Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adja...Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.展开更多
BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditi...BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditional culture methods are only able to detect a limited number of pathogens and are time-consuming;serologic detection has window periods,false-positive and false-negative problems;and nucleic acid molecular detection methods can detect several known pathogens only once.Three-generation nanopore sequencing technology provides new options for identifying pathogens.CASE SUMMARY Case 1:The patient was admitted to the hospital with abdominal pain for three days and cessation of defecation for five days,accompanied by cough and sputum.Nanopore sequencing of the drainage fluid revealed the presence of orallike bacteria,leading to a clinical diagnosis of bronchopleural fistula.Cefoperazone sodium sulbactam treatment was effective.Case 2:The patient was admitted to the hospital with fever and headache,and CT revealed lung inflammation.Antibiotic treatment for Streptococcus pneumoniae,identified through nanopore sequencing of cerebrospinal fluid,was effective.Case 3:The patient was admitted to our hospital with intermittent fever and an enlarged neck mass that had persisted for more than six months.Despite antibacterial treatment,her symptoms worsened.The nanopore sequencing results indicate that voriconazole treatment is effective for Aspergillus brookii.The patient was diagnosed with mixed cell type classical Hodgkin's lymphoma with infection.CONCLUSION Three-generation nanopore sequencing technology allows for rapid and accurate detection of pathogens in human infectious diseases.展开更多
Idiopathic pulmonary fibrosis(IPF),a chronic interstitial lung disease,is characterized by aberrant wound healing,excessive scarring and the formation of myofibroblastic foci.Although the role of alternative splicing(...Idiopathic pulmonary fibrosis(IPF),a chronic interstitial lung disease,is characterized by aberrant wound healing,excessive scarring and the formation of myofibroblastic foci.Although the role of alternative splicing(AS)in the pathogenesis of organ fibrosis has garnered increasing attention,its specific contribution to pulmonary fibrosis remains incompletely understood.In this study,we identified an up-regulation of serine/arginine-rich splicing factor 7(SRSF7)in lung fibroblasts derived from IPF patients and a bleomycin(BLM)-induced mouse model,and further characterized its functional role in both human fetal lung fibroblasts and mice.We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation.Mechanistically,we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase(PKM),leading to metabolic dysregulation and fibroblast activation.In vivo studies showed that fibroblastspecific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis.Importantly,through drug screening,we identified lomitapide as a novel modulator of SRSF7,which effectively mitigated experimental pulmonary fibrosis.Collectively,our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.展开更多
Alternative splicing(AS)serves as a fundamental regulatory mechanism in gene expression,contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinat...Alternative splicing(AS)serves as a fundamental regulatory mechanism in gene expression,contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinations.In light of the limited therapeutic options currently available,the exploration of AS as a target for drug development is of paramount importance.This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants,RNA-binding proteins,and cis-elements,highlighting their significance as clinical biomarkers.We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases,including but not limited to lung cancer,cystic fibrosis,silicosis,acute respiratory distress syndrome,pneumonia,asthma,chronic obstructive pulmonary diseases,pulmonary arterial hypertension,and idiopathic pulmonary fibrosis.The review delves into the role of AS events in the diagnosis and treatment of lung diseases,focusing on the regulatory influence of splicing factors and RNA-binding proteins,while also enumerating the mutated components implicated in AS misregulation.Consequently,a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.展开更多
Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and b...Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+osteoblasts(OB).Under the regulation of E2F family members,GTSE1+OB cells harbored enhanced proliferation activity and high differentiation potential.Augmentation of GTSE1 enhanced the abilities of cell migration and invasion,while silencing of GTSE1 impaired the abilities in human OB cell lines.Furthermore,cellular communication analysis showed the cross-talk between GTSE1+OB cells and CD8+T cells in metastasis was achieved through the MIF-(CD74-CXCR4)pair.Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma.Correlation analysis unveiled that GTSE1+OB cells and monocytes were the negatively correlated populations at the single-cell level,a finding validated in 4 independent osteosarcoma datasets comprising 226 samples.Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+OB cells.展开更多
Despite the spread of effective vaccination strategies,cervical cancer remains the second leading cause of cancer death among women aged 20 to 39.1 clinical diagnosis of cervical lesions relies on the P16INK4a(P16)mar...Despite the spread of effective vaccination strategies,cervical cancer remains the second leading cause of cancer death among women aged 20 to 39.1 clinical diagnosis of cervical lesions relies on the P16INK4a(P16)marker,but its sensitivity to low-grade cervical intraepithelial neoplasia(CIN)is limited.Exploring more sensitive and specific molecular markers is still a challenge in cervical lesion screening.In this study,we found that HMGB3 could effectively label pathological cells in different cervical lesions,especially for early CIN.Therefore,HMGB3 has the potential to be used as a novel marker for the early screening of cervical lesions.展开更多
基金supported by National Natural Science Foundation of China(52222215, 52272420, 52072051)。
文摘Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.
基金Supported by Research and Development Funding for Medical and Health Institutions,No.2021YL007.
