Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Th...Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Therefore,there is a great need for effective drugs against dTGCT with minor side effects.The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling plays a central role in rheumatoid arthritis(RA),a disease with similar characteristics as dTGCT,but its function in dTGCT remains unknown.dTGCT fibroblast-like synoviocytes(FLS)and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT.Cell viability,cell death,inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D)and macrophages were investigated for the efficacy of the JAK inhibitors.Here,we found that similar to RA,JAK/STAT signaling was markedly activated in the dTGCT synovium.Of the 5 JAK inhibitors,peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and macrophages.The potency of peficitinib was much higher than pexidartinib,which is the only FDA-approved drug for dTGCT.Mechanistically,peficitinib inhibited tyrosine kinase 2(TYK2),a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages.In summary,we not only revealed JAK/STAT(especially TYK2)signaling as the major mechanism underlying dTGCT,but also identified peficitinib as a promising drug against dTGCT.展开更多
Chicken gut microbiota plays an important role in maintaining their physiological health.However,the cultivability of chicken gut microbiota is not well understood,limiting the exploration of certain key gut bacteria ...Chicken gut microbiota plays an important role in maintaining their physiological health.However,the cultivability of chicken gut microbiota is not well understood,limiting the exploration of certain key gut bacteria in regulating intestinal health and nutritional metabolism.This study aimed to examine the cultivability of chicken cecal microbiota and to provide guidance for future chicken gut microbiota cultivation.A total of 58 different culture conditions were applied to culture broiler cecal microbiota,and the culture-dependent(CD;pooled colonies form each plate)and culture-independent(CI;broiler cecal contents)samples were collected for 16S rRNA gene sequencing and microbial analysis.The CD methods detected higher microbial richness(3,636 vs 2,331 OTUs)than CI methods,and the recovery rates of bacterial OTUs and genera reached 43.6%and 68.9%,respectively.The genera of Bacteroides(19.9%),Alistipes(11.0%)and Barnesiella(10.7%)were highly abundant detected by CI methods,however,there occupied a small proportion(<1.0%)of total cultured microbiota in CD methods.We then developed reference figures and tables showing optimal cultivation conditions for different gut bacteria taxa.Moreover,81 different lactic acid bacteria strains covering 5 genera were isolated,and 15 strains had less than 97.0%similarity to known bacteria in the national center for biotechnology information(NCBI)online database.Overall,this study provides preliminary guidance in culturing specific gut microbiota from chickens,which will contribute to future studies to characterize the biological functions of key microbes in chicken nutritional metabolism and health.展开更多
Plant diversity significantly impacts ecosystem processes and functions,yet its influence on the community assembly of leaf fungi remains poorly understood.In this study,we investigated leaf epiphytic and endophytic f...Plant diversity significantly impacts ecosystem processes and functions,yet its influence on the community assembly of leaf fungi remains poorly understood.In this study,we investigated leaf epiphytic and endophytic fungal communities in a Chinese subtropical tree species richness experiment,ranging from 1 to 16 species,using amplicon sequencing to target the internal transcribed spacer 1 region of the rDNA.We found that the community assembly of epiphytic and endophytic fungi was predominantly governed by stochastic processes,with a higher contribution of dispersal limitation on epiphytic than on endophytic fungal communities but a higher contribution of selection on endophytic than on epiphytic fungal communities.The plant-epiphytic fungus interaction network was more complex(e.g.,more highly connected and strongly nested but less specialized and modularized)than the plant-endophytic fungus interaction network.Additionally,tree species richness was positively correlated with the network complexity and diversity of epiphytic(α-,β-andγ-diversity)and endophytic(β-andγ-diversity)fungi,but was not associated with the contribution of the stochastic and deterministic processes on the community assembly of epiphytic and endophytic fungi.This study highlights that tree species diversity enhances the diversity and network complexity,rather than alters the ecological processes in community assembly of leaf-associated fungi.展开更多
In 2023,the World Obesity Atlas Federation concluded that more than 50%of the world’s population would be overweight or obese within the next 12 years.At the heart of this epidemic lies the gut microbiota,a complex e...In 2023,the World Obesity Atlas Federation concluded that more than 50%of the world’s population would be overweight or obese within the next 12 years.At the heart of this epidemic lies the gut microbiota,a complex ecosystem that profoundly influences obesity-related metabolic health.Its multifaced role encompasses energy harvesting,inflammation,satiety signaling,gut barrier function,gut-brain communication,and adipose tissue homeostasis.Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge,microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions.This narrative review analyzed the current state of knowledge,illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans.By elucidating the complex relationship between gut microflora and obesity,we aim to contribute to the growing body of knowledge underpinning this critical field,potentially paving the way for novel interventions to combat the worldwide obesity epidemic.展开更多
