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Oxidative stress is the key cause of the etiopathogenesis of several diseases associated with constipation. This study examined whether the green pine cone can improve the symptoms of constipation based on the antioxidant activities. The changes in the key parameters for the antioxidant activity and laxative effects were examined in the loperamide (Lop)-induced constipation of Sprague-Dawley (SD) rats after being treated with the methanol extracts of green pine cone (MPC, unripe fruits of Pinus densiflora ). MPC contained several bioactive compounds, including diterpenoid compounds such as dehydroabietic acid, taxodone, and ferruginol. In addition, it exhibited high scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. These effects of MPC successfully reflected the improvement in nicotinamide adenine dinucleotide phosphate oxidase (NADP) H oxidase transcription, superoxide dismutase (SOD) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels in the mid colon of Lop+MPC-treated SD rats. Furthermore, significant improvements in the stool parameters, gastrointestinal (GI) transit, intestine length, and histopathological structure of the mid colon were detected in the Lop-induced constipation rats after MPC treatment. The other parameters, including the regulators for the adherens junction (AJ) and tight junction (TJ), and GI hormone secretion for laxative effects, were improved significantly in Lop+MPC-treated SD rats. These effects were also verified in Lop+MPC-treated primary rat intestine smooth muscle cells (pRISMCs) through analyses for antioxidant defense mechanisms. Overall, the finding of this study offers novel scientific evidence that MPC could be considered as a significant laxative for chronic constipation based on its antioxidant activity.

Background/Objectives: Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T RM ) cells and tissue-resident memory B (B RM ) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses. However, the interactions between RSV vaccines and mucosal immune responses within the respiratory tract are poorly understood. We evaluated a mucosal immune system following immunization by RSV vaccine with poly-sorbitol transporter (RSV-PST), a nanoparticle adjuvant. Methods: We intranasally immunized the RSV-PST and identified the systemic and mucosal immune responses. Furthermore, we challenged with RSV A2 strain after immunization and investigated the protective effects. Results: Consequently, antigen-specific CD8 + T RM cells were markedly elevated in the lung parenchyma, yet exhibited impaired cytokine expression. In contrast, humoral immunity, with systemic antibody production from serum, but not in the respiratory tract, was significantly increased by RSV-PST immunization. Interestingly, the production of respiratory mucosal antigen-specific IgG after RSV A2 challenge dramatically increased in the bronchoalveolar lavage fluid (BALF) of the RSV-PST immunized group in the presence of FTY720, and the lung-infected RSV titer was significantly lower in this group. Furthermore, after RSV A2 challenge, CD69 + IgG + B RM cells were significantly increased in lung tissues in the RSV-PST group. Conclusions: The RSV-PST vaccine has protective effects against RSV infection by promoting both systemic and local humoral immunity rather than cellular immunity.

Background/Objectives: Aortic stenosis (AS) is a critical valvular heart disease associated with significant morbidity and mortality if not managed promptly. Previous studies have highlighted the "weekend effect", where the day of admission impacts outcomes in various cardiac conditions. This study evaluates the impact of weekend versus weekday admissions on outcomes in patients admitted with acutely decompensated aortic stenosis. Methods: We conducted a retrospective cohort study using the National Inpatient Sample database, focusing on patients emergently admitted with decompensated aortic stenosis. Patient outcomes were compared between those admitted on weekends (midnight Friday to midnight Sunday) and weekdays. Results: Among 94,320 patients included, 4537 (4.81%) were admitted on weekends. Weekend admissions were associated with significantly higher mortality (aOR 1.86; 95% CI 1.27-2.74) and longer hospital stays (mean increase 3.18 days; p < 0.001) compared to weekday admissions. Complication rates were also higher on weekends, including cardiogenic shock (aOR 2.1; 95% CI 1.54-2.87; p < 0.001), acute kidney injury (aOR 2.48; 95% CI 2.09-2.94; p < 0.001), and acute respiratory failure (aOR 2.88; 95% CI 2.38-3.49; p < 0.001). Additionally, weekend admissions had lower rates of transcatheter aortic valve replacement (TAVR) (aOR 0.49; 95% CI 0.40-0.62; p < 0.01) than weekday admissions. Conclusions: Patients with aortic stenosis admitted on weekends face significantly higher mortality, extended hospital stays, and increased complication rates compared to weekday admissions. Transcatheter aortic valve replacement (TAVR) rates were also lower for patients admitted on weekends. The "weekend effect" markedly influences outcomes, underscoring the need for hospital and administrative strategies to mitigate these adverse effects. Implementing standardized protocols and optimizing resource allocation during weekends could potentially reduce mortality and improve patient outcomes, offering a path to more equitable healthcare delivery.

