Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to ...Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.展开更多
The environmental contamination caused by antibiotics is increasingly conspicuous due to their widespread manufacture and misuse. Plasma has been employed in recent years for the remediation of antibiotic pollution in...The environmental contamination caused by antibiotics is increasingly conspicuous due to their widespread manufacture and misuse. Plasma has been employed in recent years for the remediation of antibiotic pollution in the environment. In this work, a falling-film dielectric barrier discharge was used to degrade the antibiotic tetracycline(TC) in water. The reactor combined the gas-liquid discharge and active gas bubbling to improve the TC degradation performance. The discharge characteristics, chemical species’ concentration, and degradation rates at different parameters were systematically studied. Under the optimized conditions(working gas was pure oxygen, liquid flow rate was 100 mL/min, gas flow rate was 1 L/min,voltage was 20 kV, single treatment), TC was removed beyond 70% in a single flow treatment with an energy efficiency of 145 mg/(kW·h). The reactor design facilitated gas and liquid flow in the plasma area to produce more ozone in bubbles after a single flow under pure oxygen conditions, affording fast TC degradation. Furthermore, long-term stationary experiment indicated that long-lived active species can sustain the degradation of TC. Compared with other plasma treatment systems, this work offers a fast and efficient degradation method, showing significant potential in practical industrial applications.展开更多
Data augmentation is an important task of using existing data to expand data sets.Using generative countermeasure network technology to realize data augmentation has the advantages of high-quality generated samples,si...Data augmentation is an important task of using existing data to expand data sets.Using generative countermeasure network technology to realize data augmentation has the advantages of high-quality generated samples,simple training,and fewer restrictions on the number of generated samples.However,in the field of transmission line insulator images,the freely synthesized samples are prone to produce fuzzy backgrounds and disordered samples of the main insulator features.To solve the above problems,this paper uses the cycle generative adversarial network(Cycle-GAN)used for domain conversion in the generation countermeasure network as the initial framework and uses the self-attention mechanism and channel attention mechanism to assist the conversion to realize the mutual conversion of different insulator samples.The attention module with prior knowledge is used to build the generation countermeasure network,and the generative adversarial network(GAN)model with local controllable generation is built to realize the directional generation of insulator belt defect samples.The experimental results show that the samples obtained by this method are improved in a number of quality indicators,and the quality effect of the samples obtained is excellent,which has a reference value for the data expansion of insulator images.展开更多
Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine gree...Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine green(ICG)-fluorescence imaging has been introduced as an effective tool for real-time intraoperative guidance[2].Liver anatomy is complex.Generally,liver is composed of 9 segments,each is composed of two to three subsegments,and each subsegment contains several hepatic cone units.A hepatic cone unit is dominated by a tertiary or quaternary hepatic pedicles[3].展开更多
BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes p...BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.展开更多
The uncontrolled dendrite growth of lithium metal anodes(LMAs)caused by unstable anode/electrolyte interface and uneven lithium deposition have impeded the practical applications of lithium metal batteries(LMBs).Const...The uncontrolled dendrite growth of lithium metal anodes(LMAs)caused by unstable anode/electrolyte interface and uneven lithium deposition have impeded the practical applications of lithium metal batteries(LMBs).Constructing a robust artificial solid electrolyte interphase(SEI)and regulating the lithium deposition behavior is an effective strategy to address these issues.Herein,a three-dimensional(3D)lithium anode with gradient Li_(3)N has been in-situ fabricated on carbon-based framework by thermal diffusion method(denoted as CC/Li/Li_(3)N).Density functional theory(DFT)calculations reveal that Li_(3)N can effectively promote the transport