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Background: Coronary physiology measured by fractional flow reserve (FFR) is superior to angiography for assessing the efficacy of percutaneous coronary intervention (PCI). Yet, the clinical adoption of post-PCI FFR is limited. Murray law-based quantitative flow ratio (μQFR) may represent a promising alternative, as it can quickly compute FFR from a single angiographic view. Objectives: The authors aimed to investigate the potential role of post-PCI μQFR in predicting clinical outcomes. Methods: This was a post hoc blinded analysis of the FLAVOUR trial. Patients with angiographically intermediate lesions randomized 1:1 to receive FFR or intravascular ultrasound-guided PCI were included. Post-PCI μQFR was assessed in successfully stented vessels, blinded to clinical outcomes. Suboptimal physiological outcome post-PCI was defined a priori as post-PCI μQFR

Background: Koreoleptoxis globus is an endangered candidate species of snail in South Korean streams. This species primarily inhabits streams characterized by fast current velocities and coarse-particle streambed substrates. In this study, 12 types of probability distribution models, including exponential, normal, log-normal, logistic, Weibull, gamma, beta, and Gumbel, were used to quantitatively assess the physical microhabitat preferences of K. globus. The evaluation was based on data collected from 340 sampling units across 34 sites in South Korea between April 2024 and May 2024, focusing on variables such as water depth, current velocity, and streambed substrate. Results: The best-fitting probability distribution models for each physical environmental factor were identified as follows: 1) water depth, inverted log-normal distribution, 2) current velocity, beta distribution, and 3) streambed substrate, Weibull distribution. Optimal water depth preferences ranged from 31.2 cm to 53.7 cm. Current velocity preferences ranged from 57.8 cm s-1 to 88.8 cm s-1. Substrate preferences ranged from −7.4 Φm to −5.6 Φm. The mean values for these factors were water depth of 35.8 cm, current velocity of 63.0 cm s-1, and streambed substrate of −5.7 Φm. Mode values were water depth of 44.4 cm, current velocity of 75.6 cm s-1, and substrate of −6.7 Φm. Standard deviation values were water depth of 15.8 cm, current velocity of 21.4 cm s-1, and streambed substrate of 1.5 Φm. Conclusions: Overall, the beta and Weibull distribution models demonstrated a high degree of fit, likely owing to the inherent flexibility of these models. Beta distribution models were well suited for cases with negative skewness, whereas Weibull distribution models provided a better fit for cases with positive skewness. The physical habitat characteristics of K. globus were quantitatively demontrated to correspond to riffled areas. Further research is required to explore the interactions between physical environmental factors and the impact of habitat disturbance.

Therapeutic angiogenesis by intentional formation of blood vessels is essential for treating various ischemic diseases, including limb ischemia. Because Wnt/β-catenin and angiopoietin-1/Tie2 signaling play important roles in endothelial survival and vascular stability, coactivation of these signaling pathways can potentially achieve therapeutic angiogenesis. In this study, we developed a bifunctional antibody fusion, consisting of a Tie2-agonistic antibody and the Furin domains of R-spondin 3 (RSPO3), to simultaneously activate Tie2 and Wnt/β-catenin signaling. We identified a Tie2-agonistic antibody T11 that cross-reacted with the extracellular domain of human and mouse Tie2, and evaluated its ability to increase endothelial cell survival and tube formation. We generated a bifunctional T11–RF12 by fusing T11 with the Furin-1 and −2 domains of RSPO3. T11–RF12 could bind not only to Tie2, but also to LGR5 and ZNRF3, which are counterparts of the Furin-1 and −2 domains. T11–RF12 significantly increased Wnt/β-catenin signaling, as well as the formation of capillary-like endothelial tubes, regardless of the presence of Wnt ligands. Coactivation of Tie2 and Wnt/β-catenin signaling by T11–RF12 increased the blood flow, and thereby reduced foot necrosis in a mouse hindlimb ischemia model. In particular, T11–RF12 induced therapeutic angiogenesis by promoting vessel stabilization through pericyte coverage and retaining endothelial expression of Frizzled 10 and active β-catenin. These results indicate that the agonistic synergism of Tie2 and Wnt/β-catenin signaling achieved using T11–RF12 is a novel therapeutic option with potential for treating limb ischemia and other ischemic diseases.

IntroductionTularemia, caused by the bacterium Francisella tularensis, poses health risks to humans and can spread through a variety of routes. It has also been classified as a Tier 1 Select agent by the CDC, highlighting its potential as a bioterrorism agent. Moreover, it is difficult to diagnose in a timely fashion, owing to the non-specific nature of tularemia infections. Rapid, sensitive, and accurate detection methods are required to reduce mortality rates. We aimed to develop antibodies directed against the outer membrane protein A of F. tularensis (FopA) for rapid and accurate diagnosis of tularemia.MethodsWe used a baculovirus insect cell expression vector system to produce the FopA antigen and generate anti-FopA antibodies through immunization of BALB/c mice. We then employed hybridoma and phage display technologies to screen for antibodies that could recognize unique epitopes on FopA.ResultTwo monoclonal antibodies, 6B12 and 3C1, identified through phage display screening specifically bound to recombinant FopA in a dose-dependent manner. The binding affinity of the anti-FopA 6B12 and 3C1 antibodies was observed to have an equilibrium dissociation constant of 1.76 × 10-10 M and 1.32 × 10-9 M, respectively. These antibodies were used to develop a sandwich ELISA system for the diagnosis of tularemia. This assay was found to be highly specific and sensitive, with detection limits ranging from 0.062 ng/mL in PBS to 0.064 ng/mL in skim milk matrices.DiscussionOur findings demonstrate the feasibility of a novel diagnostic approach for detecting F. tularensis based on targeting FopA, as opposed to existing tests that target the bacterial lipopolysaccharide.

