Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting...Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.展开更多
Micro/nanorobots(MNRs)are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites.However,exi...Micro/nanorobots(MNRs)are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites.However,existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues.Here,we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots(Fe3O4@PDA-TA NRs)capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies.The Fe3O4@PDA-TA nanoparticles(NPs),serving as building blocks of the nanorobots,are fabricated by in situ polymerization of dopamine followed by TA adhesion.When driven by alternating magnetic fields,Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity.Thus,the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared(NIR)light due to their efficient photothermal conversion.Additionally,they can concentrate at deep infection sites by traversing through confined,narrow,and tortuous passages,exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction.Therefore,the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections.This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies,task flexibility,and high efficiency.展开更多
Shibadong Village, the birthplace of the “targeted poverty alleviation”campaign, has set a model for China’s poverty alleviation and elimination efforts. Based on data obtained from long-term field research, this p...Shibadong Village, the birthplace of the “targeted poverty alleviation”campaign, has set a model for China’s poverty alleviation and elimination efforts. Based on data obtained from long-term field research, this paper illustrates Shibadong’s journey out of poverty by outlining its main practices of targeted poverty alleviation, and summarizing the learnings that are worth sharing. Guided by the “targeted poverty alleviation” strategy,measures were taken to unleash the endogenous development force of the village by precisely identifying targets, developing targeted rural industries, implementing specific relief plans tailored to each household, and bringing cohesion among different social forces.Thanks to these efforts, the village has undergone tremendous changes in many areas such as civility level, living conditions, industrial development, social governance, infrastructure and public services. This paper argues that Shibadong’s experience has universal applicability for poverty elimination. We believe that by building an enabling government,an effective market and an organic society, and giving full play to the synergistic effects of the three, poor villages can break out of the dilemma caused by the “triple failures” and achieve modern rural governance and development.展开更多
基金support from the National Natural Science Foundation of China(Nos.22275081,82372117)Guangzhou Science and Technology Bureau(202206010068)China Postdoctoral Science Foundation(2022M711532 and 2022T150302).
文摘Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.
基金supported by the National Key Research and Development Project(no.2021YFA1201400)the National Natural Science Foundation of China(no.52073222)the Innovation Team in Key Areas of the Innovation Talent Promotion Plan(2021)of MOST of China.
文摘Micro/nanorobots(MNRs)are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites.However,existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues.Here,we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots(Fe3O4@PDA-TA NRs)capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies.The Fe3O4@PDA-TA nanoparticles(NPs),serving as building blocks of the nanorobots,are fabricated by in situ polymerization of dopamine followed by TA adhesion.When driven by alternating magnetic fields,Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity.Thus,the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared(NIR)light due to their efficient photothermal conversion.Additionally,they can concentrate at deep infection sites by traversing through confined,narrow,and tortuous passages,exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction.Therefore,the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections.This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies,task flexibility,and high efficiency.
文摘Shibadong Village, the birthplace of the “targeted poverty alleviation”campaign, has set a model for China’s poverty alleviation and elimination efforts. Based on data obtained from long-term field research, this paper illustrates Shibadong’s journey out of poverty by outlining its main practices of targeted poverty alleviation, and summarizing the learnings that are worth sharing. Guided by the “targeted poverty alleviation” strategy,measures were taken to unleash the endogenous development force of the village by precisely identifying targets, developing targeted rural industries, implementing specific relief plans tailored to each household, and bringing cohesion among different social forces.Thanks to these efforts, the village has undergone tremendous changes in many areas such as civility level, living conditions, industrial development, social governance, infrastructure and public services. This paper argues that Shibadong’s experience has universal applicability for poverty elimination. We believe that by building an enabling government,an effective market and an organic society, and giving full play to the synergistic effects of the three, poor villages can break out of the dilemma caused by the “triple failures” and achieve modern rural governance and development.
