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The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment., (© 2024. The Author(s).)

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 10 7 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration., (© 2023. The Author(s).)

Exposure to plant toxins or microbiota that are able to digest common food ingredients to toxic structures might be responsible for biliary atresia (BA). An isoflavonoid, biliatresone is known to effectively alter the extrahepatic bile duct (EHBD) development in BALB/c mice. Biliatresone causes a reduction of Glutathione (GSH) levels, SOX17 downregulation and is effectively countered with N-Acetyl-L-cysteine treatment in vitro. Therefore, reversing GSH-loss appears to be a promising treatment target for a translational approach. Since BALB/c mice have been described as sensitive in various models, we evaluated the toxic effect of biliatresone in robust C57BL/6J mice and confirmed its toxicity. Comparison between BALB/c and C57BL/6J mice revealed similarity in the toxic model. Affected neonates exhibited clinical symptoms of BA, such as jaundice, ascites, clay-colored stools, yellow urine and impaired weight gain. The gallbladders of jaundiced neonates were hydropic and EHBD were twisted and enlarged. Serum and histological analysis proved cholestasis. No anomalies were seen in the liver and EHBD of control animals. With our study we join a chain of evidence confirming that biliatresone is an effective agent for cross-lineage targeted alteration of the EHBD system., (© 2023. The Author(s).)

Background: Retinal exudates and/or drusen (RED) can be signs of many fundus diseases that can lead to irreversible vision loss. Early detection and treatment of these diseases are critical for improving vision prognosis. However, manual RED screening on a large scale is time-consuming and labour-intensive. Here, we aim to develop and assess a deep learning system for automated detection of RED using ultra-widefield fundus (UWF) images., Methods: A total of 26,409 UWF images from 14,994 subjects were used to develop and evaluate the deep learning system. The Zhongshan Ophthalmic Center (ZOC) dataset was selected to compare the performance of the system to that of retina specialists in RED detection. The saliency map visualization technique was used to understand which areas in the UWF image had the most influence on our deep learning system when detecting RED., Results: The system for RED detection achieved areas under the receiver operating characteristic curve of 0.994 (95% confidence interval [CI]: 0.991-0.996), 0.972 (95% CI: 0.957-0.984), and 0.988 (95% CI: 0.983-0.992) in three independent datasets. The performance of the system in the ZOC dataset was comparable to that of an experienced retina specialist. Regions of RED were highlighted by saliency maps in UWF images., Conclusions: Our deep learning system is reliable in the automated detection of RED in UWF images. As a screening tool, our system may promote the early diagnosis and management of RED-related fundus diseases., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Malignant eyelid tumors can invade adjacent structures and pose a threat to vision and even life. Early identification of malignant eyelid tumors is crucial to avoiding substantial morbidity and mortality. However, differentiating malignant eyelid tumors from benign ones can be challenging for primary care physicians and even some ophthalmologists. Here, based on 1,417 photographic images from 851 patients across three hospitals, we developed an artificial intelligence system using a faster region-based convolutional neural network and deep learning classification networks to automatically locate eyelid tumors and then distinguish between malignant and benign eyelid tumors. The system performed well in both internal and external test sets (AUCs ranged from 0.899 to 0.955). The performance of the system is comparable to that of a senior ophthalmologist, indicating that this system has the potential to be used at the screening stage for promoting the early detection and treatment of malignant eyelid tumors., (© 2022. The Author(s).)

Artificial intelligence (AI) based on deep learning has shown excellent diagnostic performance in detecting various diseases with good-quality clinical images. Recently, AI diagnostic systems developed from ultra-widefield fundus (UWF) images have become popular standard-of-care tools in screening for ocular fundus diseases. However, in real-world settings, these systems must base their diagnoses on images with uncontrolled quality ("passive feeding"), leading to uncertainty about their performance. Here, using 40,562 UWF images, we develop a deep learning-based image filtering system (DLIFS) for detecting and filtering out poor-quality images in an automated fashion such that only good-quality images are transferred to the subsequent AI diagnostic system ("selective eating"). In three independent datasets from different clinical institutions, the DLIFS performed well with sensitivities of 96.9%, 95.6% and 96.6%, and specificities of 96.6%, 97.9% and 98.8%, respectively. Furthermore, we show that the application of our DLIFS significantly improves the performance of established AI diagnostic systems in real-world settings. Our work demonstrates that "selective eating" of real-world data is necessary and needs to be considered in the development of image-based AI systems., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from that of umbilical cord mesenchymal stem cells (UCMSCs), such as higher expression levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and the FDA-approved drug pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury and acute respiratory distress syndrome, our findings suggest that IMRCs are ready for clinical trials on lung disorders.

