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Previous observational studies found associations between Helicobacter pylori infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against H. pylori on AITDs using a bidirectional Mendelian randomization (MR). We found that anti-H. pylori outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti-H. pylori OMP. Our analyses indicate the mutual effects of H. pylori infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti-H. pylori OMP with hyperthyroidism and GD, resulting in a vicious circle.
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Enfermedad de Graves , Infecciones por Helicobacter , Helicobacter pylori , Análisis de la Aleatorización Mendeliana , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/complicaciones , Humanos , Enfermedad de Graves/genética , Enfermedad de Graves/microbiología , Hipertiroidismo/genética , Hipertiroidismo/microbiología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/microbiología , Antígenos Bacterianos , Proteínas BacterianasRESUMEN
Fresnel incoherent correlation holography (FINCH) can achieve high-precision and non-scanning 3D imaging. However, as a holographic imaging technology, the huge bandwidth requirements and the amount of holographic data transmitted have always been one of the important factors limiting its application. In addition, the hardware cost of pixel array-based CCD or CMOS imaging is very high under high resolution or specific wavelength conditions. Accordingly, a single-pixel Fresnel incoherent correlation holography (SP-FINCH) compressed imaging method is proposed, which replaces pixel array detector with single-pixel detector and designs a Trumpet network to achieve low-cost and high-resolution imaging. Firstly, a modified FINCH imaging system is constructed and data acquisition is carried out using a single-pixel detector. Secondly, a Trumpet network is constructed to directly map the relationship between one-dimensional sampled data and two-dimensional image in an end-to-end manner. Moreover, by comparing the reconstructed images using neural network with that using commonly used single-pixel reconstruction methods, the results indicate that the proposed SP-FINCH compressed imaging method can significantly improve the quality of image reconstruction at lower sampling rate and achieve imaging without phase-shifting operation. The proposed method has been shown to be feasible and advantageous through numerical simulations and optical experiment results.
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BACKGROUND: Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. METHODS: The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. RESULTS: We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. CONCLUSION: According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Gota , Análisis de la Aleatorización Mendeliana , Sitios de Carácter Cuantitativo , Análisis de la Célula Individual , Gota/genética , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Estudio de Asociación del Genoma Completo/métodos , Predisposición Genética a la Enfermedad/genética , Sitios de Carácter Cuantitativo/genética , Análisis de la Célula Individual/métodos , Metilación de ADN/genética , Polimorfismo de Nucleótido Simple , Mapas de Interacción de Proteínas/genética , Alcohol DeshidrogenasaRESUMEN
OBJECTIVE: Some observational studies have suggested the association between thyroid function and polycystic ovary syndrome (PCOS). However, it remains to be determined whether these associations are causal or not. The aim of this study was to investigate the underlying causal association between different thyroid function status and PCOS. METHODS: Bidirectional Mendelian randomization (MR) analysis was conducted to explore the impact of different thyroid function statuses on PCOS. The study included 10,074 individuals with PCOS and 103,164 controls for the primary analysis, with validation analysis repeated in the FinnGen R9 and EstBB PCOS cohorts. Female-specific thyroid function GWAS data were obtained from European population, including Hyperthyroidism (22,383 cases and 54,288 controls) and Hypothyroidism (27,383 cases and 54,288 controls) from the UK Biobank, and TSH (54,288 cases and 72,167 controls) and FT4 (49,269 cases and 72,167 controls) within the reference range from the ThyroidOmics Consortium. Inverse variance weighting (IVW) was chosen as the principal method, and sensitivity analysis was conducted to test for the presence of horizontal pleiotropy or heterogeneity. RESULTS: The IVW analysis indicated nominal significance between normal TSH levels and PCOS after adjusted for age and BMI [OR (95% CI) = 0.78(0.62,0.97), P = 0.029], suggesting that maintaining normal TSH levels might act as a protective factor against the pathogenesis of PCOS. Besides, in order to increase the statistical power, we pooled PCOS GWAS above together by meta-analysis and found PCOS contributed to the occurrence of hyperthyroidism [OR(95%CI) = 1.37(0.73,2.57), P = 0.012]. However, no causal relationship was found after Bonferroni correction (P-value < 0.0031). CONCLUSION: Although the MR analysis didn't indicate genetic causal association between thyroid function and PCOS after Bonferroni correction. Further efforts are needed to interpret the potential causal relationship between thyroid function and PCOS in different age and BMI subgroup.
