Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy an...Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.展开更多
A novel avian influenza A (H7N9) virus was discovered in February 2013 in China and has resulted in more than 100 comfirmed human infections including 26 fatal cases as of May 2, 2013. The situation raises many ur- ...A novel avian influenza A (H7N9) virus was discovered in February 2013 in China and has resulted in more than 100 comfirmed human infections including 26 fatal cases as of May 2, 2013. The situation raises many ur- gent questions and global public health concerns. In this study, epidemiologic characteristics of infected human cases in Jiangsu province were analyzed and risk assessment was undertaken based on the information available. Briefly, it is highly unlikely that a pandemic of human infection with avian influenza A (HTN9) virus will happen in Jiangsu Province in the near future. Iia the end, some measures are recommended to prevent the situation from becoming worse.展开更多
Live poultry markets(LPMs) are crucial places for human infection of influenza A(H7N9 virus).In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A(H7N9) virus,and t...Live poultry markets(LPMs) are crucial places for human infection of influenza A(H7N9 virus).In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A(H7N9) virus,and then reopened when no case was found.Our purpose was to quantify the effect of LPMs' operations in this region on the transmission of influenza A(H7N9) virus.We obtained information about dates of symptom onset and locations for all human influenza A(H7N9) cases reported from Shanghai,Jiangsu and Zhejiang provinces by May 31,2014,and acquired dates of closures and reopening of LPMs from official media.A two-phase Bayesian model was fitted by Markov Chain Monte Carlo methods to process the spatial and temporal influence of human cases.A total of 235 cases of influenza A(H7N9) were confirmed in Shanghai,Jiangsu and Zhejiang by May 31,2014.Using these data,our analysis showed that,after LPM closures,the influenza A(H7N9) outbreak disappeared within two weeks in Shanghai,one week in Jiangsu,and one week in Zhejiang,respectively.Local authorities reopened LPMs when there was no outbreak of influenza A(H7N9),which did not lead to reemergence of human influenza A(H7N9).LPM closures were effective in controlling the H7N9 outbreak.Reopening of LPM in summer did not increase the risk of human infection with H7N9.Our findings showed that LPMs should be closed immediately in areas where the H7N9 virus is confirmed in LPM.When there is no outbreak of H7N9 virus,LPMs can be reopened to satisfy the Chinese traditional culture of buying live poultry.In the long term,local authorities should take a cautious attitude in permanent LPM closure.展开更多
Streptococcus suis (S. suis) is a Gram-positive, facultatively anaerobic coccus that has been implicated as the cause of a wide range of clinical disease syndromes in swine and other domestic animals. S. suis has al...Streptococcus suis (S. suis) is a Gram-positive, facultatively anaerobic coccus that has been implicated as the cause of a wide range of clinical disease syndromes in swine and other domestic animals. S. suis has also been implicated in disease in humans, especially anaong abattoir workers, swine and pork handlers. Here we report a case of streptococcal toxic shock syndrome(STSS) caused by S. suis in a 59-year-old man. Despite of intensive treatment, the patient died of shock with multiple organ failure 14 h after admission. One bacterial isolate obtained from blood culture was identified to the species level by biochemical tests and serological tests as S. suis serotype 2. Identification was confirmed by PCR amplification of genes encoding 16sRNA of S. suis and the capsule of S. suis serotype 2(cps 23). Genes encoding virulence factors were also detected. An investigation to identify the source of S. suis revealed that several days before admission the affected man had been handling sick pigs or their meat. Transmission may occur through breaks in the skin of feet with tinea due to that no measures for personal protection was taken. This case should highten awareness of the potential for occupational exposure and human infection with S. suis.展开更多
