Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identi...Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
We present an application of short-pulse laser-generated hard x rays for the diagnosis of indirectly driven double shell targets. Coneinserted double shell targets were imploded through an indirect drive approach on t...We present an application of short-pulse laser-generated hard x rays for the diagnosis of indirectly driven double shell targets. Coneinserted double shell targets were imploded through an indirect drive approach on the upgraded SG-II laser facility. Then, based on thepoint-projection hard x-ray radiography technique, time-resolved radiography of the double shell targets, including that of their near-peakcompression, were obtained. The backlighter source was created by the interactions of a high-intensity short pulsed laser with a metalmicrowire target. Images of the target near peak compression were obtained with an Au microwire. In addition, radiation hydrodynamicsimulations were performed, and the target evolution obtained agrees well with the experimental results. Using the radiographic images, arealdensities of the targets were evaluated.展开更多
To improve the tribological behavior of biodiesel soot(BDS) in liquid paraffin(LP), the order of biodiesel soot was increased through thermally oxidized treatment at 500 ℃, and the oil solubility was then improved th...To improve the tribological behavior of biodiesel soot(BDS) in liquid paraffin(LP), the order of biodiesel soot was increased through thermally oxidized treatment at 500 ℃, and the oil solubility was then improved through a modification using oleylamine(OLA). The BDS and thermally oxidized oleylamine-modified BDS(T-BDS-OLA)were characterized through various methods including the use of TG, FETEM, Raman spectroscopy, FTIR, and a zeta potentiometer. The tribological properties and mechanisms of the BDS before and after the thermally oxidized treatment modification were investigated using a ball-on-disc reciprocating tribometer, FESEM, 3 D laser-scanning microscopy, and Raman spectroscopy. The results showed that T-BDS-OLA has a higher degree of order than the BDS, with an onion-like microstructure. BDS and T-BDS-OLA can both improve the antifriction and antiwear properties of LP at a soot content of 0.1%-0.4%, while T-BDS-OLA in LP shows better antifriction and antiwear properties than BDS. The tribological mechanisms can be attributed to both types of soot acting as spacing and roll bearing between the friction surfaces. In addition, the exfoliated graphitic sheets from T-BDS-OLA can form a carbon lubrication layer providing easy sliding.展开更多
Efficient and continuous monitoring of surface water is essential for water resource management.Much effort has been devoted to the task of water mapping based on remote sensing images.However,few studies have fully c...Efficient and continuous monitoring of surface water is essential for water resource management.Much effort has been devoted to the task of water mapping based on remote sensing images.However,few studies have fully considered the diverse spectral properties of water for the collection of reference samples in an automatic manner.Moreover,water area statistics are sensitive to the satellite image observation quality.This study aims to develop a fully automatic surface water mapping framework based on Google Earth Engine(GEE)with a supervised random forest classifier.A robust scheme was built to automatically construct training samples by merging the information from multi-source water occurrence products.The samples for permanent and seasonal water were mapped and collected separately,so that the supplement of seasonal samples can increase the spectral diversity of the sample space.To reduce the uncertainty of the derived water occurrences,temporal correction was applied to repair the classification maps with invalid observations.Extensive experiments showed that the proposed method can generate reliable samples and produce good-quality water mapping results.Comparative tests indicated that the proposed method produced water maps with a higher quality than the index-based detection methods,as well as the GSWD and GLAD datasets.展开更多
Ground-level ozone(O_(3))is a primary air pollutant,which can greatly harm human health and ecosystems.At present,data fusion frameworks only provided ground-level O_(3) concentrations at coarse spatial(e.g.,10 km)or ...Ground-level ozone(O_(3))is a primary air pollutant,which can greatly harm human health and ecosystems.At present,data fusion frameworks only provided ground-level O_(3) concentrations at coarse spatial(e.g.,10 km)or temporal(e.g.,daily)resolutions.As photochemical pollution continues increasing over China in the last few years,a high-spatial–temporal-resolution product is required to enhance the comprehension of ground-level O_(3) formation mechanisms.To address this issue,our study creatively explores a brand-new framework for estimating hourly 2-km ground-level O_(3) concentrations across China(except Xinjiang and Tibet)using the brightness temperature at multiple thermal infrared bands.Considering the spatial