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Background Hypertension is a kind of clinical syndrome, characterized by the increase of systemic arterial pressure. There is a lack of identifiable triggers and predictors of hypertensive disease in response to treatment at rest and during exercise. In this study, a mathematical model was used to screen and compare the indicators and related changes at rest and during exercise between normotensive and hypertensive individuals. Methods Blood pressure and ultrasound-related indicators, blood biochemical indicators and metabolic compounds were collected and logistic regression model and Principal component analysis (PCA) were used to explore the differences of indexes at rest and in different exercise states in healthy and hypertensive patients. An indicator change map for hypertension is established. Results The results reveal that hypertension is not only related to oxidative stress, inflammatory reaction and fatty acid oxidation, but also involves various amino acid metabolism. The defined mathematical models and indicators changes during exercise might be helpful for early screening of hypertension and future studies are needed to explore their value on prevention and control of hypertension. Conclusion The research shows that the main regulation indicators at different exercise states differ significantly in the normal group and the hypertensive group. The key indicators of the normal group are blood pressure and ultrasound related indicators, while those of the hypertensive group are metabolites related to lactic acid metabolism, glycolysis, aerobic oxidation and lipid metabolism.

Dipyrrolydiketones BF2 complex was synthesized and characterized by NMR, HRMS, and single crystal diffraction. In non-polar environment, this BF2 containing dye emitted bright blue-green fluorescence. No significant spectra shift was observed both in absorption and emission spectra, which indicates the insensitivity of absorption/emission toward environment. The alkyl substituted pyrrole rings lead to its highly emission character in solid state by enhancing the distance between dye molecules. Absolute quantum yields were determined to be 0.51-0.78/0.36 in selected organic medium and solid state, respectively. The emission dynamics was investigated by fluorescence lifetime and both monoexponential and bi-exponential decay was observed.

The identification of cone photoreceptor cells is important for early diagnosing of eye diseases. We proposed automatic deep-learning cone photoreceptor cell identification on adaptive optics scanning laser ophthalmoscope images. The proposed algorithm is based on DeepLab and bias field correction. Considering manual identification as reference, our algorithm is highly effective, achieving precision, recall, and F 1 score of 96.7%, 94.6%, and 95.7%, respectively. To illustrate the performance of our algorithm, we present identification results for images with different cone photoreceptor cell distributions. The experimental results show that our algorithm can achieve accurate photoreceptor cell identification on images of human retinas, which is comparable to manual identification.

BACKGROUND Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment. CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient’s T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo. CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.

miRNA-223 has been previously reported to play an essential role in hepatic cholesterol homeostasis. However, its role in regulation of biliary cholesterol secretion and gallstone formation remains unknown. Hence, mice with conventional knockout (KO), hepatocyte-specific knockout (ΔHepa) / knockdown (KD) or gain expression of miRNA-223 were included in the study and were subjected to lithogenic diet (LD) for various weeks. The gall bladders and liver tissues were harvested for cholesterol crystal imaging, gallstone mass measurement and molecular analysis. Levels of cholesterol, bile salt, phospholipids, and triglyceride were determined in serum, liver tissues, and bile by enzyme color reactive assays. A 3' UTR reporter gene assay was used to verify the direct target genes for miRNA-223. LD-induced gallstone formation was remarkably accelerated in miRNA-223 KO, ΔHepa, and KD mice with concurrent enhancement in total cholesterol levels in liver tissues and bile. Key biliary cholesterol transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented gallstone progression with reduced targets expression. Therefore, the present study demonstrates a novel role of miRNA-223 in the gallstone formation by targeting ABCG5 and ABCG8 and elevating miRNA-223 would be a potentially novel approach to overcome the sternness of cholesterol gallstone disease.

