Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations i...Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.展开更多
Due to the limited transmission resources for data relay in the tracking and data relay satellite system （TDRSS）, there are many job requirements in busy days which will be discarded in the conventional job scheduli...Due to the limited transmission resources for data relay in the tracking and data relay satellite system （TDRSS）, there are many job requirements in busy days which will be discarded in the conventional job scheduling model. Therefore, the improvement of scheduling efficiency in the TDRSS can not only help to increase the resource utilities, but also to reduce the scheduling failure ratio. A model of nonhomogeneous parallel machines scheduling problems with time window （NPM-TW） is firstly built up for the TDRSS, considering the distinct features of the variable preparation time and the nonhomogeneous transmission rates for different types of antennas on each tracking and data relay satellite （TDRS）. Then, an adaptive subsequence adjustment （ASA） framework with evolutionary asymmetric path-relinking （EvAPR） is proposed to solve this problem, in which an asymmetric progressive crossover operation is involved to overcome the local optima by the conventional job inserting methods. The numerical results show that, compared with the classical greedy randomized adaptive search procedure （GRASP） algorithm, the scheduling failure ratio of jobs can be reduced over 11% on average by the proposed ASA with EvAPR.展开更多
Unmanned autonomous Air-to-Air Refueling(AAR)capability is the key guarantee to support the distant-field,high-intensity and durable operations of the penetration counterair combat system.In the future,the long-range ...Unmanned autonomous Air-to-Air Refueling(AAR)capability is the key guarantee to support the distant-field,high-intensity and durable operations of the penetration counterair combat system.In the future,the long-range unmanned reconnaissance and attack platform can reach the maximum flight range requirement through AAR.At present,large transport aircraft platforms in China are still equipped with probe-and-drogue systems,and the refueling mode is gradually changing from manned to unmanned autonomous operation.The docking process is the riskiest and most important part,and there are strict safety,precision,and efficiency requirements for refueling operation,especially during close-distance docking and formation maintenance phases.In this paper,five issues that need to be solved to achieve autonomous AAR docking are summarized.On this basis,five key technology development needs are proposed to solve these engineering issues.Finally,some prospects are given.展开更多
Accurate and effective identification of adverse geology is crucial for safe and efficient tunnel construction.Current methods of identifying adverse geology depend on the experience of geologists and are prone to mis...Accurate and effective identification of adverse geology is crucial for safe and efficient tunnel construction.Current methods of identifying adverse geology depend on the experience of geologists and are prone to misjudgment and omissions.Here,we propose a method for adverse geology identification in tunnels based on mineral anomaly analysis.The method is based on the theory of geoanomaly,and the mineral anomalies are geological markers of the presence of adverse geology.The method uses exploration data analysis(EDA)to calculate mineral anomaly thresholds,then evaluates the mineral anomalies based on the thresholds and identifies adverse geology based on the characteristics of the mineral anomalies.We have established a dynamic expansion process for background samples to achieve the dynamic evaluation of mineral anomalies by adjusting anomaly thresholds.This method has been validated and applied in a tunnel excavated in granite.As shown herein,in the tunnel range of 142+800–142+860,the fault F37 was successfully identified based on an anomalous decrease in the diagenetic minerals plagioclase and hornblende,as well as an anomalous increase in the content of the alteration minerals chlorite,laumonite,and epidote.The proposed method provides a timely warning when a tunnel enters areas affected by adverse geology and identifies whether the tunnel is gradually approaching or moving away from the fault.In addition,the applicability,accuracy,and further improvement of the method are discussed.This method improves our ability to identify adverse geology,from qualitative to quantitative,and can provide reference and guidance for the identification of adverse geology in mining and underground engineering.展开更多
With the development of wireless communication,the 6G mobile communication technology has received wide attention.As one of the key technologies of 6G,terahertz(THz)communication technology has the characteristics of ...With the development of wireless communication,the 6G mobile communication technology has received wide attention.As one of the key technologies of 6G,terahertz(THz)communication technology has the characteristics of ultra-high bandwidth,high security and low environmental noise.In this paper,a THz duplexer with a half-wavelength coupling structure and a sub-harmonic mixer operating at 216 GHz and 204 GHz are designed and measured.Based on these key devices,a 220 GHz frequency-division multiplexing communication system is proposed,with a real-time data rate of 10.4 Gbit/s for one channel and a transmission distance of 15 m.The measured constellation diagram of two receivers is clearly visible,the signal-to-noise ratio(SNR)is higher than 22 dB,and the bit error ratio(BER)is less than 10^(−8).Furthermore,the high definition(HD)4K video can also be transmitted in real time without stutter.展开更多
