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Recent advancements in satellite remote sensing technology and computer vision have enabled rapid extraction of road networks from massive, Very High-Resolution (VHR) satellite imagery. However, current road extraction methods face the following limitations: 1) Insufficient availability of accurate and diverse training datasets for global-scale road extraction; 2) Costly and time-consuming manual labeling of millions of road samples; and 3) Limited generalization ability of deep learning models across diverse global contexts, resulting in better performance for regions well-represented in the training dataset, but worse performance when faced with domain gaps. To address these challenges, a semi-supervised framework was developed in this study, which includes a global-scale benchmark dataset – termed GlobalRoadSet (GRSet) – and a pseudo-label guided semi-supervised road extraction network – termed GlobalRoadNetSF (GRNetSF). The GRSet dataset was constructed using high-resolution satellite imagery and open-source crowdsourced OpenStreetMap (OSM) data. It comprises 47,210 samples collected from 121 capital cities across six populated continents. The GRNetSF trains the network by generating pseudo-labels for unlabeled images, combined with a few labeled samples from the target region. To enhance the quality of the pseudo-labels, strong data augmentation perturbation and auxiliary feature perturbation techniques are employed to ensure model prediction consistency. The proposed GRNetSF_GRSet framework was implemented in over 30 cities worldwide, where most of the Intersection-over-Union (IoU) values increased by more than 10%. This outcome confirms its strong generalization ability.

AbstractTriptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased β-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.

AbstractDoxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

AbstractMitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.

A novel hyaluronic acid (HA)-modified hybrid nanocomplex HA-SeSe-COOH/siR-93C@PAMAM, which could efficiently deliver siRNA into tumor cells via a redox-mediated intracellular disassembly, was constructed for enhanced antitumor efficacy. Thereinto, siR-93C (siRNA) and positive PAMAM were firstly mixed into the electrostatic nano-intermediate, and then diselenide bond (-SeSe-)-modified HA was coved to shield excessive positive charges. This hybrid nanocomplex displayed uniform dynamic sizes, high stability, controlled zeta potential and narrow PDI distribution. Moreover, the -SeSe- linkage displayed GSH/ROS dual responsive properties, improving intracellular trafficking of siRNA. In vitro assays in A549 cell line presented that HA-SeSe-COOH/siR-93C@PAMAM has low cytotoxicity, rapid lysosomal escape and significant transfection efficiency; besides, an efficient proliferation inhibition ability and enhanced apoptosis. Furthermore, in animal studies, this negative-surfaced hybrid nanocomplex showed a prolonged circulation in blood and improved inhibition of tumor growth. All these results verified our hypothesis in this study that diselenide bonds-modified HA could promote not only stability and safety of nanoparticles in vivo but also intracellular behavior of siRNA via redox-dual sensitive properties; furthermore, this hybrid nanocomplex provided a visible potential approach for siRNA delivery in the antitumor field.

Change detection is a core issue in the study of global change. Inspired by recent success of the UNet3+ architecture originally designed for image semantic segmentation, in this article we proposed a densely connected siamese network for change detection, namely Pre-SiUNet3+-CD (the combination of Pre-processing, Siamese network and UNet3+). First, our proposed pre-processing algorithm can mitigate effects of poor co-registration between bitemporal images, thus alleviating the loss of localization information in the change map. Second, several modifications have been made to UNet3+ in order to improve its fit for change detection tasks using high-resolution imagery and generate highly discriminative and informative representations to locate changed pixels. The effectiveness of the proposed method is demonstrated on several datasets, and experimental results indicated that our model provides very competitive accuracies in terms of precision, recall, F1-score, and visual performance among all the compared methods. This is because it inherits most of the advantages of UNet3+ in object location and boundary production, and the introduction of pre-processing also gives it a significant accuracy boost.

A microsphere–gel in situ forming implant (MS–Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson’s disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM–MS prepared by a modified emulsion-phase separation method and optimized by Box–Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p

Herpes zoster (HZ) or “shingles” results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65–79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65–79 y.