of Li^(+)due to the low energy barrier of Li^(+)diffusion.As expected,the Li_(3)N-rich conformal artificial SEI film can not only effectively stabilize the interface and avoid parasitic reactions,but also facilitate fast Li^(+)transport across the SEI layer.The anode matrix with uniformly distributed Li3N can enable homogenous deposition of Li,thus preventing Li dendrite propagation.Benefiting from these merits,the CC/Li/Li_(3)N anode achieves ultralong-term cycling for>1000 h at a current density of 2 m A cm^(-2)and dendrite-free Li deposition at an ultrahigh rate of 20 m A cm^(-2).Moreover,the full cells coupled with LiFePO4cathodes show extraordinary cycling stability for>300 cycles in liquidelectrolyte-based batteries and display a high-capacity retention of 96.7%after 100 cycles in solid-state cells,demonstrating the promising prospects for the practical applications of LMBs.展开更多
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.展开更多
Though the lithium-ion battery is universally applied,the reliability of lithium-ion batteries remains a challenge due to various physicochemical reactions,electrode material degradation,and even thermal runaway.Accur...Though the lithium-ion battery is universally applied,the reliability of lithium-ion batteries remains a challenge due to various physicochemical reactions,electrode material degradation,and even thermal runaway.Accurate estimation and prediction of battery health conditions are crucial for battery safety management.In this paper,an end-cloud collaboration method is proposed to approach the track of battery degradation process,integrating end-side empirical model with cloud-side data-driven model.Based on ensemble learning methods,the data-driven model is constructed by three base models to obtain cloud-side highly accurate results.The double exponential decay model is utilized as an empirical model to output highly real-time prediction results.With Kalman filter,the prediction results of end-side empirical model can be periodically updated by highly accurate results of cloud-side data-driven model to obtain highly accurate and real-time results.Subsequently,the whole framework can give an accurate prediction and tracking of battery degradation,with the mean absolute error maintained below 2%.And the execution time on the end side can reach 261μs.The proposed end-cloud collaboration method has the potential to approach highly accurate and highly real-time estimation for battery health conditions during battery full life cycle in architecture of cyber hierarchy and interactional network.展开更多
Jasmine [Jasminum sambac(L.) Ait.], a tropical and subtropical plant emits a sweet, heady fragrance during flower opening. However, the molecular mechanisms underlying this phenomenon remain largely unknown. In the pr...Jasmine [Jasminum sambac(L.) Ait.], a tropical and subtropical plant emits a sweet, heady fragrance during flower opening. However, the molecular mechanisms underlying this phenomenon remain largely unknown. In the present study, integrated Illumina sequencing, Pacbio sequencing, and high-throughput chromatin conformation capture(Hi-C) scaffolding was used to generate a 495.60 Mb genome assembly of J.sambac var. unifoliatum cultivar ‘Fuzhou Single-petal’(JSU-FSP), with contig N50 of 16.88 Mb;96.23% of the assembly was assigned to 13 pseudochromosomes. The genome harbors 30 989 protein-coding genes, and 49.47% of the assembled sequences are repetitive sequences. The analysis of duplication modes showed that 51% of genes were duplicated through dispersed duplication, and expanded gene families are mainly involved in photosynthesis, which may be responsible for the light-loving characteristic specific to jasmine. Transcriptome analysis revealed that at least 35 structural genes involved in the biosynthesis of volatile terpenes(VTs), volatile phenylpropanoid/benzenoids(VPBs),fatty acid-derived volatiles(FADVs), and indole were highly expressed in the flower-opening stage, both preharvest and postharvest, and are proposed to be important in endowing flower aroma. Additionally, at least 28 heat shock protein(HSP) and 11 β-glucosidase(BGLU) genes may be involved in the formation of floral fragrance. These findings provide insights into the formation of the floral fragrance of jasmine and will promote germplasm utilization for breeding improved jasmine varieties.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974132,81770927Hunan Provincial Health Commission,No.20220702839+1 种基金the Natural Science Foundation of Hunan Province of China,No.2022JJ30076National Key R&D Program of China,No.2021YFA1101202(all to WS)。
文摘Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.
