Hyaluronic acid-mediated epithelial-mesenchymal transition of human lens epithelial cells via CD44 and TGF-β2

ABSTRACT Purpose: The epithelial-mesenchymal transition of human lens epithelial cells plays a role in posterior capsule opacification, a fibrotic process that leads to a common type of cataract. Hyaluronic acid has been implicated in this fibrosis. Studies have investigated the role of transforming growth factor (TGF)-β2 in epithelial-mesenchymal transition. However, the role of TGF-β2 in hyaluronic acid-mediated fibrosis of lens epithelial cell remains unknown. We here examined the role of TGF-β2 in the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells. Methods: Cultured human lens epithelial cells (HLEB3) were infected with CD44-siRNA by using the Lipofectamine 3000 transfection reagent. The CCK-8 kit was used to measure cell viability, and the scratch assay was used to determine cell migration. Cell oxidative stress was analyzed in a dichloro-dihydro-fluorescein diacetate assay and by using a flow cytometer. The TGF-β2 level in HLEB3 cells was examined through immunohistochemical staining. The TGF-β2 protein level was determined through western blotting. mRNA expression levels were determined through quantitative real-time polymerase chain reaction. Results: Treatment with hyaluronic acid (1.0 μM, 24 h) increased the epithelial-mesenchymal transition of HLEB3 cells. The increase in TGF-β2 levels corresponded to an increase in CD44 levels in the culture medium. However, blocking the CD44 function significantly reduced the TGF-β2-mediated epithelial-mesenchymal transition response of HLEB3 cells. Conclusions: Our study showed that both CD44 and TGF-β2 are critical contributors to the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells, and that TGF-β2 in epithelial-mesenchymal transition is regulated by CD44. These results suggest that CD44 could be used as a target for preventing hyaluronic acid-induced posterior capsule opacification. Our findings suggest that CD44/TGF-β2 is crucial for the hyaluronic acid-induced epithelial-mesenchymal transition of lens epithelial cells.

Recurrence rates and risk factors in obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding (OGIB), defined in 2010, involves bleeding from the GI tract that remains unexplained after standard diagnostic procedures. OGIB, which accounts for about 5% of all GI bleeds, poses diagnostic and management challenges, particularly due to the anatomical features of the small intestine. Advances in capsule endoscopy (CE) and balloon-assisted endoscopy have improved the diagnostic and therapeutic landscape for small intestinal lesions. Objective: To determine the recurrence rate and identify risk factors for recurrence following diagnostic and therapeutic interventions using CE and balloon-assisted endoscopy in patients with OGIB. Methods: A retrospective cohort study at Gifu University Hospital analyzed CE procedures for patients with OGIB from 2008 to 2022. Patients underwent CE with subsequent treatments based on the findings. Statistical analyses, including Kaplan-Meier and Cox proportional hazards models, were used to estimate cumulative recurrence rates and identify recurrence risk factors. Results: Out of 417 patients, 65.2% had positive CE findings, leading to therapeutic interventions in 16.3% of cases. The cumulative recurrence rates at 12, 24, and 36 months were 4.3%, 9.0%, and 13.9%, respectively. Liver cirrhosis (hazard rate: 4.15, 95% confidence interval 1.88-9.18, p < 0.01) was identified as a significant risk factor for recurrence. Conclusions: A significant recurrence rate in OGIB patients, with liver cirrhosis being a major risk factor. Despite diagnostic and therapeutic advances, a comprehensive approach including careful follow-up and consideration of risk factors is essential for management.

Study on the underlying mechanism of Huachansu Capsule induced cardiotoxicity of normal rat by integrating transcriptomics, metabolomics and network toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.

