UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),U...UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.展开更多
Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiolo...Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiology is multifactorial,involving tobacco use,alcohol consumption,and human papillomavirus(HPV)infection.Oral leukoplakia and erythroplakia are the main precancerous lesions lesions,with oral leukoplakia being the most common.Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways.Post-translational modifications(such as ubiquitination and deubiquitination)play key roles in regulating these pathways by controlling protein stability and activity.Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways.The ubiquitination/deubiquitination process mainly involves E3 ligases(E3s)that catalyze substrate ubiquitination,deubiquitinating enzymes(DUBs)that remove ubiquitin chains,and the 26S proteasome complex that degrades ubiquitinated substrates.Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumorrelated proteins,thereby driving OSCC initiation and progression.Therefore,understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components.Here,we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway,Wnt/β-catenin pathway,Hippo pathway,and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways,along with potential drug targets.PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70%of OSCC cases.It is modulated by E3s(e.g.,FBXW7 and NEDD4)and DUBs(e.g.,USP7 and USP10):FBXW7 and USP10 inhibit signaling,while NEDD4 and USP7 potentiate it.Aberrant activation of the Wnt/β-catenin pathway leads toβ-catenin nuclear translocation and induction of cell proliferation.This pathway is modulated by E3s(e.g.,c-Cbl and RNF43)and DUBs(e.g.,USP9X and USP20):c-Cbl and RNF43 inhibit signaling,while USP9X and USP20 potentiate it.Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis.This pathway is modulated by E3s(e.g.,CRL4^(DCAF1) and SIAH2)and DUBs(e.g.,USP1 and USP21):CRL4^(DCAF1) and SIAH2 inhibit signaling,while USP1 and USP21 potentiate it.Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance.This pathway is modulated by E3s(e.g.,TRAF6 and LUBAC)and DUBs(e.g.,A20 and CYLD):A20 and CYLD inhibit signaling,while TRAF6 and LUBAC potentiate it.Targeting these E3s and DUBs provides directions for OSCC drug research.Small-molecule inhibitors such as YCH2823(a USP7 inhibitor),GSK2643943A(a USP20 inhibitor),and HOIPIN-8(a LUBAC inhibitor)have shown promising antitumor activity in preclinical models;PROTAC molecules,by binding to surface sites of target proteins and recruiting E3s,achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors,for example,PU7-1-mediated USP7 degradation,offering new strategies to overcome traditional drug limitations.Currently,NX-1607(a Cbl-b inhibitor)has entered phase I clinical trials,with preliminary results confirming its safety and antitumor activity.Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.展开更多
Heart failure prediction is crucial as cardiovascular diseases become the leading cause of death worldwide,exacerbated by the COVID-19 pandemic.Age,cholesterol,and blood pressure datasets are becoming inadequate becau...Heart failure prediction is crucial as cardiovascular diseases become the leading cause of death worldwide,exacerbated by the COVID-19 pandemic.Age,cholesterol,and blood pressure datasets are becoming inadequate because they cannot capture the complexity of emerging health indicators.These high-dimensional and heterogeneous datasets make traditional machine learning methods difficult,and Skewness and other new biomarkers and psychosocial factors bias the model’s heart health prediction across diverse patient profiles.Modern medical datasets’complexity and high dimensionality challenge traditional predictionmodels like SupportVectorMachines and Decision Trees.Quantum approaches include QSVM,QkNN,QDT,and others.These Constraints drove research.The“QHF-CS:Quantum-Enhanced Heart Failure Prediction using Quantum CNN with Optimized Feature Qubit Selection with Cuckoo Search in Skewed Clinical Data”system was developed in this research.This novel system leverages a Quantum Convolutional Neural Network(QCNN)-based quantum circuit,enhanced by meta-heuristic algorithms—Cuckoo SearchOptimization(CSO),Artificial BeeColony(ABC),and Particle SwarmOptimization(PSO)—for feature qubit selection.Among these,CSO demonstrated superior performance by consistently identifying the most optimal and least skewed feature subsets,which were then encoded into quantum states for circuit construction.By integrating advanced quantum circuit feature maps like ZZFeatureMap,RealAmplitudes,and EfficientSU2,the QHF-CS model efficiently processes complex,high-dimensional data,capturing intricate patterns that classical models overlook.The QHF-CS model improves precision,recall,F1-score,and accuracy to 0.94,0.95,0.94,and 0.94.Quantum computing could revolutionize heart failure diagnostics by improving model accuracy and computational efficiency,enabling complex healthcare diagnostic breakthroughs.展开更多
