Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techn...Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techniques. Soil contamination by heavy metals as cadmium, highlights two main aspects： on one side they interfere with the life cycle of plants and therefore reduce crop yields, and on the other hand, once adsorbed and accumulated into the plant tissues, they enter the food chain poisoning animals and humans. Considering this point of view, understanding the mechanism by which plants handle heavy metal exposure, in particular cadmium stress, is a primary goal of plant-biotechnology research or plant breeders whose aim is to create plants that are able to recover high amounts of heavy metals, which can be used for phytoremediation, or identify crop varieties that do not accumulate toxic metal in grains or fruits. In this review we focus on the main symptoms of cadmium toxicity both on root apparatus and shoots. We elucidate the mechanisms that plants activate to prevent absorption or to detoxify toxic metal ions, such as synthesis of phytochelatins, metallothioneins and enzymes involved in stress response. Finally we consider new plant-biotechnology applications that can be applied for phytoremediation.展开更多
Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerv...Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.展开更多
There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be alt...There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.展开更多
RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA...RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field.展开更多
目的 以活体^1H-MRS作为参考标准，评价三倍回波梯度回波序列对肝脏脂肪含量的量化。方法 此前瞻畦研究经伦理委员会批准，且所有病人签署了书面知情同意书。37例2型糖尿病病人（男31例，女6例，平均年龄56岁）采用3．0 T MR设备先对...目的 以活体^1H-MRS作为参考标准，评价三倍回波梯度回波序列对肝脏脂肪含量的量化。方法 此前瞻畦研究经伦理委员会批准，且所有病人签署了书面知情同意书。37例2型糖尿病病人（男31例，女6例，平均年龄56岁）采用3．0 T MR设备先对肝脏第VII段行单体素^1H-MRS，经T1和T2衰减的校正，通过4．7ppm（1ppm表示10^-6）水峰和1．3ppm甲基计算肝脏脂肪含量。展开更多
Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb...Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb amputation.For this reason,early diagnosis and appropriate treatment are essential,including treatment which is both local(of the foot)and systemic(metabolic),and this requires coordination by a multidisciplinary team.Optimal treatment also often involves extensive surgical debridement and management of the wound base,effective antibiotic therapy,consideration for revascularization and correction of metabolic abnormalities such as hyperglycemia.This article focuses on diagnosis and management of diabetic foot infections in the light of recently published data in order to help clinicians in identification,assessment and antibiotic therapy of diabetic foot infections.展开更多
In the present work,selective laser melting(SLM)technology was utilized for manufacturing CX stainless steel samples under a series of laser parameters.The effect of laser linear energy density on the microstructure c...In the present work,selective laser melting(SLM)technology was utilized for manufacturing CX stainless steel samples under a series of laser parameters.The effect of laser linear energy density on the microstructure characteristics,phase distribution,crystallographic orientation and mechanical properties of these CX stainless steel samples were investigated theoretically and experimentally via scanning electron microscope(SEM),X-ray diffraction(XRD),electron backscatter diffraction(EBSD)and transmission electron microscope(TEM).Based on the systematic study,the SLM CX stainless steel sample with best surface roughness(Ra=4.05±1.8μm)and relative density(Rd=99.72%±0.22%)under the optimal linear density(η=245 J/m)can be obtained.SLM CX stainless steel was primarily constituted by a large number of fine martensite(α’phase)structures(i.e.,cell structures,cellular dendrites and blocky grains)and a small quantity of austenite(γphase)structures.The pre ferred crystallographic orientation(i.e.,<111>direction)can be determined in the XZ plane of the SLM CX sample.Furthermore,under the optimal linear energy density,the good combinations with the highest ultimate tensile strength(UTS=1068.0%±5.9%)and the best total elongation(TE=15.70%±0.26%)of the SLM CX sample can be attained.Dislocation strengthening dominates the strengthening mechanism of the SLM CX sample in as-built state.展开更多
Over the past four years, the field of the innate immune response has been highly influenced by the discovery of the IKB kinase （IKK）-related kinases, TANK Binding Kinase I （TBK1） and IKKi, which regulate the acti...Over the past four years, the field of the innate immune response has been highly influenced by the discovery of the IKB kinase （IKK）-related kinases, TANK Binding Kinase I （TBK1） and IKKi, which regulate the activity of interferon regulatory factor （IRF）-3/IRF-7 and NF-κB transcription factors. More recently, additional essential components of the signaling pathways that activate these IKK homologues have been discovered. These include the RNA helicases RIGi and MDA5, and the downstream mitochondrial effector known as CARDIF/MAVS/VISA/IPS-1. In addition to their essential functions in controlling the innate immune response, recent studies have highlighted a role of these kinases in cell proliferation and oncogenesis. The canonical IKKs are well recognized to be a bridge linking chronic inflammation to cancer. New findings now suggest that the IKK-related kinases TBK1 and IKKi also participate in signaling pathways that impact on cell transformation and tumor progression. This review will therefore summarize and discuss the role of TBK1 and IKKi in cellular transformation and oncogenesis by focusing on their regulation and substrate specificity.展开更多