Activation and migration of donor T cells to the host target organs are critical mechanisms in the pathogenesis of graft-versus-host disease (GVHD). The role of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 in the recruitment of T cells during immune or inflammatory response is also well known. For elucidation of the mechanism of the therapeutic effect of human bone marrow derived-mesenchymal stem cells (MSC) in GVHD, we studied the effect of these cells on migration of activated donor T cells through the CCL2-CCR2 axis in vitro. MSC were expanded from donors' bone marrow mononuclear cells. After co-culturing of IL-2-activated T cells with allogeneic MSC at different ratios, the levels of CCL2 in supernatants were measured by ELISA, and CCR2 expression in CD4+/CD8+ T cells subsets were detected by flow cytometry. The effect of MSC on the migration of activated T cells in the Transwell system was studied in the absence or presence of CCL2. Our results show that CCL2 levels in supernatants of co-cultures were significantly higher than in MSC monoculture and this increase depended on the number of MSC. MSC inhibited proliferation of T cells, but did not change the percentages of CD4+ and CD8+ T cells subsets. MSC can up-regulate the CCR2 expression in CD8+ subsets rather than in CD4+ subsets; MSC enhanced migration of IL-2-activated T cells to CCL2 by increasing the expression of CCR2. The data demonstrate that MSC can enhance chemotaxis of cytokine-activated T cells through the CCL2-CCR2 axis in vitro.

Previous research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

With the popularization of the emerging 3C products (e.g., smartwatches, smart entertainment robots, and various wearable devices), printed circuit boards (PCBs), considered as the core of electronic products, have gained more attention in terms of the performance in the quality control. Many studies have been conducted and outstanding results have been obtained. However, there are still many challenges, e.g., the complexity and diversity of the PCB small defect dataset. To further cope with the above problems, the improved YOLOv4 algorithm is designed and verified in terms of the detection performance on a public PCB small defect dataset. First, the size distributions of six class defect images are analyzed; the reasonable size of anchor boxes is re-designed and assigned to multiscale feature layers. Second, the ADD-path module and the DSCBlock-W module combined with the MobiletNetv2 module are used to construct the backbone of the YOLOv4 method. Finally, the fusion of multilevel features is enhanced and the data information of the low-level feature is fully utilized, thereby enabling YOLOv4 to better detect small defects. Compared to different state-of-the-art methods, the improved YOLOv4 method obtains an mAP as high as 99.71%, which confirms the efficiency and accuracy of the improved method.

Acute demyelinating myelopathy after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, and the exact pathogenesis remains unclear. Here, we report the case of a 20-year-old patient with B-cell acute lymphocyte leukemia (B-ALL) who developed acute demyelinating myelopathy approximately 10 months after HSCT. Magnetic resonance imaging revealed high T2 signal intensity lesions from the C2-T4 levels of the spinal cord. Treatments with high doses of corticosteroids, immunoglobulins, and rituximab improved his neurologic symptoms, and he achieved 44 months of leukemia-free and graft-versus-host disease (GVHD)-free survival, with no recurrence of the demyelination myelopathy. An understanding of the contribution of immune reconstitution to the pathogenesis of demyelinating myelopathy after HSCT and the association of this disease with GVHD will require more clinical cases.

This study presents an automated registration method based on optical flow for an adaptive optics scanning laser ophthalmoscope. The method was designed to align and average images to obtain a higher signal-to-noise ratio image. A correlation based optical flow image registration method, which has large registration degrees of freedom, is adopted as a local registration method. By comparing the images before and after image registration, we show the effectiveness of our method. Furthermore, the advantage of our method, which is the containment of large registration degrees of freedom, is confirmed.

Bacterial endotoxin is considered as one of the critical risk factors in medical devices, especially implanted devices that directly or indirectly contact with blood circulating system. In that case, endotoxin limits for implanted medical devices is important in determine the safety of medical devices. According to GB/T 14233.2-2005, the requirements of endotoxin index for intrathoracic medical devices is 2.15 EU per device. However, the definition of "intrathoracic medical devices" is vague. Specifically, "for cardiovascular system application" instead of "intrathoracic application" is more reasonable. With the deeper understanding of the risk of endotoxin in medical devices and considering the internationally accepted standards, the limits of endotoxin in medical devices for cardiovascular system application is acceptable at 20 EU per device.

