Temozolomide(TMZ)is an oral alkylating agent used to treat glioblastoma multiforme(GBM)and astrocytomas.However,at least 50%of TMZ treated patients do not respond to TMZ.This is due primarily to the over-expression of...Temozolomide(TMZ)is an oral alkylating agent used to treat glioblastoma multiforme(GBM)and astrocytomas.However,at least 50%of TMZ treated patients do not respond to TMZ.This is due primarily to the over-expression of O6-methylguanine methyltransferase(MGMT)and/or lack of a DNA repair pathway in GBM cells.Multiple GBM cell lines are known to contain TMZ resistant cells and several acquired TMZ resistant GBM cell lines have been developed for use in experiments designed to define the mechanism of TMZ resistance and the testing of potential therapeutics.However,the characteristics of intrinsic and adaptive TMZ resistant GBM cells have not been systemically compared.This article reviews the characteristics and mechanisms of TMZ resistance in natural and adapted TMZ resistant GBM cell lines.It also summarizes potential treatment options for TMZ resistant GBMs.展开更多
Rapid development of energy,electrical and electronic technologies has put forward higher requirements for the thermal conductivities of polymers and their composites.However,the thermal conductivity coefficient(λ)va...Rapid development of energy,electrical and electronic technologies has put forward higher requirements for the thermal conductivities of polymers and their composites.However,the thermal conductivity coefficient(λ)values of prepared thermally conductive polymer composites are still difficult to achieve expectations,which has become the bottleneck in the fields of thermally conductive polymer composites.Aimed at that,based on the accumulation of the previous research works by related researchers and our research group,this paper proposes three possible directions for breaking through the bottlenecks:(1)preparing and synthesizing intrinsically thermally conductive polymers,(2)reducing the interfacial thermal resistance in thermally conductive polymer composites,and(3)establishing suitable thermal conduction models and studying inner thermal conduction mechanism to guide experimental optimization.Also,the future development trends of the three above-mentioned directions are foreseen,hoping to provide certain basis and guidance for the preparation,researches and development of thermally conductive polymers and their composites.展开更多
Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequen...Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequencing was used to investigate the effects of a plantderived fertilizer processed from sugarcane and beet on soil antibiotic resistance genes(ARGs)in a soybean field along crop growth stages.ARG profiles in the soils amended by plant-derived fertilizer were compared with those in the soils amended by chicken manure.The abundance and diversity of total ARGs in the soils amended by plant-derived fertilizer were significantly(P<0.05)elevated at the sprout stage,to a level comparable to that in the manured soils.Whereas,unlike chicken manure mainly introducing manure-borne ARGs to soil,the plant-derived fertilizer was indicated to mainly enrich multidrug resistance genes in soil by nourishing indigenous bacteria.ARGs with abundances in amended soils significantly(P<0.05)higher than in unamended soils at the sprout stage of soybean were considered as enriched ARGs.Decrease in the abundance of the enriched ARGs was observed in both the amended soils from the sprout to the harvest.Network analysis further identified Proteobacteria and Bacteroidetes as the primary bacterial taxa involved in the temporal variation of the enriched ARGs in the soils amended by plant-derived fertilizer,while in manured soils were Firmicutes and Actinobacteria.As revealed by multivariate statistical analyses,variation of the enriched ARGs in the soils amended by plant-derived fertilizer was majorly attributed to the response of co-occurred bacteria to depleting nutrients,which was different from the failed establishment of manure-borne bacteria in the manured soils.Our study provided field-based evidence that plant-derived fertilizer stimulated the intrinsic antibiotic resistome,and proposed attention to the un-perceived risk since some clinically relevant ARGs originate and evolve from natural resistome.展开更多
Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repeti...Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repetitive antibiotic treatment,most often with broad-spectrum gram negative coverage,patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria,and this raises concern.In such patients,extended-spectrum beta-lactamase and AmpCproducing Enterobacterales,methicillin-or vancomycin-resistant Staphylococcus aureus,vancomycin-resistant Enterococci,carbapenem-resistant Pseudomonas aeruginosa,and Acinetobacter baumannii,all of which are difficult to treat,are the most common.That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed.At the same time,our knowledge of resistance mechanisms is constantly updated.This review summarizes the current situation regarding the burden of antibiotic resistance,including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.展开更多
