MIF inhibition attenuates intervertebral disc degeneration by reducing nucleus pulposus cell apoptosis and inflammation.

Nucleus pulposus cells (NPCs) apoptosis and inflammation are the extremely critical factors of intervertebral disc degeneration (IVDD). Nevertheless, the underlying procedure remains mysterious. Macrophage migration inhibitory factor (MIF) is a cytokine that promotes inflammation and has been demonstrated to have a significant impact on apoptosis and inflammation. For this research, we employed a model of NPCs degeneration stimulated by lipopolysaccharides (LPS) and a rat acupuncture IVDD model to examine the role of MIF in vitro and in vivo, respectively. Initially, we verified that there was a significant rise of MIF expression in the NP tissues of individuals with IVDD, as well as in rat models of IVDD. Furthermore, this augmented expression of MIF was similarly evident in degenerated NPCs. Afterwards, it was discovered that ISO-1, a MIF inhibitor, effectively decreased the quantity of cells undergoing apoptosis and inhibited the release of inflammatory molecules (TNF-α, IL-1ß, IL-6). Furthermore, it has been shown that the PI3K/Akt pathway plays a vital part in the regulation of NPCs degeneration by MIF. Ultimately, we showcased that the IVDD process was impacted by the MIF inhibitor in the rat model. In summary, our experimental results substantiate the significant involvement of MIF in the degeneration of NPCs, and inhibiting MIF activity can effectively mitigate IVDD.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Ultrafast isolated molecule imaging without crystallization.

Crystallography is the standard for determining the atomic structure of molecules. Unfortunately, many interesting molecules, including an extensive array of biological macromolecules, do not form crystals. While ultrashort and intense X-ray pulses from free-electron lasers are promising for imaging single isolated molecules with the so-called "diffraction before destruction" technique, nanocrystals are still needed for producing sufficient scattering signal for structure retrieval as implemented in serial femtosecond crystallography. Here, we show that a femtosecond laser pulse train may be used to align an ensemble of isolated molecules to a high level transiently, such that the diffraction pattern from the highly aligned molecules resembles that of a single molecule, allowing one to retrieve its atomic structure with a coherent diffraction imaging technique. In our experiment with CO2 molecules, a high degree of alignment is maintained for about 100 fs, and a precisely timed ultrashort relativistic electron beam from a table-top instrument is used to record the diffraction pattern within that duration. The diffraction pattern is further used to reconstruct the distribution of CO2 molecules with atomic resolution. Our results mark a significant step toward imaging noncrystallized molecules with atomic resolution and open opportunities in the study and control of dynamics in the molecular frame that provide information inaccessible with randomly oriented molecules.

Ultrafast atomic view of laser-induced melting and breathing motion of metallic liquid clusters with MeV ultrafast electron diffraction.

Under the irradiation of an ultrafast intense laser, solid materials can be driven into nonequilibrium states undergoing an ultrafast solid-liquid phase transition. Understanding such nonequilibrium states is essential for scientific research and industrial applications because they exist in various processes including laser fusion and laser machining yet challenging in the sense that high resolution and single-shot capability are required for the measurements. Herein, an ultrafast diffraction technique with megaelectron-volt (MeV) electrons is used to resolve the atomic pathway over the entire laser-induced ultrafast melting process, from the initial loss of long-range order and the formation of high-density liquid to the progressive evolution of short-range order and relaxation into the metastable low-density liquid state. High-resolution measurements using electron pulse compression and a time-stamping technique reveal a coherent breathing motion of polyhedral clusters in transient liquid aluminum during the ultrafast melting process, as indicated by the oscillation of the interatomic distance between the center atom and atoms in the nearest-neighbor shell. Furthermore, contraction of interatomic distance was observed in a superheated liquid state with temperatures up to 6,000 K. The results provide an atomic view of melting accompanied with internal pressure relaxation and are critical for understanding the structures and properties of matter under extreme conditions.

Kyphoplasty is associated with reduced mortality risk for osteoporotic vertebral compression fractures: a systematic review and meta-analysis.

