FRET Ratiometric Nanoprobes for Nanoparticle Monitoring

Fluorescence labelling is often used for tracking nanoparticles, providing a convenient assay for monitoring nanoparticle drug delivery. However, it is difficult to be quantitative, as many factors affect the fluorescence intensity. Förster resonance energy transfer (FRET), taking advantage of the energy transfer from a donor fluorophore to an acceptor fluorophore, provides a distance ruler to probe NP drug delivery. This article provides a review of different FRET approaches for the ratiometric monitoring of the self-assembly and formation of nanoparticles, their in vivo fate, integrity and drug release. We anticipate that the fundamental understanding gained from these ratiometric studies will offer new insights into the design of new nanoparticles with improved and better-controlled properties

Multimerization Increases Tumor Enrichment of Peptide–Photosensitizer Conjugates

Photodynamic therapy (PDT) is an established therapeutic modality for the management of cancers. Conjugation with tumor-specific small molecule ligands (e.g., short peptides or peptidomimetics) could increase the tumor targeting of PDT agents, which is very important for improving the outcome of PDT. However, compared with antibody molecules, small molecule ligands have a much weaker affinity to their receptors, which means that their tumor enrichment is not always ideal. In this work, we synthesized multimeric RGD ligand-coupled conjugates of pyropheophorbide-a (Pyro) to increase the affinity through multivalent and cluster effects to improve the tumor enrichment of the conjugates. Thus, the dimeric and trimeric RGD peptide-coupled Pyro conjugates and the monomeric one for comparison were efficiently synthesized via a convergent strategy. A short polyethylene glycol spacer was introduced between two RGD motifs to increase the distance required for multivalence. A subsequent binding affinity assay verified the improvement of the binding towards integrin αvβ3 receptors after the increase in the valence, with an approximately 20-fold improvement in the binding affinity of the trimeric conjugate compared with that of the monomeric conjugate. In vivo experiments performed in tumor-bearing mice also confirmed a significant increase in the distribution of the conjugates in the tumor site via multimerization, in which the trimeric conjugate had the best tumor enrichment compared with the other two conjugates. These results indicated that the multivalence interaction can obviously increase the tumor enrichment of RGD peptide-conjugated Pyro photosensitizers, and the prepared trimeric conjugate can be used as a novel antitumor photodynamic agent with high tumor enrichment

Arthroscopy Primary Double-Bundle Repair of Anterior Cruciate Ligament With Internal Brace Augmentation and a Knotless Anchor Implant

The primary repair technique of acute anterior cruciate ligament (ACL) tears has been controversially discussed over the past few decades. Many different suture techniques have been reported for ACL repair, but these procedures showed high re-rupture rates and poor results. Recently, the literature has reported excellent outcomes with primary ACL repair. There has been a resurging interest in modernizing and augmenting primary ACL repair. This article describes a technique that uses internal brace augmentation and a knotless anchor (Arthrex) implant for primary anatomic double-bundle ACL repair after an acute proximal ACL tear. This technique aims to advocate natural healing by the high-strength internal brace augmentation and knotless anchor as a provisional scaffold during the healing phase and early mobilization. This technique might be an alternative to conventional ACL reconstruction in the appropriate selection of patients

Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection. Methods A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases. A prediction model was built on 227 cases and validated on 98 cases, which were divided by random sampling in R software. Relevant clinical, laboratory and imaging data were collected. Multivariate logistic regression models were used to determine optimal predictors and to construct nomograms. The performance of the nomogram was evaluated by the area under the characteristic curve (AUC), calibration ability and decision curve analysis (DCA). Results There were 137 (60.4%) mild and 90 (39.6%) severe RSV-associated bronchiolitis cases in the training group (n = 227) and 63 (64.3%) mild and 35 (35.7%) severe cases in the validation group (n = 98). Multivariate logistic regression analysis identified 5 variables as significant predictive factors to construct the nomogram for predicting severe RSV-associated bronchiolitis, including preterm birth (OR = 3.80; 95% CI, 1.39–10.39; P = 0.009), weight at admission (OR = 0.76; 95% CI, 0.63–0.91; P = 0.003), breathing rate (OR = 1.11; 95% CI, 1.05–1.18; P = 0.001), lymphocyte percentage (OR = 0.97; 95% CI, 0.95–0.99; P = 0.001) and outpatient use of glucocorticoids (OR = 2.27; 95% CI, 1.05–4.9; P = 0.038). The AUC value of the nomogram was 0.784 (95% CI, 0.722–0.846) in the training set and 0.832 (95% CI, 0.741–0.923) in the validation set, which showed a good fit. The calibration plot and Hosmer‒Lemeshow test indicated that the predicted probability had good consistency with the actual probability both in the training group (P = 0.817) and validation group (P = 0.290). The DCA curve shows that the nomogram has good clinical value. Conclusion A nomogram for predicting severe RSV-associated bronchiolitis in the early clinical stage was established and validated, which can help physicians identify severe RSV-associated bronchiolitis and then choose reasonable treatment

A General Approach for Encapsulation of Biomolecules Using MOF Particles

Encapsulation of biomoleucles in metal organic frameworks (MOFs) has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule protection and controlled release for various applications such as drug delivery, vaccines, etc. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process

Maximizing Thiophene–Sulfur Functional Groups in Carbon Catalysts for Highly Selective H₂O₂ Electrosynthesis

Carbon materials are promising electrocatalysts for renewable energy devices because of their abundant availability, tunability, and structural durability in harsh electrochemical environments. Future large-scale applications require the construction of carbon materials with a clear doping configuration and high dopant loading, but this is particularly challenging. In this work, we reported a molecular weaving strategy using molecules with well-defined thiophene–sulfur (S) configuration as precursors to synthesize thiophene–S-doped carbon with a high S doping mass up to 14 wt % for hydrogen peroxide (H2O2) electrosynthesis. We theoretically and experimentally showed that the as-synthesized thiophene–S-doped carbon catalyst exhibited a selectivity exceeding 90% for H2O2 production. More significantly, we assembled a thiophene–S-doped carbon-based zinc–air battery for simultaneous H2O2 and power generation, which demonstrated a H2O2 production rate of 117.7 ± 0.2 mg·mg–1Cat·h–1 and a peak power density of 82.7 ± 0.8 mW cm–2. This work extends the practical application potential of carbon-based materials in future energy conversion and storage devices