Objective: To determine epidemiologic features of an Escherichia coli O157:H7 outbreak occurred in Xuzhou, Jiangsu Province, China in 1999, and assess the incidence of E. coli O157:H7 in diarrhea patients and host ...Objective: To determine epidemiologic features of an Escherichia coli O157:H7 outbreak occurred in Xuzhou, Jiangsu Province, China in 1999, and assess the incidence of E. coli O157:H7 in diarrhea patients and host animals and its relationship with disease onset, and provide a scientific basis for establishing prevention and control strategies. Methods: Epidemiological, microbiological, and molecular methods were performed to identify risk factors and describe the ecology of E. coli O157:H7 in the enviromnent. Results: From May to September, in 1999, 99 cases of E. coli O157:H7 infection were confirmed. Fifty-six patients were enrolled in the case-control study. Bad personal health habits and poor sanitary conditions in the kitchen were associated with increased risks of infection, whereas hand washing was protective. The household survey indicated that residents in the epidemic region during the outbreak had higher than expected rates of diarrhea. The total E. coli O157:H7 carrier rate in the livestock was 12.36%(22/178), specifically 19.15% in cattle, 12.50% in goat, and 11.11% in swine. Numerical analysis of pulsed-field gel electrophoresis(PFGE) profiles divided strains into two clusters with 77.5% homology. One cluster contained 11 strains isolated from diarrheal patients, foods, and animals. The other cluster comprised 10 strains from patients and environment. Conclusion: In a large outbreak of E. coli O157:H7 infection among predominantly elderly residents in Xuzhou, high rates of carriage of E. coli O157:H7 among host animals most likely resulted in contamination of the environment, thereby leading to the outbreak. Effective and preventive control measures should be taken to avoid contamination, including environmental and family health improvement, good personal hygiene, and safe food handling practices.展开更多
Reactive oxygen species(ROS),immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease(IBD).Herein,a novel enzyme-like biomimetic ...Reactive oxygen species(ROS),immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease(IBD).Herein,a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed,using yeast cell wall(YCW)as the outer shell and zinc-doped Prussian blue analogue(ZnPBA)nanozyme inside.When orally administered,the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E.coli,meanwhile exhibiting improved intestinal epithelial barrier repair.Moreover,it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway.More importantly,the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity,significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E.coli to the same level as normal mice.Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.展开更多
Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death(ICD),a process in which tumor cells convert from nonimmunogenic to immunogenic forms.However,the antitumor immune ...Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death(ICD),a process in which tumor cells convert from nonimmunogenic to immunogenic forms.However,the antitumor immune response of ICD remains limited due to the low immunogenicity of tumor cells and the immunosuppressive tumor microenvironment.Although autophagy is involved in activating tumor immunity,the synergistic role of autophagy in ICD remains elusive and challenging.Herein,we report an autophagy amplification strategy using an ion-chelation reaction to augment chemoimmunotherapy in cancer treatments based on zinc ion(Zn^(2+))-doped,disulfiram(DSF)-loaded mesoporous silica nanoparticles(DSF@Zn-DMSNs).Upon pH-sensitive biodegradation of DSF@Zn-DMSNs,Zn2+and DSF are coreleased in the mildly acidic tumor microenvironment,leading to the formation of toxic Zn2+chelate through an in situ chelation reaction.Consequently,this chelate not only significantly stimulates cellular apoptosis and generates damage-associated molecular patterns(DAMPs)but also activates autophagy,which mediates the amplified release of DAMPs to enhance ICD.In vivo results demonstrated that DSF@Zn-DMSNs exhibit strong therapeutic efficacy via in situ ion chelation and possess the ability to activate autophagy,thus enhancing immunotherapy by promoting the infiltration of T cells.This study provides a smart in situ chelation strategy with tumor microenvironment-responsive autophagy amplification to achieve high tumor chemoimmunotherapy efficacy and biosafety.展开更多
The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology.Several intratumoral bacteria which have been identified as pathogens ...The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology.Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression,metastasis,and poor outcome of cancer,while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization.Thus,the mutually-beneficial interplay between pathogens and tumors,named“pathogentumor symbionts”,is probably a potential therapeutic site for tumor treatment.Herein,we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens,F.nucleatum,to break the symbiont and synergize to kill colorectal cancer(CRC)cells.This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme(BSA-Cu SAN)which was inspired by the structures of native enzymes that are based on protein,with metal elements as the active center.BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species(ROS)and depleting GSH.The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F.nucleatum in situ to destroy pathogentumor symbionts.As a result,ROS resistance of CRC through elevated autophagy mediated by F.nucleatum was relieved,contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN.Particularly,BSA-Cu SAN experiences renal clearance,avoiding long-term systemic toxicity.This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.展开更多
