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Lateral flow immunoassays (LFIAs) have wide application in point-of-care testing, particularly in resource-poor settings. To achieve signal amplification in a gold nanoparticle-based lateral flow assay without an additional procedure or the need for complex fabrication, a new and simple method was developed for using a “stacking pad” configuration that adds an additional membrane between the conjugation pad and test pad to the conventional AuNP-based LFIA format. This design helps to accumulate the antibody and antigen on the stacking pad, hence extending the antigen/antibody binding interactions to enhance the test’s detection sensitivity. With the enhanced lateral flow assay, as low as 1 ng/mL of Protein A and 15.5 ng/mL of C-reactive protein can be visualized with the naked eye. We also successfully applied the stacking pad system in the analysis of C-reactive protein in human serum and synovial fluid samples. These results suggest that this stacking pad LFIA can provide sensitive and on-site prognosis for detection in synovial fluid and serum samples in resource-limited settings.

Ultrasonic technologies show great promise for diagnostic imaging and drug delivery in theranostic applications. The development of functional and molecular ultrasound imaging is based on the technical breakthrough of high frame–rate ultrasound. The evolution of shear wave elastography, high-frequency ultrasound imaging, ultrasound contrast imaging, and super-resolution blood flow imaging are described in this review. Recently, the therapeutic potential of the interaction of ultrasound with microbubble cavitation or droplet vaporization has become recognized. Microbubbles and phase-change droplets not only provide effective contrast media, but also show great therapeutic potential. Interaction with ultrasound induces unique and distinguishable biophysical features in microbubbles and droplets that promote drug loading and delivery. In particular, this approach demonstrates potential for central nervous system applications. Here, we systemically review the technological developments of theranostic ultrasound including novel ultrasound imaging techniques, the synergetic use of ultrasound with microbubbles and droplets, and microbubble/droplet drug-loading strategies for anticancer applications and disease modulation. These advancements have transformed ultrasound from a purely diagnostic utility into a promising theranostic tool.

Weyl semimetals, with their unique electronic band structure, have drawn significant interest for their potential to explore quantum anomalies in condensed matter systems. In this study, we investigate the large positive magneto-thermal conductance associated with the gravitational anomaly – one of the predicted anomalies – for a Weyl semimetal based on a compressively strained HgTe layer. We clearly identify the Weyl regime in our device and accurately extract the thermal conductance by performing thermometry measurements at liquid helium temperatures using fully electronic methods. We observe the anticipated increase in thermal conductance, and it perfectly matches the electrical conductance according to the Wiedemann–Franz law. This finding indicates that, despite the unique electronic spectrum of Weyl semimetals, the mechanism governing heat transport in this system is the same as that for electrical transport, with no additional violations of conservation laws. The authors show that electronic thermal transport in an in-plane magnetic field in compressively strained HgTe at the Weyl points follows the Wiedemann–Franz law, challenging predictions of gravitational-anomaly signatures in this system.

Tumor microenvironment influences the efficacy of anti-cancer therapies. The dysfunctional tumor vasculature limits the efficiency of oxygenation and drug delivery to reduce treatment outcome. A concept of tumor vascular normalization (VN), which inhibits angiogenesis to improve vessel maturity, blood perfusion, and oxygenation, has been demonstrated under the anti-angiogenic therapy. The efficiency of drug delivery and penetration is increased by enhancing perfusion and reducing interstitial fluid pressure during the time window of VN. However, anti-angiogenic agents only induce transient VN and then prune vessels to aggravate tumor hypoxia. To repair tumor vessels without altering vessel density, we proposed to induce tumor VN by local oxygen release via oxygen microbubbles with ultrasound. With tumor perfusion enhancement under ultrasound contrast imaging tracing, the time window of VN was defined as 2-8 days after a single oxygen microbubble treatment. The enhanced tumor oxygenation after oxygen microbubble treatment inhibited hypoxia inducible factor-1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF) pathway to improve the morphology and function of tumor vasculature. The pericyte coverage and Hoechst penetration of tumor vessels increased without any changes to the vessel density. Finally, the intratumoral accumulation of anti-cancer drug doxorubicin could be increased 3-4 folds during tumor VN. These findings demonstrate that regulating tumor oxygenation by oxygen microbubbles could normalize dysfunctional vessels to enhance vascular maturity, blood perfusion, and drug penetration. Furthermore, ultrasound perfusion imaging provides a simple and non-invasive way to detect the VN time window, which increases the feasibility of VN in clinical cancer applications.