BACKGROUND: Vertebral augmentation, such as vertebroplasty (VP) or kyphoplasty (KP), has been utilized for decades to treat OVCFs; however, the precise impact of this procedure on reducing mortality risk remains a topic of controversy. This study aimed to explore the potential protective effects of vertebral augmentation on mortality in patients with osteoporotic vertebral compression fractures (OVCFs) using a large-scale meta-analysis. MATERIALS AND METHODS: Cochrane Library, Embase, MEDLINE, PubMed and Web of Science databases were employed for literature exploration until May 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized as a summary statistic via random-effect models. Statistical analysis was executed using Review Manager 5.3 software. RESULTS: After rigorous screening, a total of five studies with substantial sample sizes were included in the quantitative meta-analysis. The total number of participants included in the study was an 2,421,178, comprising of 42,934 cases of vertebral augmentation and 1,991,244 instances of non-operative management. The surgical intervention was found to be significantly associated with an 18% reduction in the risk of mortality (HR 0.82; 95% CI 0.78, 0.85). Subgroup analysis revealed a remarkable 71% reduction in mortality risk following surgical intervention during short-term follow-up (HR 0.29; 95% CI 0.26, 0.32). Furthermore, KP exhibited a superior and more credible decrease in the risk of mortality when compared to VP treatment. CONCLUSIONS: Based on a comprehensive analysis of large samples, vertebral augmentation has been shown to significantly reduce the mortality risk associated with OVCFs, particularly in the early stages following fractures. Furthermore, it has been demonstrated that KP is more reliable and effective than VP in terms of mitigating mortality risk.

κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway.

Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation. Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA. Here, we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-α and IL-6 by inhibiting macrophage M1 phenotype. Mechanistically, KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB into the nucleus. Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice. Consistently, KOR administration suppresses the expressions of M1 macrophage markers and the NF-κB pathway in the synovium of the knee. Collectively, our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.

Thiolutin, a selective NLRP3 inflammasome inhibitor, attenuates cyclophosphamide-induced impairment of sperm and fertility in mice.

OBJECTIVE: The activation of the NLRP3 inflammasome has been implicated in male infertility. Our study aimed to investigate the therapeutic role of Thiolutin (THL), an inhibitor of the NLRP3 inflammasome, on oligoasthenospermia (OA) and to elucidate its mechanisms. MATERIALS AND METHODS: Semen from 50 OA and 20 healthy males were analyzed to assess the sperm quality and levels of inflammatory markers. Their correlation was determined using Pearson's correlation coefficient. The BALB/c mice were intraperitoneal injected by cyclophosphamide at 60 mg/kg/day for five days to induce OA, followed by a two-week treatment with THL or L-carnitine. Reproductive organ size and H&E staining were determined to observe the organ and seminiferous tubule morphology. ELISA and western blotting were utilized to measure sex hormone levels, inflammatory markers, and NLRP3 inflammasome levels. Furthermore, male and female mice were co-housed to observe pregnancy success rates. RESULTS: OA patients exhibited a decrease in sperm density and motility compared to healthy individuals, along with elevated levels of IL-1ß, IL-18 and NLRP3 inflammasome. In vivo, THL ameliorated OA-induced atrophy of reproductive organs, hormonal imbalance, and improved sperm density, motility, spermatogenesis and pregnancy success rates with negligible adverse effects on weight or liver-kidney function. THL also demonstrated to be able to inhibit the activation of NLRP3 inflammasome and associated proteins in OA mice. DISCUSSION: THL can improve sperm quality and hormonal balance in OA mice through the inhibition of NLRP3 inflammasome activation. Thus, THL holds promising potential as a therapeutic agent for OA.

Flying Target Detection Technology Based on GNSS Multipath Signals.

In this study, a passive radar system that detects flying targets is developed in order to solve the problems associated with traditional flying target detection systems (i.e., their large size, high power consumption, complex systems, and poor battlefield survivability). On the basis of target detection, the system uses the multipath signal (which is usually eliminated as an error term in navigation and positioning), enhances it by supporting information, and utilizes the multi-source characteristics of ordinary omnidirectional global navigation satellite system (GNSS) signals. The results of a validation experiment showed that the system is able to locate a passenger airplane and obtain its flight trajectory using only one GNSS receiving antenna. The system is characterized by its light weight (less than 5 kg), low power consumption, simple system, good portability, low cost, and 24/7 and all-weather work. It can be installed in large quantities and has good prospects for development.

Partial Discharge Signal Pattern Recognition of Composite Insulation Defects in Cross-Linked Polyethylene Cables.

