In this paper, we describe an improved adaptive partial response maximum likelihood （PRML） method combining modulation code tbr signal waveform modulation multi-level disc. This improved adaptive PRML method employs...In this paper, we describe an improved adaptive partial response maximum likelihood （PRML） method combining modulation code tbr signal waveform modulation multi-level disc. This improved adaptive PRML method employs partial response equalizer and adaptive viterbi detector combining modulation code. Compared with the traditional adaptive PRML detector, the improved PRML detector additionally employs illogical sequence detector and corrector. Illogical sequence detector and corrector can aw）id the appearance of illogical sequences effectively, which do not follow the law of modulation code for signal waveform modulation multi-level disc, and obtain the correct sequences. We implement the improved PRML detector using a DSP and an FPGA chip. The experimental results show good performance. The higher efficient and lower complexity can be obtained by using the improved PRML method than by using the previous PRML method. Meanwhile, resource utilization of the improved PRML detector is not changed, but the bit error rate （BER） is reduced by more than 20%.展开更多
A novel read channel for signal waveform modulation multi-level disc is presented in this paper. This read channel employs timing recovery system and partial response maximum likelihood detector. Compared to the previ...A novel read channel for signal waveform modulation multi-level disc is presented in this paper. This read channel employs timing recovery system and partial response maximum likelihood detector. Compared to the previous read channel composed of level detection and run-length detection, the present read channel shows superiority in capacity increase and robust performance. Especially, relying on the partial response maximum likelihood detection, lower bit error rate can be obtained.展开更多
The sub-land/sub-pit affects the characteristic of the tracking error signal which is generated by the conventional differential phase detection （DPD） method in the signal waveform modulation multi-level （SWML） re...The sub-land/sub-pit affects the characteristic of the tracking error signal which is generated by the conventional differential phase detection （DPD） method in the signal waveform modulation multi-level （SWML） read-only disc. To solve this problem, this paper proposes a new tracking error detection method using amplitude difference. Based on the diffraction theory, the amplitude difference is proportional to the tracking error and is feasible to be used for obtaining the off-track information. The experimental system of the amplitude difference detection method is developed. The experimental results show that the tracking error signal derived from the new method has better performance in uniformity and signal-to-noise ratio than that derived from the conventional DPD method in the SWML read-only disc.展开更多
The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated....The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated.By adjusting the furnace cooling time after solution treatment and the aging temperature,Ti6422 alloy samples were developed with a multi-level lamellar microstructure,in-cluding microscaleαcolonies and α_(p) lamellae,as well as nanoscale α_(s) phases.Extending the furnace cooling time after solution treatment at 920℃ for 1 h from 240 to 540 min,followed by aging at 600℃ for 6 h,increased the α_(p) lamella content,reduced the α_(s) phase content,expanded theαcolonies and α_(p) lamellae size,and improved the impact toughness from 22.7 to 53.8 J/cm^(2).Additionally,under the same solution treatment,raising the aging temperature from 500 to 700℃ resulted in a decrease in the α_(s) phase content and a growth in the thickness of the α_(p) lamella and α_(s) phase.The impact toughness increased significantly with these changes.Samples with high α_(p) lamellae content or large α_(s) phase size exhibited high crack initiation and propagation energies.Impact deformation caused severe kinking of the α_(p) lamellae in crack initiation and propagation areas,leading to a uniform and high-density kernel average misorientation(KAM)distribu-tion,enhancing plastic deformation coordination and uniformity.Moreover,the multidirectional arrangement of coarserαcolonies and α_(p) lamellae continuously deflect the crack propagation direction,inhibiting crack propagation.展开更多
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
AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCT...AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.展开更多
Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly di...Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly divided into two groups.The combined group received auricular acupuncture with seed application combined with Chinese herbal poultice therapy,while the reference group received auricular acupuncture with seed application alone.The therapeutic outcomes of both groups were compared.Results:The combined intervention group demonstrated decreased sleep quality scores,reduced pain neurotransmitter levels,and improved lumbar spine function scores post-intervention,with significant intergroup differences(p<0.05).Conclusion:Auricular seed therapy combined with Chinese herbal poultice care effectively improves sleep quality and lumbar spine function while alleviating pain perception in patients with lumbar disc herniation,indicating superior therapeutic efficacy.展开更多
