During criminal case investigations,blood evidence tracing is critical for criminal investigation.However,the blood stains are often cleaned or covered up after the crime,resulting in trace residue and difficult track...During criminal case investigations,blood evidence tracing is critical for criminal investigation.However,the blood stains are often cleaned or covered up after the crime,resulting in trace residue and difficult tracking.Therefore,a highly sensitive and specific method for the rapid detection of human blood stains remains urgent.To solve this problem,we established a nanozyme-based strip for rapid detection of blood evidence with high sensitivity and specificity.To construct reliable nanozyme strips,we synthesized CoFe_(2)O_(4) nanozymes with high peroxidase-like activity by scaling up to gram level,which can be supplied for six million tests,and conjugated antibody as a detection probe in nanozyme strip.The developed CoFe_(2)O_(4) nanozyme strip can detect human hemoglobin(HGB)at a concentration as low as 1 ng/mL,which is 100 times lower than the commercially available colloidal gold strips(100 ng/mL).Moreover,this CoFe_(2)O_(4) nanozyme strip showed high generality on 12 substrates and high specificity to human HGB among 13 animal blood samples.Finally,we applied the developed CoFe_(2)O_(4) nanozyme strip to successfully detect blood stains in three real cases,where the current commercial colloidal gold strip failed to do.The results suggest that the CoFe_(2)O_(4) nanozyme strip can be used as an effective on-scene detection method for human blood stains,and can further be used as a long-term preserved material evidence for traceability inquiry.展开更多
Bacterial infections pose an ongoing threat to global human health,an issue of growing urgency due to the emergence of resistance against many currently available antibiotics.Recently,the World Health Organization(WHO...Bacterial infections pose an ongoing threat to global human health,an issue of growing urgency due to the emergence of resistance against many currently available antibiotics.Recently,the World Health Organization(WHO)launched a global appeal for the development of novel antibiotics to combat this issue.Ideal antibiotics should possess specific antibacterial effects,without causing resistance.However,the discovery of different antibiotics is lagging the development of drug-resistant bacteria.Many newly developed antibiotics not only are rapidly resisted by bacteria but also are ineffective against persistent bacteria embedded in biofilms and host cells.To tackle these challenges,innovative concepts and approaches are required for the discovery of novel antibacterial candidates.Agents for use against pathogenic bacteria were developed long before the discovery of antibiotics.For 3000 years,garlic has been considered an efficient antibacterial compound,utilized to prevent and treat bacterial infection worldwide,although the specific mechanisms remain unclear.Modern research shows that sulfur-containing chemicals are the primary active constituents of garlic and play key roles in its inherent antimicrobial activity,such as diallyl disulfide(DADS)and diallyl trisulfide(DATS).In contrast,inorganic sulfides for antibacterial use have not been deeply studied.It has been well-known that iron sulfides are an essential part of the geochemical and biological sulfur cycles.Both stable and metastable iron sulfides can be formed under abiotic sediment conditions and biotic process.In particular,certain bacteria species growth need iron sulfide as nutrient source or produce iron sulfide.In addition,iron sulfur clusters as special metastable iron sulfide take part in many important metabolic pathways in most organisms.These physicochemical and biological properties inspire us that iron sulfides are a type of valuable material for investigation and utilization.Below we will introduce a new antibacterial candidate based on iron sulfides,which kill bacteria via multiple mechanisms of action(MoAs).We will first discuss the types of iron sulfides with inherent antibacterial activity,i.e.,metastable species that can release iron ions and polysulfides in aqua.The intrinsic properties of iron sulfides and released iron and polysulfides are analyzed in regard to antibacterial effects under different physiological conditions.In particular,ferrous ion−polysulfide synergized ferroptosis-like death is proposed to kill bacteria with broad spectrum and selectivity.In addition,the versatile MoAs enable metastable iron sulfides(mFeSs)to kill resistant bacteria,eradicate biofilms,and suppress intracellular persistent species without causing new drug resistance.Importantly,the efficient antibacterial properties have been validated in animal models bearing infections including wounds,pneumonia,caries,and bacterial vaginosis,demonstrating great translational potential.Lastly,we will summarize the challenges of iron sulfides,proposing a possible development direction in the future.Our studies on iron sulfides can serve as a paradigm for the design and discovery of antibacterial nanomaterials,which may contribute for the war against drug-resistant pathogenic bacteria.展开更多