heterogeneity of ground-level O_(3),a novel Self-adaptive Geospatially Local scheme based on Categorical boosting(SGLboost)is developed to train the estimation models.Validation results show that SGLboost performs well in the study area,with the R2 s/RMSEs of 0.85/19.041 lg/m^(3) and 0.72/25.112 lg/m^(3) for the space-based cross-validation(CV)(2017–2019)and historical space-based CV(2019),respectively.Meanwhile,SGLboost achieves distinctly better metrics than those of some widely used machine learning methods,such as e Xtreme Gradient boosting and Random Forest.Compared to recent related works over China,the performance of SGLboost is also more desired.Regarding the spatial distribution,the estimated results present continuous spatial patterns without a significantly partitioned boundary effect.In addition,accurate hourly and seasonal variations of ground-level O_(3) concentrations can be observed in the estimated results over the study area.It is believed that the hourly 2-km results estimated by SGLboost will help further understand the formation mechanisms of ground-level O_(3) in China.展开更多
Objective:Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension(PAH),but their clinical role in children with PAH associated with congenit...Objective:Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension(PAH),but their clinical role in children with PAH associated with congenital heart defects(CHD)is unclear.This study aims to investigate acute hemodynamic responses to inhaled iloprost,and its role in prognosis in children with PAH-CHD.Methods:A retrospective analysis was conducted on 83 pediatric patients with PAH-CHD in whom invasive hemodynamics were evaluated before and after a single inhaled dose of iloprost at a single center between 2010 and 2022.Details of the CHD corrective operation,medical treatment,and outcome for each patient were obtained via medical records or telephone contact.A composite endpoint of all-cause death,admission for worsening heart failure during follow-up,and event-free survival was defined,and risk factors associated with this composite endpoint were analyzed.Results:The patient age was(11.3±4.6)years,and 60(72.3%)were female.Fifty-nine(71.1%)patients were diagnosed with Eisenmenger syndrome.After iloprost inhalation,mean pulmonary artery pressure decreased from(78.2±11.5)to(72.3±13.2)mmHg(P<0.001),and pulmonary vascular resistance index(PVRI)decreased from(18.0±7.9)to(14.5±8.1)WU·m^(2)(P<0.001).A total of 38(45.8%)patients had a positive response,defined as a PVRl decrease>25%with stable systemic pressure.Thirtyseven(44.6%)patients underwent a corrective CHD operation at a median of 24 d after hemodynamic evaluation.Nine patients died,and 15 met the composite endpoint during a follow-up period of 5.4(3.8,8.8)years.Five-year event-free survival estimates were 96.7%(95%confidence interval:90.3%-100%)in patients with a positive response,and 82.8%(95%confidence interval:71.7%-94.5%)in patients with a non-positive response(log-rank P=0.012).A positive PVRl response and higher pulmonary arterial oxygen saturation after iloprost inhalation,lower baseline brain natriuretic peptide,and PAH-targeted therapy at follow-up were significantly assoc展开更多
基金supported by the National Natural Science Foundation of China(31620103917 31970459 32070441 31702054 and 31930014)the Shenzhen Science and Technology Program(20180411143628272)the Natural Science Foundation of Guangdong Province(2019A1515011899)。
文摘Juvenile hormone(JH) and 20-hydroxyecdysone(20 E) coordinately regulate development and metamorphosis in insects. Two JH intracellular receptors, methoprene-tolerant(Met) and germ-cell expressed(Gce), have been identified in the fruit fly Drosophila melanogaster. To investigate JH membrane signaling pathway without the interference from JH intracellular signaling, we characterized phosphoproteome profiles of the Met gce double mutant in the absence or presence of JH in both chronic and acute phases.Functioning through a potential receptor tyrosine kinase and phospholipase C pathway, JH membrane signaling activated protein kinase C(PKC) which phosphorylated ultraspiracle(USP) at Ser35, the PKC phosphorylation site required for the maximal action of 20 E through its nuclear receptor complex Ec RUSP. The usp;mutant, in which Ser was replaced with Ala at position 35 by genome editing, showed decreased expression of Halloween genes that are responsible for ecdysone biosynthesis and thus attenuated 20 E signaling that delayed developmental timing. The usp;mutant also showed lower Yorkie activity that reduced body size. Altogether, JH membrane signaling phosphorylates USP at Ser35 and thus potentiates 20 E action that regulates the normal fly development. This study helps better understand the complex JH signaling network.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金supported by the National Key R&D Program of China(Grant Nos.2022YFA1603300 and 2022YFA1603200)the Science Challenge Project(Grant No.TZ2018005)in China+1 种基金the National Natural Science Foundation of China(Grant Nos.11805188 and 12175209)the Laser Fusion Research Center Funds for Young Talents(Grant No.RCFPD6-2022-1).
