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Frequency noise is a key limitation factor for frequency sensitive ultra-high precision measurement. An excellent methodology for its calibration is the error signal extracting from a cavity length locking process via Pound–Drever–Hall (PDH) technique, and also can be applied as a noise discriminator for active feedback control. However, the stabilized laser frequency noise performance was poor to meet the applications for ultra-high precision measurement, and no literature has analyzed the cause in detail. In this Letter, we found that various of noise floors in the in-loop sensing and modulation depth in the PDH error signal should be responsible for the poor noise performance. Meanwhile, differing from the theoretical prediction (1.08), the modulation depth in frequency noise feedback controlling should be optimized by simultaneously considering the detector's gain and saturation power, cavity impedance matching, and control loop gain. In our case, it was fixed to be 0.17. The experimental results confirm our theoretical analysis well. Finally, the stabilized laser frequency noises are reduced to 10 − 1 Hz / Hz for out-of-loop and 3 × 10 − 2 Hz / Hz for in-loop. The results demonstrate an efficient settlement solution for active frequency noise feedback control. • Optimizing modulation depth for frequency noise suppression is modelled. • Difference in frequency noise between in-loop and out-of-loop is demonstrated. • In-loop noise is observed on-line with the performance of out-of-loop. • Under optimal parameters, a minimum out-of-loop noise of 10 − 1 Hz / Hz so far is demonstrated. [ABSTRACT FROM AUTHOR]

• Classical phase noise is the main limited factor for phase sensitive precision measurement. • Mode cleaner plays a low-pass filtering role not only for amplitude quadrature but also for phase one. • The noise suppression process for one quadrature noise is accomplished by a noise intercoupling between the two quadratures. • A complete experimental scheme for a full phase to amplitude noise conversion has been designed for phase noise characterization. Suppression phase noise of a laser is a great practical significance in applications of phase-sensitive precision measurement. To suppress the phase noise, an ultra-stable cavity incorporating with an electrical feedback control loop is always the popular choice, in which the linewidth of the cavity should be narrower than that of the laser to provide a stable reference standard. Here, we experimentally verify that mode cleaner plays a noise suppression role for phase quadrature in the whole frequency range of the photoelectric detectors, even though its linewidth is 10 3 larger than the laser one. Meanwhile, we found that the noise suppression for one quadrature is codetermined by the noise of the two quadratures of the input field. Our demonstration provides a new and in-depth interpretation for phase noise suppression in a mode cleaner with larger linewidth than the laser one that is important in phase-sensitive sensing application. [ABSTRACT FROM AUTHOR]

One characteristic of tumor-associated CD4+Foxp3+ regulatory T cells (Tregs) is the high expression of tumor necrosis factor receptor type II (TNFR2), a receptor that mediates the decisive effect of tumor necrosis factor (TNF) in the activation and expansion of Tregs. There is increasing evidence that inhibition of TNFR2 can enhance anti-tumor immune responses. Therefore, we screened Chinese herbal extracts for their capacity to block TNF-TNFR2 interaction. The results showed that the treatment with a Chinese herb extract could inhibit TNFR2-induced biological responses in vitro , including the proliferation of TNFR2+ Tregs. Our subsequent study led to the identification of flavonoid compound scutellarin was responsible for the activity. Our results showed that scutellarin is able to disrupt the interaction of TNF-TNFR2 and inhibited the phosphorylation of p38 MAPK, a down-stream signaling component of TNFR2. Importantly, in vivo scutellarin treatment markedly enhanced the efficacy of tumor immunotherapy with CpG oligodeoxynucleotide in mouse CT26 colon cancer model. This effect of scutellarin was associated with the reduction of the number of tumor-infiltrating TNFR2-expressing Tregs and increased tumor infiltration of interferon-γ–producing CD8+ T cells. Our result also suggests that scutellarin or its analogs may be used as an adjuvant to enhance the anti-tumor effect of immunotherapeutic agent by eliminating TNFR2+ Treg activity. [ABSTRACT FROM AUTHOR]