An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome ...An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH- 5）. Among them, pHXHI and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-l-positive pathogens with pan-drug resistance proceeds via food chains.展开更多
目的探讨BIM基因缺失多态性与乳腺癌紫杉醇内源性耐药机制的关系。方法采用PCR及基因测序筛查出具备BIM缺失多态性的人乳腺癌细胞株,再通过rt PCR、Western Blot、MTS等方法,检测其对紫杉醇的敏感性以及BIM m RNA、BIM蛋白的表达水平。...目的探讨BIM基因缺失多态性与乳腺癌紫杉醇内源性耐药机制的关系。方法采用PCR及基因测序筛查出具备BIM缺失多态性的人乳腺癌细胞株,再通过rt PCR、Western Blot、MTS等方法,检测其对紫杉醇的敏感性以及BIM m RNA、BIM蛋白的表达水平。结果T47D为BIM缺失多态性的人乳腺癌细胞株,相对野生型细胞株MCF7对紫杉醇药物敏感性显著较低[T47D vs.MCF-7,IC_(50)>30μmol/L vs.IC_(50)=(0.16±0.02)μmol/L];并且,T47D相对MCF7的BIM m RNA EXON3:EXON4比值明显增高而功能性BIM蛋白则表达下调(P<0.05)。结论BIM缺失多态性可能参与了乳腺癌紫杉醇内源性耐药机制。展开更多
In order to gain insights into the seasonal dynamics of genetic variation in insecticide resistance within a natural population of Drosophila melanogaster during population growth, which we considered the most importa...In order to gain insights into the seasonal dynamics of genetic variation in insecticide resistance within a natural population of Drosophila melanogaster during population growth, which we considered the most important ecological factor there, we conducted a series of genetic analyses of resistance factors involved in that population and compared individual-based intrinsic rates of natural increase among resistance genotypes. However, some researchers have argued that it is a misconception to apply the intrinsic rate of natural increase to individuals, because it is a population parameter. We consider that their criticisms were incorrect. In this article, I described our research briefly and set forth the reasons why we conducted these studies.展开更多
Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80%...Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 months.However,the mechanisms for tumor resistance are essentially unknown.Here we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ARST0431.Methods:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)treatment.Tumor response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for evaluation.Treated tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics analysis.Results:The sensitivity to VAC of 34 RMS models was determined.EFS varied from 3 weeks to>20 weeks.Tumor models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC therapy.Resistance to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of treatment.Conclusion:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS models.As such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical resistance.These VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease.展开更多
基金These studies were supported from the Gittlen Foundation.
文摘Temozolomide(TMZ)is an oral alkylating agent used to treat glioblastoma multiforme(GBM)and astrocytomas.However,at least 50%of TMZ treated patients do not respond to TMZ.This is due primarily to the over-expression of O6-methylguanine methyltransferase(MGMT)and/or lack of a DNA repair pathway in GBM cells.Multiple GBM cell lines are known to contain TMZ resistant cells and several acquired TMZ resistant GBM cell lines have been developed for use in experiments designed to define the mechanism of TMZ resistance and the testing of potential therapeutics.However,the characteristics of intrinsic and adaptive TMZ resistant GBM cells have not been systemically compared.This article reviews the characteristics and mechanisms of TMZ resistance in natural and adapted TMZ resistant GBM cell lines.It also summarizes potential treatment options for TMZ resistant GBMs.
基金National Natural Science Foundation of China(51773169 and 51973173)Guangdong Basic and Applied Basic Research Foundation(2019B1515120093)+2 种基金Technological Base Scientific Research ProjectsNatural Science Basic Research Plan for Distinguished Young Scholars in Shaanxi Province(2019JC-11)Polymer Electromagnetic Functional Materials Innovation Team of Shaanxi Sanqin Scholars.
文摘Rapid development of energy,electrical and electronic technologies has put forward higher requirements for the thermal conductivities of polymers and their composites.However,the thermal conductivity coefficient(λ)values of prepared thermally conductive polymer composites are still difficult to achieve expectations,which has become the bottleneck in the fields of thermally conductive polymer composites.Aimed at that,based on the accumulation of the previous research works by related researchers and our research group,this paper proposes three possible directions for breaking through the bottlenecks:(1)preparing and synthesizing intrinsically thermally conductive polymers,(2)reducing the interfacial thermal resistance in thermally conductive polymer composites,and(3)establishing suitable thermal conduction models and studying inner thermal conduction mechanism to guide experimental optimization.Also,the future development trends of the three above-mentioned directions are foreseen,hoping to provide certain basis and guidance for the preparation,researches and development of thermally conductive polymers and their composites.
