Chayote(Sechium edule)is an agricultural crop in the Cucurbitaceae family that is rich in bioactive components.To enhance genetic research on chayote,we used Nanopore third-generation sequencing combined with Hi-C dat...Chayote(Sechium edule)is an agricultural crop in the Cucurbitaceae family that is rich in bioactive components.To enhance genetic research on chayote,we used Nanopore third-generation sequencing combined with Hi-C data to assemble a draft chayote genome.A chromosome-level assembly anchored on 14 chromosomes(N50 contig and scaffold sizes of 8.40 and 46.56 Mb,respectively)estimated the genome size as 606.42 Mb,which is large for the Cucurbitaceae,with 65.94%(401.08 Mb)ofthe genome comprising repetitive sequences;28,237 protein-coding genes were predicted.Comparative genome analysis indicated that chayote and snake gourd diverged from sponge gourd and that a whole-genome duplication(WGD)event occurred in chayote at 25±4 Mya.Transcriptional and metabolic analysis revealed genes involved in fruit texture,pigment,fl avor,fl avonoids,antioxidants,and plant hormones during chayote fruit development.The analysis of the genome,transcriptome,and metabolome provides insights into chayote evolution and lays the groundwork for future research on fruit and tuber development and genetic improvements in chayote.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinas...Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling.However,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been understudied.Thus,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)mice.Synovial inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)mice.Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting protein.We further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγsignaling.Mechanistically,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 transcription.Furthermore,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and angiogenesis.Altogether,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling.Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.展开更多
Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of...Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of N-(2-hydroxypropyl)methacrylamide(HPMA) polymer–drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin(Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide(MPP) and then attached to(HPMA) copolymers(P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells via endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species(ROS) as well as reduction of adenosine triphosphate(ATP)production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.展开更多
This study explores the potential of Artificial Intelligence(AI)in early screening and prognosis of Dry Eye Disease(DED),aiming to enhance the accuracy of therapeutic approaches for eye-care practitioners.Despite the ...This study explores the potential of Artificial Intelligence(AI)in early screening and prognosis of Dry Eye Disease(DED),aiming to enhance the accuracy of therapeutic approaches for eye-care practitioners.Despite the promising opportunities,challenges such as diverse diagnostic evidence,complex etiology,and interdisciplinary knowledge integration impede the interpretability,reliability,and applicability of AI-based DED detection methods.The research conducts a comprehensive review of datasets,diagnostic evidence,and standards,as well as advanced algorithms in AI-based DED detection over the past five years.The DED diagnostic methods are categorized into three groups based on their relationship with AI techniques:(1)those with ground truth and/or comparable standards,(2)potential AI-based methods with significant advantages,and(3)supplementary methods for AI-based DED detection.The study proposes suggested DED detection standards,the combination of multiple diagnostic evidence,and future research directions to guide further investigations.Ultimately,the research contributes to the advancement of ophthalmic disease detection by providing insights into knowledge foundations,advanced methods,challenges,and potential future perspectives,emphasizing the significant role of AI in both academic and practical aspects of ophthalmology.展开更多
基金the Beijing Municipal Science and Technology Commission(Z191100008619004 and Z191100004019010)the Key Project"Science and Technology Boost the Feonomy 2020",the Special Innovation Ability Construction Fund of Beijing Academy of Agricultural and Forestry Sciences(20180404 and 20200427)+4 种基金the China Agriculture Research System Project(CARS-23)the National Key Research and Ripening Program of China,Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences(201915)the Young Investigat or Fund of Beijing Academy of Agricultural and Forestry Sciences(202016)the National Natural Scienee Foundation of China(31772022)the Natural Scienee Foundation of Beijing(6182016).
