Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infe...Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.展开更多
Melatonin(MLT)is a hormonal substance found in many organisms and can improve plant stress resistance.In this study,the japonica rice variety Y32 and indica rice variety NJ6 were cultivated in hydroponics under differ...Melatonin(MLT)is a hormonal substance found in many organisms and can improve plant stress resistance.In this study,the japonica rice variety Y32 and indica rice variety NJ6 were cultivated in hydroponics under different concentrations of CdCl2 at the two-leaf stage.The growth,physiological and biochemical responses of the seedlings and the expression of cadmium(Cd)-related genes under exogenous melatonin(MLT)treatment were assessed.The results indicated that Cd stress destroyed the dynamic balance between reactive oxygen species(ROS)production and removal,resulting in ROS accumulation,membrane lipid peroxidation,and impaired growth and development.Following the application of exogenous MLT to rice seedlings,increases in plant biomass including both underground and above-ground areas were observed.MLT also scavenged the inhibition of superoxide dismutase(SOD)and peroxidase(POD)in a concentration dependent manner in response to Cd stress.Catalase(CAT)activity and malondialdehyde(MDA)expression also decreased following MLT treatment.Amongst the six Cd-related genes assessed,five genes were downregulated and one was up-regulated in response to MLT treatment.Taken together,these data demonstrate that MLT improves the resilience of rice seedlings at the biochemical,physiological,and molecular levels,and diminishes the damage caused by Cd stress.展开更多
A new polymeric ionic liquid gel was prepared with 1-[(2-methacryloyloxy)ethyl]-3-methylimidazolium bromide(MEMImBr) via radiation-induced polymerization and cross-linking at room temperature.The resultant PMEMImBr ge...A new polymeric ionic liquid gel was prepared with 1-[(2-methacryloyloxy)ethyl]-3-methylimidazolium bromide(MEMImBr) via radiation-induced polymerization and cross-linking at room temperature.The resultant PMEMImBr gel exhibits high strength and flexibility as well as special swelling behavior in oil-in-water(O/W)emulsions.The swelling behavior of PMEMImBr gel in emulsions is similar to that in water except that the swelling rate in emulsions is slightly smaller than that in water.The organic solvents with higher polarity in the emulsions contribute to the swelling of PMEMImBr gels,and the O/W proportion of emulsion in the swollen gel equals approximately that of original emulsion when the concentration of organic solvent is lower than 0.2 g/g.展开更多
We propose a terahertz hybrid metamaterial composed of subwavelength metallic slits and graphene plasmonic ribbons for sensing application.This special design can cause the interaction between the plasmon resonances o...We propose a terahertz hybrid metamaterial composed of subwavelength metallic slits and graphene plasmonic ribbons for sensing application.This special design can cause the interaction between the plasmon resonances of the metallic slits and graphene ribbons,giving rise to a strong coupling effect and Rabi splitting.Intricate balancing in the strong coupling region can be perturbed by the carrier concentration of graphene,which is subject to the analyte on its surface.Thereby,the detection of analyte can be reflected as a frequency shift of resonance in terahertz transmission spectra.The result shows that this sensor can achieve a theoretical detection limit of 325 electrons or holes per square micrometer.Meanwhile,it also works well as a refractive index sensor with the frequency sensitivity of 485 GHz/RIU.Our results may contribute to design of ultra-micro terahertz sensors.展开更多
Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] th...Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.展开更多
Wax apple(Syzygium samarangense)is an economically important fruit crop with great potential value to human health because of its richness in antioxidant substances.Here,we present a haplotype-resolved autotetraploid ...Wax apple(Syzygium samarangense)is an economically important fruit crop with great potential value to human health because of its richness in antioxidant substances.Here,we present a haplotype-resolved autotetraploid genome assembly of the wax apple with a size of 1.59 Gb.Comparative genomic analysis revealed three rounds of whole-genome duplication(WGD)events,including two independent WGDs after WGT-γ.Resequencing analysis of 35 accessions partitioned these individuals into two distinct groups,including 28 landraces and seven cultivated species,and several genes subject to selective sweeps possibly contributed to fruit growth,including the KRP1-like,IAA17-like,GME-like,and FLACCA-like genes.Transcriptome analysis of three different varieties during flower and fruit development identified key genes related to fruit size,sugar content,and male sterility.We found that AP2 also affected fruit size by regulating sepal development in wax apples.The expression of sugar transport-related genes(SWEETs and SUTs)was high in‘ZY’,likely contributing to its high sugar content.Male sterility in‘Tub’was associated with tapetal abnormalities due to the decreased expression of DYT1,TDF1,and AMS,which affected early tapetum development.The chromosome-scale genome and large-scale transcriptome data presented in this study offer new valuable resources for biological research on S.samarangense and shed new light on fruit size control,sugar metabolism,and male sterility regulatory metabolism in wax apple.展开更多