Background. It is well known that microRNAs (miRNAs) interfere with the progression of various human malignancies. This article is aimed at exploring the regulating role of miR-342-3p in acute myeloid leukemia (AML) and its mechanism. Methods. We used the Gene Expression Omnibus (GEO) database to determine miR-342-3p differential expression patterns in AML patients’ plasma and cells as well as healthy individuals’ plasma and T cells. Quantitative real-time PCR and Western blotting were performed for plasma and cell miR-342-3p and SRY-related high-mobility-group box (SOX12) expression quantification, and cell counting kit-8 assay and flow cytometry were used for the determination of AML cell growth, cycle, and apoptosis. A dual-luciferase reporter gene assay was further carried out to identify the targeted association between miR-342-3p and SOX12 mRNA 3 ′ UTR after prediction by a bioinformatics website. Pearson’s correlation analysis was performed to analyze the connection between miR-342-3p and SOX12 expressions. The LinkedOmics database was utilized to explore the downstream pathways in which SOX12 was enriched. Results. Evidently downregulated plasma miR-342-3p and markedly elevated SOX12 were observed in AML patients versus healthy individuals. miR-342-3p mimics suppressed AML cell growth, enhanced apoptosis, and induced G0/G1 phase arrest; conversely, enhanced capacity of AML cells to proliferate, suppressed apoptosis, and accelerated cell cycle were observed after treatment with miR-342-3p inhibitors. SOX12 was confirmed as miR-342-3p’s target gene. Overexpressing or knocking down SOX12 reversed miR-342-3p’s impacts on AML cell growth, apoptosis, and cycle. Upregulated SOX12 was positively related to DNA replication and RNA polymerase signaling pathways. Conclusion. miR-342-3p affects apoptosis of AML cells and their ability to proliferate via targeted regulation of SOX12.

In this work, we developed a motion estimation and correction method which real-time obtained the direction and displacement of repetitive micro bulk motion (such as cardiac and respiratory motion) on an SS-OCT system without additional tracking hardware, and reduced the motion noise in optical coherence tomography angiography (OCTA). In the approach, the direction of repetitive micro bulk motion was considered fixed, and proportional relationships between the motion components in three directions were determined; Then we performed one-dimension cross-correlation to obtain depth displacement which was further used to obtain other two motion components, and greatly reduced the computation; The processing speed on a graphic processing unit was 478 pairs of B-Scans per second, and the measurement range was larger than the range of the angiogram-based methods. Lastly, corrupt angiograms were recovered by adaptive scan protocol, and reduced acquisition time in comparison with the previous work. This article is protected by copyright. All rights reserved.

Identification of cone photoreceptor cells (CPCs) is essential for the diagnosis and treatment of various retinal disorders. In the present work, a new automated unsupervised learning-based method is proposed for the identification of CPCs in adaptive optics scanning laser ophthalmoscope images. This method consists of the following steps: image denoising, CPC number estimation, bias field correction, unsupervised CPC identification, and merging close CPC identification data. By comparing our results with those obtained manually, it was found that the proposed method showed high effectiveness, with the precision, recall and F1 score values of 92.9%, 84.4% and 88.4%, respectively. Furthermore, healthy retinal AO-SLO images with the difference in CPC densities and pathological (diabetic retinopathy) AO-SLO images are processed by our method. The results demonstrated that our method exhibited a good accuracy for the identification of CPCs in diabetic retinopathy and healthy retinas.