文摘Chayote(Sechium edule)is an agricultural crop in the Cucurbitaceae family that is rich in bioactive components.To enhance genetic research on chayote,we used Nanopore third-generation sequencing combined with Hi-C data to assemble a draft chayote genome.A chromosome-level assembly anchored on 14 chromosomes(N50 contig and scaffold sizes of 8.40 and 46.56 Mb,respectively)estimated the genome size as 606.42 Mb,which is large for the Cucurbitaceae,with 65.94%(401.08 Mb)ofthe genome comprising repetitive sequences;28,237 protein-coding genes were predicted.Comparative genome analysis indicated that chayote and snake gourd diverged from sponge gourd and that a whole-genome duplication(WGD)event occurred in chayote at 25±4 Mya.Transcriptional and metabolic analysis revealed genes involved in fruit texture,pigment,fl avor,fl avonoids,antioxidants,and plant hormones during chayote fruit development.The analysis of the genome,transcriptome,and metabolome provides insights into chayote evolution and lays the groundwork for future research on fruit and tuber development and genetic improvements in chayote.
基金We thank LetPub(www.letpub.com)for its linguistic assistance during the preparation of this manuscript.We thank all the patients who participated in providing us with synovial tissues and blood samples.Graphical abstract was created with BioRender.com(publication and licensing rights number JZ25ROGTF8)This study was supported by the National Natural Science Foundation of China(No.82003763,No.81973332,No.82173824,No.82204405,No.82204402)+2 种基金Research Fund of Anhui Institute of translational medicine(2022zhyx-B04,China)The 2022 Basic and Clinical Collaborative Research of Anhui Medical University(2022sfy015,China)Natural Science Foundation of Anhui Provincial(2108085QH383,China).
文摘Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling.However,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been understudied.Thus,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)mice.Synovial inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)mice.Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting protein.We further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγsignaling.Mechanistically,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 transcription.Furthermore,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and angiogenesis.Altogether,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling.Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.
基金financial support from the National Natural Science Foundation for Distinguished Young Scholars (81625023, China)the National Natural Science Foundation of China (81473167)Sichuan Youth Science and Technology Innovation Research Team Funding (2016TD0001, China)
文摘Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of N-(2-hydroxypropyl)methacrylamide(HPMA) polymer–drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin(Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide(MPP) and then attached to(HPMA) copolymers(P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells via endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species(ROS) as well as reduction of adenosine triphosphate(ATP)production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.
基金funded by the National Natural Science Foundation of China Natural(Nos.U22A2041,82071915,and 62372047)the Shenzhen Key Laboratory of Intelligent Bioinformatics(No.ZDSYS20220422103800001)+5 种基金the Shenzhen Science and Technology Program(No.KQTD20200820113106007)the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515220015)the Zhuhai Technology and Research Foundation(Nos.ZH22036201210034PWC,2220004000131,and 2220004002412)the Project of Humanities and Social Science of MOE(Ministry of Education in China)(No.22YJCZH213)the Science and Technology Research Program of Chongqing Municipal Education Commission(Nos.KJZD-K202203601,KJQN0202203605,and KJQN202203607)the Natural Science Foundation of Chongqing China(No.cstc2021jcyj-msxmX1108).
文摘This study explores the potential of Artificial Intelligence(AI)in early screening and prognosis of Dry Eye Disease(DED),aiming to enhance the accuracy of therapeutic approaches for eye-care practitioners.Despite the promising opportunities,challenges such as diverse diagnostic evidence,complex etiology,and interdisciplinary knowledge integration impede the interpretability,reliability,and applicability of AI-based DED detection methods.The research conducts a comprehensive review of datasets,diagnostic evidence,and standards,as well as advanced algorithms in AI-based DED detection over the past five years.The DED diagnostic methods are categorized into three groups based on their relationship with AI techniques:(1)those with ground truth and/or comparable standards,(2)potential AI-based methods with significant advantages,and(3)supplementary methods for AI-based DED detection.The study proposes suggested DED detection standards,the combination of multiple diagnostic evidence,and future research directions to guide further investigations.Ultimately,the research contributes to the advancement of ophthalmic disease detection by providing insights into knowledge foundations,advanced methods,challenges,and potential future perspectives,emphasizing the significant role of AI in both academic and practical aspects of ophthalmology.