Mating patterns in angiosperms are typically nonrandom,yet the mechanisms driving nonrandom mating remain unclear,especially regarding the effects of quantitative floral traits on plant mating success across male and ...Mating patterns in angiosperms are typically nonrandom,yet the mechanisms driving nonrandom mating remain unclear,especially regarding the effects of quantitative floral traits on plant mating success across male and female functions.In this study,we investigated how variation in spur length and flower number per plant influences mating patterns in Aquilegia rockii within a natural population.Using marker-based paternity analyses and manipulative experiments,we assessed the role of these traits in mating success across both sexual functions.We found significant variation in the mate composition between male and female function,with spur-length frequency positively associated with female outcrossing rate and mate number,but not with male outcrossing or mate number.Most mating events occurred within 10 m,and spur-length frequency positively correlated with mating distance.Regardless of selfing,there was evidence for assortative mating for spur length.Although spur length did not correlate with pollinator visitation,plants with mid-length spurs had higher seed set than those with shorter or longer spurs when autonomous selfing was excluded.Flowers number per plant was only associated with mating distance and female outcrossing rate.Our results suggest that spur length plays a key role in nonrandom mating by frequency-dependent mating,with implications for stabilizing selection and maintenance of genetic diversity.This study advances our understanding of floral diversity by dissecting the role of quantitative floral traits in plant mating through both female and male functions.展开更多
Investigating geographical variation and functional adaptation of gut microbiomes in endangered species is an emerging field in conservation biology.Here,we investigated the endangered waterbird,Scaly-sided Merganser(...Investigating geographical variation and functional adaptation of gut microbiomes in endangered species is an emerging field in conservation biology.Here,we investigated the endangered waterbird,Scaly-sided Merganser(Mergus squamatus),that is endemic to East Asia.Using metagenomic sequencing,we characterized variations in gut microbiota composition and functional adaptation across Scaly-sided Merganser populations inhabiting the Fuer River,Manjiang River,and Lushui River basins in Northeast China.Furthermore,we investigated these variations at different developmental stages(adults and juveniles).Significant differences were observed in gut microbiota composition among the river populations,with the Fuer and Lushui groups exhibiting similar compositions that differed from the Manjiang group.However,no significant differences were found in the functional characteristics of gut microbiota among the three groups;these functions were primarily enriched in core pathways related to carbohydrate metabolism,amino acid metabolism,and translation.This finding suggests functional redundancy,where key metabolic functions remain stable despite differentiation in microbial community composition.The adult Scaly-sided Merganser gut microbiota exhibited higher alpha diversity and showed significant enrichment in pathways related to detoxification metabolism,environmental adaptation,and energy conversion efficiency,suggesting the capacity to adapt to complex habitats.In contrast,the gut microbiota of juveniles was enriched in metabolic pathways related to the essential and conditionally essential amino acids methionine and cysteine,supporting the high protein synthesis demand during the rapid growth and developmental stage.This study highlights the structural plasticity and functional adaptability of the gut microbiota in the Scaly-sided Merganser,providing an empirical basis for the species'conservation and habitat management from a gut microbiome perspective.展开更多
The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biologi...The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.展开更多
