Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s ...Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s disease.Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity,the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies.We have previously established and validated budding yeast,Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ.Using colony counting based methods,oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast.We have adapted this method for high throughput screening by developing an absorbance-based growth assay.We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells.This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.展开更多
Acinetobacter baumannii is among the common nosocomial infections microorganisms in the Intensive Care Unit (ICU). Antimicrobial resistance (AMR) is one of the major significant concerns in developing nations due to e...Acinetobacter baumannii is among the common nosocomial infections microorganisms in the Intensive Care Unit (ICU). Antimicrobial resistance (AMR) is one of the major significant concerns in developing nations due to either over-use or inadequate use of antimicrobial agents. The purpose of this study was to emphasize the potential antimicrobial activity of Nepeta cataria and Basella alba against nosocomial diseases caused by Acinetobacter baumannii. Nepeta cataria and Basella alba leaves were collected from Oldonyo Sabuk National Park and Botanical garden JKUAT respectively. The leaves were dried under shade at room temperature for thirty days. After methanolic and aqueous plant extraction, the percentage yield was determined, and the extracts were subjected to toxicity testing using brine shrimp eggs and preliminary phytochemical screening. The results recorded from this study demonstrated that 70% methanolic extract of Nepeta cataria and Basella alba had greater antimicrobial effect against Acinetobacter baumannii than aqueous extracts. Nepeta cataria extracts showed greater antimicrobial effect than Basella alba extracts. The methanolic plant extracts had MIC values 60 mg/ml when tested against Acinetobacter baumannii. The phytochemical screening showed the presence of various phytochemical constituents from the methanolic and aqueous extraction of Nepeta cataria and Basella alba. The methanolic plant extracts revealed more phytochemicals as compared to aqueous extracts. More phytochemicals were detected from Nepeta cataria than Basella alba plant extracts.展开更多
In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those co...In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.展开更多
Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previo...Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.展开更多
Two pot experiments with a completely random design and 4 replications were performed in a greenhouse to examine the response difference of 17 cultivars of pakchoi (Brassica chinensis L.) grown in a Cu-spiked and a cl...Two pot experiments with a completely random design and 4 replications were performed in a greenhouse to examine the response difference of 17 cultivars of pakchoi (Brassica chinensis L.) grown in a Cu-spiked and a clean soil to Cu.relatively tolerant. When the 17 cultivars of pakchoi grew in clean garden soil, the Cu concentrations in the aboveground part were positively correlated (r = 0.6693) with their root Cu concentrations. However, when they grew in the Cu-spiked soil a highly negative correlation coefficient (r = -0.5376) was obtained in the Cu concentration between the aboveground part and the root. This meant that the Cu tolerant cultivars had a weak ability to transfer Cu from their root to their aboveground part, and therefore stored much more Cu in their root than the Cu sensitive cultivars.展开更多
Objective To comparatively study the toxicity of four metal-containing nanoparticles(MNPs) and their chemical counterparts to the air-blood barrier(ABB) permeability using an in vitro model.Methods ABB model, which wa...Objective To comparatively study the toxicity of four metal-containing nanoparticles(MNPs) and their chemical counterparts to the air-blood barrier(ABB) permeability using an in vitro model.Methods ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs(divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3(sheet and short-rod-shaped), nano-ZnO, nano-Pb S, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min.Every 10 min following exposure, the cumulative cleared volume(ΔTCL) of Lucifer yellow by the model was calculated.A clearance curve was established using linear regression analysis of ΔTCL versus time.Permeability coefficient(P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability.Results The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2.Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4;no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3;and nano-Pb S was slightly weaker than Pb(NO3)2.So clearly the MNPs possess diverse toxicity.Conclusion ABB permeability abnormality means pulmonary toxicity potential.More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.展开更多
Artificial cyanophages are considered to be an effective biological method to control harmful cyanobacterial bloom.However,no synthetic cyanophage genome has been constructed and where its obstacles are unclear.Here,w...Artificial cyanophages are considered to be an effective biological method to control harmful cyanobacterial bloom.However,no synthetic cyanophage genome has been constructed and where its obstacles are unclear.Here,we survey a stretch of 16 kb length sequence of cyanophage A-4L that is unclonable in Escherichia coli.We test 12 predicted promoters of cyanophage A-4L which were verified all active in E.coli.Next,we screen for eight ORFs that hindered the assembly of intermediate DNA fragments in E.coli and describe that seven ORFs in the 16 kb sequence could not be separately cloned in E.coli.All of unclonable ORFs in high-copy-number plasmid were successfully cloned using low-copy-number vector,suggesting that these ORFs were copy-number-dependent.We propose a clone strategy abandoned the promotor and the start codon that could be applied for unclonable ORFs.Last,we de novo synthesized and assembled the full-length genome of cyanophage A-4L.This work deepens the understanding of synthetic cyanophages studies.展开更多
基金supported by the National Health and Medical Research Council-Australian Research Council dementia research development fellowship(APP1107109)to PB
文摘Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s disease.Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity,the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies.We have previously established and validated budding yeast,Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ.Using colony counting based methods,oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast.We have adapted this method for high throughput screening by developing an absorbance-based growth assay.We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells.This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.