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating Syst...Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.展开更多
Nanocarbon materials play a critical role in the development of new or improved technologies and devices for sustainable production and use of renewable energy. This perspective paper defines some of the trends and ou...Nanocarbon materials play a critical role in the development of new or improved technologies and devices for sustainable production and use of renewable energy. This perspective paper defines some of the trends and outlooks in this exciting area, with the effort of evidencing some of the possibilities offered from the growing level of knowledge, as testified from the exponentially rising number of publications, and putting bases for a more rational design of these nanomaterials. The basic members of the new carbon family are fullerene, graphene, and carbon nanotube. Derived from them are carbon quantum dots, nanohorn, nanofiber, nano ribbon, nanocapsulate, nanocage and other nanomorphologies. Second generation nanocarbons are those which have been modified by surface functionalization or doping with heteroatoms to create specific tailored properties. The third generation of nanocarbons is the nanoarchitectured supramolecular hybrids or composites of the first and second genera- tion nanocarbons, or with organic or inorganic species. The advantages of the new carbon materials, relating to the field of sustainable energy, are discussed, evidencing the unique properties that they offer for developing next generation solar devices and energy storage solutions.展开更多
Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells （NSCs） could survive in poly...Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells （NSCs） could survive in poly（L-lactic-co-glycolic acid） （PLGA） scaffolds and, when cografted with Schwann cells （SCs）, could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. Methods NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student＇s t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance （ANOVA） was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials （CMEPs） and Basso, Beattie ＆ Bresnahan locomotor rating scale （BBB） score. The X2 test was used to determine the differences in recovery percentage of CMEPs. Results NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs （（1.7831±0.0402）% vs. （1.4911±0.0313）%, P 〈0.001）. Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA＋NSCs＋SCs group was more than that in PLGA＋NSCs group and in PLGA group （（110.25±30.46） vs. （18.25±3.30） and （11.25±5.54）, P 〈0.01）. The percentage of CMEPs recovery in PLGA＋NSCs＋SCs group was higher than in the other groups （84.8% vs, 50.0% and 37.5%, P 〈0.05）. The amplitude of CMEPs in PLGA＋NSCs＋SCs group was higher than in the other gro展开更多
Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellul...Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.展开更多
In the Medicago genus, triterpenic saponins are bioactive secondary metabolites constitutively synthesized in the aerial and subterranean parts of plants via the isoprenoid pathway. Exploitation of saponins as pharmac...In the Medicago genus, triterpenic saponins are bioactive secondary metabolites constitutively synthesized in the aerial and subterranean parts of plants via the isoprenoid pathway. Exploitation of saponins as pharmaceutics, agrochemicals and in the food and cosmetic industries has raised interest in identifying the enzymes involved in their synthesis. We have identified a cytochrome P450 （CYP72A67） involved in hemolytic sapogenin biosynthesis by a reverse genetic TILLING approach in a Medicago truncatula ethyl- methanesulfonate （EMS） mutagenized collection. Genetic and biochemical analyses, mutant complementation, and expression of the gene in a microsome yeast system showed that CYP72A67 is responsible for hydroxylation at the C-2 position downstream of oleanolic acid synthesis. The affinity of CYP72A67 for substrates with different substitutions at multiple carbon positions was investigated in the same in vitro yeast system, and in relation to two other CYP450s （CYP72A68） responsible for the production of medicagenic acid, the main sapogenin in M. truncatula leaves and roots. Full sib mutant and wild-type plants were compared for their sapogenin profile, expression patterns of the genes involved in sapogenin synthesis, and response to inoculation with Sinorhizobium meliloti. The results obtained allowed us to revise the hemolytic sapogenin pathway in M. truncatula and contribute to highlighting the tissue specificities （leaves/roots） of sapogenin synthesis.展开更多
文摘Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techniques. Soil contamination by heavy metals as cadmium, highlights two main aspects： on one side they interfere with the life cycle of plants and therefore reduce crop yields, and on the other hand, once adsorbed and accumulated into the plant tissues, they enter the food chain poisoning animals and humans. Considering this point of view, understanding the mechanism by which plants handle heavy metal exposure, in particular cadmium stress, is a primary goal of plant-biotechnology research or plant breeders whose aim is to create plants that are able to recover high amounts of heavy metals, which can be used for phytoremediation, or identify crop varieties that do not accumulate toxic metal in grains or fruits. In this review we focus on the main symptoms of cadmium toxicity both on root apparatus and shoots. We elucidate the mechanisms that plants activate to prevent absorption or to detoxify toxic metal ions, such as synthesis of phytochelatins, metallothioneins and enzymes involved in stress response. Finally we consider new plant-biotechnology applications that can be applied for phytoremediation.