As an endemic and critically-endangered wildlife species in China,the giant panda(Ailuropoda melanoleuca)has attracted widespread attention from all sectors of society regarding its survival status.In this study,the i...As an endemic and critically-endangered wildlife species in China,the giant panda(Ailuropoda melanoleuca)has attracted widespread attention from all sectors of society regarding its survival status.In this study,the impact of earthquake-dameged areas on the distribution and activities of giant pandas in the Qionglai Mountains was analyzed by comparing data from two giant panda surveys conducted in the Qionglai Mountains of Sichuan Province and combining with remote sensing(RS)data from relevant regions.The results indicated that there was only a small area of overlap between the earthquake-damaged areas and giant panda activity trace points.The main earthquake-damaged areas were distributed at elevations(3,500-4,100 m)higher than the primary elevation range of giant panda distribution(1,700-3,100 m).In the Wolong Nature Reserve,no major earthquake damage was observed in the central section east of Provincial Highway 303 with relatively more giant panda activities.Within the Caopo Nature Reserve,the earthquake-damaged areas were mostly concentrated in the northeastern corner and along the border with the Wolong Nature Reserve.However,no large-scale giant panda activity traces were detected in these areas during either of the two surveys.Overall,the range of giant panda activities showed no signs of decline.Therefore,the impact of earthquakes on giant panda activities remains limited.展开更多
基金Supported by Special Projects in Key Areas for Guangdong Provincial Colleges and Universities (No.2021ZDZX2009)Guangzhou Medical University Discipline Construction Funds (Basic Medicine)(No.JCXKJS2022A05)。
文摘UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.
文摘Oral squamous cell carcinoma(OSCC)is the most common head and neck malignancy worldwide,accounting for more than 90%of all oral cancers,and is characterized by high invasiveness and poor long-term prognosis.Its etiology is multifactorial,involving tobacco use,alcohol consumption,and human papillomavirus(HPV)infection.Oral leukoplakia and erythroplakia are the main precancerous lesions lesions,with oral leukoplakia being the most common.Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways.Post-translational modifications(such as ubiquitination and deubiquitination)play key roles in regulating these pathways by controlling protein stability and activity.Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways.The ubiquitination/deubiquitination process mainly involves E3 ligases(E3s)that catalyze substrate ubiquitination,deubiquitinating enzymes(DUBs)that remove ubiquitin chains,and the 26S proteasome complex that degrades ubiquitinated substrates.Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumorrelated proteins,thereby driving OSCC initiation and progression.Therefore,understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components.Here,we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway,Wnt/β-catenin pathway,Hippo pathway,and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways,along with potential drug targets.PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70%of OSCC cases.It is modulated by E3s(e.g.,FBXW7 and NEDD4)and DUBs(e.g.,USP7 and USP10):FBXW7 and USP10 inhibit signaling,while NEDD4 and USP7 potentiate it.Aberrant activation of the Wnt/β-catenin pathway leads toβ-catenin nuclear translocation and induction of cell proliferation.This pathway is modulated by E3s(e.g.,c-Cbl and RNF43)and DUBs(e.g.,USP9X and USP20):c-Cbl and RNF43 inhibit signaling,while USP9X and USP20 potentiate it.Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis.This pathway is modulated by E3s(e.g.,CRL4^(DCAF1) and SIAH2)and DUBs(e.g.,USP1 and USP21):CRL4^(DCAF1) and SIAH2 inhibit signaling,while USP1 and USP21 potentiate it.Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance.This pathway is modulated by E3s(e.g.,TRAF6 and LUBAC)and DUBs(e.g.,A20 and CYLD):A20 and CYLD inhibit signaling,while TRAF6 and LUBAC potentiate it.Targeting these E3s and DUBs provides directions for OSCC drug research.Small-molecule inhibitors such as YCH2823(a USP7 inhibitor),GSK2643943A(a USP20 inhibitor),and HOIPIN-8(a LUBAC inhibitor)have shown promising antitumor activity in preclinical models;PROTAC molecules,by binding to surface sites of target proteins and recruiting E3s,achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors,for example,PU7-1-mediated USP7 degradation,offering new strategies to overcome traditional drug limitations.Currently,NX-1607(a Cbl-b inhibitor)has entered phase I clinical trials,with preliminary results confirming its safety and antitumor activity.Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.