The emerging phase change materials (PCMs) have attracted much attention due to their unique properties and applications. However, the optical properties of PCM at high pressures have not been well explored. In this work, the microstructure and optical properties of GeTe and Sn-substituted GeTe at high pressures up to 30 GPa have been systematically investigated. We find that the substitution of small amounts of Sn for Ge combined with the introduction of high pressure can induce an optical contrast of 117% in crystalline GeTe, which is even higher than the highest optical contrast reported so far (90%) caused by amorphous GeTe to crystalline GeTe. The pressure-induced contrast does not originate from any phase transition as previously, but from the combined effect of Peierls distortion elimination and Ge vacancy formation, which leads to an increase in carrier concentration. The relationship between pressure/atomic composition, Peierls distortion/vacancy formation, and optical contrast can be well explained by a combination of experiments and theoretical calculations. Therefore, this study reveals the effect of high pressure on the optical properties of PCMs and provides new ideas for the design of high-optical-contrast PCMs. [ABSTRACT FROM AUTHOR]

In this study, we synthesized a bayberry-like Ni–Co–Mn ternary hydroxide with a secondary nanoneedle structure using a modified and cost-effective hydrothermal process assisted by the surfactant cetyltrimethylammonium bromide (CTAB). The incorporation of CTAB and graphene in the preparation process significantly enhances the electrochemical performance of NiCoMn–OH. The achieved results are truly impressive, with a high specific capacity of 1450 ​F ​g−1 and an outstanding capacity retention of 52.57% over 5000 cycles. The superior performance could be attributed to the specific bayberry-like microstructure with high effective specific surface area, which allowed for facile and rapid transport of ions and electrons. Moreover, the synergistic effect of CTAB and graphene proved to be crucial in stabilizing the Co2+ and Mn2+ ions within the ternary hydroxide structure. We developed a hybrid capacitor using a NiCoMn–OH-CTAB/Graphene composite electrode and an active electrode, which delivered a superior energy density of 50.79 ​Wh kg−1 at a power density of 400 ​W ​kg−1 and a cycling stability of 60.37% after 10000 cycles. These results indicate that the NiCoMn–OH-CTAB/Graphene composite electrode has great potential as an electrode material for energy storage devices. • Ni–Co–Mn ternary hydroxide is prepared by CTAB-Assisted cost-effective method. • CTAB and graphene significantly improve the electrochemical performance of NiCoMn–OH. • A high specific capacity of 1450 ​F g-1 and 52.57% capacity retention for 5000 cycles are achieved. • The bayberry-like microstructure enables fast ion and electron transport. • The synergistic effect of CTAB and G stabilizes Co2+ and Mn2+ ions in ternary hydroxide. [ABSTRACT FROM AUTHOR]

Phase change materials (PCMs) are recognized as a promising passive energy retrofit technology for existing buildings, as they are applied to the internal and external surfaces of the building with less impact on the original structure. However, the effectiveness of PCMs varies from region to region. Taking the Central Plains of China as an example, this paper investigated the effect of phase change temperature and material thickness variation on the energy efficiency of PCM when it was arranged on 14 placements including furniture through EnergyPlus (E+). And further explored the applicability of coupling PCMs with natural ventilation (NV). The results showed that: for the Central Plains of China, PCMs arranged on the internal surface of building roofs were optimal, and the reduction rate of uncomfortable degree hours could reach 38%, 26%, 24% and 40% after integrating PCMs into the roof, floor, external wall and furniture. The uncomfortable degree hour reduction rate per unit mass of PCM was 0.052%/kg for the roof, and the value of furniture was very close to the external wall and floor, which achieved 0.033%/kg. In addition, the coupling of PCM with NV improved the energy efficiency of PCM by more than twice. [ABSTRACT FROM AUTHOR]

[Display omitted] Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERβ signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer. [ABSTRACT FROM AUTHOR]