As a key node of modern transportation network,the informationization management of road tunnels is crucial to ensure the operation safety and traffic efficiency.However,the existing tunnel vehicle modeling methods ge...As a key node of modern transportation network,the informationization management of road tunnels is crucial to ensure the operation safety and traffic efficiency.However,the existing tunnel vehicle modeling methods generally have problems such as insufficient 3D scene description capability and low dynamic update efficiency,which are difficult to meet the demand of real-time accurate management.For this reason,this paper proposes a vehicle twin modeling method for road tunnels.This approach starts from the actual management needs,and supports multi-level dynamic modeling from vehicle type,size to color by constructing a vehicle model library that can be flexibly invoked;at the same time,semantic constraint rules with geometric layout,behavioral attributes,and spatial relationships are designed to ensure that the virtual model matches with the real model with a high degree of similarity;ultimately,the prototype system is constructed and the case region is selected for the case study,and the dynamic vehicle status in the tunnel is realized by integrating real-time monitoring data with semantic constraints for precise virtual-real mapping.Finally,the prototype system is constructed and case experiments are conducted in selected case areas,which are combined with real-time monitoring data to realize dynamic updating and three-dimensional visualization of vehicle states in tunnels.The experiments show that the proposed method can run smoothly with an average rendering efficiency of 17.70 ms while guaranteeing the modeling accuracy(composite similarity of 0.867),which significantly improves the real-time and intuitive tunnel management.The research results provide reliable technical support for intelligent operation and emergency response of road tunnels,and offer new ideas for digital twin modeling of complex scenes.展开更多
The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly comple...The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly complex layout combinations.Furthermore,due to constraints in component quantity and geometry within the cross-sectional layout,filler bodies must be incorporated to maintain cross-section performance.Conventional design approaches based on manual experience suffer from inefficiency,high variability,and difficulties in quantification.This paper presents a multi-level automatic filling optimization design method for umbilical cross-sectional layouts to address these limitations.Initially,the research establishes a multi-objective optimization model that considers compactness,balance,and wear resistance of the cross-section,employing an enhanced genetic algorithm to achieve a near-optimal layout.Subsequently,the study implements an image processing-based vacancy detection technique to accurately identify cross-sectional gaps.To manage the variability and diversity of these vacant regions,the research introduces a multi-level filling method that strategically selects and places filler bodies of varying dimensions,overcoming the constraints of uniform-size fillers.Additionally,the method incorporates a hierarchical strategy that subdivides the complex cross-section into multiple layers,enabling layer-by-layer optimization and filling.This approach reduces manufac-turing equipment requirements while ensuring practical production process feasibility.The methodology is validated through a specific umbilical case study.The results demonstrate improvements in compactness,balance,and wear resistance compared with the initial cross-section,offering novel insights and valuable references for filler design in umbilical cross-sections.展开更多
Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanism...Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter...Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter.Therefore,the need to monitor disc cutter wear in real-time has emerged as a technical challenge for TBMs.In this study,real-time disc cutter wear monitoring is developed based on sound and vibration sensors.For this purpose,the microphone and accelerometer were used to record the sound and vibration signals of cutting three different types of rocks with varying abrasions on a laboratory scale.The relationship between disc cutter wear and the sound and vibration signal was determined by comparing the measurements of disc cutter wear with the signal plots for each sample.The features extracted from the signals showed that the sound and vibration signals are impacted by the progression of disc wear during the rock-cutting process.The signal features obtained from the rock-cutting operation were utilized to verify the machine learning techniques.The results showed that the multilayer perceptron(MLP),random subspace-based decision tree(RS-DT),DT,and random forest(RF)methods could predict the wear level of the disc cutter with an accuracy of 0.89,0.951,0.951,and 0.927,respectively.Based on the accuracy of the models and the confusion matrix,it was found that the RS-DT model has the best estimate for predicting the level of disc wear.This research has developed a method that can potentially determine when to replace a tool and assess disc wear in real-time.展开更多
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen...Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.展开更多
Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnas...Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnastics, hockey and American football. In refractory cases to conservative treatment, microscopic discectomy or full endoscopic discectomy are used as surgical options to relieve pain and restore patient functionality. However, the ideal time for a return to sports activities remains a matter of debate due to variations in recovery times and risks of complications associated with each technique. Methods: A review was conducted, including articles published in the last 33 years (1991-2024), as it was the earliest date matching our search criteria. Clinical studies, systematic reviews, meta-analyses, and clinical guidelines were included. Results: The most common complications when returning to sport prematurely include recurrence of the hernia, persistent pain (VAS leg 7 or higher after surgery) and reduced physical performance. The return to full activity rate of patients who underwent microdiscectomy reaches up to 90%, while the endoscopic technique shows a success rate that reaches 99%. Return to play meantime was 5.19 months (range 1.00 - 8.7 months) and mean time of 4.6 months (range 2 - 8 months) with Microdiscectomy and full endoscopic discectomy respectively. Conclusions: There is no unanimous consensus on the exact timing of return to sport due to variability in recovery times and clinical outcomes. In both techniques, evidence highlights the need for a multidisciplinary approach that integrates surgeons, physical therapists and trainers to optimize recovery and ensure a safe return.展开更多
Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulp...Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.展开更多
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med...Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.61127010)
文摘In this paper, we describe an improved adaptive partial response maximum likelihood （PRML） method combining modulation code tbr signal waveform modulation multi-level disc. This improved adaptive PRML method employs partial response equalizer and adaptive viterbi detector combining modulation code. Compared with the traditional adaptive PRML detector, the improved PRML detector additionally employs illogical sequence detector and corrector. Illogical sequence detector and corrector can aw）id the appearance of illogical sequences effectively, which do not follow the law of modulation code for signal waveform modulation multi-level disc, and obtain the correct sequences. We implement the improved PRML detector using a DSP and an FPGA chip. The experimental results show good performance. The higher efficient and lower complexity can be obtained by using the improved PRML method than by using the previous PRML method. Meanwhile, resource utilization of the improved PRML detector is not changed, but the bit error rate （BER） is reduced by more than 20%.
文摘A novel read channel for signal waveform modulation multi-level disc is presented in this paper. This read channel employs timing recovery system and partial response maximum likelihood detector. Compared to the previous read channel composed of level detection and run-length detection, the present read channel shows superiority in capacity increase and robust performance. Especially, relying on the partial response maximum likelihood detection, lower bit error rate can be obtained.
基金Project supported by the National Natural Science Foundation of China (Grant No. 60977005)
文摘The sub-land/sub-pit affects the characteristic of the tracking error signal which is generated by the conventional differential phase detection （DPD） method in the signal waveform modulation multi-level （SWML） read-only disc. To solve this problem, this paper proposes a new tracking error detection method using amplitude difference. Based on the diffraction theory, the amplitude difference is proportional to the tracking error and is feasible to be used for obtaining the off-track information. The experimental system of the amplitude difference detection method is developed. The experimental results show that the tracking error signal derived from the new method has better performance in uniformity and signal-to-noise ratio than that derived from the conventional DPD method in the SWML read-only disc.
基金supported by the National Natural Science Foundation of China(No.52090041).
文摘The influence of different solution and aging conditions on the microstructure,impact toughness,and crack initiation and propagation mechanisms of the novel α+β titanium alloy Ti6422 was systematically investigated.By adjusting the furnace cooling time after solution treatment and the aging temperature,Ti6422 alloy samples were developed with a multi-level lamellar microstructure,in-cluding microscaleαcolonies and α_(p) lamellae,as well as nanoscale α_(s) phases.Extending the furnace cooling time after solution treatment at 920℃ for 1 h from 240 to 540 min,followed by aging at 600℃ for 6 h,increased the α_(p) lamella content,reduced the α_(s) phase content,expanded theαcolonies and α_(p) lamellae size,and improved the impact toughness from 22.7 to 53.8 J/cm^(2).Additionally,under the same solution treatment,raising the aging temperature from 500 to 700℃ resulted in a decrease in the α_(s) phase content and a growth in the thickness of the α_(p) lamella and α_(s) phase.The impact toughness increased significantly with these changes.Samples with high α_(p) lamellae content or large α_(s) phase size exhibited high crack initiation and propagation energies.Impact deformation caused severe kinking of the α_(p) lamellae in crack initiation and propagation areas,leading to a uniform and high-density kernel average misorientation(KAM)distribu-tion,enhancing plastic deformation coordination and uniformity.Moreover,the multidirectional arrangement of coarserαcolonies and α_(p) lamellae continuously deflect the crack propagation direction,inhibiting crack propagation.