Psoriasis is an autoimmune disease and gut microbiota participate in the establishment of intestinal immunity. This study was performed to identify the fecal microbial composition of psoriasis patients, and investigat...Psoriasis is an autoimmune disease and gut microbiota participate in the establishment of intestinal immunity. This study was performed to identify the fecal microbial composition of psoriasis patients, and investigated the influence of subgroup(type and severity) on the fecal microbial composition, and to define the key microbiota in the pathogenesis of psoriasis. Fecal samples from 35 psoriasis patients and 27 healthy controls were sequenced by 16 S rRNA and then analyzed by informatics methods. We found that the microbiota of the psoriasis group differed from that of the heathy group. The relative abundances of Firmicutes and Bacteroidetes were inverted at the phylum level, and 16 kinds of phylotype at the genus level were found with significant difference. No microbial diversity and composition alteration were observed among the four types of psoriasis. The microbiota of psoriasis patients in the severe state differs from those of psoriasis patients with more mild conditions and also the healthy controls. The veillonella in fecal microbiota showed a positive relationship with h-CRP in blood. This research proved that psoriasis patients have a significant disturbed microbiota profiles. Further study of psoriasis based on microbiota may provide novel insights into the pathogenesis of psoriasis and more evidence for the prevention and treatment of psoriasis.展开更多
Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknow...Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.展开更多
Facile achievement of gold nanorods(AuNRs) with controllable longitudinal surface plasmon resonance(LSPR) is of great importance for their applications in various fields.The LSPR of AuNRs is sensitive to their aspect ...Facile achievement of gold nanorods(AuNRs) with controllable longitudinal surface plasmon resonance(LSPR) is of great importance for their applications in various fields.The LSPR of AuNRs is sensitive to their aspect ratio,which is still hard to be precisely tuned by direct synthesis.In this work,we report a simple approach for end-selective etching of AuNRs by a rapid oxidation process with Au(Ⅲ) in cetyltrimethylammonium bromide(CTAB) solution at a mild temperature.The LSPR wavelength and the length of AuNRs blue shifted linearly as a function of the amount of Au(Ⅲ),while the diameter of Au NRs remained nearly constant.The oxidative rate is tempe rature dependent,and the oxidative process for a desired LSPR can be accomplished within 15 min at 60℃.Further investigations indicated that Br determine the occurrence of the oxidation between AuNRs and Au(Ⅲ),and a small amount of surfactant chain(CTA+) is crucial for stabilizing AuNRs.This method presents a quick but robust strategy for acquiring AuNRs with an arbitrary intermediate LSPR wavelength using the same starting AuNRs,and can be a powerful tool for subsequent applications.展开更多
基金supported by the China Postdoctoral Science Foundation(Grant No.2022M721404)the Natural Science Foundation of Jiangsu Province(Grant No.BK20220737)+1 种基金the Social Development Foundation of Clinical Frontier Technology of Jiangsu Province(Grant No.BE2017763)the Medical Research Project of Jiangsu Province Health Committee(Grant No.K2019020).
文摘Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.
基金supported by the Jiangsu Province Health Development Project with Science and Education (No.ZX201109 and RC2011085)the Research Projects of Jiangsu Preventive Medicine (No.YZ201020)
文摘A novel avian influenza A (H7N9) virus was discovered in February 2013 in China and has resulted in more than 100 comfirmed human infections including 26 fatal cases as of May 2, 2013. The situation raises many ur- gent questions and global public health concerns. In this study, epidemiologic characteristics of infected human cases in Jiangsu province were analyzed and risk assessment was undertaken based on the information available. Briefly, it is highly unlikely that a pandemic of human infection with avian influenza A (HTN9) virus will happen in Jiangsu Province in the near future. Iia the end, some measures are recommended to prevent the situation from becoming worse.