Chemokine receptors CXCR4 and CCR5 are indispensable co-receptors for HIV-1 entry into host cells. In our previous study, we identified that dopamine receptor-interacting protein 78（DRi P78） and Na＋-H＋ exchanger r...Chemokine receptors CXCR4 and CCR5 are indispensable co-receptors for HIV-1 entry into host cells. In our previous study, we identified that dopamine receptor-interacting protein 78（DRi P78） and Na＋-H＋ exchanger regulatory factor 1（NHERF1） are the CXCR4 and CCR5 homo- or hetero-dimerinteracting proteins. DRi P78 and NHERF1 are able to influence the co-receptor internalization and intracellular trafficking. Over-expression of NHERF1 affects the ligands or HIV-1 gp120-induced CCR5 internalization and HIV-1 production. It is reasonable to speculate that DRi P78 and NHERF1, as well as the signaling pathways involved in viral replication, would probably affect HIV-1 replication through regulating the co-receptors. In this present study, we designed two short hairpin RNAs（sh RNAs） targeting the DRi P78 and NHERF1, respectively, and constructed the p Lenti6/BLOCK-i T-DEST lentiviral plasmids expressing DRi P78 or NHERF1 sh RNA. The packaged lentiviruses were used to transduce the widely-applied HIV-1 model cell line GHOST（3）. Then, cells with stable knockdown were established through selecting transduced cells with Blasticidin. This study, for the first time, reported the establishment of the GHOST（3） with DRi P78 and NHERF1 knockdown, which is the first stable cell line with HIV-1 co-receptor-interacting molecular defects.展开更多
基金supported by the National Natural Science Foundation of China(32270887,82272507,32200654,82430079,and 82472519)the National Key Research and Development Program of China(2022YFA1103202)+7 种基金the Chongqing High-End Medical Talents for Middle-aged and Young(YXGD202408)the Army Scientific and Technological Innovation Talents Prioritized Suppor t Program(2023-124)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)the Postdoctoral Innovative Talent Support Program(BX20220397)the Open Project of State Key Laboratory of TraumaBurns and Combined Injury(SFLKF202201)the Project for Enhancing Innovation of Army Medical University(2023XJS39)the Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)。
文摘Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.
基金supported by the National Natural Science Foundation of China(6113200291338101+3 种基金91338108)the National S&T Major Project(2011ZX03004-001-01)the Research Fund of Tsinghua University(2011Z05117)the Co-innovation Laboratory of Aerospace Broadband Network Technology
文摘Due to the limited transmission resources for data relay in the tracking and data relay satellite system （TDRSS）, there are many job requirements in busy days which will be discarded in the conventional job scheduling model. Therefore, the improvement of scheduling efficiency in the TDRSS can not only help to increase the resource utilities, but also to reduce the scheduling failure ratio. A model of nonhomogeneous parallel machines scheduling problems with time window （NPM-TW） is firstly built up for the TDRSS, considering the distinct features of the variable preparation time and the nonhomogeneous transmission rates for different types of antennas on each tracking and data relay satellite （TDRS）. Then, an adaptive subsequence adjustment （ASA） framework with evolutionary asymmetric path-relinking （EvAPR） is proposed to solve this problem, in which an asymmetric progressive crossover operation is involved to overcome the local optima by the conventional job inserting methods. The numerical results show that, compared with the classical greedy randomized adaptive search procedure （GRASP） algorithm, the scheduling failure ratio of jobs can be reduced over 11% on average by the proposed ASA with EvAPR.
文摘Unmanned autonomous Air-to-Air Refueling(AAR)capability is the key guarantee to support the distant-field,high-intensity and durable operations of the penetration counterair combat system.In the future,the long-range unmanned reconnaissance and attack platform can reach the maximum flight range requirement through AAR.At present,large transport aircraft platforms in China are still equipped with probe-and-drogue systems,and the refueling mode is gradually changing from manned to unmanned autonomous operation.The docking process is the riskiest and most important part,and there are strict safety,precision,and efficiency requirements for refueling operation,especially during close-distance docking and formation maintenance phases.In this paper,five issues that need to be solved to achieve autonomous AAR docking are summarized.On this basis,five key technology development needs are proposed to solve these engineering issues.Finally,some prospects are given.