Enzymes are biological catalysts that can convert substrates into products in biochemical reactions.In 1926,the first enzyme,urease,was determined to be a protein by James B.Sumner who won the Nobel Prize in 1946.Sinc...Enzymes are biological catalysts that can convert substrates into products in biochemical reactions.In 1926,the first enzyme,urease,was determined to be a protein by James B.Sumner who won the Nobel Prize in 1946.Since then,enzymes have been considered to be proteins,which allows them to achieve their high catalytic activity with high specific activity under mild conditions.However,in general,the enzyme activity of proteins is lost after exposure to extremes of p H and high temperature,and proteins are also susceptible to digestion by proteases in the environment,which dramatically hinders their practical applications展开更多
Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition.Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin...Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition.Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B2(VB2)modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase(SOD)-like activities, acting as typical iron oxide nanozymes(IONzymes) with triad activities. In particular, VB2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species(ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B2 modified IONzymes(VB2-IONzymes) protect human oral keratinocytes(HOK) and BALB/3 T3 cells from hydrogen peroxide(H2O2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB2-IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.展开更多
本文制备竹节参片并进行生物等效性考察。采用超微粉碎-湿法造粒制备竹节参片;按药典规定进行质量检查;高效液相色谱法测定自制竹节参片和人参皂苷Rg3单剂量灌胃后24小时大鼠的血药浓度, DAS 2.0软件计算分析其药动学参数和相对生物利...本文制备竹节参片并进行生物等效性考察。采用超微粉碎-湿法造粒制备竹节参片;按药典规定进行质量检查;高效液相色谱法测定自制竹节参片和人参皂苷Rg3单剂量灌胃后24小时大鼠的血药浓度, DAS 2.0软件计算分析其药动学参数和相对生物利用度。结果发现,自制竹节参片质量检查各项符合2015版药典要求,与人参皂苷Rg3相比具有较高的生物利用度。因此可知,本实验竹节参片制备工艺合理、质量可控,口服吸收利用度好,为竹节参片的工业化生产和临床应用提供参考。展开更多
基金support from the National Natural Science Foundation of China(No.82072324)the National Key R&D Program of China(No.2019YFA0709200)+1 种基金National Natural Science Foundation of China Foundation of Innovative Research Group grant(No.22121003)the Chongqing Special Key Project of Technological Innovation and Application Development(No.cstc2019jscx-gksbX0053).
文摘During criminal case investigations,blood evidence tracing is critical for criminal investigation.However,the blood stains are often cleaned or covered up after the crime,resulting in trace residue and difficult tracking.Therefore,a highly sensitive and specific method for the rapid detection of human blood stains remains urgent.To solve this problem,we established a nanozyme-based strip for rapid detection of blood evidence with high sensitivity and specificity.To construct reliable nanozyme strips,we synthesized CoFe_(2)O_(4) nanozymes with high peroxidase-like activity by scaling up to gram level,which can be supplied for six million tests,and conjugated antibody as a detection probe in nanozyme strip.The developed CoFe_(2)O_(4) nanozyme strip can detect human hemoglobin(HGB)at a concentration as low as 1 ng/mL,which is 100 times lower than the commercially available colloidal gold strips(100 ng/mL).Moreover,this CoFe_(2)O_(4) nanozyme strip showed high generality on 12 substrates and high specificity to human HGB among 13 animal blood samples.Finally,we applied the developed CoFe_(2)O_(4) nanozyme strip to successfully detect blood stains in three real cases,where the current commercial colloidal gold strip failed to do.The results suggest that the CoFe_(2)O_(4) nanozyme strip can be used as an effective on-scene detection method for human blood stains,and can further be used as a long-term preserved material evidence for traceability inquiry.
基金supported by the National Key R&D Program of China grant 2019YFA0709200the National Natural Science Foundation of China(NSFC)Foundation of Innovative Research Group grant 22121003,as well as the National Natural Science Foundation of China grant 81930050.