Groundwater is an essential drinking water source for humans. However, improper groundwater management leads to fecal contamination and waterborne diseases caused by viral pathogens. Therefore, this study aimed to investigate norovirus (NoV) contamination by conducting nationwide monitoring over five years (2019–2023). Groundwater samples were analyzed for water quality parameters, indicator microorganisms, NoV prevalence, and viral genotypes. Water quality was assessed for temperature, turbidity, and residual chlorine, whereas microorganisms were analyzed for total coliforms, Escherichia coli, and NoV genotypes. Of the 600 sites, 11 (1.8%) were NoV-positive, irrespective of season or location. Low residual chlorine levels (0.02–0.75 mg/L) were observed, possibly limiting viral inactivation. Total coliforms were detected in only three NoV-positive samples, and E. coli was absent. NoV genotypes were identified as GI.1 and GII.4, with GII.4 being the most frequently detected genotype. The present study demonstrated that periodic monitoring and expanded nationwide efforts are required for effective groundwater management and public health protection.

Background/Objectives: The spread of antibiotic resistance, particularly through Enterococcus spp., in wastewater treatment plants (WWTPs) poses significant public health risks. Given that research on antibiotic-resistant enterococci and their antibiotic-resistance genes in aquatic environments is limited, we evaluated the role of Enterococcus spp. in WWTPs by comparing the antibiotic resistance rates, gene prevalence, biofilm formation, and residual antibiotics in the influent and effluent using culture-based methods. Methods: In 2022, influent and effluent samples were collected from 11 WWTPs in South Korea. Overall, 804 Enterococcus strains were isolated, and their resistance to 16 antibiotics was assessed using the microdilution method. Results: High resistance to tetracycline, ciprofloxacin, kanamycin, and erythromycin was observed. However, no significant differences in the overall resistance rates and biofilm formation were observed between the influent and effluent. Rates of resistance to ampicillin, ciprofloxacin, and gentamicin, as well as the prevalence of the tetM and qnrS genes, increased in the effluent, whereas resistance rates to chloramphenicol, florfenicol, erythromycin, and tylosin tartrate, along with the prevalence of the optrA gene, decreased. E. faecium, E. hirae, and E. faecalis were the dominant species, with E. faecalis exhibiting the highest resistance. Conclusions: Our results suggest that WWTPs do not effectively reduce the rates of resistant Enterococcus spp., indicating the need for continuous monitoring and improvement of the treatment process to mitigate the environmental release of antibiotic-resistant bacteria.

Cellulose nanofibrils (CNFs) are versatile materials, but their sensitivity to humidity affects performance. Esterification with fatty acids enhances the hydrophobicity of CNF films. This study compared gas- and liquid-phase esterification using three fatty acid chlorides at different dosages. Gas-phase esterification minimally affected cellulose crystallinity, maintaining a crystallinity index exceeding 55.8%, whereas liquid-phase esterification significantly reduced crystallinity. Gas-phase esterification achieved hydrophobicity (water contact angle >100°) with less fatty acid chlorides (0.50 eq/OH) compared to liquid-phase esterification (1.00 eq/OH). Tensile strength significantly dropped in the liquid phase (68.4–6 MPa) and up to an 8-fold decrease in the elastic modulus. Conversely, gas-phase esterification maintained tensile strength over 40 MPa, and elastic modulus increased by a minimum of 2.5 times. However, gas-phase esterification resulted in a 5-fold reduction in elongation at break (%). Thermogravimetric analysis indicated a high T max of 362°C for liquid-phase esterified samples and a substantial 24.9% residual weight for gas-phase esterified samples.

Abstract Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin‐mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension‐dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin αvβ3 and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell‐substrate interfaces. This data reveals that integrin‐mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures.

Esterified nanofibrillated cellulose (eNFC) with varying degrees of substitution was prepared using fatty acid chloride. Furthermore, the effect of esterification on properties of pure NFC and its composites with polybutylene succinate (PBS) was investigated. Lauroyl chloride (LC) with 12 carbon atoms was used for esterification. An increase in the amount of LC increased the degree of substitution (DS), which significantly decreased the water contact angle and improved the hydrophobicity of NFC. The addition of fatty acid to NFCs lowered their crystallinity. However, the fatty acid increased the hydrophobicity of NFCs, thereby improving their dispersibility in nonpolar solvents. Compared with pure NFCs, eNFC exhibited enhanced compatibility with PBS, and the addition of eNFC with an appropriate DS increased the tensile strength and elastic modulus of PBS. These findings suggest the potential of NFC esterification for improving the performance of NFC-based composite materials.