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Background/Aims Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear. Methods Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease. Results LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues. Conclusions These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Porcine group A rotavirus (PoRVA; family, Reovirideae) strains cause acute viral gastroenteritis in piglets (especially suckling and weaned pigs), resulting in significant economic losses. In this study, we analyzed the VP7 and VP4 genes of PoRVA isolated between 2014 and 2018 from domestic pigs in South Korea to investigate the prevalence of predominant circulating genotypes (G and P types). The prevalence of the PoRVA antigen in the diarrheic fecal samples was 14.1% (53/377). Further genetic characterization of the VP7 and VP4 genes of 53 PoRVA isolates identified six different G-genotypes and five different P genotypes. The G4 and G9 genotypes were the most common (each 39.6%) in PoRVA-positive pigs, followed by P[7] and P[6] (33.9% and 30.1%, respectively). Because the G5 and G9 genotype vaccines are currently mainly used in South Korea, this result provides valuable epidemiological information about the genetic characteristics of PoRVA circulating on domestic pig farms. Development of a novel PoRVA vaccine that targets the current strains circulating in South Korea may be required for more effective virus control on pig farms.

In order to better assist Latinas in STEM, it is imperative to understand the impact of cultural values in their educational persistence. This study uses a national dataset of Latina STEM college students to examine the relationship between positive and negative marianismo beliefs and how this impacts mental health and educational persistence. Findings from the study demonstrated that endorsing positive aspects of marianismo beliefs benefited the educational persistence of Latinx STEM college students. Results can inform institutions on how to develop programs that increase Latina STEM student persistence.

This study aimed to examine whether Asian international students' mental health literacy predicts mental health help-seeking behaviors above and beyond known influencing factors. Hierarchical logistic regression was conducted in analyzing a national sample of 460 Asian international students who reported depressive symptomatology. Results indicated that students who identified as female and experienced more days of academic impairment were more likely to seek counseling. Additionally, having more knowledge on mental disorders and treatments and campus mental health services were positively related to help-seeking behavior. However, the ability to recognize the development of mental disorders in others was negatively associated with seeking mental health help. Implications for administrators, college program planners, and mental health providers are discussed.

Abstract Metastasis and recurrence are the main challenges in cancer treatment. Among various therapeutic approaches, immunotherapy holds promise for preventing metastasis and recurrence. In this study, we evaluated the efficacy of treating primary cancer and blocking metastasis and recurrence with photo-immunotherapeutic nanoparticles, which were synthesized using two types of charged polysaccharides. Codium fragile polysaccharide (CFP), which exhibits immune-stimulating properties and carries a negative charge, was combined with positively charged chitosan to synthesize nanoparticles. Additionally, indocyanine green (ICG), a photosensitizer, was loaded inside these particles and was referred to as chitosan-CFP-ICG (CC-ICG). Murine colon cancer cells (CT-26) internalized CC-ICG, and subsequent 808-nanometer laser irradiation promoted apoptotic/necrotic cell death. Moreover, intratumoral injection of CC-ICG, with 808-nanometer laser irradiation eliminated CT-26 tumors in mice. Rechallenged lung metastases of CT-26 cancer were inhibited by dendritic cell activation-mediated cytotoxic T lymphocyte stimulation in mice cured by CC-ICG. These results demonstrated that CC-ICG is a natural tumor therapeutic with the potential to treat primary tumors and suppress metastasis and recurrence.