文摘Bacterial infections pose an ongoing threat to global human health,an issue of growing urgency due to the emergence of resistance against many currently available antibiotics.Recently,the World Health Organization(WHO)launched a global appeal for the development of novel antibiotics to combat this issue.Ideal antibiotics should possess specific antibacterial effects,without causing resistance.However,the discovery of different antibiotics is lagging the development of drug-resistant bacteria.Many newly developed antibiotics not only are rapidly resisted by bacteria but also are ineffective against persistent bacteria embedded in biofilms and host cells.To tackle these challenges,innovative concepts and approaches are required for the discovery of novel antibacterial candidates.Agents for use against pathogenic bacteria were developed long before the discovery of antibiotics.For 3000 years,garlic has been considered an efficient antibacterial compound,utilized to prevent and treat bacterial infection worldwide,although the specific mechanisms remain unclear.Modern research shows that sulfur-containing chemicals are the primary active constituents of garlic and play key roles in its inherent antimicrobial activity,such as diallyl disulfide(DADS)and diallyl trisulfide(DATS).In contrast,inorganic sulfides for antibacterial use have not been deeply studied.It has been well-known that iron sulfides are an essential part of the geochemical and biological sulfur cycles.Both stable and metastable iron sulfides can be formed under abiotic sediment conditions and biotic process.In particular,certain bacteria species growth need iron sulfide as nutrient source or produce iron sulfide.In addition,iron sulfur clusters as special metastable iron sulfide take part in many important metabolic pathways in most organisms.These physicochemical and biological properties inspire us that iron sulfides are a type of valuable material for investigation and utilization.Below we will introduce a new antibacterial candidate based on iron sulfides,which kill bacteria via multiple mechanisms of action(MoAs).We will first discuss the types of iron sulfides with inherent antibacterial activity,i.e.,metastable species that can release iron ions and polysulfides in aqua.The intrinsic properties of iron sulfides and released iron and polysulfides are analyzed in regard to antibacterial effects under different physiological conditions.In particular,ferrous ion−polysulfide synergized ferroptosis-like death is proposed to kill bacteria with broad spectrum and selectivity.In addition,the versatile MoAs enable metastable iron sulfides(mFeSs)to kill resistant bacteria,eradicate biofilms,and suppress intracellular persistent species without causing new drug resistance.Importantly,the efficient antibacterial properties have been validated in animal models bearing infections including wounds,pneumonia,caries,and bacterial vaginosis,demonstrating great translational potential.Lastly,we will summarize the challenges of iron sulfides,proposing a possible development direction in the future.Our studies on iron sulfides can serve as a paradigm for the design and discovery of antibacterial nanomaterials,which may contribute for the war against drug-resistant pathogenic bacteria.
文摘Enzymes are biological catalysts that can convert substrates into products in biochemical reactions.In 1926,the first enzyme,urease,was determined to be a protein by James B.Sumner who won the Nobel Prize in 1946.Since then,enzymes have been considered to be proteins,which allows them to achieve their high catalytic activity with high specific activity under mild conditions.However,in general,the enzyme activity of proteins is lost after exposure to extremes of p H and high temperature,and proteins are also susceptible to digestion by proteases in the environment,which dramatically hinders their practical applications
基金supported by the National Key Research and Development Program of China(2018YFC1003500)the National Natural Science Foundation of China(81671810 and 31701236)the Jiangsu Provincial Basic Research Program for the Natural Science Foundation(BK20161333)
文摘Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition.Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B2(VB2)modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase(SOD)-like activities, acting as typical iron oxide nanozymes(IONzymes) with triad activities. In particular, VB2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species(ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B2 modified IONzymes(VB2-IONzymes) protect human oral keratinocytes(HOK) and BALB/3 T3 cells from hydrogen peroxide(H2O2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB2-IONzymes exerted an antibacterial activity against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.
基金Postgraduate Research Innovation Program of Yangzhou University(Grant No.XKYCX18_128)
文摘本文制备竹节参片并进行生物等效性考察。采用超微粉碎-湿法造粒制备竹节参片;按药典规定进行质量检查;高效液相色谱法测定自制竹节参片和人参皂苷Rg3单剂量灌胃后24小时大鼠的血药浓度, DAS 2.0软件计算分析其药动学参数和相对生物利用度。结果发现,自制竹节参片质量检查各项符合2015版药典要求,与人参皂苷Rg3相比具有较高的生物利用度。因此可知,本实验竹节参片制备工艺合理、质量可控,口服吸收利用度好,为竹节参片的工业化生产和临床应用提供参考。