This study evaluated illness uncertainty, anxiety and depression among glaucoma patients and cataract patients in China. 263 patients with primary glaucoma and 100 patients with age-related cataract were recruited sequentially from Zhongshan Ophthalmic Center between October 2013 and March 2016. All the participants completed questionnaires for socio-demographic information, Mishel Uncertainty in Illness Scale (MUIS) and Hospital Anxiety and Depression Scale (HADS). 25 of the 263 glaucoma patients and 21 of the100 cataract patients finished two copies of the same questionnaires before and after surgery. Statistics were analyzed using SPSS17.0 software. We observed that glaucoma patients had higher MUIS and HADS score than did cataract patients. Multivariate logistic regression analysis indicated risk factors for illness uncertainty, anxiety and depression for glaucoma patients were high HADS score, poor visual acuity (VA) in the better eye and education level respectively. Risk factors for the same parameters of cataract patients were high HADS-A score, poor VA in the better eye and high illness uncertainty respectively. Scores of MUIS and HADS both decreased after surgery, but the change in HADS score among glaucoma patients was not significant. Clinical workers should take these factors into account to improve therapy, especially for glaucoma patients who undergo surgery.

The flow-stimulated intracellular Ca(2+) concentration ([Ca(2+)]i) rise in endothelial cells is an important early event leading to flow-induced blood vessel dilation. Transient receptor potential vanilloid subtype 4 (TRPV4), a Ca(2+)-permeable cation channel, facilitates the flow-stimulated [Ca(2+)]i rise. To determine whether TRPV4 is involved in age-related flow-induced blood vessel dilation impairment, we measured blood vessel diameter and nitric oxide (NO) levels and performed Ca(2+) imaging, immunoblotting, and immunostaining assays in rats. We found that the flow-induced and TRPV4 activator 4α-PDD-induced dilation of mesenteric arteries from aged rats were significantly decreased compared with those from young rats. The flow- or 4α-PDD-induced [Ca(2+)]i rise was also markedly reduced in primary cultured mesenteric artery endothelial cells (MAECs) from aged rats. Immunoblotting and immunostaining results showed an age-related decrease of TRPV4 expression levels in MAECs. Additionally, the 4α-PDD-induced NO production was significantly reduced in aged MAECs. Compared with lentiviral GFP-treated aged rats, lentiviral vector delivery of TRPV4 increased TRPV4 expression level in aged MAECs and restored the flow- and 4α-PDD-induced vessel dilation in aged mesenteric arteries. We concluded that impaired TRPV4-mediated Ca(2+) signaling causes endothelial dysfunction and that TRPV4 is a potential target for clinical treatment of age-related vascular system diseases.

Ultrahigh density well-registered oxide nanocapacitors are very essential for large scale integrated microelectronic devices. We report the fabrication of well-ordered multiferroic BiFeO3 nanocapacitor arrays by a combination of pulsed laser deposition (PLD) method and anodic aluminum oxide (AAO) template method. The capacitor cells consist of BiFeO3/SrRuO3 (BFO/SRO) heterostructural nanodots on conductive Nb-doped SrTiO3 (Nb-STO) substrates with a lateral size of ~60 nm. These capacitors also show reversible polarization domain structures, and well-established piezoresponse hysteresis loops. Moreover, apparent current-rectification and resistive switching behaviors were identified in these nanocapacitor cells using conductive-AFM technique, which are attributed to the polarization modulated p-n junctions. These make it possible to utilize these nanocapacitors in high-density (>100 Gbit/inch(2)) nonvolatile memories and other oxide nanoelectronic devices.

Recent advances in the four-dimensional ultrafast transmission electron microscope (4D-UTEM) with combined spatial and temporal resolutions have made it possible to directly visualize structural dynamics of materials at the atomic level. Herein, we report on our development on a 4D-UTEM which can be operated properly on either the photo-emission or the thermionic mode. We demonstrate its ability to obtain sequences of snapshots with high spatial and temporal resolutions in the study of lattice dynamics of the multi-walled carbon nanotubes (MWCNTs). This investigation provides an atomic level description of remarkable anisotropic lattice dynamics at the picosecond timescales. Moreover, our UTEM measurements clearly reveal that distinguishable lattice relaxations appear in intra-tubular sheets on an ultrafast timescale of a few picoseconds and after then an evident lattice expansion along the radial direction. These anisotropic behaviors in the MWCNTs are considered arising from the variety of chemical bonding, i.e. the weak van der Waals bonding between the tubular planes and the strong covalent sp(2)-hybridized bonds in the tubular sheets.