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Central High-Level Traditional Chinese Medicine Hospital Project of Eye Hospital China Academy of Chinese Medical Science(No.GSP5-83,No.GSP4-02No.GSP5-06)+1 种基金Supported by National Natural Science Foundation of China(General ProgramNo.82474582).
文摘AIM:To evaluate the therapeutic effects of ranibizumab on optic disc and macular microvascular perfusion in central retinal vein occlusion(CRVO)with macular edema(ME).METHODS:Optical coherence tomography angiology(OCTA)parameters,including optic disc vessel density(VD;including whole-disc VD,intra-disc VD,and peripapillary VD),superficial/deep capillary plexus(SCP/DCP)VD,and central macular thickness(CMT)were analyzed.Additional assessments included best-corrected visual acuity(BCVA)via Early Treatment Diabetic Retinopathy Study(ETDRS)chart and hemorheological profiling.CRVO patients received monthly intravitreal ranibizumab injections for three consecutive months.Pre-and post-treatment parameters were statistically compared.RESULTS:The study comprised 60 CRVO-ME patients(28 males;32 females),aged 50-78y(mean 63.3±7.6y)and 60 age-/sex-matched healthy controls.As compared with participants exhibiting normal funduscopic findings,CRVO patients demonstrated significantly elevated levels of low-shear-rate whole blood viscosity(LSR-WBV),high-shearrate whole blood viscosity(HSR-WBV),and aggregation index(AI,all P<0.05).In CRVO-affected eyes,vertical cupto-disc(C/D)ratio and optic cup volume were significantly smaller,whereas retinal nerve fiber layer(RNFL)thickness was significantly greater,compared to both unaffected contralateral eyes and normal control eyes(all P<0.05).Following treatment,VD of the entire optic disc(P<0.05),intra-disc VD(P<0.05),and peripapillary VD(P<0.05)all increased significantly relative to baseline.CMT decreased significantly(P<0.05),whereas macular SCP-VD and macular DCP-VD showed non-significant slight reductions(P>0.05).At baseline,BCVA of CRVO eyes correlated with whole-disc VD(r=-0.276,P=0.033),intra-disc VD(r=-0.342,P=0.009),and peripapillary VD(r=-0.335,P=0.007),with intra-disc VD demonstrating the strongest association.Besides,BCVA improvement,after the treatment,correlated positively with whole-disc VD(r=0.342,P=0.008)and intradisc VD(r=0.396,P=0.002).CONCLUSION:Optic disc blood perfusion is more closely associated with visual acuity than macular perfusion,suggesting intra-disc VD may serve as a potential biomarker for monitoring visual acuity changes in CRVO.Multiple ranibizumab injections significantly improve optic disc perfusion but may have exerted detrimental effects on the macula.CRVO patients shows higher hemorheological parameters than those with normal fundi.Reduced vertical C/D ratio and optic cup volume may be linked to CRVO incidence,potentially acting as susceptibility factors.
文摘Objective:To evaluate the nursing effects of auricular seed therapy combined with Chinese herbal poultice treatment for patients with lumbar disc herniation(LDH).Method:A total of 80 patients with LDH were randomly divided into two groups.The combined group received auricular acupuncture with seed application combined with Chinese herbal poultice therapy,while the reference group received auricular acupuncture with seed application alone.The therapeutic outcomes of both groups were compared.Results:The combined intervention group demonstrated decreased sleep quality scores,reduced pain neurotransmitter levels,and improved lumbar spine function scores post-intervention,with significant intergroup differences(p<0.05).Conclusion:Auricular seed therapy combined with Chinese herbal poultice care effectively improves sleep quality and lumbar spine function while alleviating pain perception in patients with lumbar disc herniation,indicating superior therapeutic efficacy.