基金funded by National Natural Science Foundation of China(81871570,81560313).
文摘Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.
文摘There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.
基金supported by the National Natural Science Foundation of China(31871003,31901053)the Hunan Provincial Natural Science Foundation of China(2018JJ1019,2019JJ50196)+3 种基金the Hu-Xiang Young Talent Program(2018RS3094)the Fundamental Research Funds for the Central Universities(3052018065)the Beijing Institute of Technology Research Fund Program for Young Scholars.It was also supported,in part,by grants from the National Science and Technology Major Project of China(2019ZX09301-132)Program for Changjiang Scholars and Innovative Research Team in University of China(IRT_15R13).
文摘RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field.
文摘目的 以活体^1H-MRS作为参考标准，评价三倍回波梯度回波序列对肝脏脂肪含量的量化。方法 此前瞻畦研究经伦理委员会批准，且所有病人签署了书面知情同意书。37例2型糖尿病病人（男31例，女6例，平均年龄56岁）采用3．0 T MR设备先对肝脏第VII段行单体素^1H-MRS，经T1和T2衰减的校正，通过4．7ppm（1ppm表示10^-6）水峰和1．3ppm甲基计算肝脏脂肪含量。
基金Supported by Institut National de la SantéEt de la Recherche Médicale,the French Speaking Association for Diabetes and Metabolic Diseases(ALFEDIAM grant)the University of Montpellier 1,the Languedoc-Roussillon Area(Chercheur d'avenir Grant) and the City of Nmes
文摘Foot ulcers are common in diabetic patients,have a cumulative lifetime incidence rate as high as 25%and frequently become infected.The spread of infection to soft tissue and bone is a major causal factor for lowerlimb amputation.For this reason,early diagnosis and appropriate treatment are essential,including treatment which is both local(of the foot)and systemic(metabolic),and this requires coordination by a multidisciplinary team.Optimal treatment also often involves extensive surgical debridement and management of the wound base,effective antibiotic therapy,consideration for revascularization and correction of metabolic abnormalities such as hyperglycemia.This article focuses on diagnosis and management of diabetic foot infections in the light of recently published data in order to help clinicians in identification,assessment and antibiotic therapy of diabetic foot infections.
基金supported financially by the Sciences Platform Environment and Capacity Building Projects of GDAS(No.2019GDASYL-0502006)the Key R&D Program of Guangdong Province(No.2020B090923002)+3 种基金the Guangdong Academy of Science Projects(No.2021GDASYL-20210102005)the Guangdong Province Science and Technology Plan Projects(No.2020A1515011096)the Guangzhou Project of Science&Technology(Nos.202007020008 and 201807010030)the support from the Program of CSC(No.201801810106)。
文摘In the present work,selective laser melting(SLM)technology was utilized for manufacturing CX stainless steel samples under a series of laser parameters.The effect of laser linear energy density on the microstructure characteristics,phase distribution,crystallographic orientation and mechanical properties of these CX stainless steel samples were investigated theoretically and experimentally via scanning electron microscope(SEM),X-ray diffraction(XRD),electron backscatter diffraction(EBSD)and transmission electron microscope(TEM).Based on the systematic study,the SLM CX stainless steel sample with best surface roughness(Ra=4.05±1.8μm)and relative density(Rd=99.72%±0.22%)under the optimal linear density(η=245 J/m)can be obtained.SLM CX stainless steel was primarily constituted by a large number of fine martensite(α’phase)structures(i.e.,cell structures,cellular dendrites and blocky grains)and a small quantity of austenite(γphase)structures.The pre ferred crystallographic orientation(i.e.,<111>direction)can be determined in the XZ plane of the SLM CX sample.Furthermore,under the optimal linear energy density,the good combinations with the highest ultimate tensile strength(UTS=1068.0%±5.9%)and the best total elongation(TE=15.70%±0.26%)of the SLM CX sample can be attained.Dislocation strengthening dominates the strengthening mechanism of the SLM CX sample in as-built state.