Exploring new therapeutic diseases for existing drugs plays an essential role in reducing drug development costs. However, existing methods for predicting drug–disease association (DDA) lack fusion to multi-neighborhood information, which limits their ability to generalize and forces them to rely on prior knowledge. To this end, we propose a novel DDA model called the Neighborhood Contrastive Learning Heterogeneous Networks (NCH-DDA). NCH-DDA uses both single-neighborhood and multi-neighborhood feature extraction modules to extract important features of drugs and diseases in parallel from multiple potential spaces, such as heterogeneous networks and similarity networks. NCH-DDA fuses single-neighborhood and multi-neighborhood features using contrastive learning to enhance information interaction in different neighborhood spaces, ultimately obtaining universal domain features of drugs and diseases. NCH-DDA uses a combination of predictive loss and triplet loss to reduce dependence on prior knowledge. In different partition schemes of multiple datasets, NCH-DDA achieved the best performance in predicting DDA, outperforming several current state-of-the-art methods. Moreover, NCH-DDA demonstrated better performance in experiments on data sparsity and drug repositioning for Alzheimer's disease, indicating its greater potential in DDA prediction with sparse omics data and drug repositioning applications. • Neighborhood contrastive model for heterogeneous representation and DDA prediction. • MNFEM and SNFEM capture the important features in multiple potential spaces. • Contrast learning aggregated generic neighborhood features of drugs and diseases. • Presented a mixing optimization strategy to reduce the dependence on prior knowledge. • Four of the top five drugs recommended for AD by NCH-DDA were proved to be effective. [ABSTRACT FROM AUTHOR]

With the development of quantum computing and other fields, dilution refrigerators are required to have greater cooling capacity. More cooling power means larger 3He flow rate and the corresponding gas circulation system. In dry dilution refrigerators, 3He needs to be pressurized by compressor for the high inlet pressure. This paper introduces a dry dilution refrigerator driven by a designed high-power two-stage linear compressor, and the reliability of the compressor is verified by experiments. 3He can be pressurized to a pressure above 200 kPa at a flow rate of nearly 1 mmol/s and be condensed successfully in the condensatiion process. The refrigerator, precooled by a pulse tube cryocooler, can obtain a minimum temperature of 19 mK and a cooling capacity of 250 μW at about 100 mK at the total flow rate of about 0.45 mmol/s. The maximum power of 3He compressor can reach 300 W and the maximum compression ratio is over 10, which can be used as the 3He driver of high-power dilution refrigerators or closed-cycle space dilution refrigerators. [ABSTRACT FROM AUTHOR]

• A new air conditioning system is explored by experiment. • The system starts mode H is the most stable, and the maximum superheat is 11°C. • A unique phenomenon occurs in the production of hot water. • The system fluctuates periodically in the refrigeration mode. • The drop in discharge pressure can be used as a parameter for defrost control. Air source heat pump (ASHP) and heat pump water heater (HPWH) have the advantages of convenience and high efficiency. The newly proposed refrigeration, heating and hot water combined air-conditioning system (RHHAC) combines traditional ASHP with HPWH. The demands of users for cooling, heating and hot water are effectively satisfied with this equipment. In this study, five groups of experiments were conducted to study the starting and operating characteristics of the system. Besides, two sets of experimental cases were carried out to explore the operating characteristics of the system under the frosting process. Results show that the maximum superheat degree is 11°C when the system starts in hot water mode, while the maximum superheat degree is more than 22°C when the system starts in the other modes. As the temperature of hot water rises when the system runs in hot water mode, the maximum value of the discharge pressure can reach 3.7MPa. Besides, the analysis parameters will have regular pulsations when the system is in cooling mode. For example, in the experimental case 5, the fluctuation range of the superheat degree is 5.1°C-16.2°C. [ABSTRACT FROM AUTHOR]

Microglia, as the intrinsic immune cells in the brain, are activated following ischemic stroke. Activated microglia participate in the pathological processes after stroke through polarization, autophagy, phagocytosis, pyroptosis, ferroptosis, apoptosis, and necrosis, thereby influencing the injury and repair following stroke. It has been established that polarized M1 and M2 microglia exhibit pro-inflammatory and anti-inflammatory effects, respectively. Autophagy and phagocytosis in microglia following ischemia are dynamic processes, where moderate levels promote cell survival, while excessive responses may exacerbate neurofunctional deficits following stroke. Additionally, pyroptosis and ferroptosis in microglia after ischemic stroke contribute to the release of harmful cytokines, further aggravating the damage to brain tissue due to ischemia. This article discusses the different functional states of microglia in ischemic stroke research, highlighting current research trends and gaps, and provides insights and guidance for further study of ischemic stroke. • Microglia is important in the repair of ischemic stroke. • Microglial polarization is a double-edged sword in ischemic stroke. • Microglial proper autophagy and phagocytosis contribute to functional recovery after ischemic stroke, while excessive activation may worsen the damage. • Microglial pyroptosis, ferroptosis, apoptosis and necrosis in ischemic stroke is in the preliminary stage. [ABSTRACT FROM AUTHOR]