Abstract Background Toothbrushing is the most commonly used method to physically remove dental plaque. However, there are many areas of the mouth that are difficult to reach with a toothbrush. The type of toothbrush is a critical factor influencing the effectiveness of oral care. The purpose of the study was to evaluate a toothbrush with a thin head, slender-neck and super-tapered bristles to target hard-to-reach areas in the oral cavity for reducing dental plaque and gingivitis. Methods This crossover study included 58 adults aged 20 years and older. All participants were randomly assigned to use test and control toothbrushes (the latter had a normal head and round bristles) for two 4-week phases. Participants brushed their teeth twice daily in their habitual manner. At the start and end of each phase the Silness-Lӧe plaque index (PI), Lӧe -Silness gingival index (GI) and bleeding-on-probing index (BOP) were assessed and performed plaque fluorescence tests using quantitative light-induced fluorescence technology. Results After using the test toothbrush, PI, GI and BOP decreased by 25%, 30% and 48%, respectively (P

Abstract Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Abstract The Ames test is used worldwide to initially screen the mutagenic potential of new chemicals. In the standard Ames test, S. typhimurium strains (TA100, TA98, TA1535, and TA1537) and Escherichia coli (WP2uvrA) are treated with substances with/without cytochrome P450s (CYPs)-induced rat S9 fractions for identifying mutagens and pro-mutagens. However, many substances show completely different toxicity patterns depending on whether the liver S9 fraction belongs to rats or humans. The natural product Polygoni Multiflori Radix (PMR) can also show bacterial reverse mutation, followed by the rat or human liver S9 fraction. While PMR elicits reverse mutations in the TA1537 strain in rat liver S9 but not in human liver S9, this mechanism has not been verified yet. To explain this, the differences in metabolic enzymes compositions commonly observed between rats and humans have been implicated. This study aimed to explore the key factors that cause differences in the genotoxicity of PMR between rat and human liver S9 metabolic enzymes. The results of next-generation sequencing (NGS) analysis showed that both rat and human metabolic enzymes caused similar mutations in TA1537. However, when the metabolic enzymes in each S9 fraction were analyzed using ion mobility tandem mass spectrometry (IM-MS), rat- and human-specific enzymes were identified among the cytochrome (CYP) family, especially aryl hydrocarbon receptor (AHR)-related CYPs. These findings suggest that CYP1A1 isoforms contribute to the mechanism of PMR in the Ames test. Therefore, an in vitro Ames test might be more reliable in predicting genotoxicity for both rodents and humans. This will also help overcome the limitations of laboratory animal-based toxicity evaluations, which provide unreliable results due to interspecies differences between humans and rodents.

Abstract Background Limited research has analyzed the association between diastolic blood pressure (DBP) and survival after pediatric cardiopulmonary resuscitation (CPR). This study aimed to explore the association between post-resuscitation diastolic blood pressure and survival in pediatric patients who underwent CPR. Method This retrospective single-center study included pediatric patients admitted to the pediatric intensive care unit of Asan Medical Center between January 2016 to November 2022. Patients undergoing extracorporeal CPR and those with unavailable data were excluded. The primary endpoint was survival to ICU discharge. Results A total of 106 patients were included, with 67 (63.2%) achieving survival to ICU discharge. Multivariate logistic regression analysis identified DBP within 1 h after ROSC as the sole significant variable (p = 0.002, aOR, 1.043; 95% CI, 1.016–1.070). Additionally, DBP within 1 h demonstrated an area under the ROC curve of 0.7 (0.592–0.809) for survival to ICU discharge, along with mean blood pressure within the same timeframe. Conclusion Our study highlights the importance of DBP within 1-hour post-ROSC as a significant prognostic factor for survival to ICU discharge. However, further validation through further prospective large-scale studies is warranted to confirm the appropriate post-resuscitation DBP of pediatric patients.

This case report discusses a patient diagnosed with L1 burst fracture, right lateral femoral condyle and proximal tibial and fibular head and neck comminuted fractures, and left medial femoral condyle and suspected tibial fractures after a traffic accident. She received integrated Korean medicine treatment, including motion- style acupuncture treatment (MSAT), electroacupuncture, acupuncture, herbal medicine, moxibustion, and cupping therapy for 112 days. The scores improved for the low back pain Numeric Rating Scale (NRS) (from 7 to 3), Oswestry Disability Index (from 94 to 38), bilateral leg pain NRS (from 6 to 2), Lysholm Knee Scoring Scale (from 0 to 66), left ankle manual muscle test (from Poor− to Normal), Korean version of the modified Barthel index (from 32 to 92), and EuroQol 5-dimension 5-level (from 25 to 9), as did mobility. Radiological scans also showed fracture healing. This study suggests the potential of MSAT in high-energy polytrauma care, particularly for fractures.