基金National Natural Science Foundation of China(Nos.42301473,42271424,42171397)Chinese Postdoctoral Innovation Talents Support Program(No.BX20230299)+2 种基金China Postdoctoral Science Foundation(No.2023M742884)Natural Science Foundation of Sichuan Province(Nos.24NSFSC2264,2025ZNSFSC0322)Key Research and Development Project of Sichuan Province(No.24ZDYF0633).
文摘As a key node of modern transportation network,the informationization management of road tunnels is crucial to ensure the operation safety and traffic efficiency.However,the existing tunnel vehicle modeling methods generally have problems such as insufficient 3D scene description capability and low dynamic update efficiency,which are difficult to meet the demand of real-time accurate management.For this reason,this paper proposes a vehicle twin modeling method for road tunnels.This approach starts from the actual management needs,and supports multi-level dynamic modeling from vehicle type,size to color by constructing a vehicle model library that can be flexibly invoked;at the same time,semantic constraint rules with geometric layout,behavioral attributes,and spatial relationships are designed to ensure that the virtual model matches with the real model with a high degree of similarity;ultimately,the prototype system is constructed and the case region is selected for the case study,and the dynamic vehicle status in the tunnel is realized by integrating real-time monitoring data with semantic constraints for precise virtual-real mapping.Finally,the prototype system is constructed and case experiments are conducted in selected case areas,which are combined with real-time monitoring data to realize dynamic updating and three-dimensional visualization of vehicle states in tunnels.The experiments show that the proposed method can run smoothly with an average rendering efficiency of 17.70 ms while guaranteeing the modeling accuracy(composite similarity of 0.867),which significantly improves the real-time and intuitive tunnel management.The research results provide reliable technical support for intelligent operation and emergency response of road tunnels,and offer new ideas for digital twin modeling of complex scenes.
基金financially supported by Guangdong Province Basic and Applied Basic Research Fund Project(Grant No.2022B1515250009)Liaoning Provincial Natural Science Foundation-Doctoral Research Start-up Fund Project(Grant No.2024-BSBA-05)+1 种基金Major Science and Technology Innovation Project in Shandong Province(Grant No.2024CXGC010803)the National Natural Science Foundation of China(Grant Nos.52271269 and 12302147).
文摘The umbilical,a key component in offshore energy extraction,plays a vital role in ensuring the stable operation of the entire production system.The extensive variety of cross-sectional components creates highly complex layout combinations.Furthermore,due to constraints in component quantity and geometry within the cross-sectional layout,filler bodies must be incorporated to maintain cross-section performance.Conventional design approaches based on manual experience suffer from inefficiency,high variability,and difficulties in quantification.This paper presents a multi-level automatic filling optimization design method for umbilical cross-sectional layouts to address these limitations.Initially,the research establishes a multi-objective optimization model that considers compactness,balance,and wear resistance of the cross-section,employing an enhanced genetic algorithm to achieve a near-optimal layout.Subsequently,the study implements an image processing-based vacancy detection technique to accurately identify cross-sectional gaps.To manage the variability and diversity of these vacant regions,the research introduces a multi-level filling method that strategically selects and places filler bodies of varying dimensions,overcoming the constraints of uniform-size fillers.Additionally,the method incorporates a hierarchical strategy that subdivides the complex cross-section into multiple layers,enabling layer-by-layer optimization and filling.This approach reduces manufac-turing equipment requirements while ensuring practical production process feasibility.The methodology is validated through a specific umbilical case study.The results demonstrate improvements in compactness,balance,and wear resistance compared with the initial cross-section,offering novel insights and valuable references for filler design in umbilical cross-sections.