文摘Heart failure prediction is crucial as cardiovascular diseases become the leading cause of death worldwide,exacerbated by the COVID-19 pandemic.Age,cholesterol,and blood pressure datasets are becoming inadequate because they cannot capture the complexity of emerging health indicators.These high-dimensional and heterogeneous datasets make traditional machine learning methods difficult,and Skewness and other new biomarkers and psychosocial factors bias the model’s heart health prediction across diverse patient profiles.Modern medical datasets’complexity and high dimensionality challenge traditional predictionmodels like SupportVectorMachines and Decision Trees.Quantum approaches include QSVM,QkNN,QDT,and others.These Constraints drove research.The“QHF-CS:Quantum-Enhanced Heart Failure Prediction using Quantum CNN with Optimized Feature Qubit Selection with Cuckoo Search in Skewed Clinical Data”system was developed in this research.This novel system leverages a Quantum Convolutional Neural Network(QCNN)-based quantum circuit,enhanced by meta-heuristic algorithms—Cuckoo SearchOptimization(CSO),Artificial BeeColony(ABC),and Particle SwarmOptimization(PSO)—for feature qubit selection.Among these,CSO demonstrated superior performance by consistently identifying the most optimal and least skewed feature subsets,which were then encoded into quantum states for circuit construction.By integrating advanced quantum circuit feature maps like ZZFeatureMap,RealAmplitudes,and EfficientSU2,the QHF-CS model efficiently processes complex,high-dimensional data,capturing intricate patterns that classical models overlook.The QHF-CS model improves precision,recall,F1-score,and accuracy to 0.94,0.95,0.94,and 0.94.Quantum computing could revolutionize heart failure diagnostics by improving model accuracy and computational efficiency,enabling complex healthcare diagnostic breakthroughs.
基金financially supported by the National Natural Science Foundation of China(32271693)the Cultivating Plan Program for the Leader in Science and Technology of Yunnan Province(202405AC350111)to ZQZ.
文摘Mating patterns in angiosperms are typically nonrandom,yet the mechanisms driving nonrandom mating remain unclear,especially regarding the effects of quantitative floral traits on plant mating success across male and female functions.In this study,we investigated how variation in spur length and flower number per plant influences mating patterns in Aquilegia rockii within a natural population.Using marker-based paternity analyses and manipulative experiments,we assessed the role of these traits in mating success across both sexual functions.We found significant variation in the mate composition between male and female function,with spur-length frequency positively associated with female outcrossing rate and mate number,but not with male outcrossing or mate number.Most mating events occurred within 10 m,and spur-length frequency positively correlated with mating distance.Regardless of selfing,there was evidence for assortative mating for spur length.Although spur length did not correlate with pollinator visitation,plants with mid-length spurs had higher seed set than those with shorter or longer spurs when autonomous selfing was excluded.Flowers number per plant was only associated with mating distance and female outcrossing rate.Our results suggest that spur length plays a key role in nonrandom mating by frequency-dependent mating,with implications for stabilizing selection and maintenance of genetic diversity.This study advances our understanding of floral diversity by dissecting the role of quantitative floral traits in plant mating through both female and male functions.
