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Abstract Background To explore the functional and morphological variations of retinal vessels in diabetes with no clinically detectable retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) and to establish a high-performance mild NPDR diagnostic model. Methods Normal subjects and type 2 diabetes patients with NDR and mild NPDR were recruited. Oxygen-saturation-related functional parameter (optical density ratio ODR) and morphological characteristics (fractal dimension Df, vessel area rate VAR, mean vascular diameter Dm, vessel tortuosity τ) of different vascular areas were extracted with single fundus photography and comprehensively analyzed among groups. An interpretable model combining marine predator algorithm (MPA) and support vector machine (SVM) based on characteristic selection was proposed for mild NPDR diagnosis. Results A total of 91 NDR subjects, 75 mild NPDR subjects, and 111 sex- and age-matched normal controls were analyzed. Increased main vessels ODR, while lower VAR of all areas except outer ring macula, lower Dm of all vessels and decreased τ of all areas were associate with NDR (e.g. main vessels ODR: OR [95%CI] 1.42[1.07–1.89], full macula τ:0.53[0.38–0.74]). Increased ODR of all areas, higher Dm of all areas except inner ring macula, increased inner ring macula τ, while decreased Df of full and inner ring macula, lower VAR of all areas were associate with mild NPDR (e.g. main vessels ODR:5.68[3.03–10.65], inner ring macula VAR: 0.48[0.33–0.69]). The MPA-SVM model with selected characteristics obtained the best diagnosis performance (AUC:0.940 ± 0.014; Accuracy:90.4 ± 3.9%; Sensitivity:89.2 ± 6.4%; Specificity:91.3 ± 6.4%). Conclusions More significant retinal vascular variations are associate with the incidence of mild NPDR than NDR. High-precision mild NPDR diagnosis is achieved combining the morphological and functional vascular characteristics based on characteristic selection.

Abstract Background The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure–function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). Methods A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient’s whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein–protein docking (HADDOCK) algorithm and protein–ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. Results Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. Conclusion Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Introduction Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). Methods Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. Results NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. Conclusion Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.

Abstract Gastric cancer (GC) is a pressing global clinical issue, with few treatment options and a poor prognosis. The onset and spread of stomach cancer are significantly influenced by changes in lipid metabolism-related pathways. This study aimed to discover a predictive signature for GC using lipid metabolism-related genes (LMRGs) and examine its correlation with the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients with GC were collected from the TCGA and GEO databases. Data from GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentially expressed LMRGs (DE-LMRGs), differential expression and prognosis studies were carried out. We built a predictive signature using LASSO regression and tested it on the TCGA and GSE84437 datasets. In addition, the correlation of the prognostic signature with the TIME was comprehensively analyzed. In this study, we identified 258 DE-LMRGs in GC and further screened seven survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed genes (DEGs) between the three branches. Two critical genes (GPX3 and NNMT) were identified using the above two gene groups. In addition, a predictive risk score that relies on GPX3 and NNMT was developed. Survival studies in both the TCGA and GEO datasets revealed that patients categorized to be at low danger had a significantly greater prognosis than those identified to be at high danger. Additionally, by employing calibration plots based on TCGA data, the study demonstrated the substantial predictive capacity of a prognostic nomogram, which incorporated a risk score along with various clinical factors. Within the high-risk group, there was a noticeable abundance of active natural killer (NK) cells, quiescent monocytes, macrophages, mast cells, and activated CD4 + T cells. In summary, a two-gene signature and a predictive nomogram have been developed, offering accurate prognostic predictions for general survival in GC patients. These findings have the potential to assist healthcare professionals in making informed medical decisions and providing personalized treatment approaches.

To respond the recent experimental advances, the phase stability, mechanical properties, phonon as well as infrared- and Raman-active modes, thermal expansion and heat capacity were investigated by density functional theory for the S-containing MAX carbides and borides (M from III B to VIII B), of importance, well consistent with the available experimental results. After examining the thermodynamic competition with all the competing phases and intrinsic stability by their lattice dynamics, 18 MAX phases were screened out from 138 ones. Using the “bond stiffness” model as well as the associated criterion for damage tolerance and fracture toughness, the ratio of bond stiffness of weakest M−S to the strongest M-X bonds (kmin/kmax) over 1/2 indicates their intrinsic brittleness of all S-containing MAX phases except Nb4SC3. Including the contributions from phonon and electrons, their linear thermal expansion coefficients [(8.1–13.6)×10−6 K−1, 300–1,300 K] and heat capacities (Cp) as a function of temperature are predicted. Of much interest, a well-established relationship between molar Cp of the MAX and MX phases is theoretically deduced in the present work.