Naoxintong capsule accelerates mitophagy in cerebral ischemia-reperfusion injury via TP53/PINK1/PRKN pathway based on network pharmacology analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality of cerebrovascular diseases are increasing year by year. Cerebral ischemia-reperfusion injury (CIRI) is common in patients with ischemic stroke. Naoxintong (NXT) is composed of a variety of Chinese medicines and has the ability to treat CIRI. AIM OF THE STUDY: The aim of this study is to investigate whether NXT regulates mitophagy in CIRI based on network pharmacology analysis and experimental validation. MATERIALS AND METHODS: Oxygen and glucose deprivation/re-oxygenation (OGD/R, 2/22 h) model of PC12 cells and transient middle cerebral artery occlusion (tMCAO, 2/22 h) model of rats were established. Pharmacodynamic indicators include neurological deficit score, 2,3,5-triphenyte-trazoliumchloride (TTC) staining, hematoxylin-eosin (HE) staining and cell viability. Network pharmacology was used to predict pharmacological mechanisms. Pharmacological mechanism indexes include transmission electron microscopy (TEM), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), immunohistochemistry (IHC), western blot (WB) and immunofluorescence (IF). Kevetrin (an agonists of p53) and pifithrin-α (an inhibitor of p53) used to detect the key role of p53 in mitophagy of NXT. RESULTS: NXT (1% serum containing NXT and 110 mg/kg) improved the damage of OGD/R PC12 cells and tMCAO rats, and this protective effect was related to the anti-oxidation and ability to promote mitophagy of NXT. NXT and pifithrin-α increased the expression of promoting-mitophagy targets (PINK1, PRKN and LC3B) and inhibited the expression of inhibiting-mitophagy targets (p52) via restraining p53, and finally accelerated mitophagy caused by CIRI. CONCLUSION: This study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro.

Clinical usefulness and acceptability of small-bowel capsule endoscopy with panoramic imaging compared with axial imaging in Japanese patients.

Objectives: We aimed to evaluate the usefulness and acceptability of CapsoCam Plus (CapsoCam) in Japanese patients. Methods: This retrospective single-center study enrolled 930 patients with suspected small-bowel bleeding (SSBB) who underwent capsule endoscopy. Thirty-three patients using CapsoCam and PillCam SB3 (SB3) were matched using propensity score matching. The diagnostic yield and the acceptability of CapsoCam were evaluated. Results: There was no SSBB case where capsule endoscopy was performed within 48 h of bleeding. CapsoCam had a significantly higher observation rate of the entire small bowel (97% vs. 73%, p = 0.006) and Vater's papilla (82% vs. 15%, p < 0.001) than SB3. The reading time of CapsoCam was significantly longer than that of SB3 (30 vs. 25 min, p < 0.001), and CapsoCam's time from the capsule endoscopy swallowing to read completion was longer than that of SB3 (37 vs. 12 h, p < 0.001). The two groups showed no difference in the capsule endoscopy findings according to the P classification. Notably, 85% of the patients using CapsoCam reported examination distress as "not at all" or "almost not," and 94% reported swallowing difficulty as "very easy" or "easy." Conclusions: CapsoCam took time to read; however, it is a well-tolerated examination with a high observation rate of Vater's papilla and entire small-bowel mucosa. Detectability of bleeding sources was comparable in both modalities for cases of occult SSBB and overt SSBB more than 48 h after bleeding. CapsoCam is a useful modality for patients with SSBB.

Serum untargeted metabolomics analysis of mice after myocardial infarction affected by qiliqiangxin capsule.

Qiliqiangxin (QLQX) capsule consists of 11 herbs, namely Huang qi (astragalus membranaceus), Ren shen (ginseng), Fu zi (radix aconiti carmichaeli), Dan shen (salvia miltiorrhiza), Ting li zi (lepidium seed), Ze xie (rhizoma alismatis), Yu zhu (radix polygonati officinalis), Gui zhi (cassia twig), Hong hua (carthamus tinctorious), Xiang jia Pi (cortex periplocae), Chen Pi (pericarpium citri reticulatae), and it is a standardized commercial formula designed to address yang deficiency and to restore the balance of qi in the heart. QLQX is also known to invigorate the blood and promote the circulation of the blood and to promote the use of fluids to relieve water retention and edema, and can be used in cardiovascular diseases such as mild to moderate congestive heart failure resulting from coronary artery disease and hypertension. The further research on the effect of QLQX on cardiac function in mice after myocardial infarction was manipulated. QLQX was given to mice in myocardial infarction model by gavage with appropriate dosage and the samples were analyzed at the end of the animal experiments through the UHPLC-Q-Exactive LC-MS. The liquid mass spectrometry was used to collect and followed by further analysis of the corresponding metabolites and metabolic pathways using metabolomics analysis. As a result, 9 differential metabolites were identified, with 15 being up-regulated and 4 down-regulated following intervention with QLQX. Then the metabolic pathways by KEGG enrichment pathway bubble diagram was analyzed, and 4 metabolic pathways were obtained, and combined with the metabolites that had been screened and analyzed together, finally the two differential metabolites, 2,5-Dihydroxybenzenesulfonic Acid and o-Cresol sulfate were found. The Glycerophospholipid metabolism pathway was closely related to the remaining seven differential metabolites, and the pathway might be an important pathway related to the effects of QLQX on cardiac function in mice.

