The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge....The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.展开更多
BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevan...BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.展开更多
Introduction: Infections represent a real public health problem aggravating the morbidity and mortality of hospitalized patients. Methods: This was a retrospective study with descriptive purposes over a period of 05 y...Introduction: Infections represent a real public health problem aggravating the morbidity and mortality of hospitalized patients. Methods: This was a retrospective study with descriptive purposes over a period of 05 years, in the Pneumology Department of the University Hospital of Cocody. Results: The average age in our population was 42 years. We observed a male predo- minance of 64.5%, with a sex ratio of 1.8. Medical history was dominated by HIV infection (23.5%), followed by tuberculosis (15.6%). Concerning lifestyle, smoking was found in 38% of cases. Symptoms progressed chronically in 80% of cases. An infectious syndrome was found in 75% of cases. Microbial culture was positive in 42% of cases. Pseudomonas aeruginosa and Klebsiella pneumoniae were encountered in 26.4% of cases each, followed by Echerichia coli in 10.4% of cases. Klebsiella pneumoniae in the first three years topped the list, but gradually. Pseudomonas aeruginosa maintained its leadership over the last three years. Pseudomonas aeruginosa isolates expressed a resistance rate of 9.8% to ceftazidime and 8.1% to imipenem;to aztreonam (36%), ticarcillin (33.3%) and levofloxacin. These strains were susceptible to fosfomycin (100%), mero- penem (96.6%) and amikacin (96%). For isolated strains of Entero- bacteria- ceae, resistance was observed about ticarcillin (83.3%) and amoxicillin clavula- nic acid (71.2%). Streptococcaceae showed resistance to tetracycline (69.2%) and erythromycin (50%). Over the years there has been an increase in re- sistance to amoxicillin-clavulanic acid ceftriaxone. The death rate was 14%. Conclusion: The bacterial profile of infections is dominated by germs respon- sible for nosocomial infection with significant mortality.展开更多
Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of an...Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of antibiotics,extensive agricultural antibiotic use,and the increasingly complex hospitalized patient populations undergoing treatment,all fuel the rise of highly MDR“superbugs.”Unfortunately,host-directed therapies to boost immune resistance to infection are not currently available for treatment of MDR pathogens.Hematopoietic cells are endowed with a variety ofmechanismsto control microbial invasion.Macrophages in particular have long been appreciated as potent antimicrobial immune cells equipped with several receptors that allow for rapid recognition,phagocytosis,and killing of pathogenic microbes,coupled to secretion of immunostimulatory cytokines to further orchestrate a robust multifaceted antibacterial immune response.To investigate the utility of macrophages as a cell therapy for MDR bacterial infections,we developed a therapeutically translatable process to generate,harvest,and cryopreserve monocyte-derived macrophages(ICONIMACTM).These cells effectively killed both Gram-positive and Gram-negative MDR pathogens in vitro,and conferred protection in vivo against experimental lethal peritonitis and lung infection.Our discoveries provide a proof-of-concept for a novel immunotherapeutic approach against MDR bacterial infections,urgently needed to supplement the diminishing antibiotic pipeline.展开更多
Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic...Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs.The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics.Herein,a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented,encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms.Furthermore,the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy,mainly focusing on skin,bone,periodontal and tendon tissues regeneration and repair,are systematically summarized and discussed.In particular,for the treatment of skin infection wounds,we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs,including(i)single model therapies such as metal ion therapy,chemodynamic therapy,photothermal therapy,and photodynamic therapy;and(ii)multimodel therapies involving arbitrary combinations of these single models.Additionally,the limitations,challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed.We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.展开更多
Photodynamic antibacterial therapy(PDAT)is a kind of rejuvenating strategy that combats bacterial infection due to its admirable characteristics of noninvasiveness and broad-spectrum antibacterial capability.However,t...Photodynamic antibacterial therapy(PDAT)is a kind of rejuvenating strategy that combats bacterial infection due to its admirable characteristics of noninvasiveness and broad-spectrum antibacterial capability.However,the efficiency of PDAT can be greatly hindered by limited light irradiation.Herein,we propose an enhanced PDAT by employing photonic composite films(PCFs)via slow photon and multiple scattering effects.The PCFs are obtained by UV light-initiated polymerization of poly(ethylene glycol)phenyl ether acrylate with a self-assembled SiO_(2)colloidal particle array,followed by the deposition of photosensitizers(PSs).The PCFs can prompt the PSs with matched absorption,which are deposited on their surface,to sufficiently utilize the incident light and generate more reactive oxygen species based on the slow photon phenomenon of photonic crystals and multiple scattering effects of the SiO_(2)colloidal particles.This finding demonstrates the great potential and significance of PCFs in the field of PDAT,which may reduce the requirements of excitation equipment and avoid damage to normal tissues from exposure to huge light energy.展开更多
