The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT.

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Hypoxia is a hostile hallmark of most solid tumors, which often leads to multidrug resistance (MDR) and causes the failure of chemotherapy. Hypoxia also promotes epithelial–mesenchymal transition (EMT), leading to acceleration of tumor metastasis. Many chemotherapeutic drugs can further exacerbate hypoxia and thus promote metastasis. Therefore, relieving hypoxia is necessary for chemotherapy to inhibit both MDR and EMT. Herein, highly stable cerasomal perfluorocarbon nanodroplets with an atomic layer of polyorganosiloxane surface and pH-sensitive tumor-targeting peptide (D-vPCs-O2) were fabricated to co-deliver oxygen and therapeutic drug, doxorubicin. High-intensity focused ultrasound (HIFU) was utilized to trigger the co-release of doxorubicin and oxygen and simultaneously enhance ultrasound imaging, therefore achieving imaging-guided drug delivery. Mild-temperature HIFU (M-HIFU) not only triggered oxygen release from nanodroplets but also slightly elevated tumor temperature to accelerate tumor blood flow. The oxygen release and temperature elevation jointly relieved tumor hypoxia and alleviated MDR, which greatly enhanced the drug therapeutic efficacy as compared to clinically used doxorubicin and Doxil. Overall side effects were also largely reduced owing to the ultrastable drug loading of cerasome. The improvement of insufficient chemotherapy and the relief of tumor hypoxia corporately down-regulated TGF-β1, leading to the alleviation of EMT, and therefore significantly inhibited tumor metastasis. When “D-vPCs-O2 + M-HIFU” was utilized as a neoadjuvant chemotherapy, nanodroplets down-regulated heat shock proteins, reducing tumor relapse after the high-temperature HIFU (H-HIFU)-mediated hyperthermia ablation. The chemo-hyperthermia therapy totally eradicated tumors without any relapse or metastasis, providing a promising way to treat the triple-negative breast cancer, which is highly malignant, easily metastatic, and lacks effective treatments.

Atrazine (ATR), an environmental persistent and bioaccumulative herbicide, has been associated with environmental nephrosis. Lycopene (LYC) exhibits important properties of nephroprotection, but there are limited data on the specific underlying mechanism. The primary objective of this study was to explore the therapeutic effect of LYC on ATRinduced nephrotoxicity in mice. The mice were divided randomly into 6 groups and treated as follows: control group (C), 5 mg/kg LYC group (L), 50 mg/kg ATR group (A1), 200 mg/kg ATR group (A2), 50 mg/kg ATR plus 5 mg/kg LYC group (A1+L), and 200 mg/kg ATR plus 5 mg/kg LYC group (A2+L) by oral gavage administration for 21 days. We found that pretreatment with LYC significantly suppressed the ATR-induced renal tubular epithelial cell swelling. Furthermore, LYC mitigated ATR-induced dysregulation of oxidative stress markers by reducing MDA, H 2 O 2 levels, and increasing SOD, GPx, CAT concentration, and Nrf2 activation. Moreover, LYC activated the autophagic flux by a detectable change in autophagy-related genes (Beclin-1 and ATGs) and proteins (p62/SQSTM) and by the formation of autophagic vacuole (AV) and LC3 aggregation, in parallel with AMPK activation (pAMPK/AMPK). Herein, ATR-up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes, including quinoneoxidoreductase-1 (NQO1) and heme oxidase-1 (HO1), whereas LYC down-regulated those of the above genes. In addition, LYC suppressed ATR-induced activation of autophagy (increased LC3II/LC3I, ATGs, Beclin1, and p62, in parallel with increased AMPK activation). Collectively, our findings identified a cross talk between AMPK-activated autophagy and the Nrf2 signaling pathway in LYC-mediated nephroprotection against ATR-induced toxicity in mice kidney.

PAAs must be seriously classified by aetiology to be treated appropriately. Patients with giant-size PAAs, and those with pulmonary hypertension, anatomical anomalies, and rapid growth and compression of neighbouring critical structures, are proper candidates for surgery. Surgical options include aneurysm repair and replacement with allogeneic/synthetic grafts, depending on the situation. Additionally, the correction of associated abnormalities should be performed simultaneously during surgery. Surgical outcomes are effective, and long-term prognoses are satisfactory.

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Ischemia−reperfusion (I/R) injury leads to a low success rate of skin flap transplantation in reconstruction surgery, thus requiring development of new treatments. Necroptosis and apoptosis pathways, along with overexpression of reactive oxygen species and pro-inflammatory factors in skin flap transplantation, are deemed as potential therapeutic targets. This study provides a paradigm for nanozyme-mediated microenvironment maintenance to improve the survival rate of the transplanted skin flap. Prussian blue nanozyme (PBzyme) with multiple intrinsic biological activities was constructed and selected for this proof-of-concept study. The prepared PBzyme shows anti-inflammatory, antiapoptotic, antinecroptotic, and antioxidant activities in both in vitro and in vivo models of I/R injured skin flaps. The multiple inhibitory effects of PBzyme maintained a normal microenvironment and thus significantly promoted the survival rate of the I/R injured skin flap (from 37.21 ± 8.205% to 79.61 ± 7.5%). Of note, PBzyme regulated the expression of the characteristic signal molecules of necroptosis, including Rip 1, Rip 3, and pMLKL, indicating that PBzyme may be a therapeutic agent for necroptosis-related diseases. This study shows great prospects for clinical application of PBzyme in the treatment of skin flaps via local administration.

Ovarian cancer accounts for the major part of the mortality attributable to female reproductive system malignant tumors worldwide. Recently, the incidence of ovarian cancer has been increasing annually, and there remains a lack of suitable treatment methods that can significantly improve the 5-year survival rates of patients. Therefore, it is necessary to identify more effective treatments for ovarian cancer. It is established that microRNAs (miRNAs) have important roles in the diagnosis and treatment of ovarian cancer and a specific miRNA, miR-762, can promote the development of a variety of tumors. Menin is encoded by MEN1, a tumor suppressor gene, that is usually downregulated in ovarian cancer. In this study, we evaluated the expression levels of miR-762 and menin in ovarian cancer tissues and demonstrated that they were correlated. In addition, we found that miR-762 can downregulate the expression of menin through a binding site in its 3′-UTR and consequently upregulate the Wnt cell signaling pathway to promote the development of ovarian cancer. These results indicate that miR-762 is a promising potential target for the treatment of ovarian cancer.