文摘Live poultry markets(LPMs) are crucial places for human infection of influenza A(H7N9 virus).In Yangtze River Delta,LPMs were closed after the outbreak of human infection with avian influenza A(H7N9) virus,and then reopened when no case was found.Our purpose was to quantify the effect of LPMs' operations in this region on the transmission of influenza A(H7N9) virus.We obtained information about dates of symptom onset and locations for all human influenza A(H7N9) cases reported from Shanghai,Jiangsu and Zhejiang provinces by May 31,2014,and acquired dates of closures and reopening of LPMs from official media.A two-phase Bayesian model was fitted by Markov Chain Monte Carlo methods to process the spatial and temporal influence of human cases.A total of 235 cases of influenza A(H7N9) were confirmed in Shanghai,Jiangsu and Zhejiang by May 31,2014.Using these data,our analysis showed that,after LPM closures,the influenza A(H7N9) outbreak disappeared within two weeks in Shanghai,one week in Jiangsu,and one week in Zhejiang,respectively.Local authorities reopened LPMs when there was no outbreak of influenza A(H7N9),which did not lead to reemergence of human influenza A(H7N9).LPM closures were effective in controlling the H7N9 outbreak.Reopening of LPM in summer did not increase the risk of human infection with H7N9.Our findings showed that LPMs should be closed immediately in areas where the H7N9 virus is confirmed in LPM.When there is no outbreak of H7N9 virus,LPMs can be reopened to satisfy the Chinese traditional culture of buying live poultry.In the long term,local authorities should take a cautious attitude in permanent LPM closure.
文摘Streptococcus suis (S. suis) is a Gram-positive, facultatively anaerobic coccus that has been implicated as the cause of a wide range of clinical disease syndromes in swine and other domestic animals. S. suis has also been implicated in disease in humans, especially anaong abattoir workers, swine and pork handlers. Here we report a case of streptococcal toxic shock syndrome(STSS) caused by S. suis in a 59-year-old man. Despite of intensive treatment, the patient died of shock with multiple organ failure 14 h after admission. One bacterial isolate obtained from blood culture was identified to the species level by biochemical tests and serological tests as S. suis serotype 2. Identification was confirmed by PCR amplification of genes encoding 16sRNA of S. suis and the capsule of S. suis serotype 2(cps 23). Genes encoding virulence factors were also detected. An investigation to identify the source of S. suis revealed that several days before admission the affected man had been handling sick pigs or their meat. Transmission may occur through breaks in the skin of feet with tinea due to that no measures for personal protection was taken. This case should highten awareness of the potential for occupational exposure and human infection with S. suis.
基金supported by National High-tech R&D Program (863 Program) (2007AA02Z409)
文摘Objective: To determine epidemiologic features of an Escherichia coli O157:H7 outbreak occurred in Xuzhou, Jiangsu Province, China in 1999, and assess the incidence of E. coli O157:H7 in diarrhea patients and host animals and its relationship with disease onset, and provide a scientific basis for establishing prevention and control strategies. Methods: Epidemiological, microbiological, and molecular methods were performed to identify risk factors and describe the ecology of E. coli O157:H7 in the enviromnent. Results: From May to September, in 1999, 99 cases of E. coli O157:H7 infection were confirmed. Fifty-six patients were enrolled in the case-control study. Bad personal health habits and poor sanitary conditions in the kitchen were associated with increased risks of infection, whereas hand washing was protective. The household survey indicated that residents in the epidemic region during the outbreak had higher than expected rates of diarrhea. The total E. coli O157:H7 carrier rate in the livestock was 12.36%(22/178), specifically 19.15% in cattle, 12.50% in goat, and 11.11% in swine. Numerical analysis of pulsed-field gel electrophoresis(PFGE) profiles divided strains into two clusters with 77.5% homology. One cluster contained 11 strains isolated from diarrheal patients, foods, and animals. The other cluster comprised 10 strains from patients and environment. Conclusion: In a large outbreak of E. coli O157:H7 infection among predominantly elderly residents in Xuzhou, high rates of carriage of E. coli O157:H7 among host animals most likely resulted in contamination of the environment, thereby leading to the outbreak. Effective and preventive control measures should be taken to avoid contamination, including environmental and family health improvement, good personal hygiene, and safe food handling practices.