To investigate the pattern recognition of complex defect types in XLPE (cross-linked polyethylene) cable partial discharges and analyze the effectiveness of identifying partial discharge signal patterns, this study employs the variational mode decomposition (VMD) algorithm alongside entropy theories such as power spectrum entropy, fuzzy entropy, and permutation entropy for feature extraction from partial discharge signals of composite insulation defects. The mean power spectrum entropy (PS), mean fuzzy entropy (FU), mean permutation entropy (PE), as well as the permutation entropy values of IMF2 and IMF13 (Pe) are selected as the characteristic quantities for four categories of partial discharge signals associated with composite defects. Six hundred samples are selected from the partial discharge signals of each type of compound defect, amounting to a total of 2400 samples for the four types of compound defects combined. Each sample comprises five feature values, which are compiled into a dataset. A Snake Optimization Algorithm-optimized Support Vector Machine (SO-SVM) model is designed and trained, using the extracted features from cable partial discharge datasets as case examples for recognizing cable partial discharge signals. The identification outcomes from the SO-SVM model are then compared with those from conventional learning models. The results demonstrate that for partial discharge signals of XLPE cable composite insulation defects, the SO-SVM model yields better identification results than traditional learning models. In terms of recognition accuracy, for scratch and water ingress defects, SO-SVM improves by 14.00% over BP (Back Propagation) neural networks, by 5.66% over GA-BP (Genetic Algorithm-Back Propagation), and by 12.50% over SVM (support vector machine). For defects involving metal impurities and scratches, SO-SVM improves by 13.39% over BP, 9.34% over GA-BP, and 12.56% over SVM. For defects with metal impurities and water ingress, SO-SVM shows enhancements of 13.80% over BP, 9.47% over GA-BP, and 13.97% over SVM. Lastly, for defects combining metal impurities, water ingress, and scratches, SO-SVM registers increases of 11.90% over BP, 9.59% over GA-BP, and 12.05% over SVM.

Integrated Microfluidic Chip for Rapid Antimicrobial Susceptibility Testing Directly from Positive Blood Cultures.

Rapid and accurate antimicrobial prescriptions are critical for bloodstream infection (BSI) patients, as they can guide drug use and decrease mortality significantly. The traditional antimicrobial susceptibility testing (AST) for BSI is time-consuming and tedious, taking 2-3 days. Avoiding lengthy monoclonal cultures and shortening the drug sensitivity incubation time are keys to accelerating the AST. Here, we introduced a bacteria separation integrated AST (BSI-AST) chip, which could extract bacteria directly from positive blood cultures (PBCs) within 10 min and quickly give susceptibility information within 3 h. The integrated chip includes a bacteria separation chamber, multiple AST chambers, and connection channels. The separator gel was first preloaded into the bacteria separation chamber, enabling the swift separation of bacteria cells from PBCs through on-chip centrifugation. Then, the bacteria suspension was distributed in the AST chambers with preloaded antibiotics through a quick vacuum-assisted aliquoting strategy. Through centrifuge-assisted on-chip enrichment, detectable growth of the phenotype under different antibiotics could be easily observed in the taper tips of AST chambers within a few hours. As a proof of concept, direct AST from artificial PBCs with Escherichia coli against 18 antibiotics was performed on the BSI-AST chip, and the whole process from bacteria extraction to AST result output was less than 3.5 h. Moreover, the integrated chip was successfully applied to the diagnosis of clinical PBCs, showing 93.3% categorical agreement with clinical standard methods. The reliable and fast pathogen characterization of the integrated chip suggested its great potential application in clinical diagnosis.

Control over Berry Curvature Dipole with Electric Field in WTe_{2}.

Berry curvature dipole plays an important role in various nonlinear quantum phenomena. However, the maximum symmetry allowed for nonzero Berry curvature dipole in the transport plane is a single mirror line, which strongly limits its effects in materials. Here, via probing the nonlinear Hall effect, we demonstrate the generation of Berry curvature dipole by applied dc electric field in WTe_{2}, which is used to break the symmetry constraint. A linear dependence between the dipole moment of Berry curvature and the dc electric field is observed. The polarization direction of the Berry curvature is controlled by the relative orientation of the electric field and crystal axis, which can be further reversed by changing the polarity of the dc field. Our Letter provides a route to generate and control Berry curvature dipole in broad material systems and to facilitate the development of nonlinear quantum devices.

Rapid Mycobacterium abscessus antimicrobial susceptibility testing based on antibiotic treatment response mapping via Raman Microspectroscopy.