A 314-type MAB phase V3PB4 with hexagonal crystal structure is synthesized by self-propagating high temperature combustion synthesis (SHS), with the help of the full first-principles predictions for the phase stability and adiabatic combustion temperature of SHS. Using XRD and TEM, V3PB4 crystallizes in the space group of P6¯m2, with the lattice parameters a = 3.030 Å and c = 9.148 Å, of much interest, well with the predicted one. Furthermore, the electronic structure, chemical bonding, and elastic properties of hex-V3PB4 are predicted by first-principles. No bandgap around Fermi energy indicates its electronic conductor. And the strong covalent bonding is present between the B and V atoms with, significantly, much weaker V-P bond. With the help of the theoretical model of bond stiffness, the significantly high ratio of bond stiffness of weakest bonds to the strongest ones (0.873) of hex-V3PB4 indicates its poor damage tolerance and fracture toughness. The high bond stiffness results in its high moduli in comparison with other MAB phases. As the number of inserted P atoms increases, the engineering elastic modulus decrease, without the price of an increase in density.

Background. The primary pathogen responsible for bronchoscope contamination is Pseudomonas aeruginosa. Conventional techniques for bronchoscopy disinfection and pathogen identification methods are characterized by time-consuming and operation complexly. The objective of this research is to establish a prompt and precise method for the identification of Pseudomonas aeruginosa, with the ultimate goal of mitigating the risk of nosocomial infections linked to this pathogen. Methods. The magnetic nanoparticles (MNPs) were synthesized in a single step, followed by the optimization of the coating process with antibodies and invertase to produce the bifunctionalized IMIc. Monoclonal antibodies were immobilized on microplates for the specific capture and enrichment of Pseudomonas aeruginosa. Upon the presence of Pseudomonas aeruginosa, the monoclonal antibodies, the test sample, and the IMIc formed sandwich structures. The subsequent addition of a sucrose solution allowed for the detection of glucose produced through invertase hydrolysis by a personal glucose meter, enabling quantitative assessment of Pseudomonas aeruginosa concentration. Results. TEM image demonstrates that the MNPs exhibit a consistent spherical shape. NTA determined that the grain diameter of magnetic nanoparticles was 200 nm. FTIR spectrum revealed the successful modification of two carboxyl groups on the MNPs. The optimization of the incubation pH of the microplate-coated antibody was 7. The optimization of the incubation time of the microplate-coated antibody was 2 h. The optimization of the ligation pH for the polyclonal antibody was 5. Reaction times of polyclonal antibodies linked to magnetic beads was 1 h. The pH of invertase linked by magnetic beads was 4. Conclusion. This article presents a novel qualitative and quantitative immunoassay for point-of-care monitoring of P. aeruginosa utilizing PGM as a readout. The PGM represents a convenient and accurate quantitative detection method suitable for potential clinical diagnostic applications.

Abstract Background Accumulated evidence highlights the significance of the crosstalk between epigenetic and epitranscriptomic mechanisms, notably 5-methylcytosine (5mC) and N6-methyladenosine (m6A). Herein, we conducted a widespread analysis regarding the crosstalk between 5mC and m6A regulators in hepatocellular carcinoma (HCC). Methods Pan-cancer genomic analysis of the crosstalk between 5mC and m6A regulators was presented at transcriptomic, genomic, epigenetic, and other multi-omics levels. Hub 5mC and m6A regulators were summarized to define an epigenetic and epitranscriptomic module eigengene (EME), which reflected both the pre- and post-transcriptional modifications. Results 5mC and m6A regulators interacted with one another at the multi-omic levels across pan-cancer, including HCC. The EME scoring system enabled to greatly optimize risk stratification and accurately predict HCC patients’ clinical outcomes and progression. Additionally, the EME accurately predicted the responses to mainstream therapies (TACE and sorafenib) and immunotherapy as well as hyper-progression. In vitro, 5mC and m6A regulators cooperatively weakened apoptosis and facilitated proliferation, DNA damage repair, G2/M arrest, migration, invasion and epithelial-to-mesenchymal transition (EMT) in HCC cells. The EME scoring system was remarkably linked to potential extrinsic and intrinsic immune escape mechanisms, and the high EME might contribute to a reduced copy number gain/loss frequency. Finally, we determined potential therapeutic compounds and druggable targets (TUBB1 and P2RY4) for HCC patients with high EME. Conclusions Our findings suggest that HCC may result from a unique synergistic combination of 5mC-epigenetic mechanism mixed with m6A-epitranscriptomic mechanism, and their crosstalk defines therapeutic response and pharmacogenomic landscape.