As an important emerging pollutant, antibiotic resistance genes (ARGs) monitoring is crucial to protect the ecological environment and public health, but its rapid and accurate detection is still a major challenge. In this study, a new single-labeled dual-signal output ratiometric electrochemical genosensor (E-DNA) was developed for the rapid and highly sensitive detection of ARGs using a synergistic signal amplification strategy of T 3 C 2 @Au nanoparticles (T 3 C 2 @AuNPs) and isothermal strand displacement polymerase reaction (ISDPR). Specially, two-dimensional monolayer T 3 C 2 nanosheets loaded with uniformly gold nanoparticles were prepared and used as the sensing platform of the E-DNA sensor. Benefiting from excellent conductivity and large specific surface area of Ti 3 C 2 @AuNPs, the probe immobilization capacity of the E-DNA sensor is doubled, and electrochemical response signals of the E-DNA sensor were significantly improved. The proposed single-labeled dual-signal output ratiometric sensing strategy exhibits three to six times higher sensitivity for the sul2 gene than the single-signal sensing strategy, which significantly reduces cost meanwhile retaining the advantages of high sensitivity and reliability offered by conventional dual-labeled ratiometric sensors. Coupled with ISDPR amplification technology, the E-DNA sensor has a wider linear range from 10 fM to 10 nM and a limit of detection as low as 2.04 fM (S/N=3). More importantly, the E-DNA sensor demonstrates excellent specificity, good stability and reproducibility for target ARGs detection in real water samples. The proposed new sensing strategy provides a highly sensitive and versatile tool for the rapid and accurate quantitative analysis of various ARGs in environmental water samples. [ABSTRACT FROM AUTHOR]

• A high accuracy deformation measurement method for semi-continuous materials is proposed. • The deformation field of 3D printed scaffolds is accurately measured. • The first visualization of cell differentiation on scaffolds was achieved by experimental measurements. • The effects of loading in vitro and water content on cell differentiation were investigated. • This work corroborates that in vitro loading culture and modulation of scaffold pore structure can be exploited to design scaffolds with regions that guide specific tissue development. Three-dimensional (3D) mechanical microenvironments, such as 3D strain fields in tissue engineering scaffolds have a crucial impact on the interactions between scaffold architecture, mechanical stimuli, and tissue differentiation. However, the discontinuity induced by the pores poses a challenge to the measurement of the 3D strains of the scaffolds. Herein, we present a tissue engineering scaffold optical coherence elastography (TES-OCE) method to visualize the full-field 3D strain fields of the tissue engineering scaffolds when cells are cultured on them and to explore the relationship between mechanical stimulation and cell differentiation. A semi-continuous digital volume correlation (SC-DVC) method based on a material component identification algorithm was proposed to automatically extract the scaffold architecture information and obtain the 3D strain fields with high accuracy. The non-uniform deformation field of a 3D printed tissue engineering scaffold with various water contents under loading in vitro was measured by the TES-OCE method, based on the tissue shear strain field obtained above, the area of cell differentiation phenotype on tissue engineering scaffolds was accurately predicted. Experimental results show that the loads and water absorption of the scaffold significantly affects the 3D tissue shear strain field in the tissue engineering scaffold. Thus, the cell differentiation fate can be modulated by loading culture and scaffold pore structure. The TES-OCE provides a new experimental method to delineate the interrelationship between tissue engineering scaffolds, the mechanical microenvironment, and cell proliferation and differentiation. It may be further developed as an effective tool to guide the design and development of superior tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