OBJECTIVES: Antimicrobial susceptibility tests (ASTs) are pivotal tools for detecting and combating infections caused by multidrug-resistant rapidly growing mycobacteria (RGM) but are time-consuming and labor-intensive. DESIGN: We used a Mycobacterium abscessus-based RGM model to develop a rapid (24-h) AST from the beginning of the strain culture, the Clinical Antimicrobials Susceptibility Test Ramanometry for RGM (CAST-R-RGM). The ASTs obtained for 21 clarithromycin (CLA)-treated and 18 linezolid (LZD)-treated RGM isolates. RESULTS: CAST-R-RGM employs D2O-probed Raman microspectroscopy to monitor RGM metabolic activity, while also revealing bacterial antimicrobial drug resistance mechanisms. The results of clarithromycin (CLA)-treated and linezolid (LZD)-treated RGM isolates exhibited 90% and 83% categorical agreement, respectively, with conventional AST results of the same isolates. Furthermore, comparisons of time- and concentration-dependent Raman results between CLA- and LZD-treated RGM strains revealed distinct metabolic profiles after 48-h and 72-h drug treatments, despite similar profiles obtained for both drugs after 24-h treatments. CONCLUSIONS: Ultimately, the rapid, accurate, and low-cost CAST-R-RGM assay offers advantages over conventional culture-based ASTs that warrant its use as a tool for improving patient treatment outcomes and revealing bacterial drug resistance mechanisms.

Three-wavelength digital photoelasticity.

A three-wavelength photoelasticity method is proposed to simplify the optical setup and speed up data acquisition. By recording six intensity images with circularly polarized illuminations of three close wavelengths, the phase retardation and corresponding inner stress can be computed accurately with a correspondingly developed computational algorithm. Since the mechanical rotations of wave plates and polarizers required by classic photoelasticity techniques are avoided, the data acquisition of this proposed method is very speedy, and measurement of a dynamic sample can be achieved with a very simple and compact optical setup. Besides theoretical analyses, numerical and experimental evidences are also used to confirm the feasibility of this suggested three-wavelength digital photoelasticity method.

Dual-channel binary diffuser-based coherent modulation imaging.

To improve the performance of binary diffuser-based coherent modulation imaging (CMI), a double-channel optical alignment was proposed. Two diffraction patterns formed by the reflection and transmission of a binary diffuser were simultaneously captured and adopted for iterative reconstruction in combination. The information involved in reflected light, not considered in the traditional single-channel optical alignment, was also reconstructed in this dual-channel binary diffuser-based coherent modulation imaging (DB-CMI). The reconstruction quality and speed were improved and verified by both numerical simulations and proof-of-principle experiments. Therefore, DB-CMI improves traditional CMI and provides a powerful tool for quantitative phase imaging.

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study.

BACKGROUND: Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy. METHODS: This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People's Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy. RESULTS: A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period. CONCLUSIONS: Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.

Comparison of Simulated and Measured Power of the Earth-Space Link for Satellite-Based AIS Signals.

This research aims to analyze the impact of the Earth-Space link on the Automatic Identification System (AIS) signals of ships. To achieve this, we established a simulation system that measures the receiving power of AIS signals via satellite platforms. We validated the system by utilizing observation data from Tiantuo-5. Through this simulation, we quantitatively analyzed the effects of ionospheric TEC (Total Electron Content) and space loss on the received power. During the processing of observation data, we construct a geometric propagation model utilizing the measured positions of both the satellite and the ship. We then calculate the antenna gain and remove any system errors. Additionally, we eliminate the deviation of elevation and azimuth angles caused by satellite motion. This allows us to determine the actual power of different ships reaching the receiving platform. Upon comparing the measured power data with the simulated power, it was noted that both exhibited an increasing trend as the elevation angle increased. This led to an RMSE (Root Mean Square Error) result of approximately one, indicating the accuracy of the simulation system. These findings hold significant implications for analyzing interference factors in satellite-ground links.

Superconducting Proximity in Intrinsic Magnetic Topological Insulator MnBi2Te4-NbN Hybrid Device Modulated by Coulomb Blockade Effect.