Hypoxia-induced drug resistance (HDR) is a critical issue in cancer therapy. The presence of hypoxic tumor cells impedes drug uptake and reduces the cytotoxicity of chemotherapeutic drugs, leading to HDR and increasing the probability of tumor recurrence and metastasis. Microbubbles, which are used as an ultrasound contrast agent and drug/gas carrier, can locally deliver drugs/gas and produce an acousto–mechanical effect to enhance cell permeability under ultrasound sonication. The present study applied oxygen-loaded microbubbles (OMBs) to evaluate the mechanisms of overcoming HDR via promotion of drug uptake and reoxygenation. A hypoxic mouse prostate tumor cell model was established by hypoxic incubation for 4 h. After OMB treatment, the permeability of HDR cells was enhanced by 23 ± 5% and doxorubicin uptake was increased by 11 ± 7%. The 61 ± 14% reoxygenation of HDR cells increased the cytotoxicity of doxorubicin from 18 ± 4% to 58 ± 6%. In combination treatment with OMB and doxorubicin, the relative contributions of uptake promotion and reoxygenation towards overcoming HDR were 11 ± 7% and 28 ± 10%, respectively. Our study demonstrated that reoxygenation of hypoxic conditions is a critical mechanism in the inhibition of HDR and enhancing the outcome of OMB treatment.

Background/Objectives: Anti-vascular therapy presents a potential strategy for activating anti-tumor immunity. Disrupted vascular debris provides effective antigens that activate dendritic cells, leading to subsequent immune responses. However, the resulting tumor hypoxia following vascular disruption may contribute to immune suppression, thereby hindering effective immune activation. Ultrasound-stimulated microbubble cavitation can locally disrupt tumor vessels through mechanical effects to achieve physical anti-vascular therapy. Therefore, this study designed oxygen-loaded nanobubbles (ONBs) to combine anti-vascular effects with local oxygen release under ultrasound stimulation. The feasibility of enhancing anti-tumor immune activation by alleviating tumor hypoxia was evaluated. Methods: A murine pancreatic subcutaneous solid tumor model was used to evaluate the efficacy of anti-vascular therapy-associated immunotherapy. Results: After ONB treatment, tumor perfusion was reduced to 52 ± 5%, which resulted in a subsequent 57 ± 11% necrosis and a 29 ± 4% reduction in hypoxia, demonstrating the anti-vascular effect and reoxygenation, respectively. However, subsequent immune responses exhibited no significant activation in intratumoral cytokine expression or splenic immune cell composition. Primary tumors exhibited a 15.7 ± 5.0% increase in necrosis following ONB treatment, but distant tumor growth was not significantly inhibited. Conclusions: These results highlighted a crucial issue regarding the complex correlations between vessel disruption, antigen production, oxygen delivery, hypoxia, and immunity when combining anti-vascular therapy with immunotherapy.