基金supported by the National Natural Science Foundation of China(Grant Nos.32030061,32271384)Shanghai International Cooperation Project(No.23490712900)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000).
文摘Reactive oxygen species(ROS),immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease(IBD).Herein,a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed,using yeast cell wall(YCW)as the outer shell and zinc-doped Prussian blue analogue(ZnPBA)nanozyme inside.When orally administered,the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E.coli,meanwhile exhibiting improved intestinal epithelial barrier repair.Moreover,it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway.More importantly,the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity,significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E.coli to the same level as normal mice.Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.
基金the National Natural Science Foundation of China(Grant No.81730102,32271384)Shanghai Basic Research Program(Grant No.20JC1411702)Shanghai Science and Technology Program(Grant No.20ZR1456100).
文摘Chemotherapy can induce a robust T cell antitumor immune response by triggering immunogenic cell death(ICD),a process in which tumor cells convert from nonimmunogenic to immunogenic forms.However,the antitumor immune response of ICD remains limited due to the low immunogenicity of tumor cells and the immunosuppressive tumor microenvironment.Although autophagy is involved in activating tumor immunity,the synergistic role of autophagy in ICD remains elusive and challenging.Herein,we report an autophagy amplification strategy using an ion-chelation reaction to augment chemoimmunotherapy in cancer treatments based on zinc ion(Zn^(2+))-doped,disulfiram(DSF)-loaded mesoporous silica nanoparticles(DSF@Zn-DMSNs).Upon pH-sensitive biodegradation of DSF@Zn-DMSNs,Zn2+and DSF are coreleased in the mildly acidic tumor microenvironment,leading to the formation of toxic Zn2+chelate through an in situ chelation reaction.Consequently,this chelate not only significantly stimulates cellular apoptosis and generates damage-associated molecular patterns(DAMPs)but also activates autophagy,which mediates the amplified release of DAMPs to enhance ICD.In vivo results demonstrated that DSF@Zn-DMSNs exhibit strong therapeutic efficacy via in situ ion chelation and possess the ability to activate autophagy,thus enhancing immunotherapy by promoting the infiltration of T cells.This study provides a smart in situ chelation strategy with tumor microenvironment-responsive autophagy amplification to achieve high tumor chemoimmunotherapy efficacy and biosafety.
基金This article was supported by the National Natural Science Foundation of China(Grant Nos.81730102,32271384)Shanghai Basic Research Program(Grant No.20JC1411702)+5 种基金Shanghai Science and Technology Program(Grant No.20ZR1456100)Basic Study on Public Projects in Zhejiang Province(Grant No.LGF20H060017)the National Key Research and Development Program of China(Grant No.2021YFB3801001)China Postdoctoral Science Foundation(Grant No.2021M702484)Shanghai Post-doctoral Excellence Program(Grant No.2020382)Shanghai General Hospital Integrated Traditional Chinese and Western Medicine Special Project(Grant No.ZHYY-ZXYJHZX-202105).The authors would like to thank the workers from Shiyanjia Lab(www.shiyanjia.com)for tests of XANES and EXAFS.
文摘The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology.Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression,metastasis,and poor outcome of cancer,while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization.Thus,the mutually-beneficial interplay between pathogens and tumors,named“pathogentumor symbionts”,is probably a potential therapeutic site for tumor treatment.Herein,we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens,F.nucleatum,to break the symbiont and synergize to kill colorectal cancer(CRC)cells.This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme(BSA-Cu SAN)which was inspired by the structures of native enzymes that are based on protein,with metal elements as the active center.BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species(ROS)and depleting GSH.The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F.nucleatum in situ to destroy pathogentumor symbionts.As a result,ROS resistance of CRC through elevated autophagy mediated by F.nucleatum was relieved,contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN.Particularly,BSA-Cu SAN experiences renal clearance,avoiding long-term systemic toxicity.This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.