文摘We present an application of short-pulse laser-generated hard x rays for the diagnosis of indirectly driven double shell targets. Coneinserted double shell targets were imploded through an indirect drive approach on the upgraded SG-II laser facility. Then, based on thepoint-projection hard x-ray radiography technique, time-resolved radiography of the double shell targets, including that of their near-peakcompression, were obtained. The backlighter source was created by the interactions of a high-intensity short pulsed laser with a metalmicrowire target. Images of the target near peak compression were obtained with an Au microwire. In addition, radiation hydrodynamicsimulations were performed, and the target evolution obtained agrees well with the experimental results. Using the radiographic images, arealdensities of the targets were evaluated.
基金supported by the National Natural Science Foundation of China (Grant No. 51675153)the Major Science and Technology Special Project in Anhui (Grant No. 17030901084)
文摘To improve the tribological behavior of biodiesel soot(BDS) in liquid paraffin(LP), the order of biodiesel soot was increased through thermally oxidized treatment at 500 ℃, and the oil solubility was then improved through a modification using oleylamine(OLA). The BDS and thermally oxidized oleylamine-modified BDS(T-BDS-OLA)were characterized through various methods including the use of TG, FETEM, Raman spectroscopy, FTIR, and a zeta potentiometer. The tribological properties and mechanisms of the BDS before and after the thermally oxidized treatment modification were investigated using a ball-on-disc reciprocating tribometer, FESEM, 3 D laser-scanning microscopy, and Raman spectroscopy. The results showed that T-BDS-OLA has a higher degree of order than the BDS, with an onion-like microstructure. BDS and T-BDS-OLA can both improve the antifriction and antiwear properties of LP at a soot content of 0.1%-0.4%, while T-BDS-OLA in LP shows better antifriction and antiwear properties than BDS. The tribological mechanisms can be attributed to both types of soot acting as spacing and roll bearing between the friction surfaces. In addition, the exfoliated graphitic sheets from T-BDS-OLA can form a carbon lubrication layer providing easy sliding.
基金supported by the National Natural Science Foundation of China[grants numbers 42171375 and 41801263].