BACKGROUND The Nuclear factor erythroid 2-related factor 2(NRF2)transcription factor has attracted much attention in the context of neurological diseases.However,none of the studies have systematically clarified this ...BACKGROUND The Nuclear factor erythroid 2-related factor 2(NRF2)transcription factor has attracted much attention in the context of neurological diseases.However,none of the studies have systematically clarified this field's research hotspots and evolution rules.AIM To investigate the research hotspots,evolution patterns,and future research trends in this field in recent years.METHODS We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods:(((((TS=(NFE2 L2))OR TS=(Nfe2 L2 protein,mouse))OR TS=(NF-E2-Related Factor 2))OR TS=(NRF2))OR TS=(NFE2L2))OR TS=(Nuclear factor erythroid2-related factor 2)AND(((((((TS=(neurological diseases))OR TS=(neurological disorder))OR TS=(brain disorder))OR TS=(brain injury))OR TS=(central nervous system disease))OR TS=(CNS disease))OR TS=(central nervous system disorder))OR TS=(CNS disorder)AND Language=English from 2010 to 2022.There are just two forms of literature available:Articles and reviews.Data were processed with the software Cite-Space(version 6.1.R6).RESULTS We analyzed 1884 articles from 200 schools in 72 countries/regions.Since 2015,the number of publications in this field has increased rapidly.China has the largest number of publications,but the articles published in the United States have better centrality and H-index.Among the top ten authors with the most published papers,five of them are from China,and the author with the most published papers is Wang Handong.The institution with the most articles was Nanjing University.To their credit,three of the top 10 most cited articles were written by Chinese scholars.The keyword co-occurrence map showed that"oxidative stress","NRF2","activation","expression"and"brain"were the five most frequently used keywords.CONCLUSION Research on the role of NRF2 in neurological diseases continues unabated.Researchers in developed countries published more influential papers,while Chinese scholars provided the largest number of articles.There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases.NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases.However,despite decades of research,our knowledge of NRF2 transcription factor in nervous system diseases is still limited.Further studies are needed in the future.展开更多
基金supported by the National Basic Research Program of China(2020YFA0804000,2020YFC0842000,2020YFA0112200,2021YFC2301703)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)+6 种基金Special Associate Research Program of the Chinese Academy of Sciences(E1290601)National Natural Science Foundation of China(32122037,81891001,32192411,32100512,U1902215)Collaborative Research Fund of the Chinese Institute for Brain Research,Beijing(2020-NKX-PT-03)CAS Project for Young Scientists in Basic Research(YSBR-013)Young Elite Scientist Sponsorship Program by the China Association for Science and Technology(2020QNRC001)National Resource Center for Non-Human Primates。
文摘Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.
基金supported by Hangzhou Scientific and Technological Program(20170432B03)the National Key Technology Research and Development Program(2015BAD01B02)the National Natural Science Foundation of China(31661143006).
文摘Melatonin(MLT)is a hormonal substance found in many organisms and can improve plant stress resistance.In this study,the japonica rice variety Y32 and indica rice variety NJ6 were cultivated in hydroponics under different concentrations of CdCl2 at the two-leaf stage.The growth,physiological and biochemical responses of the seedlings and the expression of cadmium(Cd)-related genes under exogenous melatonin(MLT)treatment were assessed.The results indicated that Cd stress destroyed the dynamic balance between reactive oxygen species(ROS)production and removal,resulting in ROS accumulation,membrane lipid peroxidation,and impaired growth and development.Following the application of exogenous MLT to rice seedlings,increases in plant biomass including both underground and above-ground areas were observed.MLT also scavenged the inhibition of superoxide dismutase(SOD)and peroxidase(POD)in a concentration dependent manner in response to Cd stress.Catalase(CAT)activity and malondialdehyde(MDA)expression also decreased following MLT treatment.Amongst the six Cd-related genes assessed,five genes were downregulated and one was up-regulated in response to MLT treatment.Taken together,these data demonstrate that MLT improves the resilience of rice seedlings at the biochemical,physiological,and molecular levels,and diminishes the damage caused by Cd stress.
基金supported by the National Natural Science Foundation of China (No. 11375019)
文摘A new polymeric ionic liquid gel was prepared with 1-[(2-methacryloyloxy)ethyl]-3-methylimidazolium bromide(MEMImBr) via radiation-induced polymerization and cross-linking at room temperature.The resultant PMEMImBr gel exhibits high strength and flexibility as well as special swelling behavior in oil-in-water(O/W)emulsions.The swelling behavior of PMEMImBr gel in emulsions is similar to that in water except that the swelling rate in emulsions is slightly smaller than that in water.The organic solvents with higher polarity in the emulsions contribute to the swelling of PMEMImBr gels,and the O/W proportion of emulsion in the swollen gel equals approximately that of original emulsion when the concentration of organic solvent is lower than 0.2 g/g.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61865009,61927813,and 62005168).