基金supported by the National Natural Science Foundation of China (81230057, 81200264, 81372615, 81472262)the Emerging Cutting-Edge Technology Joint Research Projects of Shanghai (SHDC12012106)the Tongji University Subject Pilot Program (162385)
文摘Psoriasis is an autoimmune disease and gut microbiota participate in the establishment of intestinal immunity. This study was performed to identify the fecal microbial composition of psoriasis patients, and investigated the influence of subgroup(type and severity) on the fecal microbial composition, and to define the key microbiota in the pathogenesis of psoriasis. Fecal samples from 35 psoriasis patients and 27 healthy controls were sequenced by 16 S rRNA and then analyzed by informatics methods. We found that the microbiota of the psoriasis group differed from that of the heathy group. The relative abundances of Firmicutes and Bacteroidetes were inverted at the phylum level, and 16 kinds of phylotype at the genus level were found with significant difference. No microbial diversity and composition alteration were observed among the four types of psoriasis. The microbiota of psoriasis patients in the severe state differs from those of psoriasis patients with more mild conditions and also the healthy controls. The veillonella in fecal microbiota showed a positive relationship with h-CRP in blood. This research proved that psoriasis patients have a significant disturbed microbiota profiles. Further study of psoriasis based on microbiota may provide novel insights into the pathogenesis of psoriasis and more evidence for the prevention and treatment of psoriasis.
基金The present work was supported by the National Nature Science Foundation of China(No.81972221,81730102,81920108026,81871964,and 81902422)Emerging Cutting-Edge Technology Joint Research projects of Shanghai(SHDC12017112)+8 种基金the National Ten Thousand Plan Young Top Talents(for Dr.Yanlei Ma)the Shanghai Young Top Talents(for Dr.Yanlei Ma.No.QNBJ1701)the Shanghai Science and Technology Development Fund(No.19410713300,No.20XD1421200)the CSCO-Roche Tumor Research Fund(No.Y-2019Roche-079)the Fudan University Excellence 2025 Talent Cultivation Plan(for Dr.Yanlei Ma)Tongji University Subject Pilot Program(1501141201)Special Construction of Integrated Traditional Chinese Medicine and Western Medicine in Shanghai General Hospital(ZHYY-ZXYJHZX-1-201704)Program of Jiangsu Commission of Health(No.M2020024)Social Development Program of Yangzhou Science and Technology Bureau(No.YZ2020078).
文摘Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
基金financially supported by the National Natural Science foundation of China(No.81701849)Science and Technology Support Project of Jiangsu Province(No.BE2017763)。
文摘Facile achievement of gold nanorods(AuNRs) with controllable longitudinal surface plasmon resonance(LSPR) is of great importance for their applications in various fields.The LSPR of AuNRs is sensitive to their aspect ratio,which is still hard to be precisely tuned by direct synthesis.In this work,we report a simple approach for end-selective etching of AuNRs by a rapid oxidation process with Au(Ⅲ) in cetyltrimethylammonium bromide(CTAB) solution at a mild temperature.The LSPR wavelength and the length of AuNRs blue shifted linearly as a function of the amount of Au(Ⅲ),while the diameter of Au NRs remained nearly constant.The oxidative rate is tempe rature dependent,and the oxidative process for a desired LSPR can be accomplished within 15 min at 60℃.Further investigations indicated that Br determine the occurrence of the oxidation between AuNRs and Au(Ⅲ),and a small amount of surfactant chain(CTA+) is crucial for stabilizing AuNRs.This method presents a quick but robust strategy for acquiring AuNRs with an arbitrary intermediate LSPR wavelength using the same starting AuNRs,and can be a powerful tool for subsequent applications.