The Tan-Re-Qing Capsule mitigates acute lung injury by suppressing the NLRP3 inflammasome and MAPK/NF-κB signaling pathways.

OBJECTIVE: The Tan-Re-Qing Capsule (TRQC), a traditional Chinese medicine (TCM) preparation, has been historically utilized in treating acute lung injury (ALI) and COVID-19-induced pulmonary diseases. This study aimed to explore the effect and underlying mechanisms of TRQC in lipopolysaccharide (LPS)-induced ALI models. METHODS: The changes of acute lung injury and inflammatory response were observed after TRQC treatment of the LPS-induced ALI mouse model. Based on active compounds in TRQC and network pharmacology analysis, potential targeting signals were identified. The effects of TRQC on signaling in LPS-stimulated BMDMs were investigated. Additionally, the defecatory status of mice and the mechanism of Cl- secretion in HBE cells and T84 colonic epithelial cells were examined. RESULTS: TRQC exhibited a notable amelioration of inflammatory injuries in ALI mice. Utilizing a systems-pharmacology approach based on active chemical compounds, TRQC was found to regulate inflammation-related pathways, including NF-κB, NOD-like signaling, and MAPK signaling. In vitro experiments demonstrated that TRQC effectively suppressed LPS-induced activation of macrophages and the assembly of the NLRP3 inflammasome induced by LPS and Nigericin. These effects were attributed to the suppression of NF-κB and NOD-like signaling pathways. Furthermore, TRQC blocked MAPK signaling, thereby mitigating the inhibitory effects of LPS and Nigericin on Ca2+-dependent Cl- efflux across colonic epithelial cells. This mechanism generated a cathartic effect, potentially aiding in the removal of harmful substances and pathogenic bacteria. CONCLUSION: Our study demonstrates that TRQC significantly mitigates ALI by effectively suppressing the NLRP3 inflammasome and MAPK/NF-κB signaling pathways. These findings suggest that TRQC could serve as a promising therapeutic candidate for inflammatory lung diseases, offering a novel approach to managing conditions like ALI and potentially extending to other inflammatory diseases.

Establishing an AI model and application for automated capsule endoscopy recognition based on convolutional neural networks (with video).

BACKGROUND: Although capsule endoscopy (CE) is a crucial tool for diagnosing small bowel diseases, the need to process a vast number of images imposes a significant workload on physicians, leading to a high risk of missed diagnoses. This study aims to develop an artificial intelligence (AI) model and application based on convolutional neural networks that can automatically recognize various lesions in small bowel capsule endoscopy. METHODS: Three small bowel capsule endoscopy datasets were used for AI model training, validation, and testing, encompassing 12 categories of images. The model's performance was evaluated using metrics such as AUC, sensitivity, specificity, precision, accuracy, and F1 score to select the best model. A human-machine comparison experiment was conducted using the best model and endoscopists with varying levels of experience. Model interpretability was analyzed using Grad-CAM and SHAP techniques. Finally, a clinical application was developed based on the best model using PyQt5 technology. RESULTS: A total of 34,303 images were included in this study. The best model, MobileNetv3-large, achieved a weighted average sensitivity of 87.17%, specificity of 98.77%, and an AUC of 0.9897 across all categories. The application developed based on this model performed exceptionally well in comparison with endoscopists, achieving an accuracy of 87.17% and a processing speed of 75.04 frames per second, surpassing endoscopists of varying experience levels. CONCLUSION: The AI model and application developed based on convolutional neural networks can quickly and accurately identify 12 types of small bowel lesions. With its high sensitivity, this system can effectively assist physicians in interpreting small bowel capsule endoscopy images.Future studies will validate the AI system for video evaluations and real-world clinical integration.

Gastrointestinal manifestations and pathogenesis in childhood immunoglobulin A vasculitis.

Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common form of systemic vasculitis in childhood. The primary organs involved are the skin, gastrointestinal (GI) tract, joints, and kidneys. The spectrum of GI involvement in IgAV ranges from being mild and self-limited to severe manifestations often requiring surgical intervention. Galactose-deficient IgA1 on the immunoglobulin hinge region and its immune complexes are thought to play a central pathogenetic role in IgAV, however, an association between such molecules and specific GI mucosal damage remains unclear. GI endoscopy (both upper and lower) shows a variety of mucosal findings, many of which are not specific for IgAV. In upper GI endoscopy, however, the mucosal features can be diagnostic when found localized in the more distal part of upper GI tract (second and/or third parts of the duodenum). Abdominal computed tomography and capsule endoscopy have demonstrated that the small intestine is most commonly involved in IgAV. The GI mucosal involvement when evaluated microscopically shows IgA deposition which is histologically diagnostic. Conversely, leukocytoclastic vasculitis is less useful. Since the 1960s, cases of duodenojejunitis, in which IgAV was suspected but evident purpura was not dermatologically present, have often been labeled as "idiopathic". In a pediatric case series, IgA enteropathy, without dermatological manifestations (i.e., purpura), was reported to have similar symptoms, as well as endoscopic characteristics and immunohistological findings as in IgAV. Subsequently, several case reports provide additional supportive evidence that IgA enteropathy must be a variant of IgAV. Thus, the immunologically driven auto-immune vasculitis results in the symptom complex dependent on the organ system involved, and the subsequent clinical features which are manifested. Present classification criteria are useful and universally available for diagnosing IgAV. However, based upon current knowledge including IgA enteropathy, minor modification of the IgAV criteria is proposed in the review.

Relationship between capsule production and biofilm formation by Mannheimia haemolytica, and establishment of a poly-species biofilm with other Pasteurellaceae.

Mannheimia haemolytica is one of the bacterial agents responsible for bovine respiratory disease (BRD). The capability of M. haemolytica to form a biofilm may contribute to the development of chronic BRD infection by making the bacteria more resistant to host innate immunity and antibiotics. To improve therapy and prevent BRD, a greater understanding of the association between M. haemolytica surface components and biofilm formation is needed. M. haemolytica strain 619 (wild-type) made a poorly adherent, low-biomass biofilm. To examine the relationship between capsule and biofilm formation, a capsule-deficient mutant of wild-type M. haemolytica was obtained following mutagenesis with ethyl methanesulfonate to obtain mutant E09. Loss of capsular polysaccharide (CPS) in mutant E09 was supported by transmission electron microscopy and Maneval's staining. Mutant E09 attached to polyvinyl chloride plates more effectively, and produced a significantly denser and more uniform biofilm than the wild-type, as determined by crystal violet staining, scanning electron microscopy, and confocal laser scanning microscopy with COMSTAT analysis. The biofilm matrix of E09 contained predominately protein and significantly more eDNA than the wild-type, but not a distinct exopolysaccharide. Furthermore, treatment with DNase I significantly reduced the biofilm content of both the wild-type and E09 mutant. DNA sequencing of E09 showed that a point mutation occurred in the capsule biosynthesis gene wecB. The complementation of wecB in trans in mutant E09 successfully restored CPS production and reduced bacterial attachment/biofilm to levels similar to that of the wild-type. Fluorescence in-situ hybridization microscopy showed that M. haemolytica formed a poly-microbial biofilm with Histophilus somni and Pasteurella multocida. Overall, CPS production by M. haemolytica was inversely correlated with biofilm formation, the integrity of which required eDNA. A poly-microbial biofilm was readily formed between M. haemolytica, H. somni, and P. multocida, suggesting a mutualistic or synergistic interaction that may benefit bacterial colonization of the bovine respiratory tract.

Patient-Reported Outcomes After Arthroscopic Superior Capsule Reconstruction With an Acellular Porcine Dermal Xenograft for Irreparable Rotator Cuff Tears.