The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene ...The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene therapy,cell localization,cell lineage tracking,synthetic biology,information storage,etc.However,developing idealized editors in various fields is still a goal for future development.This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system.It first explains the application of ideas for improvement such as“substitution”,“combination”,“adaptation”,and“adjustment”in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology.It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system.Finally,it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.展开更多
Transgenic plants are extensively utilized in research,enabling scientists to explore gene functions in controlled environments,leading to crops with higher productivity and greater resistance to biotic and abiotic st...Transgenic plants are extensively utilized in research,enabling scientists to explore gene functions in controlled environments,leading to crops with higher productivity and greater resistance to biotic and abiotic stressors(Oyebamiji et al.,2024).Traditional transgene integration techniques,such as particle bombardment and Agrobacterium T-DNA integration,often lead to unintended mutations and unpredictable insertion sites,emphasizing the necessity for developing targeted transgene integration(Ahuja and Fladung,2014).Current methods for targeted transgene integration,like homologous recombination(HR)and CRISPR-Cas,including their variants like prime editing and homology-directed repair(HDR),face challenges due to low integration efficiency and high deletion rates,hampering their practical application in crop genetic engineering(Dong and Ronald,2021;Tzfira and Citovsky,2006).展开更多
Dear Editor,The German cockroach,Blattella germanica(Insecta,Blattodea),is one of the most synanthropic cosmopolitan pests affecting public health,which is often described as“little mighty”because of its extreme vit...Dear Editor,The German cockroach,Blattella germanica(Insecta,Blattodea),is one of the most synanthropic cosmopolitan pests affecting public health,which is often described as“little mighty”because of its extreme vitality and adaptability.This characterization in cockroaches is primarily due to two crucial biological traits,strong regenerative capacity and excellent fecundity(Ren et al.,2023),but nothing is known about the underlying relationship between these two traits in terms of physiology and behavior.Insects have evolved diverse appendages(i.e.antenna,labial palp,maxillary palp,leg,wing,and cercus)that are used for locomotion,feeding,communication,and other vital functions(Chen et al.,2022;Li et al.,2024).As a crucial adaptive strategy,appendage regeneration enables animals to restore injured body parts and their associated functions(Tanaka,2016),significantly enhancing survival ability and ecological adaptation(Zhong et al.,2023).Moreover,cockroaches exhibit extremely prominent capacity of leg regeneration in the insect kingdom(Li et al.,2018;Ren et al.,2024;Zhang et al.,2024).展开更多
Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and ...Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and pathogen prevention.Their design and production are of great significance,as they can enhance the effectiveness of targeted therapy by improving the accuracy and efficiency of attacks against multiple targets.However,compared with traditional monoclonal antibodies,the design and production of bsAbs are more complex.One major challenge facing the conventional IgG bispecific format is the efficient pairing of different chains,known as the chain association issue.To overcome this,researchers have sought to promote heavychain heterodimerization through Fc engineering techniques,such as knobs-intoholes(KiH)and controlled Fab arm exchange.Others have highlighted the benefit of simple heavy-light chain paired formats,as they completely bypass the chain association issue while offering improved manufacturability.展开更多
Incorporating noncanonical amino acids(ncAAs)beyond these naturally occurring ones into proteins has proven to be a powerful method for modifying their properties,leading to significant advancements in both fundamenta...Incorporating noncanonical amino acids(ncAAs)beyond these naturally occurring ones into proteins has proven to be a powerful method for modifying their properties,leading to significant advancements in both fundamental and applied sciences.Currently,over 300 nc AAs can be genetically encoded with varying degrees of efficiency.Thus,genetic code expansion(GCE)technology,which extends the range of amino acids available for protein synthesis,represents a major and exciting area of research.A GCE system precisely incorporates nc AAs into proteins using custom-designed orthogonal aminoacyl-t RNA synthetases(aaRSs)and t RNA pairs along with specific codons.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFF0501401,2018YFA0800501)National Natural Science Foundation of China(82325004,92168114,82172447)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0047).
文摘Diffuse-type tenosynovial giant cell tumor(dTGCT)is a destructive but rare benign proliferative synovial neoplasm.Although surgery is currently the main treatment modality for dTGCT,the recurrence risk is up to 50%.Therefore,there is a great need for effective drugs against dTGCT with minor side effects.The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling plays a central role in rheumatoid arthritis(RA),a disease with similar characteristics as dTGCT,but its function in dTGCT remains unknown.dTGCT fibroblast-like synoviocytes(FLS)and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT.Cell viability,cell death,inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D)and macrophages were investigated for the efficacy of the JAK inhibitors.Here,we found that similar to RA,JAK/STAT signaling was markedly activated in the dTGCT synovium.Of the 5 JAK inhibitors,peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and macrophages.The potency of peficitinib was much higher than pexidartinib,which is the only FDA-approved drug for dTGCT.Mechanistically,peficitinib inhibited tyrosine kinase 2(TYK2),a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages.In summary,we not only revealed JAK/STAT(especially TYK2)signaling as the major mechanism underlying dTGCT,but also identified peficitinib as a promising drug against dTGCT.