文摘Efficient and continuous monitoring of surface water is essential for water resource management.Much effort has been devoted to the task of water mapping based on remote sensing images.However,few studies have fully considered the diverse spectral properties of water for the collection of reference samples in an automatic manner.Moreover,water area statistics are sensitive to the satellite image observation quality.This study aims to develop a fully automatic surface water mapping framework based on Google Earth Engine(GEE)with a supervised random forest classifier.A robust scheme was built to automatically construct training samples by merging the information from multi-source water occurrence products.The samples for permanent and seasonal water were mapped and collected separately,so that the supplement of seasonal samples can increase the spectral diversity of the sample space.To reduce the uncertainty of the derived water occurrences,temporal correction was applied to repair the classification maps with invalid observations.Extensive experiments showed that the proposed method can generate reliable samples and produce good-quality water mapping results.Comparative tests indicated that the proposed method produced water maps with a higher quality than the index-based detection methods,as well as the GSWD and GLAD datasets.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA19090104)the National Natural Science Foundation of China(No.41922008)the Hubei Provincial Natural Science Foundation of China(No.2020CFA051)。
文摘Ground-level ozone(O_(3))is a primary air pollutant,which can greatly harm human health and ecosystems.At present,data fusion frameworks only provided ground-level O_(3) concentrations at coarse spatial(e.g.,10 km)or temporal(e.g.,daily)resolutions.As photochemical pollution continues increasing over China in the last few years,a high-spatial–temporal-resolution product is required to enhance the comprehension of ground-level O_(3) formation mechanisms.To address this issue,our study creatively explores a brand-new framework for estimating hourly 2-km ground-level O_(3) concentrations across China(except Xinjiang and Tibet)using the brightness temperature at multiple thermal infrared bands.Considering the spatial heterogeneity of ground-level O_(3),a novel Self-adaptive Geospatially Local scheme based on Categorical boosting(SGLboost)is developed to train the estimation models.Validation results show that SGLboost performs well in the study area,with the R2 s/RMSEs of 0.85/19.041 lg/m^(3) and 0.72/25.112 lg/m^(3) for the space-based cross-validation(CV)(2017–2019)and historical space-based CV(2019),respectively.Meanwhile,SGLboost achieves distinctly better metrics than those of some widely used machine learning methods,such as e Xtreme Gradient boosting and Random Forest.Compared to recent related works over China,the performance of SGLboost is also more desired.Regarding the spatial distribution,the estimated results present continuous spatial patterns without a significantly partitioned boundary effect.In addition,accurate hourly and seasonal variations of ground-level O_(3) concentrations can be observed in the estimated results over the study area.It is believed that the hourly 2-km results estimated by SGLboost will help further understand the formation mechanisms of ground-level O_(3) in China.
基金supported by the National Natural Science Foundation of China(82070243).
文摘Objective:Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension(PAH),but their clinical role in children with PAH associated with congenital heart defects(CHD)is unclear.This study aims to investigate acute hemodynamic responses to inhaled iloprost,and its role in prognosis in children with PAH-CHD.Methods:A retrospective analysis was conducted on 83 pediatric patients with PAH-CHD in whom invasive hemodynamics were evaluated before and after a single inhaled dose of iloprost at a single center between 2010 and 2022.Details of the CHD corrective operation,medical treatment,and outcome for each patient were obtained via medical records or telephone contact.A composite endpoint of all-cause death,admission for worsening heart failure during follow-up,and event-free survival was defined,and risk factors associated with this composite endpoint were analyzed.Results:The patient age was(11.3±4.6)years,and 60(72.3%)were female.Fifty-nine(71.1%)patients were diagnosed with Eisenmenger syndrome.After iloprost inhalation,mean pulmonary artery pressure decreased from(78.2±11.5)to(72.3±13.2)mmHg(P<0.001),and pulmonary vascular resistance index(PVRI)decreased from(18.0±7.9)to(14.5±8.1)WU·m^(2)(P<0.001).A total of 38(45.8%)patients had a positive response,defined as a PVRl decrease>25%with stable systemic pressure.Thirtyseven(44.6%)patients underwent a corrective CHD operation at a median of 24 d after hemodynamic evaluation.Nine patients died,and 15 met the composite endpoint during a follow-up period of 5.4(3.8,8.8)years.Five-year event-free survival estimates were 96.7%(95%confidence interval:90.3%-100%)in patients with a positive response,and 82.8%(95%confidence interval:71.7%-94.5%)in patients with a non-positive response(log-rank P=0.012).A positive PVRl response and higher pulmonary arterial oxygen saturation after iloprost inhalation,lower baseline brain natriuretic peptide,and PAH-targeted therapy at follow-up were significantly assoc