基金supported by the National Science Fund for Distinguished Young Scholars(No.51925703)National Natural Science Foundation of China(Nos.52022096 and 52261145695)。
文摘The environmental contamination caused by antibiotics is increasingly conspicuous due to their widespread manufacture and misuse. Plasma has been employed in recent years for the remediation of antibiotic pollution in the environment. In this work, a falling-film dielectric barrier discharge was used to degrade the antibiotic tetracycline(TC) in water. The reactor combined the gas-liquid discharge and active gas bubbling to improve the TC degradation performance. The discharge characteristics, chemical species’ concentration, and degradation rates at different parameters were systematically studied. Under the optimized conditions(working gas was pure oxygen, liquid flow rate was 100 mL/min, gas flow rate was 1 L/min,voltage was 20 kV, single treatment), TC was removed beyond 70% in a single flow treatment with an energy efficiency of 145 mg/(kW·h). The reactor design facilitated gas and liquid flow in the plasma area to produce more ozone in bubbles after a single flow under pure oxygen conditions, affording fast TC degradation. Furthermore, long-term stationary experiment indicated that long-lived active species can sustain the degradation of TC. Compared with other plasma treatment systems, this work offers a fast and efficient degradation method, showing significant potential in practical industrial applications.
基金supported in part by the National Natural Science Foundation of China under Grant No.61973055Fundamental Research Funds for the Central Universities under Grant No.ZYGX2020J011Regional Innovation Cooperation Funds of Sichuan under Grant No.2024YFHZ0089.
文摘Data augmentation is an important task of using existing data to expand data sets.Using generative countermeasure network technology to realize data augmentation has the advantages of high-quality generated samples,simple training,and fewer restrictions on the number of generated samples.However,in the field of transmission line insulator images,the freely synthesized samples are prone to produce fuzzy backgrounds and disordered samples of the main insulator features.To solve the above problems,this paper uses the cycle generative adversarial network(Cycle-GAN)used for domain conversion in the generation countermeasure network as the initial framework and uses the self-attention mechanism and channel attention mechanism to assist the conversion to realize the mutual conversion of different insulator samples.The attention module with prior knowledge is used to build the generation countermeasure network,and the generative adversarial network(GAN)model with local controllable generation is built to realize the directional generation of insulator belt defect samples.The experimental results show that the samples obtained by this method are improved in a number of quality indicators,and the quality effect of the samples obtained is excellent,which has a reference value for the data expansion of insulator images.
基金from Health Commission of Zhejiang Province(JBZX-202004)the National Natural Science Foundation of China(82002925)the National Key Research and Development Program of China(2022YFC2407304).
文摘Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine green(ICG)-fluorescence imaging has been introduced as an effective tool for real-time intraoperative guidance[2].Liver anatomy is complex.Generally,liver is composed of 9 segments,each is composed of two to three subsegments,and each subsegment contains several hepatic cone units.A hepatic cone unit is dominated by a tertiary or quaternary hepatic pedicles[3].
基金supported by Major Program of National Natural Science Foundation of China (82192910)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202009 and ZYYCXTD-D-202207)。
基金supported by the Major Program of the National Natural Science Foundation of China (grant nos.82192910 and 82192911)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (grant nos.ZYYCXTD-D-202207 and ZYYCXTD-C-202009)。
基金Supported by the Key Specialty Construction Project of Shanghai Pudong New Area Health Commission,No.PWZzk2022-17Shanghai East Hospital Clinical Research Project,No.DFLC2022019and the Featured Clinical Discipline Project of Shanghai Pudong District,No.PWYts2021-06.
文摘BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.
基金supported by the National Natural Science Foundation of China(22078251)the National Key R&D Program of China(2021YFB2012000)+1 种基金the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education,Jianghan University(JDGD-202211)the Graduate Innovation Fund of Wuhan Institute of Technology(CX2021014)。
文摘The uncontrolled dendrite growth of lithium metal anodes(LMAs)caused by unstable anode/electrolyte interface and uneven lithium deposition have impeded the practical applications of lithium metal batteries(LMBs).Constructing a robust artificial solid electrolyte interphase(SEI)and regulating the lithium deposition behavior is an effective strategy to address these issues.Herein,a three-dimensional(3D)lithium anode with gradient Li_(3)N has been in-situ fabricated on carbon-based framework by thermal diffusion method(denoted as CC/Li/Li_(3)N).Density functional theory(DFT)calculations reveal that Li_(3)N can effectively promote the transport of Li^(+)due to the low energy barrier of Li^(+)diffusion.As expected,the Li_(3)N-rich conformal artificial SEI film can not only effectively stabilize the interface and avoid parasitic reactions,but also facilitate fast Li^(+)transport across the SEI layer.The anode matrix with uniformly distributed Li3N can enable homogenous deposition of Li,thus preventing Li dendrite propagation.Benefiting from these merits,the CC/Li/Li_(3)N anode achieves ultralong-term cycling for>1000 h at a current density of 2 m A cm^(-2)and dendrite-free Li deposition at an ultrahigh rate of 20 m A cm^(-2).Moreover,the full cells coupled with LiFePO4cathodes show extraordinary cycling stability for>300 cycles in liquidelectrolyte-based batteries and display a high-capacity retention of 96.7%after 100 cycles in solid-state cells,demonstrating the promising prospects for the practical applications of LMBs.