Background: Currently, there is no consensus on the adequate management of irreparable rotator cuff tears. Arthroscopic superior capsule reconstruction (SCR) seems to be an alternative treatment option. Purpose/Hypothesis: The purpose of this study was to evaluate patient-reported outcomes up to 2 years after the treatment of irreparable rotator cuff tears with SCR using an acellular porcine dermal xenograft. It was hypothesized that SCR treatment with an acellular porcine dermal xenograft would not result in a significant clinical improvement or pain relief in patients with irreparable rotator cuff tears if the xenograft fails. Study Design: Case series; Level of evidence, 4. Methods: A total of 26 consecutive patients with irreparable rotator cuff tears were enrolled in the study between 2015 and 2019. All patients underwent SCR with acellular porcine dermal xenograft. Patient-reported outcome measures including visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Veterans RAND 12- Item Health Survey (VR-12), and the Single Assessment Numeric Evaluation (SANE) were followed up for 2 years. For statistical analysis, the 1-way analysis of variance was used to compare means for VAS, ASES, VR-12, and SANE results between pre- and posttreatment. Magnetic resonance imaging (MRI) records were obtained at 1 year postoperatively to evaluate graft integrity. Results: In total, 22 patients were included in the patient-reported outcomes with 4 being lost at final follow-up. The mean VAS score decreased from 4.2 ± 2.5 to 1.0 ± 1.4 (P < .001) from pretreatment to 2 years postoperatively. The mean ASES - index score improved significantly from 47.7 ± 15.3 to 86.4 ± 12.9 (P < .001) and the SANE score improved from 34.0 ± 20.4 to 77.3 ± 20.2 (P < .001). In addition, a clinically important difference in the patients' quality of life was achieved, as shown by the mean changes in the VR-12 physical (+4.3) and mental scores (+9.3). Based on postoperative MRI, the dermal graft on the humeral side was intact in 15 (68.2%) patients after surgery. Conclusion: Our arthroscopic SCR with an acellular porcine dermal matrix showed significant and continuous improvement in pain and clinical scores up to a 2-year follow-up in patients with irreparable rotator cuff tears, even with structural graft failure. However, further studies and evaluation of larger patient groups are needed to evaluate the long-term effect of this procedure.

Hypervirulent Carbapenem-Susceptible Klebsiella pneumoniae ST412/K57 with Strong Biofilm Formation: association with gas gangrene and sepsis.

Hypervirulent Klebsiella pneumoniae (hvKp) poses a serious public health threat. Gas gangrene caused by hvKp was rarely reported, potentially resulting in a poor prognosis. In this study, we described the case of a hospitalized patient with gas gangrene and sepsis by hvKP. The carbapenem-susceptible hypervirulent Klebsiella pneumoniae (CS-hvKp) strains KPLSN and KPLSX were isolated from the knee joint pus and blood specimens of the patient for further investigations. Whole genome sequencing revealed that KPLSN and KPLSX were highly homologous (SNPs<10) and belonging to ST412/K57. The minimum inhibitory concentration and minimum bactericidal concentration under biofilm values of meropenem in KPLSN and KPLSX were significantly higher than planktonic state (>128 mg/L versus 0.25 mg/L, P<0.0001). These two strains had high biofilm formation ability, and fluorescence staining experiments results showed that they were not easily killed by meropenem in the biofilm state. KPLSN and KPLSX showed high capsular production and were confirmed with high virulence through experiments with the Galleria mellonella and BALB/c mice abdominal infection model. The persistent symptoms may be due to enhanced biofilm and capsule formation. Global ST412 strains phylogenetic analysis showed their evolution towards higher virulence and resistance. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat special infections caused by these pathogens.

Coinciding Diabetic Retinopathy and Diabetic Macular Edema Grading With Rat Swarm Optimization Algorithm for Enhanced Capsule Generation Adversarial Network.