Objective To assess whether performing exercises during hemodialysis reduces the risk of developing intradialytic hypotension and enhances exercise capacity in patients with chronic kidney disease. Methods This study included patients aged ≥18 years undergoing hemodialysis. Participants performed exercises using a portable lower extremity ergometer during hemodialysis sessions for 3 weeks. Data regarding walking distance, knee strength, quality of life, fat-free mass, arterial pressure, blood pressure, heart rate, frequency of intradialytic hypotension, fatigue, and duration of hemodialysis were collected and analyzed. Results Significant improvements in walking distance and knee strength were observed following the implementation of exercise training during hemodialysis. Although there was no significant reduction in the frequency of intradialytic hypotension, a decreasing trend was noted. Other parameters such as quality of life and fatigue did not show significant changes. Conclusion Using a portable ergometer during hemodialysis improved exercise capacity and knee strength in patients with chronic kidney disease. There was a trend toward reduced intradialytic hypotension, suggesting potential cardiovascular benefits. Further research with larger sample sizes is needed to confirm these findings.

Abstract Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells. Inoculation of S. epidermidis also suppressed IAV infection and the concentration of polyamines including putrescine, spermidine, and spermine was completely attenuated in S. epidermidis-inoculated NHNE cells. S. epidermidis activated the enzyme involved in the production of ornithine from arginine and downregulated the activity of the enzyme involved in the production of putrescine from ornithine in nasal epithelium. S. epidermidis also induced the activation of enzymes that promote the extracellular export of spermine and spermidine in NHNE cells. Our findings demonstrate that S. epidermidis is shown to be able of creating an intracellular environment lacking polyamines in the nasal epithelium and promote the balance of cellular polyamines in favor of the host to restrict influenza virus replication.

Objective. Compare measurements of skeletal and dental areas on the CBCT to the corresponding soft-tissue measures taken from a 3D Facial Scanner. Methods. 30 patients with CBCT and 3D Facial scanner photos were selected from the orthodontic program database. 30 different distance measurements were obtained from CBCT and facial scan. OrthoInsight software was used to obtain the measurements from the facial scan images, and AVIZO software was used for corresponding CBCT landmarks. The Euclidean distance formula was used to determine the distances for the corresponding x, y, and z coordinates of the CBCT. Reliability for CBCT and Facial Scanner was completed by calculating 30 distances for 10 patients, 3 times. Once reliability was determined, all 30 distances were calculated once for CBCT and facial scanner on each patient and descriptive statistics and paired t-test were applied. Results. All distances measured presented excellent reliability, the lowest one being the left eye width for the facial scanner (ICC 0.847). The landmark with the highest mean error on the CBCT was 2.0 ± 1.6 mm on the z-axis for the spinal level landmark. The Facial Scanner’s largest mean measurement error was 1.5 ± 0.9 mm for the distance of the left corner of the mouth to gonion. All data except width between outer eye corners were statistically significant (p

ABSTRACTSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-β signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

A new system for the easy loading and NIR light-triggered release of drugs is introduced. It consists of poly(ε-caprolactone) (PCL) hollow nanoparticles with surface openings containing a biodegradable fatty acid with phase-change ability and a biocompatible photothermal agent. These openings, which can enhance the connectivity between the interior and the exterior, enable the easy loading of drug molecules into the interior voids, and their successive sealing ensures a stable encapsulation of the drug. Upon exposure to an external NIR light irradiation, the photothermal agent generates heat that raises the local temperature of the hollow particles above the melting point of the fatty acid, leading to the formation of nanopores on their shells, and consequently, the instant release of the encapsulated drug molecules through the pores. The synergistic activity of the hyperthermia effect from the photothermal agent and the NIR-triggered release of the drug molecules results in noticeable anticancer efficacy.