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
基金supported by USTC Research Funds of the Double First-Class Initiative(YD2060002024)Youth Innovation Promotion Association CAS(2020448)+2 种基金National Natur-al Science Foundation of China(22171254)Anhui Provincial Natural Science Foundation(2108085MB58)Start-up Research Fund from University of Science and Technology of China(KY2060000216).
基金financially supported by the National Natural Science Foundation of China(No.52102470)。
文摘Though the lithium-ion battery is universally applied,the reliability of lithium-ion batteries remains a challenge due to various physicochemical reactions,electrode material degradation,and even thermal runaway.Accurate estimation and prediction of battery health conditions are crucial for battery safety management.In this paper,an end-cloud collaboration method is proposed to approach the track of battery degradation process,integrating end-side empirical model with cloud-side data-driven model.Based on ensemble learning methods,the data-driven model is constructed by three base models to obtain cloud-side highly accurate results.The double exponential decay model is utilized as an empirical model to output highly real-time prediction results.With Kalman filter,the prediction results of end-side empirical model can be periodically updated by highly accurate results of cloud-side data-driven model to obtain highly accurate and real-time results.Subsequently,the whole framework can give an accurate prediction and tracking of battery degradation,with the mean absolute error maintained below 2%.And the execution time on the end side can reach 261μs.The proposed end-cloud collaboration method has the potential to approach highly accurate and highly real-time estimation for battery health conditions during battery full life cycle in architecture of cyber hierarchy and interactional network.
基金supported by the Construction of Plateau Discipline of Fujian Province (Grant No. 102/71201801101)the Construction Project for Technological Innovation and Service System of Tea Industry Chain of Fujian Agriculture and Forestry University (Grant No. K1520005A01)。
文摘Jasmine [Jasminum sambac(L.) Ait.], a tropical and subtropical plant emits a sweet, heady fragrance during flower opening. However, the molecular mechanisms underlying this phenomenon remain largely unknown. In the present study, integrated Illumina sequencing, Pacbio sequencing, and high-throughput chromatin conformation capture(Hi-C) scaffolding was used to generate a 495.60 Mb genome assembly of J.sambac var. unifoliatum cultivar ‘Fuzhou Single-petal’(JSU-FSP), with contig N50 of 16.88 Mb;96.23% of the assembly was assigned to 13 pseudochromosomes. The genome harbors 30 989 protein-coding genes, and 49.47% of the assembled sequences are repetitive sequences. The analysis of duplication modes showed that 51% of genes were duplicated through dispersed duplication, and expanded gene families are mainly involved in photosynthesis, which may be responsible for the light-loving characteristic specific to jasmine. Transcriptome analysis revealed that at least 35 structural genes involved in the biosynthesis of volatile terpenes(VTs), volatile phenylpropanoid/benzenoids(VPBs),fatty acid-derived volatiles(FADVs), and indole were highly expressed in the flower-opening stage, both preharvest and postharvest, and are proposed to be important in endowing flower aroma. Additionally, at least 28 heat shock protein(HSP) and 11 β-glucosidase(BGLU) genes may be involved in the formation of floral fragrance. These findings provide insights into the formation of the floral fragrance of jasmine and will promote germplasm utilization for breeding improved jasmine varieties.