基金financial support from the National Natural Science Foundation of China(52022053 and 52009073)the Natural Science Foundation of Shandong Province(ZR201910270116)。
文摘Accurate and effective identification of adverse geology is crucial for safe and efficient tunnel construction.Current methods of identifying adverse geology depend on the experience of geologists and are prone to misjudgment and omissions.Here,we propose a method for adverse geology identification in tunnels based on mineral anomaly analysis.The method is based on the theory of geoanomaly,and the mineral anomalies are geological markers of the presence of adverse geology.The method uses exploration data analysis(EDA)to calculate mineral anomaly thresholds,then evaluates the mineral anomalies based on the thresholds and identifies adverse geology based on the characteristics of the mineral anomalies.We have established a dynamic expansion process for background samples to achieve the dynamic evaluation of mineral anomalies by adjusting anomaly thresholds.This method has been validated and applied in a tunnel excavated in granite.As shown herein,in the tunnel range of 142+800–142+860,the fault F37 was successfully identified based on an anomalous decrease in the diagenetic minerals plagioclase and hornblende,as well as an anomalous increase in the content of the alteration minerals chlorite,laumonite,and epidote.The proposed method provides a timely warning when a tunnel enters areas affected by adverse geology and identifies whether the tunnel is gradually approaching or moving away from the fault.In addition,the applicability,accuracy,and further improvement of the method are discussed.This method improves our ability to identify adverse geology,from qualitative to quantitative,and can provide reference and guidance for the identification of adverse geology in mining and underground engineering.
基金supported by the National Natural Science Foundation of China under Grant Nos.62022022 and 62101107the National Key R&D Program of China under Grant No.2018YFB1801502+1 种基金China Postdoctoral Science Foundation under Grant No.2021TQ0057ZTE Industry-Uni⁃versity-Institute Cooperation Funds.
文摘With the development of wireless communication,the 6G mobile communication technology has received wide attention.As one of the key technologies of 6G,terahertz(THz)communication technology has the characteristics of ultra-high bandwidth,high security and low environmental noise.In this paper,a THz duplexer with a half-wavelength coupling structure and a sub-harmonic mixer operating at 216 GHz and 204 GHz are designed and measured.Based on these key devices,a 220 GHz frequency-division multiplexing communication system is proposed,with a real-time data rate of 10.4 Gbit/s for one channel and a transmission distance of 15 m.The measured constellation diagram of two receivers is clearly visible,the signal-to-noise ratio(SNR)is higher than 22 dB,and the bit error ratio(BER)is less than 10^(−8).Furthermore,the high definition(HD)4K video can also be transmitted in real time without stutter.
基金supported by the Science and Technology Planning Project of Guangdong Province of China（2012B031800267）the Natural Science Foundation of Guangdong Province of China（S2013010011860）the National Natural Science Foundation of China（31200130 and 81371812）
文摘Chemokine receptors CXCR4 and CCR5 are indispensable co-receptors for HIV-1 entry into host cells. In our previous study, we identified that dopamine receptor-interacting protein 78（DRi P78） and Na＋-H＋ exchanger regulatory factor 1（NHERF1） are the CXCR4 and CCR5 homo- or hetero-dimerinteracting proteins. DRi P78 and NHERF1 are able to influence the co-receptor internalization and intracellular trafficking. Over-expression of NHERF1 affects the ligands or HIV-1 gp120-induced CCR5 internalization and HIV-1 production. It is reasonable to speculate that DRi P78 and NHERF1, as well as the signaling pathways involved in viral replication, would probably affect HIV-1 replication through regulating the co-receptors. In this present study, we designed two short hairpin RNAs（sh RNAs） targeting the DRi P78 and NHERF1, respectively, and constructed the p Lenti6/BLOCK-i T-DEST lentiviral plasmids expressing DRi P78 or NHERF1 sh RNA. The packaged lentiviruses were used to transduce the widely-applied HIV-1 model cell line GHOST（3）. Then, cells with stable knockdown were established through selecting transduced cells with Blasticidin. This study, for the first time, reported the establishment of the GHOST（3） with DRi P78 and NHERF1 knockdown, which is the first stable cell line with HIV-1 co-receptor-interacting molecular defects.
