Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhanc...Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhance telomerase activity.In present study,the metagenomics sequencing and quantitative real-time polymerase chain reaction analysis were employed to characterize the composition and diversity of gut microbiome in aging flies.And the alterations in the gut barrier,gut morphology,and other gut physiological indicators of aging flies were evaluated.Here,the results showed that ergothioneine induced little variations in gut microbiota composition in flies at mid-life,and significant alterations in the gut microbiota populations were only observed in flies at late-life.And ergothioneine attenuated age-related gut injuries,including decreasing reactive oxygen species levels in intestinal enterocytes,reduction of intestinal cells death,and preservation of gut integrity in aging flies.Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy.And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.展开更多
Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody si...Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined.In this phase 2 trial(ChiCTR1900027433)with a safety run-in,we included patients aged 18–70 with newly diagnosed PCNSL.Participants underwent six 21-day cycles of a SMTR regimen,which includes sintilimab(200 mg,Day 0),rituximab(375 mg/m2,Day 0),methotrexate(3.0 g/m2,Day 1 or 1.0 g/m2 for patients aged≥65 years),and temozolomide(150 mg/m2/d,Days 1–5).Among 27 evaluable patients,the overall response rate(ORR)was 96.3%(95%confidence interval:81–99.9%),with 25 complete responses.At a median follow-up of 24.4 months,the medians for duration of response,progression-free survival(PFS),and overall survival were not reached.The most common grade 3–4 treatment-related toxicities were increased levels of alanine aminotransferase(17.9%)and aspartate aminotransferase(14.3%).Additionally,baseline levels of interferon-αand the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS,achieving areas under the curve of 0.88 and 0.84,respectively,at 2 years.Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group,while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group.These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL,warranting further investigation.展开更多
Absorption coefficient and chlorophyll concentration(Chl)are important optical and biological properties of the aquatic environment,which can be estimated from the spectrum of water color,commonly measured by the remo...Absorption coefficient and chlorophyll concentration(Chl)are important optical and biological properties of the aquatic environment,which can be estimated from the spectrum of water color,commonly measured by the remote sensing reflectance(Rrs).In this study,we extended the band-difference scheme for Chl of oceanic waters developed a decade ago to the estimation of absorption coefficient at 440 nm(a(440)).As demonstrated earlier for the estimation of Chl,a(440)product from the band difference of Rrs showed much smoother spatial pattern than that from a semianalytical algorithm.More importantly,it is found that the upper limit of using band difference of Rrs can be extended from−0.0005 sr^(−1)(the upper limit set a decade ago for the estimation of Chl)to~0.0005 sr^(-1)(corresponding to a(440)~0.08 m^(-1)),which covers~91% of the global ocean.We further converted a(440)to Chl based on the“Case-1”water assumption and found that the standard Chl product of oligotrophic waters(Chl~0.1 mg/m^(3))distributed by NASA is generally~20% higher than Chl converted from a(440),possibly a result of different datasets used to determine the algorithm coefficients.These results not only extended the application of the band-difference scheme for more oceanic waters but also highlighted the need of more accurate field measurements of Chl and R_(rs) in oligotrophic oceans in order to minimize the discrepancies observed in satellite Chl products derived using the same algorithm concept but different empirical approaches.展开更多
基金supported by the National Natural Science Foundation of China(32072646,31772373,and 32001832).
文摘Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhance telomerase activity.In present study,the metagenomics sequencing and quantitative real-time polymerase chain reaction analysis were employed to characterize the composition and diversity of gut microbiome in aging flies.And the alterations in the gut barrier,gut morphology,and other gut physiological indicators of aging flies were evaluated.Here,the results showed that ergothioneine induced little variations in gut microbiota composition in flies at mid-life,and significant alterations in the gut microbiota populations were only observed in flies at late-life.And ergothioneine attenuated age-related gut injuries,including decreasing reactive oxygen species levels in intestinal enterocytes,reduction of intestinal cells death,and preservation of gut integrity in aging flies.Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy.And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.
基金https://doi.org/10.1038/s41392-024-01941-x Fujian Provincial Health Technology Project[grant number 2023CXA028]Joint Funds for the Innovation of Science and Technology,Fujian Province(grant number 2023Y9021)+2 种基金National Science Foundation of Fujian Province[grant number 2022J02036]Clinical research project of Wu Jieping Medical Foundation[grant number 320.6750.19094-41]National Natural Science Foundation of China[grant number 82070218,81400160].
文摘Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined.In this phase 2 trial(ChiCTR1900027433)with a safety run-in,we included patients aged 18–70 with newly diagnosed PCNSL.Participants underwent six 21-day cycles of a SMTR regimen,which includes sintilimab(200 mg,Day 0),rituximab(375 mg/m2,Day 0),methotrexate(3.0 g/m2,Day 1 or 1.0 g/m2 for patients aged≥65 years),and temozolomide(150 mg/m2/d,Days 1–5).Among 27 evaluable patients,the overall response rate(ORR)was 96.3%(95%confidence interval:81–99.9%),with 25 complete responses.At a median follow-up of 24.4 months,the medians for duration of response,progression-free survival(PFS),and overall survival were not reached.The most common grade 3–4 treatment-related toxicities were increased levels of alanine aminotransferase(17.9%)and aspartate aminotransferase(14.3%).Additionally,baseline levels of interferon-αand the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS,achieving areas under the curve of 0.88 and 0.84,respectively,at 2 years.Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group,while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group.These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL,warranting further investigation.
基金Financial support by the National Natural Science Foundation of China(#41890803,#41830102,#41941008,and#42250710150)is greatly appreciated.
文摘Absorption coefficient and chlorophyll concentration(Chl)are important optical and biological properties of the aquatic environment,which can be estimated from the spectrum of water color,commonly measured by the remote sensing reflectance(Rrs).In this study,we extended the band-difference scheme for Chl of oceanic waters developed a decade ago to the estimation of absorption coefficient at 440 nm(a(440)).As demonstrated earlier for the estimation of Chl,a(440)product from the band difference of Rrs showed much smoother spatial pattern than that from a semianalytical algorithm.More importantly,it is found that the upper limit of using band difference of Rrs can be extended from−0.0005 sr^(−1)(the upper limit set a decade ago for the estimation of Chl)to~0.0005 sr^(-1)(corresponding to a(440)~0.08 m^(-1)),which covers~91% of the global ocean.We further converted a(440)to Chl based on the“Case-1”water assumption and found that the standard Chl product of oligotrophic waters(Chl~0.1 mg/m^(3))distributed by NASA is generally~20% higher than Chl converted from a(440),possibly a result of different datasets used to determine the algorithm coefficients.These results not only extended the application of the band-difference scheme for more oceanic waters but also highlighted the need of more accurate field measurements of Chl and R_(rs) in oligotrophic oceans in order to minimize the discrepancies observed in satellite Chl products derived using the same algorithm concept but different empirical approaches.