Silica nanoparticles are innovative solutions of surgical glue that can readily adhere to various tissue-like substrates without the need for time-consuming chemical reactions or ultraviolet irradiation. Herein, 10 nm-sized silica nanoparticle (SiNP 10 ) treatment exhibited maximum adhesion strength in the porcine heart tissue model, which was approximately 7.15 times higher than that of the control group of non-treatment. We assessed the effects of silica nanoparticle treatment on in vivo skin wounds by scoring tissue adhesion and inflammation using histological images. Compared to the commercial cyanoacrylate skin adhesive (Dermabond), suppression of inflammatory cytokine levels in the incision wound skin was observed. We further quantified the expression of angiogenic growth factors and connective tissue formation-related proteins. On day 5 after wound closing treatment, the expression levels of PDGF-BB growth factor were significantly higher in SiNP 10 treatment (0.64 ± 0.03) compared to Dermabond (0.07 ± 0.05). This stimulated angiogenesis and connective tissue formation in the skin of the incision wound may be associated with the promoting effects of SiNP 10 treatment on wound closure and tissue adhesion.

The aim of this study is to describe the general features and eco-friendly biosynthesis of silver nanoparticles (AgNPs) from the marine bacterium Aggregatimonas sangjinii F202Z8 T . To the best of our knowledge, no previous study has reported the biosynthesis of AgNPs using this strain. The formation of AgNPs using F202Z8 T was synthesized intracellularly without the addition of any disturbing factors, such as antibiotics, nutrient stress, or electron donors. The AgNPs were examined using UV-vis spectrophotometry, transmission electron microscopy, energy-dispersive X-ray spectroscopy, nanoparticle tracking analysis, and Fourier transform infrared spectrometry. The UV-vis spectrum showed a peak for the synthesized AgNPs at 465 nm. The AgNPs were spherical, with sizes ranging from 27 to 82 nm, as denoted by TEM and NTA. FTIR showed various biomolecules including proteins and enzymes that may be involved in the synthesis and stabilization of AgNPs. Notably, the AgNPs demonstrated broad-spectrum antibacterial effects against various pathogenic Gram-positive and Gram-negative bacteria, including Escherichia coli , Bacillus subtilis , and Staphylococcus aureus . The minimum inhibitory concentrations and minimum bactericidal concentrations of the F202Z8 T -formed AgNPs were 80 and 100 µg/mL, 40 and 50 µg/mL, and 30 and 40 µg/mL against E. coli , B. subtilis , and S. aureus , respectively. This study suggests that A . sangjinii F202Z8 T is a candidate for the efficient synthesis of AgNPs and may be suitable for the formulation of new types of bactericidal substances.

The city of Seoul will limit the maximum particulate matter (PM 10 ) concentration to ≤35 μg/m 3 (from 2024). Herein, a numerical parametric study was conducted on the PM removal efficiency of the heating, ventilation, and air conditioning (HVAC) filters installed in the ceiling of subway cabins. The PM 10 concentration distribution was explored according to the flow rate and flow rate ratio of the air introduced into the cabin. Under the current ventilation conditions of the subway train HVAC system, the PM 10 concentration was highest in the cabin central area where exhaust outlets are located and decreased toward both ends of the cabin. The indoor airflow was improved and the PM 10 concentration was reduced by increasing the flow rate of the supplied air at both ends of the cabin while decreasing it in the central area. It was found that the strengthened PM 10 concentration criterion of Seoul can be met by increasing the ventilation flow rate to 700 CMH (currently, 500 CMH) and the filter efficiency to 85% (currently, 70%) while maintaining the current flow rate ratio. These results are expected to be used as important reference data for reducing the PM concentration in subway cabins and thereby improving indoor air quality.

Acupuncture point (AP) selections can vary depending on clinicians' acupuncture style, and therefore, acupuncture style is an important factor in determining the efficacy of acupuncture treatment. However, few studies have examined the differences in AP selections according to the acupuncture styles and theoretical backgrounds causing the differences. We compared the AP prescriptions used for 14 diseases in three classical medical textbooks, Dongeuibogam (DEBG), Saamdoinchimgooyogyeol (SADI), and Chimgoogyeongheombang (CGGHB), which represent unique acupuncture styles and have affected clinicians during this time. AP prescriptions showed more diversity between textbooks than between types of diseases. Among the three textbooks, AP prescriptions of SADI were most different compared to those of DEBG and CGGHB. Importantly, we found each style can be more clearly explained by AP attributes than by the APs per se. Specifically, SADI, DEBG, and CGGHB preferred five transport points located on the limbs, APs of the extra meridians , and source points , respectively. This suggests the possibility that the theoretical diversity of acupuncture styles results in the heterogeneity of AP selections.