基金supported by the National Natural Science Foundation of China Nos.82370983,81671015(X.W.),82230030(Y.L.),82101043(S.C.)and 82370922(Y.F.)Beijing International Science and Technology Cooperation Project No.Z221100002722003(Y.L.)+4 种基金Beijing Natural Science Foundation Nos.L234017,JL23002(Y.L.),No.7242282(S.C.)and 7232217(Y.G.)Clinical Medicine Plus X-Young Scholars Project of Peking University No.PKU2024LCXQ039(Y.L.)National Program for Multidisciplinary Cooperative Treatment on Major Diseases No.PKUSSNMP-202013(X.W.)Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing No.HP2023-12-509001(J.Z.)Young Clinical Research Fund of the Chinese Stomatological Association No.CSA-02022-03(J.Z.).
文摘Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
文摘Large portions of the tunnel boring machine(TBM)construction cost are attributed to disc cutter consumption,and assessing the disc cutter's wear level can help determine the optimal time to replace the disc cutter.Therefore,the need to monitor disc cutter wear in real-time has emerged as a technical challenge for TBMs.In this study,real-time disc cutter wear monitoring is developed based on sound and vibration sensors.For this purpose,the microphone and accelerometer were used to record the sound and vibration signals of cutting three different types of rocks with varying abrasions on a laboratory scale.The relationship between disc cutter wear and the sound and vibration signal was determined by comparing the measurements of disc cutter wear with the signal plots for each sample.The features extracted from the signals showed that the sound and vibration signals are impacted by the progression of disc wear during the rock-cutting process.The signal features obtained from the rock-cutting operation were utilized to verify the machine learning techniques.The results showed that the multilayer perceptron(MLP),random subspace-based decision tree(RS-DT),DT,and random forest(RF)methods could predict the wear level of the disc cutter with an accuracy of 0.89,0.951,0.951,and 0.927,respectively.Based on the accuracy of the models and the confusion matrix,it was found that the RS-DT model has the best estimate for predicting the level of disc wear.This research has developed a method that can potentially determine when to replace a tool and assess disc wear in real-time.
基金supported by the Michael Michelson Gift FundNIA grants R01AG073349 (M.V.R.), R01AG044034 (R.F.L.), and R01AG078609 (J.C.)
文摘Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.
文摘Background: Lumbar disc herniation is a common injury among athletes, especially those who practice disciplines with repetitive flexion movements, twisting and axial loading on the spine, such as weightlifting, gymnastics, hockey and American football. In refractory cases to conservative treatment, microscopic discectomy or full endoscopic discectomy are used as surgical options to relieve pain and restore patient functionality. However, the ideal time for a return to sports activities remains a matter of debate due to variations in recovery times and risks of complications associated with each technique. Methods: A review was conducted, including articles published in the last 33 years (1991-2024), as it was the earliest date matching our search criteria. Clinical studies, systematic reviews, meta-analyses, and clinical guidelines were included. Results: The most common complications when returning to sport prematurely include recurrence of the hernia, persistent pain (VAS leg 7 or higher after surgery) and reduced physical performance. The return to full activity rate of patients who underwent microdiscectomy reaches up to 90%, while the endoscopic technique shows a success rate that reaches 99%. Return to play meantime was 5.19 months (range 1.00 - 8.7 months) and mean time of 4.6 months (range 2 - 8 months) with Microdiscectomy and full endoscopic discectomy respectively. Conclusions: There is no unanimous consensus on the exact timing of return to sport due to variability in recovery times and clinical outcomes. In both techniques, evidence highlights the need for a multidisciplinary approach that integrates surgeons, physical therapists and trainers to optimize recovery and ensure a safe return.
基金supported by National Natural Science Foundation of China(82272549,82472505,and 82472498)National key Research and Development plan,Ministry of Science and Technology of the People’s Republic of China(2022YFC2407203)+2 种基金the Young Health Talents of Shanghai Municipal Health Commission,China(2022YQ011)China Medical Education Association(3030537245)The Youth Talent Project of Huashan Hospital(30302164006).
文摘Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing.
基金supported by the National Natural Science Foundation of China (NSFC) (No.82172497)
文摘Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.
