The causal and mediation effect of chronic obstructive pulmonary disease on lung cancer subtypes: a two-sample mendelian randomization study.

PURPOSE: This study aims to determine the causal effect of chronic obstructive pulmonary disease (COPD) on different subtypes of lung cancer and to investigate the mediation effects of COPD between smoking and the subtypes of lung cancer. METHODS: The study utilized summary level data from genome-wide association studies. It extracted independent single nucleotide polymorphisms (SNP) to serve as instrumental variables (IV). We conducted two-sample MR analyses primarily using inverse-variance weighting, as well as MR-Egger and MR-PRESSO to establish and validate the causal impact of COPD on lung cancer subtypes. Additionally, multivariable MR analysis was employed to ascertain the mediating role of COPD between smoking and lung cancers. RESULTS: The two-sample MR analysis demonstrated that COPD is linked to an elevated risk of lung adenocarcinoma (OR: 1.48, 95% CI 1.35-1.61, p = 0.009) and squamous cell carcinoma (OR: 1.78, 95% CI 1.62-1.93, p = 0.001). Further, using multivariable MR, it was established that COPD mediates the causal effects of smoking on lung adenocarcinoma by 56.52% (95% CI 17.51-95.52%) and 63.61% (95% CI 38.31-88.92%) in lung squamous cell carcinoma. CONCLUSION: Our study found that COPD was a risk factor for developing both lung adenocarcinoma and squamous cell carcinoma. COPD also played a crucial role in mediating the causal effects of smoking on these two subtypes of lung cancer.

Combining functional and morphological retinal vascular characteristics achieves high-precision diagnosis of mild non-proliferative diabetic retinopathy.

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.

In silico analysis of the wild-type and mutant-type of BRCA2 gene.

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.

Lipid and sugar metabolism play an essential role in pollen development and male sterility: a case analysis in Brassica napus.

AIMS: The genic male sterility (GMS) system is an important strategy for generating heterosis in plants. To better understand the essential role of lipid and sugar metabolism and to identify additional candidates for pollen development and male sterility, transcriptome and metabolome analysis of a GMS line of 1205AB in B. napus was used as a case study. DATA RESOURCES GENERATED: To characterize the GMS system, the transcriptome and metabolome profiles were generated for 24 samples and 48 samples of 1205AB in B. napus, respectively. Transcriptome analysis yielded a total of 156.52 Gb of clean data and revealed the expression levels of 109,541 genes and 8,501 novel genes. In addition, a total of 1,353 metabolites were detected in the metabolomic analysis, including 784 in positive ion mode and 569 in negative ion mode. KEY RESULTS: A total of 15,635 differentially expressed genes (DEGs) and 83 differential metabolites (DMs) were identified from different comparison groups, most of which were involved in lipid and sugar metabolism. The combination of transcriptome and metabolome analysis revealed 49 orthologous GMS genes related to lipid metabolism and 46 orthologous GMS genes related to sugar metabolism, as well as 45 novel genes. UTILITY OF THE RESOURCE: The transcriptome and metabolome profiles and their analysis provide useful reference data for the future discovery of additional GMS genes and the development of more robust male sterility breeding systems for use in the production of plant hybrids.

Involvement of mitochondrial fatty acid ß-oxidation in the antiviral innate immune response in head kidney macrophages of large yellow croaker (Larimichthys crocea).

As a vital pathway for cellular energy production, mitochondrial fatty acid ß-oxidation (FAO) is essential in regulating immune responses to bacterial pathogens and maintaining intracellular homeostasis in vertebrates. However, the specific role of FAO in antiviral innate immune response in macrophages remains insufficiently understood. In this study, virus infection simulated by poly(I:C) inhibited FAO, as indicated by the reduced expression of FAO-related genes and proteins in the head kidney of large yellow croaker, with similar results observed in poly(I:C)-stimulated macrophages. Then, inhibition of FAO by supplementary mildronate in vivo and etomoxir treatment in vitro revealed varying increases in the mRNA expression of antiviral innate immune response genes after stimulated by poly(I:C) in the head kidney and macrophages. Notably, etomoxir significantly facilitated the transcriptional up-regulation of the IFNh promoter by IRF3. Moreover, inhibiting FAO by knockdown of cpt1b promoted antiviral innate immune response triggered by poly(I:C) in macrophages. Conversely, activating FAO through overexpression of cpt1b or cpt2 significantly reduced the mRNA levels of antiviral response genes in macrophages stimulated by poly(I:C). Unlike etomoxir, cpt1b overexpression inhibited the transcriptional up-regulation of the IFNh promoter by IRF3. Furthermore, in vivo dietary palm oil feeding and in vitro exposure to palmitic acid inhibited the antiviral innate immune response triggered by poly(I:C) in the head kidney and macrophages, respectively. These effects were partly associated with FAO activation, as evidenced by etomoxir. In summary, this study elucidates FAO's critical role in regulating antiviral innate immune response in head kidney macrophages. These findings not only deepen insights into the interaction between metabolic remodeling and host immune responses, but also offer valuable guidance for developing nutritional strategies to improve antiviral immunity in aquaculture.

Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer.

AIMS: Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer. METHODS: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo. RESULTS: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells. CONCLUSIONS: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.

Crosstalk between 5-methylcytosine and N6-methyladenosine machinery defines disease progression, therapeutic response and pharmacogenomic landscape in hepatocellular carcinoma.

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.

Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing.

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.

Holo Protein Conformation Generation from Apo Structures by Ligand Binding Site Refinement.