Backgroud: Pressure injuries (PIs) bring a considerable physical and mental burden on immobile patients, and have put families and government under tremendous pressure to cover the cost of treatment. Therefore, this protocol proposes to identify risk factors of developing PIs in immobile patients from systematic reviews (SRs) and clinical practice guidelines (CPGs), in order to establish a risk prediction model for developing PIs and identify individual risk factors that can be modified to aid prevention. Methods: Electronic databases and specific databases for CPGs and SRs will be searched. Study selection and data collection will be performed independently by two reviewers. All included SRs and CPGs will be subject to critical appraisal. RevMan 5.3 will be used to calculate the pooled odds ratio (ORP) after appraising the quality of eligible studies, and the risk predictive model will be established using logistic regression model. A narrative synthesis, evidence summary table, and Sankey diagram will also be performed. Results: The results of this study will be submitted to a peer-reviewed journal for publication. Conclusion: This systematic review will provide a risk prediction model of PI developing. INSPLAY registration number: INPLASY2020100097

BackgroudMiRNA-223 has previously been reported to play an essential role in hepatic cholesterol homeostasis by suppressing cholesterol synthesis, attenuating cholesterol uptake by hepatocyte from and promoting cholesterol efflux into the blood. However, its role in regulation of biliary cholesterol secretion and gallstone formation remains unknown.MethodsMice with conventional knockout (KO), hepatocyte-specific knockout (ΔHepa) / knockdown (KD) or gain expression of miRNA-223 were included in the study and were subjected to lithogenic diet (LD) for various weeks. The gallbladders were harvested and subjected to cholesterol crystal imaging and gallstone mass measurement. Liver tissues were collected for western blotting, RT-qPCR, and immunohistochemistry staining. Levels of cholesterol, bile salt, phospholipids, and triglyceride were determined in serum, liver tissues, and bile by enzyme color reactive assays. 3’ UTR reporter gene assays were used to verify the direct target genes for miRNA-223.ResultsLD-induced gallstone formation was remarkably accelerated in miRNA-223 KO, ΔHepa, and KD mice with concurrent enhancement in total cholesterol levels in liver tissue and bile. Key biliary cholesterol transporters ABCG5 and ABCG8 were identified as direct targets of miRNA-223. Reversely, AAV-mediated hepatocyte-specific miRNA-223 overexpression prevented gallstone progression with reduced targets protein expression.ConclusionThe present study demonstrates a novel role of miRNA-223 in the regulation of hepatic bile cholesterol secretion pathway and gallstone formation by targeting ABCG5 and ABCG8 expression. Therefore, elevating miRNA-223 would be a potentially novel approach to overcome the sternness of cholesterol gallstone disease.Graphical Abstract

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN.

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases.

W2Zr intermetallic is an important reason for the brittleness of W–Zr binary system. When W–Zr alloys are used as the energetic fragment, the integrity of a projectile cannot be maintained under the explosion even propellant loading process, resulting in severe fracture of the projectile. Moreover, due to the strong atomic bonding in W2Zr intermetallic, the oxidation reactivity of the Zr atoms with oxygen in the air is significantly suppressed, limiting the effective energy release of W–Zr fragment under high-speed impacting process. In this study, based on the thermodynamic analysis, 30W-xTi-(70-x)Zr (wt.%) alloys were designed and prepared by powder metallurgy. It was found that the formation and stabilization temperature of W2Zr phase can be reduced by increasing the Ti content. The hard W-rich phase has changed from the coarse W2Zr particle to fine W2Zr precipitate and finally to the WTix solid solution with the increase of Ti content. Meanwhile, a semi-coherent interface between fine W2Zr precipitate and α matrix and even coherent interface between WTix and α matrix were formed, by which the intergranular fracture ratio between W-rich phases and α matrix was significantly decreased in the W–Ti–Zr alloys. Consequently, higher dynamic compressive strength and ductility of the W–Ti–Zr alloys were obtained by increasing the Ti content. The selected W–Ti–Zr alloys with high strength and proper failure strain exhibited good penetration and energy-releasing behaviors when they were used as reactive bullet launching at a velocity of about 1250 m/s. The relationship among the dynamic compressive strength, ductility and ballistic performance of the W–Ti–Zr reactive structural alloys was also discussed in detail.