Purpose: To develop a computational method for oxygen-saturation-related functional parameter analysis of retinal vessels based on traditional color fundus photography, and to explore their characteristic alterations in type 2 diabetes mellitus (DM).Methods: 50 type 2 DM patients with no-clinically detectable retinopathy (NDR) and 50 healthy subjects were enrolled in the study. An optical density ratio (ODR) extraction algorithm based on the separation of oxygen-sensitive and oxygen-insensitive channels in color fundus photography was proposed. With precise vascular network segmentation and arteriovenous labeling, ODRs were acquired from different vascular subgroups, and the global ODR variability (ODRv) was calculated. Student’s t-test was used to analyze the differences of the functional parameters between groups, and regression analysis and receiver operating characteristic (ROC) curves were used to explore the discrimination efficiency of DM patients from healthy subjects based on these functional parameters.Results: There was no significant difference in the baseline characteristics between the NDR and healthy normal groups. The ODRs of all vascular subgroups except the micro venule were significantly higher (p

Ocular imaging plays an irreplaceable role in the evaluation of eye diseases. Developing cellular-resolution ophthalmic imaging technique for more accurate and effective diagnosis and pathogenesis analysis of ocular diseases is a hot topic in the cross-cutting areas of ophthalmology and imaging. Currently, ocular imaging with traditional optical coherence tomography (OCT) is limited in lateral resolution and thus can hardly resolve cellular structures. Conventional OCT technology obtains ultra-high resolution at the expense of a certain imaging range and cannot achieve full field of view imaging. In the early years, Time-domain full-field OCT (TD-FF-OCT) has been mainly used for ex vivo ophthalmic tissue studies, limited by the low speed and low full-well capacity of existing two-dimensional (2D) cameras. The recent improvements in system design opened new imaging possibilities for in vivo applications thanks to its distinctive optical properties of TD-FF-OCT such as a spatial resolution almost insensitive to aberrations, and the possibility to control the curvature of the optical slice. This review also attempts to look at the future directions of TD-FF-OCT evolution, for example, the potential transfer of the functional-imaging dynamic TD-FF-OCT from the ex vivo into in vivo use and its expected benefit in basic and clinical ophthalmic research. Through non-invasive, wide-field, and cellular-resolution imaging, TD-FF-OCT has great potential to be the next-generation imaging modality to improve our understanding of human eye physiology and pathology.

Methylated SHOX2 and RASSF1A genes are potential biomarkers for lung cancer diagnosis. Therefore, we explored the role of methylation detection combined with morphological bronchoscopic evaluation for lung cancer diagnosis. Bronchoscopy, methylation outcome, and pathological data were collected from 585 patients with lung cancer and 101 controls. The methylation status of the SHOX2 and RASSF1A genes were detected using real-time polymerase chain reaction quantification. Further, the sensitivity and area under the receiver operating characteristic curve of the three methods were analyzed. Among 686 patients, 57.1% had new lesions detected through bronchoscopy and 93.1% of these patients were diagnosed with malignant tumors. Besides, 42.9% of patients had no visible changes under bronchoscopy but there were still 74.8% of them diagnosed with malignant tumors. Bronchoscopy revealed that lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer mainly occurred in the upper and middle lobes. The sensitivity and specificity of methylation detection were 72.8% and 87.1% (vs. cytology 10.4% & 100%), respectively. Therefore, methylated SHOX2 and RASSF1A genes may be promising tumor markers in lung cancer diagnosis. Methylation detection can be an excellent supplementary tool for cytological diagnosis and, combined with bronchoscopy, could form a more effective diagnostic process.

Objectives The problem of autonomous obstacle avoidance of unmanned surface vehicles (USV) under dense obstacle sea conditions is studied. Methods An improved dual-window dynamic window approach (DWA) obstacle avoidance algorithm based on a fuzzy control strategy is proposed; that is, a sensing window based on an onboard sensor is designed on the basis of the conventional speed window, and a dual-window model composed of the speed window and sensing window is further optimized. The speed space is constrained and the weight of the evaluation function is dynamically adjusted based on the fuzzy control strategy in accordance with the obstacle distribution state and distance between the USV and obstacles. Results The simulation experimental results show that, compared with the original DWA algorithm, the path planned by the improved algorithm under unknown dense obstacle sea conditions is smoother and more reasonable, which not only solves the problem of USVs detouring outside dense obstacle groups, but also improves the safety of obstacle avoidance navigation and reduces the number of iterations and running time by more than 20%. Conclusions The results of this study have certain reference value for research on the autonomous obstacle avoidance technology of USVs.

An organoid is a miniaturized and simplified in vitro model with a similar structure and function to a real organ. In recent years, the use of organoids has increased explosively in the field of growth and development, disease simulation, drug screening, cell therapy, etc. In order to obtain necessary information, such as morphological structure, cell function and dynamic signals, it is necessary and important to directly monitor the culture process of organoids. Among different detection technologies, imaging technology is a simple and convenient choice and can realize direct observation and quantitative research. In this review, the principle, advantages and disadvantages of imaging technologies that have been applied in organoids research are introduced. We also offer an overview of prospective technologies for organoid imaging. This review aims to help biologists find appropriate imaging techniques for different areas of organoid research, and also contribute to the development of organoid imaging systems.