文摘Over the past four years, the field of the innate immune response has been highly influenced by the discovery of the IKB kinase （IKK）-related kinases, TANK Binding Kinase I （TBK1） and IKKi, which regulate the activity of interferon regulatory factor （IRF）-3/IRF-7 and NF-κB transcription factors. More recently, additional essential components of the signaling pathways that activate these IKK homologues have been discovered. These include the RNA helicases RIGi and MDA5, and the downstream mitochondrial effector known as CARDIF/MAVS/VISA/IPS-1. In addition to their essential functions in controlling the innate immune response, recent studies have highlighted a role of these kinases in cell proliferation and oncogenesis. The canonical IKKs are well recognized to be a bridge linking chronic inflammation to cancer. New findings now suggest that the IKK-related kinases TBK1 and IKKi also participate in signaling pathways that impact on cell transformation and tumor progression. This review will therefore summarize and discuss the role of TBK1 and IKKi in cellular transformation and oncogenesis by focusing on their regulation and substrate specificity.
文摘Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.
基金the financial support by MOST (2011CBA00504)NSFC (21133010, 50921004, 212111074) of China
文摘Nanocarbon materials play a critical role in the development of new or improved technologies and devices for sustainable production and use of renewable energy. This perspective paper defines some of the trends and outlooks in this exciting area, with the effort of evidencing some of the possibilities offered from the growing level of knowledge, as testified from the exponentially rising number of publications, and putting bases for a more rational design of these nanomaterials. The basic members of the new carbon family are fullerene, graphene, and carbon nanotube. Derived from them are carbon quantum dots, nanohorn, nanofiber, nano ribbon, nanocapsulate, nanocage and other nanomorphologies. Second generation nanocarbons are those which have been modified by surface functionalization or doping with heteroatoms to create specific tailored properties. The third generation of nanocarbons is the nanoarchitectured supramolecular hybrids or composites of the first and second genera- tion nanocarbons, or with organic or inorganic species. The advantages of the new carbon materials, relating to the field of sustainable energy, are discussed, evidencing the unique properties that they offer for developing next generation solar devices and energy storage solutions.
基金This work was supported by the grant from the International Cooperation Research Foundation of National Natural Science Foundation of China （No. 30540450581）. Conflict of interest： none.
文摘Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells （NSCs） could survive in poly（L-lactic-co-glycolic acid） （PLGA） scaffolds and, when cografted with Schwann cells （SCs）, could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. Methods NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student＇s t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance （ANOVA） was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials （CMEPs） and Basso, Beattie ＆ Bresnahan locomotor rating scale （BBB） score. The X2 test was used to determine the differences in recovery percentage of CMEPs. Results NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs （（1.7831±0.0402）% vs. （1.4911±0.0313）%, P 〈0.001）. Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA＋NSCs＋SCs group was more than that in PLGA＋NSCs group and in PLGA group （（110.25±30.46） vs. （18.25±3.30） and （11.25±5.54）, P 〈0.01）. The percentage of CMEPs recovery in PLGA＋NSCs＋SCs group was higher than in the other groups （84.8% vs, 50.0% and 37.5%, P 〈0.05）. The amplitude of CMEPs in PLGA＋NSCs＋SCs group was higher than in the other gro
基金supported by the National Natural Science Foundation of China(Nos.81430072,81421003,81602641,81572929).
文摘Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.
文摘In the Medicago genus, triterpenic saponins are bioactive secondary metabolites constitutively synthesized in the aerial and subterranean parts of plants via the isoprenoid pathway. Exploitation of saponins as pharmaceutics, agrochemicals and in the food and cosmetic industries has raised interest in identifying the enzymes involved in their synthesis. We have identified a cytochrome P450 （CYP72A67） involved in hemolytic sapogenin biosynthesis by a reverse genetic TILLING approach in a Medicago truncatula ethyl- methanesulfonate （EMS） mutagenized collection. Genetic and biochemical analyses, mutant complementation, and expression of the gene in a microsome yeast system showed that CYP72A67 is responsible for hydroxylation at the C-2 position downstream of oleanolic acid synthesis. The affinity of CYP72A67 for substrates with different substitutions at multiple carbon positions was investigated in the same in vitro yeast system, and in relation to two other CYP450s （CYP72A68） responsible for the production of medicagenic acid, the main sapogenin in M. truncatula leaves and roots. Full sib mutant and wild-type plants were compared for their sapogenin profile, expression patterns of the genes involved in sapogenin synthesis, and response to inoculation with Sinorhizobium meliloti. The results obtained allowed us to revise the hemolytic sapogenin pathway in M. truncatula and contribute to highlighting the tissue specificities （leaves/roots） of sapogenin synthesis.