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Análisis de la Aleatorización Mendeliana , Síndrome del Ovario Poliquístico , Glándula Tiroides , Tirotropina , Humanos , Síndrome del Ovario Poliquístico/genética , Femenino , Tirotropina/sangre , Adulto , Hipertiroidismo/genética , Hipertiroidismo/epidemiología , Hipotiroidismo/genética , Hipotiroidismo/epidemiología , Estudio de Asociación del Genoma Completo , Pruebas de Función de la TiroidesRESUMEN
Objective: To validate the performance of our laboratory-developed whole-genome screening assay within clinical preimplantation genetic testing environments. Design: Perform a laboratory-developed whole-genome assay on both cell lines and trophectoderm biopsies, subsequently employing the next-generation sequencing procedure to reach a sequencing depth of 30X. Adhere to the Genome Analysis Toolkit best practices for accuracy, sensitivity, specificity, and precision calculations by comparing samples with references. Our assay was then applied to cell lines and biopsies harboring known pathogenic variants, aiming to ascertain these changes solely from the next-generation sequencing data, independent of parental genome information. Settings: Clinical laboratory. Patients: Coriell cell lines and research embryos with known chromosomal or genetic variants. Research trophectoderm biopsies from a couple that are heterozygous carriers for distinct variants in the same autosomal recessive gene (HOGA1). Intervention: Not applicable. Main Outcome Measures: Accuracy, sensitivity, specificity, and precision were assessed by comparing the samples to their references. For samples with known variants, we calculated our sensitivity to detecting established variants. For the research embryos, noncarrier, carrier, and compound heterozygous states of inherited HOGA1 variants were distinguished independently of parental samples. Results: Amplification of DNA from cell lines and embryos yielded success rates exceeding 99.9% and 98.2%, respectively, although maintaining an accuracy of >99.9% for aneuploidy assessment. The accuracy (99.99%), specificity (99.99%), sensitivity (98.0%), and precision (98.1%) of amplified genome in the bottle (reference NA12878) and embryo biopsies were comparable to results on genomic DNA, including mitochondrial heteroplasmy. Using our assay, we achieved >99.99% sensitivity when examining samples with known chromosomal and genetic variants. This encompassed pathogenic CFTR, BRCA1, and other variants, along with uniparental isodisomies and microdeletions such as DiGeorge syndrome. Our research study identified noncarrier, carrier, and compound heterozygous states within trophectoderm biopsies while simultaneously screening for 1,300 other severe monogenic diseases. Conclusion: To our knowledge, this is the first clinical validation of whole-genome embryo screening. In this study, we demonstrated high accuracy for aneuploidy calls (>99.9%) and genetic variants (99.99%), even in the absence of parental genomes. This assay demonstrates advancements in genomic screening and an extended scope for testing capabilities in the realm of preimplantation genetic testing.
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Fresnel incoherent correlation holography (FINCH) realizes non-scanning three-dimension (3D) images using spatial incoherent illumination, but it requires phase-shifting technology to remove the disturbance of the DC term and twin term that appears in the reconstruction field, thus increasing the complexity of the experiment and limits the real-time performance of FINCH. Here, we propose a single-shot Fresnel incoherent correlation holography via deep learning based phase-shifting (FINCH/DLPS) method to realize rapid and high-precision image reconstruction using only a collected interferogram. A phase-shifting network is designed to implement the phase-shifting operation of FINCH. The trained network can conveniently predict two interferograms with the phase shift of 2/3 π and 4/3 π from one input interferogram. Using the conventional three-step phase-shifting algorithm, we can conveniently remove the DC term and twin term of the FINCH reconstruction and obtain high-precision reconstruction through the back propagation algorithm. The Mixed National Institute of Standards and Technology (MNIST) dataset is used to verify the feasibility of the proposed method through experiments. In the test with the MNIST dataset, the reconstruction results demonstrate that in addition to high-precision reconstruction, the proposed FINCH/DLPS method also can effectively retain the 3D information by calibrating the back propagation distance in the case of reducing the complexity of the experiment, further indicating the feasibility and superiority of the proposed FINCH/DLPS method.