• Building a complete gas-gap heat switch model that covers the entire switching process. • Integrating activated carbon's adsorption characteristics into the theoretical model. • Designing the 4He gas-gap heat switch based on the model and testing its performance to validate the model. • Applying the gas-gap heat switch to a 4He sub-Kelvin sorption cooler and achieving a temperature of 773 mK. Gas-gap heat switches (GGHSs) are significant components in sub-Kelvin sorption coolers (SKSCs). To develop an effective GGHS for SKSCs, a complete GGHS theoretical model is proposed by integrating the adsorption characteristics of activated carbon and the principle of GGHSs. This model establishes a relationship between the temperature of activated carbon and the corresponding thermal conductance of GGHSs. Based on this model, a 4He GGHS was designed, which consists of two cylindrical copper blocks separated by a 0.2 mm gas gap and a surface area of 9.896 cm2. The device was charged with 100 kPa of 4He at 297 K. Near the base temperature of the GM cryocooler of 3 K, an ON thermal resistance of 20 K/W and an OFF thermal resistance of 21,650 K/W with 1 mW applied to the hot end were obtained, achieving a switching ratio of 1082.5. The experimental results were analyzed and compared with the theoretical data, and proved to be in good agreement. Finally, the GGHS was integrated with a SKSC, achieving an ultimate temperature of 773 mK. [ABSTRACT FROM AUTHOR]

A biomaterial that can remove remaining oral squamous cell carcinoma (OSCC) cells and repair oral mucosal damage is urgently needed. This graphical abstract described a composite scaffold that would simultaneously kill OSCC cells and promote the regeneration of the oral mucosa. [Display omitted] • Quercetin acts as an inhibitor when heat shock proteins make tumor cells more resistant to photothermal therapy. • Ti 3 C 2 MXene and quercetin are effectively carried by scaffold made of collagen and silk fibroin. • The composite scaffold successfully limits tumor cells migration and promotes oral mucosal defects regeneration. The most prevalent oral and maxillofacial cancer is oral squamous cell carcinoma (OSCC). Patient survival is compromised by relapse due to post-operative tumor remnants and significant mucosal defects. Photothermal therapy (PTT) is used to ablate local malignancies, but the capacity of tumor cells to resist it is correlated with the overexpression of heat shock protein 70 (HSP70). In this work, PTT and tissue engineering scaffold were rationally integrated to construct a Ti 3 C 2 MXene, collagen, silk fibroin and quercetin composite scaffold (M-CSQ scaffold), a 3D printed biomaterial that simultaneously kill OSCC cells and promote the regeneration of the mucosal defects. The M-CSQ scaffolds were prepared by cryogenic 3D printing and freeze-drying techniques with sufficient pores that allow an abundant cell migration and provide a proliferation space. Ti 3 C 2 MXene has excellent photothermal conversion ability and stability. Quercetin targeted HSP70 to decrease its expression in OSCC cells, consequently weakening their resistance to high temperature and enhancing the effect of PTT. The M-CSQ scaffold effectively killed OSCC cells in vitro and inhibited tumor growth in vivo. In addition, the M-CSQ scaffold provided adhesion sites for Sprague-Dawley rat (SD rat) buccal mucosal fibroblasts and promoted the repair of buccal mucosal wounds. [ABSTRACT FROM AUTHOR]