Although three established models for predicting the return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) exist, combinational external validation of these models remains limited. This study aimed to externally validate and compare the performance of three predictive models—RACA, P-ROSC, and UB-ROSC–and provide evidence to guide the selection and application of predictive models for prehospital ROSC in diverse settings. A retrospective validation was conducted using the National Taiwan University Hospital Hsinchu and Yunlin Branch Out-of-Hospital Cardiac Arrest Research Databases. Patients with EMS-treated OHCAs admitted to the hospital between January 2016 and July 2023 were recruited. The primary outcome was prehospital ROSC. Model performance was evaluated using discrimination, calibration, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio. Calibration and density distribution plots were generated. All three models demonstrated moderate-to-high discrimination with AUROCs of 0.758 (RACA), 0.755 (P-ROSC), and 0.747 (UB-ROSC). The RACA score exhibited better calibration across the risk deciles, whereas the P-ROSC and UB-ROSC scores tended to overestimate the probabilities at higher predicted risk levels. The P-ROSC score required fewer variables and showed the best separation between prehospital and non-prehospital ROSC cases. Optimal cut-off values for the RACA, P-ROSC, and UB-ROSC scores were 0.45, 41, and − 13, respectively, with corresponding sensitivities of 62 %, 56 %, and 71 % and specificities of 78 %, 82 %, and 69 %. All models achieved high NPVs (>96 %), but PPVs remained low (16–21 %). The P-ROSC, which requires fewer variables, has emerged as the most practical model for Taiwanese populations. However, the choice of the model should be guided by the availability of variables, regional EMS characteristics, and trends in prehospital ROSC rates. [Display omitted]

BackgroundIschemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.MethodsThe murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.ResultsThe percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves the prognosis of in-hospital cardiac arrest (IHCA). The six-factor RESCUE-IHCA score (resuscitation using ECPR during IHCA) was developed to predict outcomes of post-IHCA ECPR-treated adult patients. Our goal was to validate the score in an Asian medical center with a high volume and experience of ECPR performance and to compare the differences in patient characteristics between the current study and the original cohort in a 2022 observational study. Method: For this single-center, retrospective cohort study we enrolled 324 ECPR-treated adult IHCA patients. The primary outcome was in-hospital mortality. We used the area under the receiver operating curve (AUROC) to externally validate the RESCUE-IHCA score. The calibration of the model was tested by the decile calibration plot as well as Hosmer–Lemeshow goodness-of-fit with an associated P-value. Results: Of the 324 participants, 231 (71%) died before hospital discharge. The discriminative performance of the RESCUE-IHCA score was comparable with the originally validated cohort, with an AUC of 0.63. A prolonged duration of cardiac arrest was associated with an increased risk of mortality (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.03, P = .006). An initial rhythm of ventricular tachycardia (OR 0.14, 95% CI 0.04–0.51, P = .003), ventricular fibrillation (OR 0.11, 95% CI 0.03–0.46, P = .003), and palpable pulse (OR 0.26, 95% CI 0.07–0.92, P = 0.04) were associated with a reduced mortality risk compared to asystole or pulseless electrical activity. In contrast to the original study, age (P = 0.28), resuscitation timing (P = 0.14), disease category (P = 0.18), and pre-existing renal insufficiency (P = 0.12) were not associated with in-hospital death. Conclusion: In external validation, the RESCUE-IHCA score exhibited performance comparable to its original validation within the single-center population. Further investigation on hospital experience, time-of-day effect, and specific disease categories is warranted to improve the selection criteria for ECPR candidates during IHCA.

In this study, we investigated the antibacterial activity of silver-coated gold nanoparticles (Au-Ag NPs) immobilized on cellulose paper. Ag NPs are known to have strong antibacterial properties, while Au NPs are biocompatible and relatively simple to prepare. We made the Au-Ag NPs using a facile process called Ag enhancement, in which Au NPs serve as the nuclei for precipitation of a Ag coating, the thickness of which can be easily controlled by varying the ratio of the reactants. After synthesis, electron microscopy showed that the Au-Ag NPs displayed a core-shell structure, and that they could be successfully immobilized onto a cellulose membrane by heat treatment. We then investigated the antibacterial properties of this NP-coated cellulose paper against E . coli JM109. The inhibition rate, growth curve, and AATCC 100 activity test showed that cellulose paper coated with 15 nm Au-Ag NPs possessed excellent antibacterial activity against E . coli JM109. These results suggest that Au-Ag NPs immobilized on cellulose paper could be a valuable antibacterial technology for applications such as food packaging, clothing, wound dressings, and other personal care products.