基金supported by the National Natural Science Foundation of China (Nos.32141002 and 22076203)。
文摘Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequencing was used to investigate the effects of a plantderived fertilizer processed from sugarcane and beet on soil antibiotic resistance genes(ARGs)in a soybean field along crop growth stages.ARG profiles in the soils amended by plant-derived fertilizer were compared with those in the soils amended by chicken manure.The abundance and diversity of total ARGs in the soils amended by plant-derived fertilizer were significantly(P<0.05)elevated at the sprout stage,to a level comparable to that in the manured soils.Whereas,unlike chicken manure mainly introducing manure-borne ARGs to soil,the plant-derived fertilizer was indicated to mainly enrich multidrug resistance genes in soil by nourishing indigenous bacteria.ARGs with abundances in amended soils significantly(P<0.05)higher than in unamended soils at the sprout stage of soybean were considered as enriched ARGs.Decrease in the abundance of the enriched ARGs was observed in both the amended soils from the sprout to the harvest.Network analysis further identified Proteobacteria and Bacteroidetes as the primary bacterial taxa involved in the temporal variation of the enriched ARGs in the soils amended by plant-derived fertilizer,while in manured soils were Firmicutes and Actinobacteria.As revealed by multivariate statistical analyses,variation of the enriched ARGs in the soils amended by plant-derived fertilizer was majorly attributed to the response of co-occurred bacteria to depleting nutrients,which was different from the failed establishment of manure-borne bacteria in the manured soils.Our study provided field-based evidence that plant-derived fertilizer stimulated the intrinsic antibiotic resistome,and proposed attention to the un-perceived risk since some clinically relevant ARGs originate and evolve from natural resistome.
文摘Regardless of etiology,complications with bacterial infection in patients with cirrhosis are reported in the range of 25%-46%according to the most recent data.Due to frequent episodes of bacterial infection and repetitive antibiotic treatment,most often with broad-spectrum gram negative coverage,patients with cirrhosis are at increased risk of encountering multidrug resistant bacteria,and this raises concern.In such patients,extended-spectrum beta-lactamase and AmpCproducing Enterobacterales,methicillin-or vancomycin-resistant Staphylococcus aureus,vancomycin-resistant Enterococci,carbapenem-resistant Pseudomonas aeruginosa,and Acinetobacter baumannii,all of which are difficult to treat,are the most common.That is why novel approaches to the prophylaxis and treatment of bacterial infections to avoid antibiotic resistance have recently been developed.At the same time,our knowledge of resistance mechanisms is constantly updated.This review summarizes the current situation regarding the burden of antibiotic resistance,including the prevalence and mechanisms of intrinsic and acquired resistance in bacterial species that most frequently cause complications in patients with liver cirrhosis and recent developments on how to deal with multidrug resistant bacteria.
基金supported by National Key R&D Program of China (2017YFD0500202,YF)National Key Basic Research Program of China (2016YFC1200100,YF)National Natural Science Foundation of China (31570027 & 81772142,YF)
文摘An endemic multi-drug resistant ST117 E. coil isolate coproducing MCR-I and 3 ESBL loci was, for the first time, detected from diseased chicken, Liaoning Province, in Northeast China, from 2011 to 2012. Whole- genome sequencing revealed 5 unique plasmids, namely pHXH-1, pHXH-2, pHXH-3, pHXH-4 and pHXH- 5）. Among them, pHXHI and pHXH4 encode ESBL, and pHXH-5 mediates MCR-1 colistin resistance. The results indicate that the potentially-national dissemination of MCR-l-positive pathogens with pan-drug resistance proceeds via food chains.
文摘目的探讨BIM基因缺失多态性与乳腺癌紫杉醇内源性耐药机制的关系。方法采用PCR及基因测序筛查出具备BIM缺失多态性的人乳腺癌细胞株,再通过rt PCR、Western Blot、MTS等方法,检测其对紫杉醇的敏感性以及BIM m RNA、BIM蛋白的表达水平。结果T47D为BIM缺失多态性的人乳腺癌细胞株,相对野生型细胞株MCF7对紫杉醇药物敏感性显著较低[T47D vs.MCF-7,IC_(50)>30μmol/L vs.IC_(50)=(0.16±0.02)μmol/L];并且,T47D相对MCF7的BIM m RNA EXON3:EXON4比值明显增高而功能性BIM蛋白则表达下调(P<0.05)。结论BIM缺失多态性可能参与了乳腺癌紫杉醇内源性耐药机制。
文摘In order to gain insights into the seasonal dynamics of genetic variation in insecticide resistance within a natural population of Drosophila melanogaster during population growth, which we considered the most important ecological factor there, we conducted a series of genetic analyses of resistance factors involved in that population and compared individual-based intrinsic rates of natural increase among resistance genotypes. However, some researchers have argued that it is a misconception to apply the intrinsic rate of natural increase to individuals, because it is a population parameter. We consider that their criticisms were incorrect. In this article, I described our research briefly and set forth the reasons why we conducted these studies.
基金supported by CA23099,NO1-CM42216,UO1CA199297,RO1CA169368,PO1CA165995 and CPRIT RP160716.
文摘Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 months.However,the mechanisms for tumor resistance are essentially unknown.Here we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ARST0431.Methods:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)treatment.Tumor response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for evaluation.Treated tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics analysis.Results:The sensitivity to VAC of 34 RMS models was determined.EFS varied from 3 weeks to>20 weeks.Tumor models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC therapy.Resistance to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of treatment.Conclusion:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS models.As such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical resistance.These VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease.