基金supported in part by the National Key Research and Development Program of China Projects(2022YFD1300402)fundamental research funds for the Central Universities(2662022DKPY002)the Top-Notch Young Talent Supporting Program(to LH Sun).
文摘Chicken gut microbiota plays an important role in maintaining their physiological health.However,the cultivability of chicken gut microbiota is not well understood,limiting the exploration of certain key gut bacteria in regulating intestinal health and nutritional metabolism.This study aimed to examine the cultivability of chicken cecal microbiota and to provide guidance for future chicken gut microbiota cultivation.A total of 58 different culture conditions were applied to culture broiler cecal microbiota,and the culture-dependent(CD;pooled colonies form each plate)and culture-independent(CI;broiler cecal contents)samples were collected for 16S rRNA gene sequencing and microbial analysis.The CD methods detected higher microbial richness(3,636 vs 2,331 OTUs)than CI methods,and the recovery rates of bacterial OTUs and genera reached 43.6%and 68.9%,respectively.The genera of Bacteroides(19.9%),Alistipes(11.0%)and Barnesiella(10.7%)were highly abundant detected by CI methods,however,there occupied a small proportion(<1.0%)of total cultured microbiota in CD methods.We then developed reference figures and tables showing optimal cultivation conditions for different gut bacteria taxa.Moreover,81 different lactic acid bacteria strains covering 5 genera were isolated,and 15 strains had less than 97.0%similarity to known bacteria in the national center for biotechnology information(NCBI)online database.Overall,this study provides preliminary guidance in culturing specific gut microbiota from chickens,which will contribute to future studies to characterize the biological functions of key microbes in chicken nutritional metabolism and health.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB31030000)the National Natural Science Foundation of China (31971496,32170120)+2 种基金the support of Zhejiang Qianjiangyuan Forest Biodiversity National Observation and Research Stationthe International Research Training Group Tree Dìjointly funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 319936945/GRK2324)the University of Chinese Academy of Science(UCAS).
文摘Plant diversity significantly impacts ecosystem processes and functions,yet its influence on the community assembly of leaf fungi remains poorly understood.In this study,we investigated leaf epiphytic and endophytic fungal communities in a Chinese subtropical tree species richness experiment,ranging from 1 to 16 species,using amplicon sequencing to target the internal transcribed spacer 1 region of the rDNA.We found that the community assembly of epiphytic and endophytic fungi was predominantly governed by stochastic processes,with a higher contribution of dispersal limitation on epiphytic than on endophytic fungal communities but a higher contribution of selection on endophytic than on epiphytic fungal communities.The plant-epiphytic fungus interaction network was more complex(e.g.,more highly connected and strongly nested but less specialized and modularized)than the plant-endophytic fungus interaction network.Additionally,tree species richness was positively correlated with the network complexity and diversity of epiphytic(α-,β-andγ-diversity)and endophytic(β-andγ-diversity)fungi,but was not associated with the contribution of the stochastic and deterministic processes on the community assembly of epiphytic and endophytic fungi.This study highlights that tree species diversity enhances the diversity and network complexity,rather than alters the ecological processes in community assembly of leaf-associated fungi.
基金supported by the Ministry of Science and Technology of China(2023YFF1304900 and 2022YFC2105003)Guangxi Key Research and Development Program(AB24010109)+5 种基金the National Natural Science Foundation of China(31930015 and 32370538)Chinese Academy of Sciences(KFJ-BRP-008)Yunnan Province(202003AD150008 and 202305AH340006)Kunming Science and Technology Bureau(2022SCP007)Shenzhen New Cornerstone Science Foundation(NCI202238)the University Chinese Academy of Sciences and Alliance of International Science Organization(ANSO)through 2022A8010415002.
文摘In 2023,the World Obesity Atlas Federation concluded that more than 50%of the world’s population would be overweight or obese within the next 12 years.At the heart of this epidemic lies the gut microbiota,a complex ecosystem that profoundly influences obesity-related metabolic health.Its multifaced role encompasses energy harvesting,inflammation,satiety signaling,gut barrier function,gut-brain communication,and adipose tissue homeostasis.Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge,microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions.This narrative review analyzed the current state of knowledge,illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans.By elucidating the complex relationship between gut microflora and obesity,we aim to contribute to the growing body of knowledge underpinning this critical field,potentially paving the way for novel interventions to combat the worldwide obesity epidemic.