文摘BACKGROUND Infectious diseases are still one of the greatest threats to human health,and the etiology of 20%of cases of clinical fever is unknown;therefore,rapid identification of pathogens is highly important.Traditional culture methods are only able to detect a limited number of pathogens and are time-consuming;serologic detection has window periods,false-positive and false-negative problems;and nucleic acid molecular detection methods can detect several known pathogens only once.Three-generation nanopore sequencing technology provides new options for identifying pathogens.CASE SUMMARY Case 1:The patient was admitted to the hospital with abdominal pain for three days and cessation of defecation for five days,accompanied by cough and sputum.Nanopore sequencing of the drainage fluid revealed the presence of orallike bacteria,leading to a clinical diagnosis of bronchopleural fistula.Cefoperazone sodium sulbactam treatment was effective.Case 2:The patient was admitted to the hospital with fever and headache,and CT revealed lung inflammation.Antibiotic treatment for Streptococcus pneumoniae,identified through nanopore sequencing of cerebrospinal fluid,was effective.Case 3:The patient was admitted to our hospital with intermittent fever and an enlarged neck mass that had persisted for more than six months.Despite antibacterial treatment,her symptoms worsened.The nanopore sequencing results indicate that voriconazole treatment is effective for Aspergillus brookii.The patient was diagnosed with mixed cell type classical Hodgkin's lymphoma with infection.CONCLUSION Three-generation nanopore sequencing technology allows for rapid and accurate detection of pathogens in human infectious diseases.
基金supported by the National Natural Science Foundation of China(U24A20645,32171127,82200070)the Scientific Fund Project of Heilongjiang Province(JQ2022H001,China)+1 种基金the Science and technology project of Xiamen Medical College(K2023-08,China)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-078,China).
文摘Idiopathic pulmonary fibrosis(IPF),a chronic interstitial lung disease,is characterized by aberrant wound healing,excessive scarring and the formation of myofibroblastic foci.Although the role of alternative splicing(AS)in the pathogenesis of organ fibrosis has garnered increasing attention,its specific contribution to pulmonary fibrosis remains incompletely understood.In this study,we identified an up-regulation of serine/arginine-rich splicing factor 7(SRSF7)in lung fibroblasts derived from IPF patients and a bleomycin(BLM)-induced mouse model,and further characterized its functional role in both human fetal lung fibroblasts and mice.We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation.Mechanistically,we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase(PKM),leading to metabolic dysregulation and fibroblast activation.In vivo studies showed that fibroblastspecific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis.Importantly,through drug screening,we identified lomitapide as a novel modulator of SRSF7,which effectively mitigated experimental pulmonary fibrosis.Collectively,our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.
基金supported by the National Natural Science Foundation of China(Grant Nos.82200070,32171127,and U24A20645)the Scientific Fund Project of Heilongjiang Province(JQ2022H001,China)+2 种基金the Harbin Medical University Graduate Research and Practice Innovation Project(Grant No.YJSCX2023-37HYD,China)the Innovation and Development Joint Fund of the Natural Science Foundation of Chongqing(Grant No.CSTB2023NSCQ-LMX0037,China)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-078,China).
文摘Alternative splicing(AS)serves as a fundamental regulatory mechanism in gene expression,contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinations.In light of the limited therapeutic options currently available,the exploration of AS as a target for drug development is of paramount importance.This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants,RNA-binding proteins,and cis-elements,highlighting their significance as clinical biomarkers.We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases,including but not limited to lung cancer,cystic fibrosis,silicosis,acute respiratory distress syndrome,pneumonia,asthma,chronic obstructive pulmonary diseases,pulmonary arterial hypertension,and idiopathic pulmonary fibrosis.The review delves into the role of AS events in the diagnosis and treatment of lung diseases,focusing on the regulatory influence of splicing factors and RNA-binding proteins,while also enumerating the mutated components implicated in AS misregulation.Consequently,a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.
基金supported by the National Key Research and Development Program of China(No.2023YFF1204600 to Lei Yang)the National Natural Science Foundation of China(No.81972117 to Lei Yang,32270710 to Yunyan Gu)+2 种基金the Natural Science Foundation of Heilongjiang Province,China(No.JQ2020H001 to Lei Yang)the Key R&D Program of Heilongjiang Province,China(No.GA23C002 to Lei Yang)the First Affiliated Hospital of Harbin Medical University Excellent Young Talents Funding,China(No.HYD2020JQ0013 to Lei Yang).
文摘Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+osteoblasts(OB).Under the regulation of E2F family members,GTSE1+OB cells harbored enhanced proliferation activity and high differentiation potential.Augmentation of GTSE1 enhanced the abilities of cell migration and invasion,while silencing of GTSE1 impaired the abilities in human OB cell lines.Furthermore,cellular communication analysis showed the cross-talk between GTSE1+OB cells and CD8+T cells in metastasis was achieved through the MIF-(CD74-CXCR4)pair.Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma.Correlation analysis unveiled that GTSE1+OB cells and monocytes were the negatively correlated populations at the single-cell level,a finding validated in 4 independent osteosarcoma datasets comprising 226 samples.Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+OB cells.
基金supported by the National Natural Science Foundation of China(No.81872276)the Hefei City Natural Science Foundation(Anhui,China)(No.2022050)the Foundation of Anhui Province Key Laboratory of Medical Physics and Technology(China)(No.LMPT201908).
文摘Despite the spread of effective vaccination strategies,cervical cancer remains the second leading cause of cancer death among women aged 20 to 39.1 clinical diagnosis of cervical lesions relies on the P16INK4a(P16)marker,but its sensitivity to low-grade cervical intraepithelial neoplasia(CIN)is limited.Exploring more sensitive and specific molecular markers is still a challenge in cervical lesion screening.In this study,we found that HMGB3 could effectively label pathological cells in different cervical lesions,especially for early CIN.Therefore,HMGB3 has the potential to be used as a novel marker for the early screening of cervical lesions.
