A black hole is essentially a relativistic as well as a quantum object. Therefore the information paradox of black holes is a consequence of the clash between these two most fundamental theories of modern physics. It is logical to conclude that a resolution of the problem requires some form of a quantum gravity theory. The present work proposes such a resolution using set theory and pointless spacetime geometry.
基金supported by a grant from the National Key Research and Development Plan of China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332,11102235,8167050417+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 μM genistein), a rote- none group (treated with 50 μM rotenone), and a rotenone + genistein group (incubated with 20 μM genistein and then treated with 50μM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin ! levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SYSY cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.
基金supported by the National Natural Science Foundation of China (Grant Nos. 31572166, 31772344, 31871691 and 31972444)。
文摘Marigold(Tagetes erecta L., African marigold) is a widely grown ornamental plant and a main source of the carotenoid lutein for the industrial production of pharmaceuticals, food coloring, and feed additives. To gain a deeper understanding of the genetic mechanism of lutein in marigold, a chromosome-scale assembly of the marigold(T. erecta V-01) genome was completed based on Illumina, PacBio, and Hi-C reads. The707.21-Mb assembled genome consisted of 35 834 annotated protein-coding genes, with 97.7% genomic integrity. We anchored 87.8% of the contigs(covering 621.20 Mb) to 12 pseudochromosomes, bringing the scaffold N50 length to 54.15 Mb. Phylogenetic analysis showed that marigold was closely related to the Asteraceae species bitter vine(Mikania micrantha) and sunflower(Helianthus annuus), all three of which originated in the Americas. Marigold diverged from the sunflower clade 23.57 million years ago(MYA) and from M. micrantha 19.59 MYA.Marigold has undergone three whole-genome duplication events, as well as a recent whole-genome duplication event(WGD-2) common to H.annuus and M. micrantha. Marigold gene families were significantly less expanded than those of M. micrantha or H. annuus, and the marigold genome contained significantly fewer interspersed repeats, which might account for its smaller genome. In addition, a range of candidate genes involved in the lutein biosynthetic pathway were identified. The high-quality reference genome obtained in this study provided a valuable genomic resource for studying the evolution of the Asteraceae family and for improving marigold breeding strategies.
基金supported by the National Natural Science Foundation of China(81660649),and Innovative Scientific Research Project for Postgraduates of Hainan Medical University(HYYS2020-05)。
文摘In order to develop and utilize the tropical medicinal resource Amomum(A.)longiligulare T.L.Wu more reasonably and effectively,this paper summarizes the research progress in chemical constituents and pharmacological activities of A.longiligulare by consulting the literatures,so as to provide a certain theoretical basis for exploring its material basis.The chemical constituents of A.longiligulare mainly include volatile oil,diphenylheptane and flavonoids,which have good efficacy in anti-peptic ulcer,as well as antioxidant,analgesic and other pharmacological activities.This paper briefly discusses the reasons for the differences in the composition of volatile oil studied by different scholars.By summarizing its pharmacological activities,it is found that its various pharmacological activities may be the basis of its anti-peptic ulcer.
文摘Medicinal plants are facing threats due to loss of habitat and overexploitation of knows species. Therefore the present work shows utilization of essential oil from discarded leaves of Psidium guajava Linn. against human dermatophytic fungi Trichophyton rubrum, T. mentagrophytes, Trichophyton violaceum, Trichophyton tonsurans, Epidermophyton floccosum, Microsporum gypseum and Microsporum canis. The oil was found to be fungicidal at 3.0 μl/ml and it tolerated heavy inoculum of pathogens at fungicidal concentrations. The fungicidal activity of the oil was thermostable, up to 70°C and shelf life was found to be six months, which was maximum the time taken into consideration. The oil having cineole, caryophyllane, copaene, azulene and eucalyptol as main constituents, exhibited broad fungicidal activity. The oil did not show any adverse effect on mammalian skin upto 5% concentration. Phylogeny of the dermatophytes with respect to toxicity of the oil has also been discussed using molecular data. The cost effective formulation from waste leaves can be exploited after undergoing double blind successful multicentral topical testing.