This paper introduces a new fibrous system for synergistic cancer therapy, which consists of gold nanocage (AuNC)-loaded poly(ε-caprolactone) (PCL) fibers with encapsulation of a chemotherapeutic anticancer drug in their core and loading of a phase-changeable fatty acid in their sheath. Under on⁻off switching of near-infrared (NIR) light irradiation, the excellent photothermal ability and photostability of AuNCs allows repeated, significant heating of the fibers to a temperature available to hyperthermia. Simultaneously, the NIR light-induced heat generation enables the melting out of the loaded fatty acid, leading to a rapid release of the drug molecules from the fibers. The combination of this NIR light-triggered drug release with the repeated hyperthermia treatment exhibits excellent anticancer efficacy.

Background Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited. Methods Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model. Results A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577–6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051–1.461; p = 0.01). Conclusion While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI.

Background Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. Methods This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. Results No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (–1.90 g/dL vs. –2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. Conclusion NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.

Herpes zoster virus infection is common and results in significant morbidity in patients who have undergone solid organ transplantation. Herpes zoster can involve the cranial nerves, and vagus nerve involvement is an infrequent primary manifestation of herpes zoster. Here, we describe a rare presentation of disseminated herpes zoster infection with vagus nerve involvement in a kidney transplant recipient. A 62-year-old man who had undergone kidney transplantation 3 years prior presented to our clinic with sore throat and hoarseness, followed by multiple vesicular-pustular rashes on the face and trunk. Flexible laryngoscopy revealed left paramedian vocal cord paralysis with multiple ulcerative lesions extending from the left pyriform sinus to the epiglottis. Computed tomography of the neck, abdomen, and chest revealed no significant abnormalities that could have caused vocal cord paralysis. We confirmed the diagnosis of disseminated herpes zoster after herpes zoster laryngitis based on positive blood tests and polymerase chain reaction for varicella zoster virus antibodies. The skin rashes and laryngeal ulcers rapidly resolved after treatment with intravenous acyclovir and high-dose steroids. The patient still had persistent dysphagia and microaspiration as assessed by a video fluoroscopic swallowing study, but showed improvement in dysphagia in response to swallowing rehabilitation therapy. This case provides valuable insights into the presenting symptoms of disseminated herpes zoster, which can cause acute vagus neuritis in solid organ transplantation recipients.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0–79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan–Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Soybean (Glycine max), a crucial global crop, experiences yearly yield reduction due to diseases such as anthracnose (Colletotrichum truncatum) and root rot (Fusarium spp.). The use of fungicides, which have traditionally been employed to control these phytopathogens, is now facing challenges due to the emergence of fungicide-resistant strains. Streptomyces bacillaris S8 strain S8 is previously known to produce valinomycin t through a nonribosomal peptide synthetase (NRPS) pathway. The objective of this study was to evaluate the antifungal activity of S. bacillaris S8 against C. truncatum and Fusarium sp., assessing its efficacy against soybean pathogens. The results indicate that strain S8 effectively controlled both above-ground and underground soybean diseases, using the NRPS and NRPS-related compound, suggesting its potential as a biological control in plant-microbe interactions. These findings underscore the pivotal role of the stain S8 in fostering healthy soybean microbial communities and emphasize the significance of microbiota structure studies in unveiling potent biocontrol agents.

BackgroundSinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC.MethodsMedical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria.ResultsTotal 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506).ConclusionNAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Abstract Autonomously self‐healing, reversible, and soft adhesive microarchitectures and structured electric elements could be important features in stable and versatile bioelectronic devices adhere to complex surfaces of the human body (rough, dry, wet, and vulnerable). In this study, we propose an autonomous self‐healing multi‐layered adhesive patch inspired by the octopus, which possess self‐healing and robust adhesion properties in dry/underwater conditions. To implement autonomously self‐healing octopus‐inspired architectures, a dynamic polymer reflow model based on structural and material design suggests criteria for three‐dimensional patterning self‐healing elastomers. In addition, self‐healing multi‐layered microstructures with different moduli endows efficient self‐healing ability, human‐friendly reversible bio‐adhesion, and stable mechanical deformability. Through programmed molecular behavior of microlevel hybrid multiscale architectures, the bioinspired adhesive patch exhibited robust adhesion against rough skin surface under both dry and underwater conditions while enabling autonomous adhesion restoring performance after damaged (over 95% healing efficiency under both conditions for 24 h at 30°C). Finally, we developed a self‐healing skin‐mountable adhesive electronics with repeated attachment and minimal skin irritation by laminating thin gold electrodes on octopus‐like structures. Based on the robust adhesion and intimate contact with skin, we successfully obtained reliable measurements during dynamic motion under dry, wet, and damaged conditions.

IntroductionThe phenomenon in which the damage of plant diseases is suppressed by continuous cropping is defined as “suppressiveness” and the development of suppressive soils and key beneficial microorganisms have been identified through various previous studies. However, no studies have been conducted on microbial communities related to disease occurrence before the initial occurrence of diseases in crop monoculture.MethodsWe aimed to investigate the ecological modifications of pathogen population density in soil, disease occurrence rate, and microbiota community shifting during ginseng monoculture to better understand the tripartite social relationships in the monoculture system. To achieve the study’s objectives, a long-term monoculture of ginseng was established. The microbial diversity and community structure were analyzed using high-throughput sequencing, and the pathogen population density and disease occurrence rate were determined using qPCR and observation.Results and discussionThe results showed that the initial rhizosphere bacterial community of ginseng had already collapsed before the development of the root rot disease. The study also identified the crucial role of soil-borne pathogens in causing disease and the loss of initial keystone taxa populations in the early stages of monoculture. Our study revealed a novel aspect of soil microbiota dynamics during ginseng monoculture, with seven distinct microbes (Beijerinckiaceae, Comamonadaceae, Devosiaceae, Rhizobiaceae, Sphingobacteriaceae, Sphingomonadaceae, and Xanthomonadaceae) participating in soil nitrogen metabolism as an ‘initial community’ that regulates root rot disease through nutritional competition. The findings contribute to ecological research on disease-suppressiveness soil, disease management, and sustainable agriculture.

Guiding endogenous regeneration of bone defects using biomaterials and regenerative medicine is considered an optimal strategy. One of the effective therapeutic approaches involves using transgene-expressed stem cells to treat tissue destruction and replace damaged parts. Among the various gene editing techniques for cells, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is considered as a promising method owing to the increasing therapeutic potential of cells by targeting specific sites. Herein, a vitamin D-incorporated poly(lactic-co-glycolic acid) (PLGA) scaffold with bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF)-overexpressed tonsil-derived MSCs (ToMSCs) via CRISPR/Cas9 was introduced for bone tissue regeneration. The optimized seeding ratio of engineered ToMSCs on the scaffold demonstrated favorable immunomodulatory function, angiogenesis, and osteogenic activity in vitro. The multifunctional scaffold could potentially support stem cell in vivo and induce the transition from M1 to M2 macrophage with magnesium hydroxide and vitamin D. This study highlights the improved synergistic effect of a vitamin D-incorporated PLGA scaffold and a gene-edited ToMSCs for bone tissue engineering and regenerative medicine.