A double acid corrosion and subsequent hydrothermal treatment were used to fabricate a micro–nano-structured Ti substrates(Ti–M–N).Afterward,the mesoporous polydopamine(MPDA)nanoparticles as photothermal agent were...A double acid corrosion and subsequent hydrothermal treatment were used to fabricate a micro–nano-structured Ti substrates(Ti–M–N).Afterward,the mesoporous polydopamine(MPDA)nanoparticles as photothermal agent were prepared and immobilized on the surface of Ti–M–N samples,in order to obtain Ti–M–NMPDA sample.Unique micro–nanostructure properties and the photothermal effect of the modified Ti implant caused physical stress on the bacteria and the bacterial membrane damage,and eventually led to bacteria death.More importantly,based on excellent bioactivity and cytocompatibility of mussel-inspired materials,MPDA promoted adhesion,proliferation and osteogenic differentiation of mesenchymal stem cells in vitro.Furthermore,animal experiments in vivo further confirmed that the modified Ti implants could enhance osseointegration.展开更多
It is of great significance to develop effective antibacterial agents and methods to combat drug resistant bacterial infections due to its increasing threaten to human health and the ineffectiveness of antibiotics.Her...It is of great significance to develop effective antibacterial agents and methods to combat drug resistant bacterial infections due to its increasing threaten to human health and the ineffectiveness of antibiotics.Herein,a multifunctional hybrid nano-assembly(M1-Fe NPs)based on conjugated oligomer and ferrous ion was engineered with favorable bactericidal activity for synergetic antibacterial therapy.The chelation of ferrous ion not only enhances the photothermal conversion efficiency of M1 but also endows the nano-assembly with catalytic capability of transferring H_(2)O_(2) into stronger oxidant hydroxyl radicals(·OH).Meanwhile,the generated heat can further promote the Fenton reaction activity.By generating cytotoxic heat and oxidative·OH,M1-Fe NPs can effectively kill Staphylococcus aureus in vitro and in vivo with the aid of low dosage of H_(2)O_(2).The work provides a new multifunctional platform for combinational drug resistant antibacterial therapy and even antitumor therapy.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:92163126,52293380,52293383Fundamental Research Funds for the Central Universities,Grant/Award Numbers:63241614,63233051Beijing National Laboratory for Molecular Sciences,Grant/Award Number:BNLMS202308。
文摘The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.
文摘BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.
文摘Introduction: Infections represent a real public health problem aggravating the morbidity and mortality of hospitalized patients. Methods: This was a retrospective study with descriptive purposes over a period of 05 years, in the Pneumology Department of the University Hospital of Cocody. Results: The average age in our population was 42 years. We observed a male predo- minance of 64.5%, with a sex ratio of 1.8. Medical history was dominated by HIV infection (23.5%), followed by tuberculosis (15.6%). Concerning lifestyle, smoking was found in 38% of cases. Symptoms progressed chronically in 80% of cases. An infectious syndrome was found in 75% of cases. Microbial culture was positive in 42% of cases. Pseudomonas aeruginosa and Klebsiella pneumoniae were encountered in 26.4% of cases each, followed by Echerichia coli in 10.4% of cases. Klebsiella pneumoniae in the first three years topped the list, but gradually. Pseudomonas aeruginosa maintained its leadership over the last three years. Pseudomonas aeruginosa isolates expressed a resistance rate of 9.8% to ceftazidime and 8.1% to imipenem;to aztreonam (36%), ticarcillin (33.3%) and levofloxacin. These strains were susceptible to fosfomycin (100%), mero- penem (96.6%) and amikacin (96%). For isolated strains of Entero- bacteria- ceae, resistance was observed about ticarcillin (83.3%) and amoxicillin clavula- nic acid (71.2%). Streptococcaceae showed resistance to tetracycline (69.2%) and erythromycin (50%). Over the years there has been an increase in re- sistance to amoxicillin-clavulanic acid ceftriaxone. The death rate was 14%. Conclusion: The bacterial profile of infections is dominated by germs respon- sible for nosocomial infection with significant mortality.
文摘Multidrug-resistant(MDR)bacterial infections exert a tremendous burden on the public health system throughout the developing and developedworld.Slowing development of novel antibiotic scaffolds,over-prescription of antibiotics,extensive agricultural antibiotic use,and the increasingly complex hospitalized patient populations undergoing treatment,all fuel the rise of highly MDR“superbugs.”Unfortunately,host-directed therapies to boost immune resistance to infection are not currently available for treatment of MDR pathogens.Hematopoietic cells are endowed with a variety ofmechanismsto control microbial invasion.Macrophages in particular have long been appreciated as potent antimicrobial immune cells equipped with several receptors that allow for rapid recognition,phagocytosis,and killing of pathogenic microbes,coupled to secretion of immunostimulatory cytokines to further orchestrate a robust multifaceted antibacterial immune response.To investigate the utility of macrophages as a cell therapy for MDR bacterial infections,we developed a therapeutically translatable process to generate,harvest,and cryopreserve monocyte-derived macrophages(ICONIMACTM).These cells effectively killed both Gram-positive and Gram-negative MDR pathogens in vitro,and conferred protection in vivo against experimental lethal peritonitis and lung infection.Our discoveries provide a proof-of-concept for a novel immunotherapeutic approach against MDR bacterial infections,urgently needed to supplement the diminishing antibiotic pipeline.