基金funded by the National Natural Science Foundation of China(grant number 32471566)the Scientific Research Project of the Education Department of Jilin Province,China(grant number JJKH20241422KJ)the Natural Science Foundation of Jilin Province,China(grant number 20230101160JC)。
文摘Investigating geographical variation and functional adaptation of gut microbiomes in endangered species is an emerging field in conservation biology.Here,we investigated the endangered waterbird,Scaly-sided Merganser(Mergus squamatus),that is endemic to East Asia.Using metagenomic sequencing,we characterized variations in gut microbiota composition and functional adaptation across Scaly-sided Merganser populations inhabiting the Fuer River,Manjiang River,and Lushui River basins in Northeast China.Furthermore,we investigated these variations at different developmental stages(adults and juveniles).Significant differences were observed in gut microbiota composition among the river populations,with the Fuer and Lushui groups exhibiting similar compositions that differed from the Manjiang group.However,no significant differences were found in the functional characteristics of gut microbiota among the three groups;these functions were primarily enriched in core pathways related to carbohydrate metabolism,amino acid metabolism,and translation.This finding suggests functional redundancy,where key metabolic functions remain stable despite differentiation in microbial community composition.The adult Scaly-sided Merganser gut microbiota exhibited higher alpha diversity and showed significant enrichment in pathways related to detoxification metabolism,environmental adaptation,and energy conversion efficiency,suggesting the capacity to adapt to complex habitats.In contrast,the gut microbiota of juveniles was enriched in metabolic pathways related to the essential and conditionally essential amino acids methionine and cysteine,supporting the high protein synthesis demand during the rapid growth and developmental stage.This study highlights the structural plasticity and functional adaptability of the gut microbiota in the Scaly-sided Merganser,providing an empirical basis for the species'conservation and habitat management from a gut microbiome perspective.
基金supported by the National Natural Science Foundation of China(No.31872547)the Natural Science Foundation of Zhejiang Province,China(No.LTGN24C190015)the Excellent Postdoctoral Program of Jiangsu Province(No.314865)。
文摘The novel identified receptor,GPR103,now renamed QRFPR(also referred to as SP9155 or AQ27),is the endogenous receptor for the neuropeptide QRFP(also referred to as 26RFa).The distribution pattern,structure,and biological actions,such as feeding behavior,bone formation,and hormone secretion of QRFPR have been largely described in chordate species,while no research on QRFPR has been reported in non-chordate species.Here,the first non-chordates QRFP-like peptide receptor gene in the cephalopod Sepiella japonica(Sj_QRFPLR)was identified and characterized.Evidence from multiple alignments,phylogenetic analysis,and in vitro subcellular localization analysis indicated that Sj_QRFPLR is a class A GPCR and it belongs to the QRFPR family.Meanwhile,QRFPR is likely to be structurally conserved in cephalopod species.In situ hybridization and RT-PCR data revealed a widespread distribution pattern of Sj_QRFPLR in multiple function lobes of the female brain and numerous peripheral tissues in both male and female cuttlefish.Subsequently,a food deprivation and refeeding experiment showed that Sj_QRFPLR is likely to stimulate food intake in cuttlefish.Additionally,a possible link between Sj_QRFPLR and immune response was briefly detected in cuttlefish.The results will contribute to our understanding of QRFPR in the cephalopod as well as the peptidergic regulation of the QRFP/QRFPR system in non-chordates.
文摘As an endemic and critically-endangered wildlife species in China,the giant panda(Ailuropoda melanoleuca)has attracted widespread attention from all sectors of society regarding its survival status.In this study,the impact of earthquake-dameged areas on the distribution and activities of giant pandas in the Qionglai Mountains was analyzed by comparing data from two giant panda surveys conducted in the Qionglai Mountains of Sichuan Province and combining with remote sensing(RS)data from relevant regions.The results indicated that there was only a small area of overlap between the earthquake-damaged areas and giant panda activity trace points.The main earthquake-damaged areas were distributed at elevations(3,500-4,100 m)higher than the primary elevation range of giant panda distribution(1,700-3,100 m).In the Wolong Nature Reserve,no major earthquake damage was observed in the central section east of Provincial Highway 303 with relatively more giant panda activities.Within the Caopo Nature Reserve,the earthquake-damaged areas were mostly concentrated in the northeastern corner and along the border with the Wolong Nature Reserve.However,no large-scale giant panda activity traces were detected in these areas during either of the two surveys.Overall,the range of giant panda activities showed no signs of decline.Therefore,the impact of earthquakes on giant panda activities remains limited.