Abstract The relation between the improvement of mechanical quality factor (Qm) and internal electric field (Ei) generated during the aging process in lead‐free piezoelectric BiFeO3‐BaTiO3 ceramics is investigated for hard piezoelectric application of power transducers. The change of built‐in Ei depends on the ferroelectric polarization (P) direction during the aging process. For the aging process with P parallel to Ei, Qm and Ei increases but Qm and Ei decreases with P antiparallel to Ei. These results are attributed to the migration of defects by depolarization fields and domain‐wall pinning. This work provides the systematic guidance to develop high‐power piezoelectric transducers with lead‐free ceramics.

Due to the large amounts of pharmaceuticals and personal care products (PPCPs) currently being consumed and released into the environment, this study provides a comprehensive analysis of pharmaceutical pollution in both raw and treated water from full-scale drinking water treatment plants nationwide. Our investigation revealed that 30 out of 37 PPCPs were present in raw water with mean concentrations ranging from 0.01–131 ng/L. The raw water sources, surface water (ND – 147 ng/L), subsurface water (ND – 123 ng/L) and reservoir sources (ND – 135 ng/L) exhibited higher mean concentration levels of pharmaceutical residues compared to groundwater sources (ND – 1.89 ng/L). Meanwhile, in treated water, 17 of the 37 analyzed PPCPs were present with carbamazepine, clarithromycin, fluconazole, telmisartan, valsartan, and cotinine being the most common (detection frequency > 40 %), and having mean concentrations of 1.22, 0.12, 3.48, 40.1, 6.36, and 3.73 ng/L, respectively. These findings highlight that, while water treatment processes are effective, there are some persistent compounds that prove challenging to fully eliminate. Using Monte Carlo simulations, risk assessment indicated that most of these compounds are likely to have negligible impact on human health, except for the antihypertensives. Telmisartan was identified as posing the highest ecological risk (RQ > 1), warranting further investigation, and monitoring. The study concludes by prioritizing specific 14 pharmaceuticals, including telmisartan, clarithromycin, lamotrigine, cotinine, lidocaine, tramadol, and others, for future monitoring to safeguard both ecological and human health.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements.

Chronic low-grade inflammation is a hallmark of aging, aka “inflammaging”, which is linked to a wide range of age-associated diseases. Immune dysfunction increases disease susceptibility, and increases morbidity and mortality of aging. Innate immune cells, including monocytes, macrophages and neutrophils, are the first responders of host defense and the key mediators of various metabolic and inflammatory insults. Currently, the understanding of innate immune programming in aging is largely fragmented. Here we investigated the phenotypic and functional properties of innate immune cells in various peripheral tissues of young and aged mice under normal and endotoxic conditions. Under the steady state, aged mice showed elevated pro-inflammatory monocytes/macrophages in peripheral blood, adipose tissue, liver, and colon. Under lipopolysaccharide (LPS)-induced inflammatory state, the innate immune cells of aged mice showed a different response to LPS stimulus than that of young mice. LPS-induced immune responses displayed differential profiles in different tissues and cell types. In the peripheral blood, when responding to LPS, the aged mice showed higher neutrophils, but lower pro-inflammatory monocytes than that in young mice. In the peritoneal fluid, while young mice exhibited significantly elevated pro-inflammatory neutrophils and macrophages in response to LPS, aged mice exhibited decreased pro-inflammatory neutrophils and variable cytokine responses in macrophages. In the adipose tissue, LPS induced less infiltrated neutrophils but more infiltrated macrophages in old mice than young mice. In the liver, aged mice showed a more robust increase of pro-inflammatory macrophages compared to that in young mice under LPS stimulation. In colon, macrophages showed relatively mild response to LPS in both young and old mice. We have further tested bone-marrow derived macrophages (BMDM) from young and aged mice, we found that BMDM from aged mice have impaired polarization, displaying higher expression of pro-inflammatory markers than those from young mice. These data collectively suggest that innate immunity in peripheral tissues is impaired in aging, and the dysregulation of immunity is tissue- and cell-dependent. Our findings in the rodent model underscore the complexity of aging immunity. Further investigation is needed to determine whether the immune profile observed in aged mice is applicable in age-associated diseases in humans.