基金supported by the National Natural Science Foundation of China(81970324)partially supported by grants from the National Key R&D Program of China 2023YFC3403400。
文摘The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene therapy,cell localization,cell lineage tracking,synthetic biology,information storage,etc.However,developing idealized editors in various fields is still a goal for future development.This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system.It first explains the application of ideas for improvement such as“substitution”,“combination”,“adaptation”,and“adjustment”in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology.It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system.Finally,it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.
基金supported by Jiangsu specially-appointed professor fund(337060046)the Yangzhou University Startup Fund(137012599).
文摘Transgenic plants are extensively utilized in research,enabling scientists to explore gene functions in controlled environments,leading to crops with higher productivity and greater resistance to biotic and abiotic stressors(Oyebamiji et al.,2024).Traditional transgene integration techniques,such as particle bombardment and Agrobacterium T-DNA integration,often lead to unintended mutations and unpredictable insertion sites,emphasizing the necessity for developing targeted transgene integration(Ahuja and Fladung,2014).Current methods for targeted transgene integration,like homologous recombination(HR)and CRISPR-Cas,including their variants like prime editing and homology-directed repair(HDR),face challenges due to low integration efficiency and high deletion rates,hampering their practical application in crop genetic engineering(Dong and Ronald,2021;Tzfira and Citovsky,2006).
基金supported by the National Natural Science Foundation of China(32070500,32370439,32220103003,and 31930014)the Natural Science Foundation of Guangdong Province(2021B1515020044)the Department of Science and Technology in Guangdong Province(2019B090905003)。
文摘Dear Editor,The German cockroach,Blattella germanica(Insecta,Blattodea),is one of the most synanthropic cosmopolitan pests affecting public health,which is often described as“little mighty”because of its extreme vitality and adaptability.This characterization in cockroaches is primarily due to two crucial biological traits,strong regenerative capacity and excellent fecundity(Ren et al.,2023),but nothing is known about the underlying relationship between these two traits in terms of physiology and behavior.Insects have evolved diverse appendages(i.e.antenna,labial palp,maxillary palp,leg,wing,and cercus)that are used for locomotion,feeding,communication,and other vital functions(Chen et al.,2022;Li et al.,2024).As a crucial adaptive strategy,appendage regeneration enables animals to restore injured body parts and their associated functions(Tanaka,2016),significantly enhancing survival ability and ecological adaptation(Zhong et al.,2023).Moreover,cockroaches exhibit extremely prominent capacity of leg regeneration in the insect kingdom(Li et al.,2018;Ren et al.,2024;Zhang et al.,2024).
基金supported by the National Natural Science Foundation of China(81991491,32300777)the Fundamental Research Funds for the Central Universities(20720220006)+1 种基金China Postdoctoral Science Foundation(2022M722659)CAMS Innovation Fund for Medical Sciences(2019RU022).
文摘Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and pathogen prevention.Their design and production are of great significance,as they can enhance the effectiveness of targeted therapy by improving the accuracy and efficiency of attacks against multiple targets.However,compared with traditional monoclonal antibodies,the design and production of bsAbs are more complex.One major challenge facing the conventional IgG bispecific format is the efficient pairing of different chains,known as the chain association issue.To overcome this,researchers have sought to promote heavychain heterodimerization through Fc engineering techniques,such as knobs-intoholes(KiH)and controlled Fab arm exchange.Others have highlighted the benefit of simple heavy-light chain paired formats,as they completely bypass the chain association issue while offering improved manufacturability.
基金supported by the National Key Research and Development Program of China(2021YFF1200300)the National Natural Science Foundation of China(32122050,32370074)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2021B1515020060)Guangdong Provincial Science and Technology Projects(2022A0505090009)Innovation Program of Chinese Academy of Agricultural Science,and Shenzhen Outstanding Talents Training Fund.
文摘Incorporating noncanonical amino acids(ncAAs)beyond these naturally occurring ones into proteins has proven to be a powerful method for modifying their properties,leading to significant advancements in both fundamental and applied sciences.Currently,over 300 nc AAs can be genetically encoded with varying degrees of efficiency.Thus,genetic code expansion(GCE)technology,which extends the range of amino acids available for protein synthesis,represents a major and exciting area of research.A GCE system precisely incorporates nc AAs into proteins using custom-designed orthogonal aminoacyl-t RNA synthetases(aaRSs)and t RNA pairs along with specific codons.