文摘Acinetobacter baumannii is among the common nosocomial infections microorganisms in the Intensive Care Unit (ICU). Antimicrobial resistance (AMR) is one of the major significant concerns in developing nations due to either over-use or inadequate use of antimicrobial agents. The purpose of this study was to emphasize the potential antimicrobial activity of Nepeta cataria and Basella alba against nosocomial diseases caused by Acinetobacter baumannii. Nepeta cataria and Basella alba leaves were collected from Oldonyo Sabuk National Park and Botanical garden JKUAT respectively. The leaves were dried under shade at room temperature for thirty days. After methanolic and aqueous plant extraction, the percentage yield was determined, and the extracts were subjected to toxicity testing using brine shrimp eggs and preliminary phytochemical screening. The results recorded from this study demonstrated that 70% methanolic extract of Nepeta cataria and Basella alba had greater antimicrobial effect against Acinetobacter baumannii than aqueous extracts. Nepeta cataria extracts showed greater antimicrobial effect than Basella alba extracts. The methanolic plant extracts had MIC values 60 mg/ml when tested against Acinetobacter baumannii. The phytochemical screening showed the presence of various phytochemical constituents from the methanolic and aqueous extraction of Nepeta cataria and Basella alba. The methanolic plant extracts revealed more phytochemicals as compared to aqueous extracts. More phytochemicals were detected from Nepeta cataria than Basella alba plant extracts.
基金supported by the Ministry of Science and Technology of the People’s Republic of China (No.2020YFA0907500)the National Natural Science Foundation of China (Nos.22150710514,22021003,and 22106174)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDPB200202)the Postdoc Science Foundation of China (No.2021M693322)。
文摘In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,respectively.Previous studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to animals.Thus,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during development.We employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals.We show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers up-regulated.Human liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and OPEs.Our findings suggest that NEOs and OPEs interfere with human early embryonic development.
基金supported by grants from the National Key Research and Development Program of China(2020YFA0907500)the National Natural Science Foundation of China(22193051,21277062,21806058)+1 种基金the Excellent Discipline Cultivation Project by JHUN(2023XKZ029)the PLA Logistics Research Project of China(2023).
文摘Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous studies.However,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and health.Given the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug resistance.In this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 cells.The developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial substances.Collectively,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.
文摘Two pot experiments with a completely random design and 4 replications were performed in a greenhouse to examine the response difference of 17 cultivars of pakchoi (Brassica chinensis L.) grown in a Cu-spiked and a clean soil to Cu.relatively tolerant. When the 17 cultivars of pakchoi grew in clean garden soil, the Cu concentrations in the aboveground part were positively correlated (r = 0.6693) with their root Cu concentrations. However, when they grew in the Cu-spiked soil a highly negative correlation coefficient (r = -0.5376) was obtained in the Cu concentration between the aboveground part and the root. This meant that the Cu tolerant cultivars had a weak ability to transfer Cu from their root to their aboveground part, and therefore stored much more Cu in their root than the Cu sensitive cultivars.
基金sponsored by the National Natural Science Foundation of China [No.81372949]the Young Scholar Scientific Research Foundation of China CDC [No.2016A206]
文摘Objective To comparatively study the toxicity of four metal-containing nanoparticles(MNPs) and their chemical counterparts to the air-blood barrier(ABB) permeability using an in vitro model.Methods ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs(divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3(sheet and short-rod-shaped), nano-ZnO, nano-Pb S, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min.Every 10 min following exposure, the cumulative cleared volume(ΔTCL) of Lucifer yellow by the model was calculated.A clearance curve was established using linear regression analysis of ΔTCL versus time.Permeability coefficient(P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability.Results The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2.Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4;no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3;and nano-Pb S was slightly weaker than Pb(NO3)2.So clearly the MNPs possess diverse toxicity.Conclusion ABB permeability abnormality means pulmonary toxicity potential.More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.
基金supported by the grants from the National Key Research and Development Program of China (No.2018YFA0903000)the National Natural Science Foundation of China (31901019)and the China Postdoctoral Science foundation (2021M692389).
文摘Artificial cyanophages are considered to be an effective biological method to control harmful cyanobacterial bloom.However,no synthetic cyanophage genome has been constructed and where its obstacles are unclear.Here,we survey a stretch of 16 kb length sequence of cyanophage A-4L that is unclonable in Escherichia coli.We test 12 predicted promoters of cyanophage A-4L which were verified all active in E.coli.Next,we screen for eight ORFs that hindered the assembly of intermediate DNA fragments in E.coli and describe that seven ORFs in the 16 kb sequence could not be separately cloned in E.coli.All of unclonable ORFs in high-copy-number plasmid were successfully cloned using low-copy-number vector,suggesting that these ORFs were copy-number-dependent.We propose a clone strategy abandoned the promotor and the start codon that could be applied for unclonable ORFs.Last,we de novo synthesized and assembled the full-length genome of cyanophage A-4L.This work deepens the understanding of synthetic cyanophages studies.