In the worldwide working-age population, visual disability and blindness are common conditions caused by diabetic retinopathy (DR) and diabetic macular edema (DME). Nowadays, due to diabetes, many people are affected by eye-related issues. Among these, DR and DME are the two foremost eye diseases, the severity of which may lead to some eye-related problems and blindness. Early detection of DR and DME is essential to preventing vision loss. Therefore, an enhanced capsule generation adversarial network (ECGAN) optimized with the rat swarm optimization (RSO) approach is proposed in this article to coincide with DR and DME grading (DR-DME-ECGAN-RSO-ISBI 2018 IDRiD). The input images are obtained from the ISBI 2018 unbalanced DR grading data set. Then, the input fundus images are preprocessed using the Savitzky-Golay (SG) filter filtering technique, which reduces noise from the input image. The preprocessed image is fed to the discrete shearlet transform (DST) for feature extraction. The extracting features of DR-DME are given to the ECGAN-RSO algorithm to categorize the grading of DR and DME disorders. The proposed approach is implemented in Python and achieves better accuracy by 7.94%, 36.66%, and 4.88% compared to the existing models, such as the combined DR with DME grading for the cross-disease attention network (DR-DME-CANet-ISBI 2018 IDRiD), category attention block for unbalanced grading of DR (DR-DME-HDLCNN-MGMO-ISBI 2018 IDRiD), combined DR-DME classification with a deep learning-convolutional neural network-based modified gray-wolf optimizer with variable weights (DR-DME-ANN-ISBI 2018 IDRiD).

Capsule robots for the monitoring, diagnosis, and treatment of intestinal diseases.

Current evidence suggests that the intestine as the new frontier for human health directly impacts both our physical and mental health. Therefore, it is highly desirable to develop the intelligent tool for the enhanced diagnosis and treatment of intestinal diseases. During the past 20 years, capsule robots have opened new avenues for research and clinical applications, potentially revolutionizing human health monitor, disease diagnosis and treatment. In this review, we summarize the research progress of edible multifunctional capsule robots in intestinal diseases. To begin, we introduce the correlation between the intestinal microbiome, intestinal gas and human diseases. After that, we focus on the technical structure of edible multifunctional robots. Subsequently, the biomedical applications in the monitoring, diagnosis and treatment of intestinal diseases are discussed in detail. Last but not least, the main challenges of multifunctional capsule robots during the development process are summarized, followed by a vision for future development opportunities.

The evolution of muscle spindles.

Muscle spindles are stretch-sensitive mechanoreceptors found in the skeletal muscles of most four-limbed vertebrates. They are unique amongst sensory receptors in the ability to regulate their sensitivity by contraction of the intrafusal muscle fibres on which the sensory endings lie. Muscle spindles have revealed a remarkable diversity of functions, including reflex action in posture and locomotion, contributing to bodily self awareness, and influencing wound healing. What were the circumstances which gave rise to the evolution of such complex end-organs? We argue that spindles first appeared in early amniotes and only later in frogs and toads. This was considered an example of convergent evolution. Spindles in amphibians and reptiles are characterised by their simple structure, pointing to key features essential for spindle function. Spindle sensitivity in amphibians and reptiles is controlled by intrafusal fibre contractions evoked by branches of motor axons supplying extrafusal muscle. Modern phylogenetic evidence has revised our views on the origin of birds, placing them closer to the dinosaurs than had previously been thought. Birds are the only group, other than mammals, which has a dedicated fusimotor innervation of spindles, another example of convergent evolution, given the widely different origins of the two groups. One factor that may have played a role here was that both groups are endotherms, allowing motor control to develop further in an optimal internal environment. This, as well as other changes within the spindle, has led to the astonishing sophistication of motor control observed especially in many modern mammals.

Assessment of Treatment Response in Known Crohn's Disease-A Prospective Blinded Study Comparing the Diagnostic Accuracy of Intestinal Ultrasound, Magnetic Resonance Enterocolonography, Panenteric Capsule Endoscopy, and Fecal Calprotectin.

BACKGROUND: Minimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn's disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD. METHODS: This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn's Disease (SES-CD) with IC defined treatment response. RESULTS: Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn's Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9 mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively. CONCLUSIONS: IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.

Monitoring is vital for effective Crohn's disease management. We prospectively evaluated intestinal ultrasound (IUS), magnetic resonance enterocolonography, panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for treatment response. IUS and FC are equally effective. Strictures limit the use of PCE.

A supramolecular approach towards the photorelease of encapsulated caged acids in water: 7-diethylaminothio-4-coumarinyl molecules as triggers.