[Display omitted] The tissue engineering is a promising method for cartilage regeneration studies. The rough in vivo initial repair environment of articular cartilage is a challenge for the development of cartilage tissue engineering. Hereon, in this study, a silk fibroin/collagen type II scaffold was designed. The optimal mechanical environment for chondrocyte/scaffold complex in vitro maturation culture was determined and in vitro cultured mature artificial cartilage was evaluated for in vivo defect repair. Our research shows that the silk fibroin/collagen type II scaffold has good performance and can meet the special requirements of cartilage repair. 10 % compressive strain is the optimal compressive loading in vitro. Under optimal compression loading in vitro , chondrocytes can proliferate and grow rapidly on the scaffold to achieve better "maturation". The in vitro cultured chondrocyte/scaffold complex effectively improves the cartilage repair effect after implantation. The compressive elastic modulus of the new tissue reached 0.682 ± 0.010 MPa after 12 weeks of repair (0.714 ± 0.011 MPa for the surrounding host cartilage). Therefore, this study not only enhance the effect of cartilage repair but also provides a promising strategy for mechanical stimulation to promote functional in situ regeneration of articular cartilage. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at exploring a new tooth development evaluation method for age assessment and investigating the dynamic alteration and potential trend of tooth development by orthopantomograms (OPGs), in order to provide references for tooth development prediction and forensic purpose.Materials and Methods: A total of 132 OPGs of children aged 3-8 years were collected. The developmental stages of the permanent mandibular second molar (M2)were evaluated by experienced examiners according to the Nolla method and Mimics software, respectively. Quantitative analysis of the ratio of the radiopaque calcified area to the dental follicle (RCA/DF) in different stages, ages, sexes and quadrants were evaluated and compared via descriptive statistics and Spearman's correlation coefficient analysis.Results: There was a strong, positive correlation between the examiners' evaluation and mimics analysis results. With the age increased, the Nolla stage of M2 observed by OPGs increased, and the RCA/DF showed increased trends both in males and females. There were significant differences of the RCA/DF of the M2 at various ages. The tooth calcification development of female was 9.08% earlier than that of male between 3 and 8 years old. However, teeth of male seemed to develop faster than that of female during this period. There was no significant difference between left and right quadrant either according to the Nolla stage or RCA/DF.Conclusions: The RCA/DF value obtained from OPGs of the developmental mandibular second permanent molars could be used as a reliable indicator for tooth maturity and age estimation in children aged 3-8 years.Clinical Relevance: Age assessment based on radiographs is considered as a reliable and efficient indicator for judging different types of malocclusion, making suitable orthodontic treatment plan, deciding the extraction time of retained deciduous teeth in clinic practice. [ABSTRACT FROM AUTHOR]

• We assessed effects of chronic UNO on motor representation of AD muscle during growth. • UNO during growth induces motor representation changes in cortical masticatory area. • This may affect respiratory and orofacial functions. • Respiratory dysfunction onset should be monitored and corrected in a timely manner. The cortical masticatory area (CMA) regulates masticatory movements. However, there is limited information regarding the effect of respiratory disturbances on the functional development of the CMA. This study aimed to examine the effect of chronic unilateral nasal obstruction (UNO) on the CMA during the growth period. Forty-eight 8-day-old male Wistar albino rats were randomized into control (CONT, n = 24) and UNO (n = 24) groups. Arterial oxygen saturation (SpO 2) and the number of positive intracortical microstimulation (ICMS) sites in the anterior digastric (AD) muscle were recorded at 5, 7, and 9 weeks of age. ICMS was performed under anesthesia. The CONT group exhibited significantly higher SpO 2 values than the UNO group at each age. Furthermore, the number of positive ICMS sites in the AD muscle was significantly higher in the UNO group than in the CONT group at each age. The right AD was more strongly affected by UNO than the left AD. In addition, it was found that the P-area was more strongly affected by UNO than the A-area. These findings suggest that UNO during development induces changes in the motor representation in the CMA, which may affect respiratory and orofacial functions in rats. Therefore, we suggest that the development of respiratory dysfunction needs to be monitored and corrected promptly to avoid complications in physiological function. [ABSTRACT FROM AUTHOR]

Cracks may change the mechanical properties of articular cartilage, and further lead to early osteoarthritis. The study aimed to probe the mechanical properties of cracked cartilage under uniaxial tensile loading. The fracture process of cracked cartilage can be divided into two stages, namely crack-tip blunting stage and crack growth stage. The creep strain of cracked cartilage increases rapidly and then slowly with time, and it is well predicted by the nonlinear viscoelastic creep model. Compared with intact cartilage, cracked cartilage shows larger creep strain. During cyclic loading, the mean strain, degree of necking and crack-tip blunting of cracked cartilage increase with the increase of peak stress, while they decrease with the increase of loading frequency. The crack-tip morphology shows that cyclic loading has induced irreversible deformation in cartilage with a large number of collagen fibrils yielding, and further damaged the collagen fibril network of cartilage. However, no obvious crack growth is observed under the testing conditions. [ABSTRACT FROM AUTHOR]