Cone photoreceptor cell identification is important for the early diagnosis of retinopathy. In this study, an object detection algorithm is used for cone cell identification in confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images. An effectiveness evaluation of identification using the proposed method reveals precision, recall, and [Formula: see text]-score of 95.8%, 96.5%, and 96.1%, respectively, considering manual identification as the ground truth. Various object detection and identification results from images with different cone photoreceptor cell distributions further demonstrate the performance of the proposed method. Overall, the proposed method can accurately identify cone photoreceptor cells on confocal adaptive optics scanning laser ophthalmoscope images, being comparable to manual identification.

A reliable single-image denoising method is presented for adaptive optics scanning laser ophthalmoscopy. This method firstly averaged multiple images and then used the averaged image as the reference to adjust the parameters of the filtering process that was subsequently applied to other individual images. Six filtering methods, including the mean, median, Gaussian, fast adaptive nonlocal synthetic aperture radar despeckling, K-single value decomposition, and block matching and three-dimensional filtering, were utilized. The effectiveness of our method was verified based on the comparison of sets of images without and with parameter adjustments. Furthermore, we applied the same parameter settings as those obtained from the filter adjustments of another adaptive optics scanning laser ophthalmoscope image acquired by the same instrument. The filtered images showed that the parameter-adjusted filters work well on other images, which is helpful for improving the image quality of adaptive optics scanning laser ophthalmoscope images.

The damage effect of reactive structural materials (RSMs) is one of the focuses in this field. In this study, four new Zr-Ti-W alloys were prepared by adding Ti element on the basis of W-Zr alloys. These alloys have different densities and mechanical properties. The damage effect of these alloys on 18 mm thick Q235 steel plate under the condition of 1600— 1700 m/s impacting speed was investigated. The results show that the penetration power of Zr-Ti-W alloy is mainly affected by the density of the alloy. The higher the density is, the greater the penetration depth and crater diameter of the alloy bullet are. In addition to the high penetration depth and large crater diameter, the 20Ti alloy also exhibits excellent energy-releasing behavior. This alloy has the tremendous potential to be used as reactive fragments in military application. Besides, the Zr-Ti-W alloys designed in this study maintain good integrity under extreme loading conditions, which had successfully overcome the problem of poor overload resistance of W-Zr alloys.

peer-reviewed .Inorganic scintillating material used in optical fibre sensors (OFS) when used as dosimeters for measuring percentage depth dose (PDD) characteristics have exhibited significant differences when compared to those measured using an ionization chamber (IC), which is the clinical gold standard for quality assurance (QA) assessments. The percentage difference between the two measurements is as high as 16.5% for a 10 × 10 cm2 field at 10 cm depth below the surface. Two reasons have been suggested for this: the presence of an energy effect and Cerenkov radiation. These two factors are analysed in detail and evaluated quantitatively. It is established that the influence of the energy effect is only a maximum of 2.5% difference for a beam size 10 × 10 cm2 compared with the measured ionization chamber values. And the influence of the Cerenkov radiation is less than 0.14% in an inorganic scintillating material in the case of OFS when using Gd2O2S:Tb as the luminescent material. Therefore, there must be other mechanisms leading to over-response. The luminescence mechanism of inorganic scintillating material is theoretically analysed and a new model is proposed and validated that helps explain the over-response phenomenon PUBLISHED peer-reviewed

Cone cell identification is essential for diagnosing and studying eye diseases. In this paper, we propose an automated cone cell identification method that involves TV-L1 optical flow estimation and K-means clustering. The proposed algorithm consists of the following steps: image denoising based on TV-L1 optical flow registration, bias field correction, cone cell identification based on K-means clustering, duplicate identification removal, identification based on threshold segmentation, and merging of closed identified cone cells. Compared with manually labelled ground-truth images, the proposed method shows high effectiveness with precision, recall, and F1 scores of 93.10%, 94.97%, and 94.03%, respectively. The method performance is further evaluated on adaptive optics scanning laser ophthalmoscope images obtained from a healthy subject with low cone cell density and subjects with either diabetic retinopathy or acute zonal occult outer retinopathy. The evaluation results demonstrate that the proposed method can accurately identify cone cells in subjects with healthy retinas and retinal diseases.