文摘We propose a terahertz hybrid metamaterial composed of subwavelength metallic slits and graphene plasmonic ribbons for sensing application.This special design can cause the interaction between the plasmon resonances of the metallic slits and graphene ribbons,giving rise to a strong coupling effect and Rabi splitting.Intricate balancing in the strong coupling region can be perturbed by the carrier concentration of graphene,which is subject to the analyte on its surface.Thereby,the detection of analyte can be reflected as a frequency shift of resonance in terahertz transmission spectra.The result shows that this sensor can achieve a theoretical detection limit of 325 electrons or holes per square micrometer.Meanwhile,it also works well as a refractive index sensor with the frequency sensitivity of 485 GHz/RIU.Our results may contribute to design of ultra-micro terahertz sensors.
基金supported by Beijing Science and Technology Innovation Medical Development Foundation (No. KC2021-JF-0167-01 and No. KC2021-JF-0167-24)。
文摘Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.
基金This work was supported by the Natural Science Foundation of Fujian Province(2020 J011361)the High-quality Development beyond the‘5511’Collaborative Innovation Project in Fujian Province(XTCXGC2021016-4).We thank Ping Zhou(Fujian Academy of Agricultural Sciences)for the data analysis program.
文摘Wax apple(Syzygium samarangense)is an economically important fruit crop with great potential value to human health because of its richness in antioxidant substances.Here,we present a haplotype-resolved autotetraploid genome assembly of the wax apple with a size of 1.59 Gb.Comparative genomic analysis revealed three rounds of whole-genome duplication(WGD)events,including two independent WGDs after WGT-γ.Resequencing analysis of 35 accessions partitioned these individuals into two distinct groups,including 28 landraces and seven cultivated species,and several genes subject to selective sweeps possibly contributed to fruit growth,including the KRP1-like,IAA17-like,GME-like,and FLACCA-like genes.Transcriptome analysis of three different varieties during flower and fruit development identified key genes related to fruit size,sugar content,and male sterility.We found that AP2 also affected fruit size by regulating sepal development in wax apples.The expression of sugar transport-related genes(SWEETs and SUTs)was high in‘ZY’,likely contributing to its high sugar content.Male sterility in‘Tub’was associated with tapetal abnormalities due to the decreased expression of DYT1,TDF1,and AMS,which affected early tapetum development.The chromosome-scale genome and large-scale transcriptome data presented in this study offer new valuable resources for biological research on S.samarangense and shed new light on fruit size control,sugar metabolism,and male sterility regulatory metabolism in wax apple.
文摘BACKGROUND The Nuclear factor erythroid 2-related factor 2(NRF2)transcription factor has attracted much attention in the context of neurological diseases.However,none of the studies have systematically clarified this field's research hotspots and evolution rules.AIM To investigate the research hotspots,evolution patterns,and future research trends in this field in recent years.METHODS We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods:(((((TS=(NFE2 L2))OR TS=(Nfe2 L2 protein,mouse))OR TS=(NF-E2-Related Factor 2))OR TS=(NRF2))OR TS=(NFE2L2))OR TS=(Nuclear factor erythroid2-related factor 2)AND(((((((TS=(neurological diseases))OR TS=(neurological disorder))OR TS=(brain disorder))OR TS=(brain injury))OR TS=(central nervous system disease))OR TS=(CNS disease))OR TS=(central nervous system disorder))OR TS=(CNS disorder)AND Language=English from 2010 to 2022.There are just two forms of literature available:Articles and reviews.Data were processed with the software Cite-Space(version 6.1.R6).RESULTS We analyzed 1884 articles from 200 schools in 72 countries/regions.Since 2015,the number of publications in this field has increased rapidly.China has the largest number of publications,but the articles published in the United States have better centrality and H-index.Among the top ten authors with the most published papers,five of them are from China,and the author with the most published papers is Wang Handong.The institution with the most articles was Nanjing University.To their credit,three of the top 10 most cited articles were written by Chinese scholars.The keyword co-occurrence map showed that"oxidative stress","NRF2","activation","expression"and"brain"were the five most frequently used keywords.CONCLUSION Research on the role of NRF2 in neurological diseases continues unabated.Researchers in developed countries published more influential papers,while Chinese scholars provided the largest number of articles.There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases.NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases.However,despite decades of research,our knowledge of NRF2 transcription factor in nervous system diseases is still limited.Further studies are needed in the future.