基金Supported by Thailand Research Fund grants RTA5280006 (Chattipakorn N)BRG5480003(Chattipakorn S)+1 种基金the National Research Council of Thailand(Chattipakorn N)the Thai-land Research Fund Royal Golden Jubilee project(Kumfu S and Chattipakorn N)
文摘Iron overload can lead to iron deposits in many tissues,particularly in the heart.It has also been shown to be associated with elevated oxidative stress in tissues.Elevated cardiac iron deposits can lead to iron overload cardiomyopathy,a condition which provokes mortality due to heart failure in iron-overloaded patients.Currently,the mechanism of iron uptake into cardiomyocytes is still not clearly understood.Growing evidence suggests L-type Ca2+channels(LTCCs)as a possible pathway for ferrous iron(Fe2+)uptake into cardiomyocytes under iron overload conditions.Nevertheless,controversy still exists since some findings on pharmacological interventions and those using different cell types do not support LTCC’s role as a portal for iron uptake in cardiac cells.Recently,T-type Ca2+channels (TTCC)have been shown to play an important role in the diseased heart.Although TTCC and iron uptake in cardiomyocytes has not been investigated greatly,a recent finding indicated that TTCC could be an important portal in thalassemic hearts.In this review,comprehensive findings collected from previous studies as well as a discussion of the controversy regarding iron uptake mechanisms into cardiomyocytes via calcium channels are presented with the hope that understanding the cellular iron uptake mechanism in cardiomyocytes will lead to improved treatment and prevention strategies,particularly in iron-overloaded patients.
基金The National Natural Science Foundation of China(No10671033)Southeast University Science Foundation ( NoXJ0607230)
文摘L( s, t)-labeling is a variation of graph coloring which is motivated by a special kind of the channel assignment problem. Let s and t be any two nonnegative integers. An L (s, t)-labeling of a graph G is an assignment of integers to the vertices of G such that adjacent vertices receive integers which differ by at least s, and vertices that are at distance of two receive integers which differ by at least t. Given an L(s, t) -labeling f of a graph G, the L(s, t) edge span of f, βst ( G, f) = max { |f(u) -f(v)|: ( u, v) ∈ E(G) } is defined. The L( s, t) edge span of G, βst(G), is minβst(G,f), where the minimum runs over all L(s, t)-labelings f of G. Let T be any tree with a maximum degree of △≥2. It is proved that if 2s≥t≥0, then βst(T) =( [△/2 ] - 1)t +s; if 0≤2s 〈 t and △ is even, then βst(T) = [ (△ - 1) t/2 ] ; and if 0 ≤2s 〈 t and △ is odd, then βst(T) = (△ - 1) t/2 + s. Thus, the L(s, t) edge spans of the Cartesian product of two paths and of the square lattice are completely determined.
文摘Spinach (Spinacia oleracea L.) develops leaf rosettes under short-day conditions, and starts reproductive growth including bolting and flowering under long-day conditions. Japanese people prefer Oriental spinach that bolts easily with a shorter photoperiod than European spinach. This is one of the main reasons that Oriental spinach is difficult to grow year-round. In order to understand spinach flowering mechanisms and obtain knowledge for spinach breeding, we isolated one CONSTANS-like (COL) and two FLOWERING LOCUS T (FT) homologs, which are key components of photoperiodic regulation of flowering time, from a Japanese cultivar. The expression of SoCOL1 showed diurnal rhythm with the highest expression at the end of the dark cycle. This diurnal rhythm is similar to the expression of BvCOL1 from sugar beet (Beta vulgaris), whose flower-promoting effect was observed when overexpressed in Arabidopsis. Phylogenetic analysis showed that SoCOL1 is the closest homolog of BvCOL1, suggesting that SoCOL1 is an ortholog of BvCOL1. SoFT1 and SoFT2 are closely related to BvFT1 and BvFT2, respectively. The expression of SoFT1 and SoFT2 were induced in advance of flower bud formation after changing the photoperiod, but the expression level of SoFT1 was much lower than SoFT2. Currently, we are speculating that SoFT2 is a flower-promoting factor of spinach, and that SoFT1 has a role in light signaling because the expression of SoFT1 showed a diurnal rhythm.
基金Supported by National Natural Science Foundation of China(No.81460652)Key Research and Development and Achievements Transformation Program of Qinghai Province(No.2018-SF-144)Project Funded by Key Laboratory of Medicinal Animal and Plant Resources of Qinghai-Tibet Plateau in Qinghai Province(No.2017-z-y25)
文摘[Objectives]To study the effects of Fruticosa potentilla L.on the expression of key enzymes and hormones related to glucose and lipid metabolism in T2DM rats.[Methods]The ethyl acetate fraction of 95%methanol extract of F.potentilla(MEE)was administered orally to the T2DM rats,and the level of glucose and expression of insulin,resistin,leptin,glucokinase(GK)and glucose-6-phosphatase(G-6-Pase)in the rats were measured and detected.[Results]In the T2DM rats administered with MEE,the postprandial blood glucose level decreased,the expression levels of resistin,leptin and G-6-Pase were down-regulated,and the expression levels of insulin and GK were up-regulated(P<0.05,P<0.01).[Conclusions]F.potentilla can reduce effectively postprandial blood glucose level,regulate the expression of a variety of enzymes and hormones related to glucose and lipid metabolism and recover partially the insulin level in T2DM rats to achieve resistance to T2DM.