Although docetaxel-based regimens are common and effective for early-stage triple-negative breast cancer (TNBC) treatment, acquired drug resistance frequently occurs. Therefore, a novel therapeutic strategy for docetaxel-resistant TNBC is urgently required. Signal transducer and activator of transcription 3 (STAT3) plays a pivotal role in the tumorigenesis and metastasis of numerous cancers, and STAT3 signaling is aberrantly activated in TNBC cells. In this study, a docetaxel-resistant TNBC cell line (MDA-MB-231-DTR) was established, and mechanisms for the antitumor activity of pulvomycin, a novel STAT3 inhibitor isolated from marine-derived actinomycete, were investigated. Levels of activated STAT3 (p-STAT3 (Y705)) increased in docetaxel-resistant cells, and knockdown of STAT3 recovered the sensitivity to docetaxel in MDA-MB-231-DTR cells. Pulvomycin effectively inhibited the proliferation of both cell lines. In addition, pulvomycin suppressed the activation of STAT3 and subsequently induced G 0 /G 1 cell cycle arrest and apoptosis. Pulvomycin also significantly inhibited the invasion and migration of MDA-MB-231-DTR cells through the modulation of epithelial-mesenchymal transition markers. In an MDA-MB-231-DTR-bearing xenograft mouse model, the combination of pulvomycin and docetaxel effectively inhibited tumor growth through STAT3 regulation. Thus, our findings demonstrate that the combination of docetaxel and STAT3 inhibitors is an effective strategy for overcoming docetaxel resistance in TNBC.

This study aimed to identify the prognostic subgroups of stage 4 high-risk neuroblastoma based on metastatic burden and explore their distinct clinical and genomic features. Patients aged ≥18 months with stage 4 and metaiodobenzylguanidine-avid neuroblastoma were enrolled. One hundred and thirty eligible patients were treated under the tandem high-dose chemotherapy scheme. Prognostic significance of metastatic burden measured by the modified Curie score was analyzed using a competing risk approach, and the optimal cut-point was determined. Metastasis-specific subgroups (cut-point: 26) were compared using clinicopathological variables, and differential gene expression analysis and gene set variation analysis (GSVA) were performed using RNA sequencing (RNA-seq). Metastatic burden at diagnosis showed a progressive association with relapse/progression. After applying the cut-point, patients with high metastatic burden showed >3-fold higher risk of relapse/progression than those with low metastatic burden. Moreover, patients with high metastatic burden showed smaller primary tumors and higher biochemical marker levels than those with low metastatic burden. In the genomic analysis, 51 genes were found to be differentially expressed based on the set criteria. GSVA revealed 55 gene sets, which significantly distinguished patients with high metastatic burden from those with low metastatic burden at a false discovery rate <0.25. The results indicated the prognostic significance of metastatic burden in stage 4 high-risk neuroblastoma, and we identified the distinct clinicopathological and genomic features based on metastatic burden. This study may aid in the better understanding and risk-stratification of stage 4 high-risk neuroblastoma patients.

Changes in kidney function in extremely preterm infants (EPT) with conservatively managed hemodynamically significant (HS) patent ductus arteriosus (PDA) are not known well. We aimed to present the postnatal course in serum creatinine levels (sCr), prevalence of acute kidney injury (AKI), then relevance between AKI and adverse outcomes in EPT with conservatively managed HS PDA. By review of medical records, we analyzed the postnatal course of sCr and prevalence of stage 3 AKI defined by the modified Kidney Disease Improving Global Outcome (KDIGO) in EPT at gestational age of 23 to 26 weeks with conservatively treated HS PDA. We investigated if the presence and/or prolonged duration of stage 3 AKI elevated the risk of adverse outcomes. The results showed that, neither factor was associated with adverse outcomes. While the average PDA closure date was at postnatal day (P) 41 and 53, sCr peaked at P 10 and 14 and the cumulative prevalence of stage 3 AKI was 57% and 72% in the EPT of 25-26 and 23-24 weeks' gestation, respectively. The high prevalence of stage 3 AKI without adverse outcomes in EPT with conservatively managed HS PDA suggests that it might reflect renal immaturity rather than pathologic conditions.