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To reduce the acquisition time of interferogram and provide a dynamic phase retrieval method with arbitrary phase shift using a dual-channel simultaneous polarization phase-shifting system, a two-step orthogonalization phase demodulation method (TOPD) based on a single differential interferogram is proposed in this paper. In this method, the differential interferogram obtained by subtracting two phase-shifting interferograms and one of the Gaussian filtered based-interferograms are used to normalize and orthogonalize, and then the phase related parameters are solved by the Lissajous ellipse fitting method. Finally, the measured phase is obtained with high accuracy. The proposed method further reduces the deviation caused by the filtering operation performed in the two-step phase demodulation method. At the same time, combined it with the Lissajou ellipse fitting method reduces the limitation associated with the approximation conditions of the orthogonalization and normalization method. The experimental and simulation results demonstrate that this method provides a solution with high accuracy, high stability, strong practicability, and few restrictions for phase extraction in quantitative phase imaging.
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Convolutional neural networks have been widely used in optical information processing and the generalization ability of the network depends greatly on the scale and diversity of the datasets, however, the acquisition of mass datasets and later annotation have become a common problem that hinders its further progress. In this study, a model transfer-based quantitative phase imaging (QPI) method is proposed, which fine-tunes the network parameters through loading pre-training base model and transfer learning, enable the network with good generalization ability. Most importantly, a feature fusion method based on moment reconstruction is proposed for training dataset generation, which can construct rich enough datasets that can cover most situations and accurately annotated, it fundamentally solves the problem from the scale and representational ability of the datasets. Besides, a feature distribution distance scoring (FDDS) rule is proposed to evaluate the rationality of the constructed datasets. The experimental results show that this method is suitable for different types of samples to achieve fast and high-accuracy phase imaging, which greatly relieves the pressure of data, tagging and generalization ability in the data-driven method.
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Diagnóstico por Imagen , Redes Neurales de la Computación , Aprendizaje AutomáticoRESUMEN
Citrate salts (CSs), as one type of organic salts, have been widely used in the food and pharmaceutical industries. Accurate and quantitative detection of CSs in food and medicine is very important for health and safety. In this study, an asymmetric double-opening ring metamaterial sensor is designed, fabricated, and used to detect citrate salts combined with THz spectroscopy. Factors that influence the sensitivity of the metamaterial sensor including the opening positions and the arrangement of the metal opening ring unit, the refraction index and the thickness of the analyte deposited on the metamaterial sensor were analyzed and discussed from electromagnetic simulations and THz spectroscopy measurements. Based on the high sensitivity of the metamaterial sensor to the refractive index of the analyte, six different citrate salt solutions with low concentrations were well identified. Therefore, THz spectroscopy combined with a metamaterials sensor can provide a new, rapid, and accurate detection of citrate salts.
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Ácido Cítrico , Sales (Química) , Refractometría/métodosRESUMEN
In this paper, we propose a two-to-one deep learning (DL) framework for three- wavelength phase-shifting interferometry. The interferograms at two different wavelengths are used as the input of the proposed hybrid-net, and the interferogram of the third wavelength is used as the output. Using the advantages of the hybrid learning network, the interferogram of the third wavelength can be obtained accurately. Finally, the three-wavelength phase-shifting interferometry is realized. Compared with the previous DL-based dual-wavelength interferometry (DWI), the proposed method can further improve the measurement range of the sample without changing the DWI system. Especially for the independent step sample, the problem of limited measurement range is solved due to the input of auxiliary information. More importantly, the third wavelength can be set freely according to the measurement requirements, which is no longer limited by the actual laser and can provide more measuring ruler for phase measurement. Both experimental results and simulation analysis demonstrate the proposed method in the feasibility and the performance in improving the measurement range.
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In this manuscript, we propose a quantitative phase imaging method based on deep learning, using a single wavelength illumination to realize dual-wavelength phase-shifting phase recovery. By using the conditional generative adversarial network (CGAN), from one interferogram recorded at a single wavelength, we obtain interferograms at other wavelengths, the corresponding wrapped phases and then the phases at synthetic wavelengths. The feasibility of the proposed method is verified by simulation and experiments. The results demonstrate that the measurement range of single-wavelength interferometry (SWI) is improved by keeping a simple setup, avoiding the difficulty caused by using two wavelengths simultaneously. This will provide an effective solution for the problem of phase unwrapping and the measurement range limitation in phase-shifting interferometry.