基金supported by the National Natural Science Foundation of China(82172211,92268206)the National Key Research and Development Programs of China(2022YFA1104300)+5 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research Projects(2022-JCJQ-ZB-09600,2023-JSKY-SSQG-006)the Natural Science Foundation of Sichuan Province(2023NSFSC0339)the 1·3·5 Project for Disciplines of Excellence of West China Hospital,Sichuan University(ZYGD22008)the China Postdoctoral Science Foundation(2022TQ0223,2022M722256)the Post-Doctor Research Project of West China Hospital,Sichuan University(2023HXBH031).
文摘Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs.The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics.Herein,a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented,encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms.Furthermore,the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy,mainly focusing on skin,bone,periodontal and tendon tissues regeneration and repair,are systematically summarized and discussed.In particular,for the treatment of skin infection wounds,we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs,including(i)single model therapies such as metal ion therapy,chemodynamic therapy,photothermal therapy,and photodynamic therapy;and(ii)multimodel therapies involving arbitrary combinations of these single models.Additionally,the limitations,challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed.We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.
基金This work was supported by the National Natural Science Foundation of China(52022032).
文摘Photodynamic antibacterial therapy(PDAT)is a kind of rejuvenating strategy that combats bacterial infection due to its admirable characteristics of noninvasiveness and broad-spectrum antibacterial capability.However,the efficiency of PDAT can be greatly hindered by limited light irradiation.Herein,we propose an enhanced PDAT by employing photonic composite films(PCFs)via slow photon and multiple scattering effects.The PCFs are obtained by UV light-initiated polymerization of poly(ethylene glycol)phenyl ether acrylate with a self-assembled SiO_(2)colloidal particle array,followed by the deposition of photosensitizers(PSs).The PCFs can prompt the PSs with matched absorption,which are deposited on their surface,to sufficiently utilize the incident light and generate more reactive oxygen species based on the slow photon phenomenon of photonic crystals and multiple scattering effects of the SiO_(2)colloidal particles.This finding demonstrates the great potential and significance of PCFs in the field of PDAT,which may reduce the requirements of excitation equipment and avoid damage to normal tissues from exposure to huge light energy.
基金This work was financially supported by the State Key Project of Research and Development(Nos.2016YFC1100300 and 2017YFB0702603)the National Natural Science Foundation of China(Nos.51825302,21734002 and 51673032).The Analytical and Testing Center of Chongqing University is greatly acknowledged for the help with the characterization of materials.
文摘A double acid corrosion and subsequent hydrothermal treatment were used to fabricate a micro–nano-structured Ti substrates(Ti–M–N).Afterward,the mesoporous polydopamine(MPDA)nanoparticles as photothermal agent were prepared and immobilized on the surface of Ti–M–N samples,in order to obtain Ti–M–NMPDA sample.Unique micro–nanostructure properties and the photothermal effect of the modified Ti implant caused physical stress on the bacteria and the bacterial membrane damage,and eventually led to bacteria death.More importantly,based on excellent bioactivity and cytocompatibility of mussel-inspired materials,MPDA promoted adhesion,proliferation and osteogenic differentiation of mesenchymal stem cells in vitro.Furthermore,animal experiments in vivo further confirmed that the modified Ti implants could enhance osseointegration.
基金the National Natural Science Foundation of China(Nos.21977065,22177065 and 21807067)Sanjin Scholars Support Planunder Special Funding(No.2017-06)+2 种基金Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(Nos.201802106,2019L0022)Supported by the Fund for Shanxi“1331”Project(1331)the Program for Introducing Overseas High-level Talents of Shanxi(Hundred Talents Plan)。
文摘It is of great significance to develop effective antibacterial agents and methods to combat drug resistant bacterial infections due to its increasing threaten to human health and the ineffectiveness of antibiotics.Herein,a multifunctional hybrid nano-assembly(M1-Fe NPs)based on conjugated oligomer and ferrous ion was engineered with favorable bactericidal activity for synergetic antibacterial therapy.The chelation of ferrous ion not only enhances the photothermal conversion efficiency of M1 but also endows the nano-assembly with catalytic capability of transferring H_(2)O_(2) into stronger oxidant hydroxyl radicals(·OH).Meanwhile,the generated heat can further promote the Fenton reaction activity.By generating cytotoxic heat and oxidative·OH,M1-Fe NPs can effectively kill Staphylococcus aureus in vitro and in vivo with the aid of low dosage of H_(2)O_(2).The work provides a new multifunctional platform for combinational drug resistant antibacterial therapy and even antitumor therapy.