The combination of nontrivial topology, magnetism, and superconductivity could offer the potential to realize exotic excitations of quasiparticles. MnBi2Te4, as an intrinsic magnetic topological insulator, may be a good platform to create Majorana fermions if coupled to an s-wave superconductor. Here, we report the transport properties of a MnBi2Te4-NbN hybrid device. This device exhibits clear Coulomb blockade oscillations. We observe a large zero-bias conductance peak that exists over considerable changes in gate voltage, magnetic field, and temperature, which is interpreted as a not fully developed supercurrent. The zero-bias peak shows a nonmonotonic evolution with a magnetic field and an abrupt π phase shift with changing temperature. Zero-energy bound states and a topological phase transition may exist in this hybrid system. Our results provide the first experimental investigation into the properties of the intrinsic magnetic topological insulator/superconductor hybrid structures modulated by the Coulomb blockade effect.

Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation.

The dysregulation of lipid metabolic pathways (cholesterol uptake and efflux) in macrophages results in the formation of lipid-dense macrophages, named foam cells, that participate in plaque formation. NPY binding to NPY receptors in macrophages can modulate cell functions and affect the process of atherosclerotic plaques. The present study aimed to determine whether NPY affects the formation of macrophage-derived foam cells and its underlying mechanisms in macrophages. THP-1-derived macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) and treated with different concentrations of NPY. We analysed the relative levels of proteins related to cholesterol uptake and efflux. We found that NPY effectively increased cholesterol uptake and intracellular cholesterol content via the Y1 and Y5 receptors, and this effect was blocked by Y1 and Y5 antagonists. Mechanistically, NPY enhanced the expression of SRA and CD36 via the PKC/PPARγ pathways, promoting macrophage cholesterol uptake. Moreover, NPY significantly decreased cholesterol efflux to the extracellular cholesterol acceptors ApoA1 and HDL in macrophages. NPY mediated decreases in ABCA1, ABCG1 and SR-BI expression through the inhibition of the JAK/STAT3 pathways. Our results suggest that NPY binding to the Y1 and Y5 receptors enhances foam cell formation by regulating cholesterol uptake and efflux in macrophages.

Single-Cell Identification, Drug Susceptibility Test, and Whole-genome Sequencing of Helicobacter pylori Directly from Gastric Biopsy by Clinical Antimicrobial Susceptibility Test Ramanometry.

BACKGROUND: The battle against Helicobacter pylori (H. pylori) infections demands fast, reliable, and sensitive methods for pathogen identification (ID), antimicrobial susceptibility tests (ASTs) based on metabolic response, and genome-wide mutation profiling that reveals resistance mechanisms. METHODS: Here we introduce Clinical Antimicrobial Susceptibility Test Ramanometry for H. pylori (CAST-R-HP), and its validation with clinical samples. This method performs rapid ID, metabolism inhibition-based AST, and high-quality whole-genome sequencing for cells of targeted resistance phenotype, all at precisely 1-cell resolution and directly from biopsy samples. RESULTS: In CAST-R-HP, automated acquisition and machine learning of single-cell Raman spectra (SCRS) enable distinguishing individual H. pylori cells directly from a biopsy sample, with 98.5 ± 0.27% accuracy in ID. Moreover, by adding a 48- to72-h D2O feeding and drug exposure step prior to SCRS acquisition, CAST-R-HP reports AST for levofloxacin and clarithromycin with 100% accuracy, based on metabolic inhibition level. Furthermore, CAST-R-HP supports rapid sorting, low-bias DNA amplification, and full genome sequencing of single H. pylori cells with the SCRS defined, targeted drug-susceptibility phenotype, via Raman-activated gravity-driven cell encapsulation and sequencing. The genome-wide mutation map (maximum 99.70% coverage), at precisely 1-cell resolution, not only elucidates the drug-susceptibility phenotypes but also unveils their underlying molecular mechanisms. CONCLUSION: The culture independency, shorter turnaround time, high resolution, and comprehensive information output suggest that CAST-R-HP is a powerful tool for diagnosing and treating H. pylori infections.

Quantitative detection of defect size based on infrared thermography: temperature integral method.

Quantitative detection of the defect size by infrared thermography is difficult. In this paper, a novel temperature integral method (TIM) is introduced for the quantitative detection of the defect size. The TIM integrates the temperature values of each pixel across the defect area to obtain the defect sizes quantitatively and conveniently. The performance of the TIM on the defect size detection is evaluated thoroughly with both experiments and simulations. Furthermore, the TIM method was compared with existing methods for quantitative detection of defect size. The results indicate robustness and accuracy of TIM.