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We present a deep learning (DL) framework based on a conditional generative adversarial network (CGAN) to perform compressive optical image hiding (COIH) with a single-pixel detector. An end-to-end compressive sensing generative adversarial network (eCSGAN) is developed, achieving the approximate equivalent model of an inverse system of a nonlinear COIH model, to reconstruct two-dimensional secret images directly from real acquired one-dimensional compressive sampling signals without the need of any security keys of the COIH system such as the sequence of illumination patterns, the host image, etc. Moreover, detailed comparisons between the image reconstructed using eCSGAN and compressive sensing (CS) shows that the proposed method can remarkably increase the quality in image reconstruction with a lower sampling rate. The feasibility and security of the proposed method are demonstrated by the numerical simulations and optical experiment results.
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This paper proposes a Tchebichef moment (TM)-based image definition assessment (IDA) method that employs the difference in the logarithmic spectra (DLS). To avoid the influence of the original image, the essential element point spread function (PSF) is extracted from the DLS to characterize the IDA function uniquely. The amplification of the PSF spot radius to the defocus amount in the micro-imaging system enhances the featural differences among the DLSs, thereby improving the sensitivity to the defocus amount. The DLS with an obvious geometric feature variation is described by a TM with a low order, which improves the anti-noise performance. The performed simulation and experiment verified the superiority of the proposed method.
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A common-path interferometer for the real-time measurement of the liquid-crystal (LC) optic-axis angle and effective refractive index distribution is proposed. This method involves adding a polarizer and polarization camera to a general optical microscope. This requires only single-exposure imaging without changing any optical elements, and greatly simplifies the measurement process and system. In addition, the measurement results are unaffected by light-source power fluctuations or a non-uniform spatial distribution. Therefore, this method is suitable for measuring the LC optic-axis angle and effective refractive index of electrically controlled LC devices. Finally, the feasibility and validity of the proposed method are verified by simulation and experimentation.
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A metal nanoparticles-based surface-enhanced Raman scattering (SERS) technique has been developed for biosensing and bioimaging due to its advantages in ultra-narrow line width for multiplexing, ultra-high sensitivity and excellent photostability. However, the "hotspots" effect between nanoparticles usually leads to unstable and nonuniform Raman enhancement, and this will greatly reduce the quality of SERS imaging. In this study, we employ the bridge gaps-enhanced Raman tags (BGERTs) to perform SERS imaging, in which BGERTs can not only reduce the influence of the "hotspots" effect between nanoparticles on Raman signal intensity but provide a great Raman enhancement when the Gold (Au) shell is thick enough. Based on BGERTs and its conjugation with the thiol-terminated polyethylene glycol (PEG) and transferrin, we construct a targeted Transferrin (TF)-PEG-BGERTs SERS nanoprobe and achieve the dynamic imaging of transferrin receptor (TfR) molecules on a single live cell, in which the role of transferrin-conjugated PEG-BGERT is for targeting TfR molecules located in cellular membrane surface. Importantly, this BGERTs-based SERS imaging could potentially provide a useful tool for studying the precise mechanism during the receptor-mediated nanoparticles endocytosis or cell proliferation, apoptosis, and other complicated molecular events.
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Berberine (BBR), a traditional Chinese herb extract medicine, reveals some anticancer effects in leukemia, but it remains controversial about the molecular mechanism of BBR-induced leukemia cell apoptosis. In this study, combining Raman spectrum and spectral imaging, both the biochemical changes of BBR-induced Jurkat cell apoptosis and the precise distribution of BBR in single cell are presented. In contrast, we also show the corresponding results of Jatrorrhizine (JTZ) and Palmatine (PMT), two structural analogues of BBR. It is found that all three structural analogues can induce cell apoptosis by breaking DNA and the main action sites are located in phosphate backbone and base pair groups, but their action on cell cycle are different, in which BBR leads to the S phase arrest while JTZ and PMT are on the G2 phase arrest. Moreover, from the Raman spectra of DNA treated with different drugs, we find that the content of phosphate backbone and base pair groups in BBR-treated DNA are larger than those in JTZ or PMT. And this result reflects the strong capability of BBR breaking DNA backbone relative to JTZ or PMT, suggesting that the existence of methylene-dioxy on the 2, 3 units of A ring on the quinoline ring can greatly enhance the capability of BBR breaking DNA backbone, so the action effect of BBR-induced Jurkat cell apoptosis is better than those of PMT or JTZ. Further, by using Raman spectral imaging approach, we achieve the precise distribution of BBR in single cell, it is found that the receptor-mediated BBR targeting delivery based single-wall carbon nanotube and folic acid (SWNT/FA) reveals excellent performance in BBR targeting delivery relative to the conventional BBR diffusion approach. Importantly, these results demonstrate that Raman spectrum and spectral imaging should be a powerful tool to study the molecular mechanism of drug-induced cell apoptosis and evaluate the efficiency of drug delivery system.