An important part in structure-based drug design is the selection of an appropriate protein structure. It has been revealed that a holo protein structure that contains a well-defined binding site is a much better choice than an apo structure in structure-based drug discovery. Therefore, it is valuable to obtain a holo-like protein conformation from apo structures in the case where no holo structure is available. Meeting the need, we present a robust approach to generate reliable holo-like structures from apo structures by ligand binding site refinement with restraints derived from holo templates with low homology. Our method was tested on a test set of 32 proteins from the DUD-E data set and compared with other approaches. It was shown that our method successfully refined the apo structures toward the corresponding holo conformations for 23 of 32 proteins, reducing the average all-heavy-atom RMSD of binding site residues by 0.48 Å. In addition, when evaluated against all the holo structures in the protein data bank, our method can improve the binding site RMSD for 14 of 19 cases that experience significant conformational changes. Furthermore, our refined structures also demonstrate their advantages over the apo structures in ligand binding mode predictions by both rigid docking and flexible docking and in virtual screening on the database of active and decoy ligands from the DUD-E. These results indicate that our method is effective in recovering holo-like conformations and will be valuable in structure-based drug discovery.

POCT Detection of Pseudomonas aeruginosa by PGM and Application of Preventing Nosocomial Infection of Bronchoscopy.

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.

LncRNA NONHSAT227443.1 Confers Esophageal Squamous Cell Carcinoma Chemotherapy Resistance by Activating PI3K/AKT Signaling via Targeting MRTFB.

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.

Time-domain full-field optical coherence tomography (TD-FF-OCT) in ophthalmic imaging.

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.

Oxygen-saturation-related functional parameter as a biomarker for diabetes mellitus-extraction method and clinical validation.

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<0.05, respectively) while ODRv was significantly lower (p<0.001) in NDR group than that in healthy normal group. In the regression analysis, the increased ODRs except micro venule and decreased ODRv were significantly correlated with the incidence of DM, and the C-statistic for discrimination DM with all ODR is 0.777 (95% CI 0.687-0.867, p<0.001). Conclusion: A computational method to extract the retinal vascular oxygen-saturation-related optical density ratios (ODRs) with single color fundus photography was developed, and increased ODRs and decreased ODRv of retinal vessels could be new potential image biomarkers of DM.

A comprehensive diagnostic scheme of morphological combined molecular methylation under bronchoscopy.

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.

A Destructive New Disease of Citrus in China Caused by Cryptosporiopsis citricarpa sp. nov.

Defoliation, dieback and mortality of Satsuma mandarin (Citrus unshiu), as well as kumquat (Fortunella margarita), in Chenggu County, Shaanxi Province, China was first noticed in 2006 and caused substantial economic losses to citrus production. The incidence of leaves infected approached 100% in some badly infected orchards. The disease prevailed only in late winter and early spring, where early symptoms were rounded and target-like spots on leaves. The disease was named target spot. Black conidiomata were observed on the upper surface of the leaves. A Cryptosporiopsis species was consistently recovered from the infected leaves, shoots, and branches. Koch's postulates were fulfilled by inoculating the conidial suspension of Cryptosporiopsis sp. onto the leaves of Satsuma mandarin. Phylogenetic analysis based on LSU sequence data indicated that this taxon clustered in Cryptosporiopsis (teleomorph: Neofabraea, Dermateaceae). Phylogenetic analysis based on ITS, SSU, and TUB indicated that the isolates of Cryptosporiopsis sp. constituted a distinct clade. Further study also demonstrated that this taxon was morphologically distinct from other species of Cryptosporiopsis, thus suggesting it might belong to an undescribed species. The name Cryptosporiopsis citricarpa sp. nov. is given to accommodate the fungal pathogen in this study.

Present Application and Perspectives of Organoid Imaging Technology.

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.

Portable boom-type ultrahigh-resolution OCT with an integrated imaging probe for supine position retinal imaging.

To expand the clinical applications and improve the ease of use of ultrahigh-resolution optical coherence tomography (UHR-OCT), we developed a portable boom-type ophthalmic UHR-OCT operating in supine position that can be used for pediatric subjects, bedridden patients and perioperative conditions. By integrating the OCT sample arm probe with real-time iris display and automatic focusing electric lens for easy alignment, coupling the probe on a self-locking multi-directional manipulator to reduce motion artifacts and operator fatigue, and installing the OCT module on a moveable cart for system mobility, our customized portable boom-type UHR-OCT enables non-contact, high-resolution and high-stability retinal examinations to be performed on subjects in supine position. The spectral-domain UHR-OCT operates at a wavelength of 845 nm with 130 nm FWHM (full width at half maximum) bandwidth, achieving an axial resolution of ≈2.3µm in tissue with an A-line acquisition rate up to 128 kHz. A high-definition two-dimensional (2D) raster protocol was used for high-quality cross-sectional imaging while a cube volume three-dimensional (3D) scan was used for three-dimensional imaging and en-face reconstruction, resolving major layer structures of the retina. The feasibility of the system was demonstrated by performing supine position 2D/3D retinal imaging on healthy human subjects, sedated infants, and non-sedated awake neonates.

Study on the Effect of Antiplatelet and Gastric Mucosal Protection of Traditional Chinese Medicine Invigorating Qi and Hemostasis.

BACKGROUND: To investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model. METHODS: A pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested. RESULTS: The area under the curve (AUC; 0-T, 300.342 ± 35.832 mg/L* h; AUC 0-∞, 320.462 ± 40.213 mg/L* h), the plasma peak concentration (30.622 ± 9.917 mg/L*), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05). CONCLUSION: TCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.