Herein, we establish the release of aliphatic acids in water upon excitation of 7-diethylaminothio-4-coumarinyl derivatives encapsulated within the organic host octa acid (OA). The 7-diethylaminothio-4-coumarinyl skeleton, employed here as the trigger, photoreleases caged molecules from the excited triplet state, in contrast to its carbonyl analogue, where the same reaction is known to occur from the excited singlet state. Encapsulation in OA solubilizes molecules in water that are otherwise water-insoluble, and retains the used trigger within itself following the release of the aliphatic acid. Such supramolecular characteristics usher in new features to the photorelease methodology. The thiocarbonyl chromophore extends the absorption of coumarinyl trigger to visible range while enhancing the intersystem crossing (ISC) to the triplet state, making it the reactive state. Despite the non-polar environment within the OA capsules the photocleavage occurs in a heterolytic fashion to release the conjugate base and the used trigger as triplet carbocation in an adiabatic process. Interestingly, the triplet carbocation crosses to the ground singlet surface (closed shell singlet carbocation) with the help of water molecules, possibly aided by C = S chromophore. Utilizing the known excited state dynamics of related thiocoumarinyl and coumarinyl systems, we have identified a few of the important mechanistic features of the photorelease process of 7-diethylaminothio-4-coumarinyl derivatives. Ultrafast excited state dynamic studies and quantum chemical calculations planned should help us better understand the photorelease process so as to effectively exploit the proposed system for potential applications.

A web-based platform for studying the impact of artificial intelligence in video capsule endoscopy.

Objective: Integrating artificial intelligence (AI) solutions into clinical practice, particularly in the field of video capsule endoscopy (VCE), necessitates the execution of rigorous clinical studies. Methods: This work introduces a novel software platform tailored to facilitate the conduct of multi-reader multi-case clinical studies in VCE. The platform, developed as a web application, prioritizes remote accessibility to accommodate multi-center studies. Notably, considerable attention was devoted to user interface and user experience design elements to ensure a seamless and engaging interface. To evaluate the usability of the platform, a pilot study is conducted. Results: The results indicate a high level of usability and acceptance among users, providing valuable insights into the expectations and preferences of gastroenterologists navigating AI-driven VCE solutions. Conclusion: This research lays a foundation for future advancements in AI integration within clinical VCE practice.

Application of small-sized magnetically controlled capsule gastroscopy in upper gastrointestinal diseases screening in asymptomatic individuals.

OBJECTIVE: To explore the application of small-sized magnetically controlled capsule gastroscopy (MCCG) in upper gastrointestinal diseases screening in asymptomatic individuals. METHODS: A retrospective analysis of the clinical data of 2163 asymptomatic individuals who underwent small-sized MCCG at our center from September 2022 to December 2023. The detection of submucosal tumors, polyps and ulcers in the upper gastrointestinal tract, the tolerance and safety of the subjects were statistically analyzed. RESULTS: Suspected submucosal tumors in the upper gastrointestinal tract were detected in 34 (1.57%) of 2136 subjects, with a higher incidence in females and no observed age difference. Polyps were detected in 328 subjects (15.16%), with a higher incidence in females and an increased detection rate with increasing age. Ulcers were detected in 27 subjects (1.25%), with a higher incidence in males and no observed age difference. There was no significant discomfort in all subjects, and no adverse event or capsule retention occurred. CONCLUSION: Small-sized MCCG can be used for focal lesion screening in the upper gastrointestinal tract and is comfortable and safe, making it a safe and efficient method for examining upper gastrointestinal diseases in the physical examination population.

Histopathologic findings of the lens capsule and persistent hyperplastic primary vitreous in Korean pediatric cataract patients.

This study aimed to measure lens capsule thickness and investigate histopathologic characteristics of persistent hyperplastic primary vitreous (PHPV) in Korean pediatric cataracts. We analyzed lens capsules from 116 eyes of 83 pediatric cataract patients treated between 2011 and 2015. The mean thickness of the anterior/posterior capsule was 7.21 ± 1.74/4.39 ± 1.41 µm. PHPV was observed in 11.2% (13/116) of eyes. Histologic examination revealed that PHPV is typically characterized by retrolenticular membranes with hypercellular membrane tissue comprising vascular structures and/or mesenchymal cells, seen in 69% of cases. Only 3 patients had hyaloid arteries and endothelium-lined blood vessels in the retrolenticular membranes, whereas six eyes showed only mesenchymal cells. Lens capsule thickness did not significantly vary with age or the presence of PHPV in Korean pediatric cataracts. The primary histological characteristic of PHPV was the presence of mesenchymal cells, with or without vascular structures, supporting the role of endothelial-mesenchymal transition as a key mechanism in vascular regression.