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Polymers with superior mechanical properties are desirable in many applications. In this work, polyethylene (PE) films reinforced with exfoliated thermally reduced graphene oxide (TrGO) fabricated using a roll-to-roll hot-drawing process are shown to have outstanding mechanical properties. The specific ultimate tensile strength and Young's modulus of PE/TrGO films increased monotonically with the drawing ratio and TrGO filler fraction, reaching up to 3.2 ± 0.5 and 109.3 ± 12.7 GPa, respectively, with a drawing ratio of 60× and a very low TrGO weight fraction of 1%. These values represent by far the highest reported to date for a polymer/graphene composite. Experimental characterizations indicate that as the polymer films are drawn, TrGO fillers are exfoliated, which is further confirmed by molecular dynamics (MD) simulations. Exfoliation increases the specific area of the TrGO fillers in contact with the PE matrix molecules. Molecular dynamics simulations show that the PE-TrGO interaction is stronger than the PE-PE intermolecular van der Waals interaction, which enhances load transfer from PE to TrGO and leverages the ultrahigh mechanical properties of TrGO.
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Rigid H-shaped pentiptycene units, with an intrinsic hierarchical structure, were employed to fabricate a highly microporous organic polymer sorbent via Friedel-Crafts reaction/polymerization. The obtained microporous polymer exhibits good thermal stability, a high Brunauer-Emmett-Teller surface area of 1604 m2 g-1, outstanding CO2, H2, and CH4 storage capacities, as well as good adsorption selectivities for the separation of CO2/N2 and CO2/CH4 gas pairs. The CO2 uptake values reached as high as 5.00 mmol g-1 (1.0 bar and 273 K), which, along with high adsorption selectivity values (e.g., 47.1 for CO2/N2), make the pentiptycene-based microporous organic polymer (PMOP) a promising sorbent material for carbon capture from flue gas and natural gas purification. Moreover, the PMOP material displayed superior absorption capacities for organic solvents and dyes. For example, the maximum adsorption capacities for methylene blue and Congo red were 394 and 932 mg g-1, respectively, promoting the potential of the PMOP as an excellent sorbent for environmental remediation and water treatment.
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Without the limitations of fringe number and fringe shape, a dual-channel simultaneous spatial and temporal polarization (DC-SSTP) phase-shifting interferometry system is proposed to achieve rapid and accurate phase retrieval through only one-time phase-shifting procedure with unknown phase shifts. First, an arbitrary phase shifts is simultaneously introduced into two channels of DC-SSTP system by a spatial light modulator (SLM). Second, by performing the subtraction operation between each pair of phase-shifting interferograms captured in the same channel, the background deduction of interferogram can be achieved easily, so the accurate phase can be retrieved rapidly. Especially, it is found even if the fringe number in interferogram is less than one, the proposed DC-SSTP method still reveals high accuracy of phase retrieval. Both the simulation and experimental results demonstrate the outstanding performance of proposed DC-SSTP method in phase measurement.
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Cell refractive index, an intrinsic optical parameter, is closely correlated with the intracellular mass and concentration. By combining optical phase-shifting interferometry (PSI) and atomic force microscope (AFM) imaging, we constructed a label free, non-invasive and quantitative refractive index of single cell measurement system, in which the accurate phase map of single cell was retrieved with PSI technique and the cell morphology with nanoscale resolution was achieved with AFM imaging. Based on the proposed AFM/PSI system, we achieved quantitative refractive index distributions of single red blood cell and Jurkat cell, respectively. Further, the quantitative change of refractive index distribution during Daunorubicin (DNR)-induced Jurkat cell apoptosis was presented, and then the content changes of intracellular biochemical components were achieved. Importantly, these results were consistent with Raman spectral analysis, indicating that the proposed PSI/AFM based refractive index system is likely to become a useful tool for intracellular biochemical components analysis measurement, and this will facilitate its application for revealing cell structure and pathological state from a new perspective.