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A radiofrequency ablation (RFA) needle integrated with a temperature sensor (T‐sensor) and pressure sensor (P‐sensor) is designed and utilized for real‐time internal steam pop monitoring during RFA. The characteristics of the sensor‐integrated RFA needle (sRFA‐needle) are investigated quantitatively using a pressure chamber system, and the feasibility and usability of the needle in preclinical and clinical trials is demonstrated. The sharp changes in the temperature and normalized pressure sensor signals induced by the abrupt release of hot and high‐pressure steam can be clearly monitored during the steam pop phenomena. The basic mechanism of the preliminary steam pop is hypothesized and verified using in situ ultrasound imaging data and computational analysis data of the RFA procedure. Moreover, the usability of the system in clinical trials is investigated, and the steam pop phenomena during the RFA procedure are detected using T‐sensor and P‐sensor. The results confirm that the sensor integration on the medical needle can provide critical data for safer and more effective medical practices. A radiofrequency ablation (RFA) needle integrated with a flexible thin‐film type temperature and a pressure sensor is reported and its clinical applications toward real‐time detection of internal steam pop and monitoring of environmental change in the ablation zone are studied. The study is performed in a pre‐clinical trial (animal study) and clinical trial (human study) to verify their usefulness in an in‐vivo environment.

There are several broadly neutralizing monoclonal antibodies that neutralize influenza viruses with different mechanisms from traditional polyclonal antibodies induced by vaccination. CT149, which is one of the broadly neutralizing antibodies, was also previously reported to neutralize group 2 and some of group 1 influenza viruses (13 out of 13 tested group 2 viruses and 5 out of 11 group 1 viruses). In this study, we developed another antibody with the aim of compensating partial coverage of CT149 against group 1 influenza viruses. CT120 was screened among different antibody candidates and mixed with CT149. Importantly, although the binding sites of CT120 and CT149 are close to each other, the two antibodies do not interfere. The mixture of CT120 and CT149, which we named as CT-P27, showed broad efficacy by neutralizing 37 viruses from 11 different subtypes, of both group 1 and 2 influenza A viruses. Moreover, CT-P27 showed in vivo therapeutic efficacy, long prophylactic potency, and synergistic effect with oseltamivir in influenza virus-challenged mouse models. Our findings provide a novel therapeutic opportunity for more efficient treatment of influenza.

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (S F ), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-S F -Gtc proved to be the superior immunogen. More importantly, rVSV-msp-S F -Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

[This corrects the article DOI: 10.1371/journal.ppat.1010092.].

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis.

PurposeFor successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine.MethodsIn this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine.ResultsAll solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide–based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide–based formulation induced.ConclusionsCTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Polyhexamethylene guanidine phosphate (PHMG-p) is a biocidal compound linked to respiratory toxicity following exposure to humidifier disinfectants, but long-term pulmonary outcomes after inhalation remain insufficiently characterized. This study evaluated the pulmonary carcinogenic effects of chronic PHMG-p inhalation in a rat model under environmentally relevant exposure conditions. Sprague-Dawley rats were exposed to aerosolized PHMG-p at concentrations of 0.01, 0.03, or 0.09 mg/m³ via whole-body inhalation for approximately 90 days and were serially assessed at 26, 52, 78, and 96 weeks using noninvasive chest computed tomography and histopathological examination to evaluate pulmonary lesion development. Pulmonary lesions demonstrated clear dose- and time-dependent patterns, with no bronchioloalveolar hyperplasia or no malignant lung tumors observed in the control or low-dose groups throughout the study period. In contrast, medium- and high-dose exposure resulted in progressive increases in hyperplastic and neoplastic lesions over time, and bronchioloalveolar adenoma/epithelioma and malignant lung tumors appeared only after prolonged exposure, predominantly in the high-dose group at later follow-up periods in both sexes. Imaging findings closely corresponded with histopathological progression, indicating that chronic inhalation exposure to PHMG-p can induce progressive pulmonary neoplastic lesions in a dose- and time-dependent manner and providing experimental evidence for potential long-term respiratory hazards associated with inhaled PHMG-p.

L-HBsAg is a third-generation hepatitis vaccine capable of inducing antibodies in non-responders and thus providing potentially therapeutic treatment. In this study, L-HBsAg was administered using microneedles (MN) without an adjuvant to induce intradermal (ID) immunization, and the efficacy of ID immunization was compared with that of intramuscular (IM) immunization that uses a conventional formulation with an adjuvant of aluminum hydroxide (L-HBsAg-AL-IM). The L-HBsAg was dip-coated onto 800-μm-long microneedles made of polylactic acid (PLA). Delivery efficiency and administration time were determined through in vitro experiments using porcine skin. The denaturation of the formulation against sterilization by gamma rays was observed. A storage test and a freeze-thaw cycle test of the microneedles with trehalose as a stabilizer (L-HBsAg-MN-Tre) were observed. An antibody titer of L-HBsAg-MN-Tre was compared with that of the conventional IM immunization of the L-HBsAg solution with aluminum hydroxide (L-HBsAg-AL-IM). The formulation containing L-HBsAg was located on the upper third of the microneedle tips. The formulation on the MN was dissolved and delivered within 30 min of insertion into porcine skin in vitro. Trehalose was selected as a stabilizer, and the stabilizing effect increased with the increase of trehalose content in the solidified formulation. L-HBsAg-MN with 15% of trehalose was stable for 7 days at 40 °C and showed increased stability compared to the conventional liquid formulations. L-HBsAg-MN-Tre showed improved stability during the freeze-thaw cycle. The antibody titer of L-HBsAg-MN-Tre at 28 days was higher than that of L-HBsAg-AL-IM. ID administration of L-HBsAg-MN-Tre showed better efficacy and improved thermal and freeze thaw stability compared to L-HBsAg-AL-IM. Therefore, L-HBsAg-MN-Tre administration showed the possibility of ID delivery of L-HBsAg without the use of an adjuvant for the efficacy, convenience, and safety of pediatric vaccination.

Real‐Time Internal Steam Pop Detection Steam pop is one of the possible threats during radiofrequency ablation (RFA), a minimally invasive therapy to eliminate the cancer tissues. In order to monitor this threat, a flexible thinfilm type multimodal (pressure, temperature) sensor was integrated into the RFA needle, and successfully detected the steam pop in real‐time in a clinical demonstration. More details can be found in article number 2100725 by Hyo Keun Lim, Inkyu Park, and co‐workers.

In this study, the seed germination and dormancy characteristics of three Ranunculus species native to Korea ( R. cantoniensis , R. chinensis , and R. sceleratus ) were determined to establish an effective dormancy-breaking protocol. The results revealed that the R. cantoniensis , R. chinensis , and R. sceleratus seeds responded differently to treatment with gibberellins (GAs) and stratification. Warm stratification at 20℃ increased the germination percentage and partially broke the dormancy of the R. cantoniensis seeds; moreover, the germination temperature range of the seeds expanded upon treatment with high-concentration GA 4 + 7 . Meanwhile, neither cold nor warm stratification was effective at breaking the dormancy of R. chinensis seeds; however, high-concentration GA 4 + 7 treatment broke the dormancy of the seeds by expanding the germination temperature range. Lastly, the R. sceleratus seeds did not respond to the treatment with GAs; however, their germination percentage increased after undergoing warm stratification at 25℃. The seeds of these three species were characterized as exhibiting nondeep morphophysiological dormancy. The findings of this study enhance our understanding of the temperature-related germination responses of the three Ranunculus species, offering valuable insights into their conservation and utilization.