ABSTRACT: The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13–15 wk, 0.25% during 16–18 wk, and 0.20% during 19–32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.

Abstract Background Speaking up by healthcare providers is an essential assertive communication strategy for ensuring patient safety and preventing incidents. However, more is needed to know about speaking up and instruments to assess it in the Korean context. Therefore, we assessed the psychometric properties of the Korean version of the Speaking Up about Patient Safety Questionnaire (KSUPS-Q) for measuring speaking up-related behavior and climate among nurses. Methods The translation and adaptation process followed the guidelines of the International Society for Pharmacoeconomics and Outcomes Research and the World Health Organization. Content validity was assessed by a six-member expert panel using the content validity index. In total, 314 nurses participated in an online survey to examine the psychometric properties. Internal consistencies were tested using Cronbach’s alpha and McDonald’s omega. Confirmatory factor analyses were conducted to examine the subscales’ construct. The convergent validity of the speaking up-related climate scale was assessed by testing correlations with teamwork and safety climate domains of the Safety Attitudes Questionnaire. In addition, we investigated the convergent validity of the speaking up-related behavior scale by examining its correlation with the climate scale. Results The reliability of the 11-item behavior scale was satisfactory. Confirmatory factor analysis confirmed that a three-subscale model (perceived concerns, withholding voice, and speaking up) was appropriate (CFI = 0.98, TLI = 0.98, and SRMR = 0.05). Furthermore, the 11-item climate scale demonstrated satisfactory internal consistency. A three-subscale model (psychological safety, encouraging environment, and resignation) was confirmed (CFI = 0.98, TLI = 0.97, and SRMR = 0.05). The convergent validity of the climate scale was verified based on correlations with the teamwork (r = 0.68, p

Abstract This retrospective study aimed to determine risk factors associated with post-operative bleeding after dentoalveolar surgery in patients taking anticoagulants. Patients taking anticoagulants who were planned to undergo periodontal flap operation, tooth extraction or implant surgery were included. Patients were divided into two subgroups according to the maintenance of anticoagulants following medical consultation: (1) maintenance group and (2) discontinuation group. The analysed patient-related factors included systemic diseases, maintenance of anticoagulants and types of anticoagulant. Intra- and post-operative treatment-related factors, haemostatic methods and post-operative bleeding were collected for statistical analyses. There were 35 post-operative bleeding complications (6.5%) in the 537 included patients: 21 (8.6%) in maintenance group and 14 (4.8%) in discontinuation group. The type of anticoagulant (p = 0.037), tooth extraction combined with bone grafting (p = 0.016) and type of implant surgery (p = 0.032) were significantly related to the post-operative bleeding rate. In the maintenance group, atrial fibrillation [odds ratio (OR) = 6.051] and vitamin K inhibitors (OR = 3.679) were associated with a significantly higher bleeding risk. From this result, it can be inferred that the decision to continue anticoagulants should be made carefully based on the types of anticoagulant and the characteristics of dentoalveolar surgeries performed: extraction with bone grafting, multiple implantations and involvement of maxillary arch.

Essential oils derived from plants are major ingredients in the medical and cosmetic industry. Here, we evaluated nine types of plant essential oils to identify potential candidates with antioxidant and elasticity‐enhancing properties. Seven essential oils showed at least 10% radical scavenging activity at the highest concentration. Essential oils extracted from Aster glehnii, Cinnamomum cassia, Citrus unshiu, Juniperus chinensis L., and Juniperus chinensis var. sargentii significantly enhanced fibroblast viability, and oils from Cit. unshiu, J. chinensis L., and J. chinensis var. sargentii significantly increased cell proliferation and migration. Expression of extracellular matrix proteins, including collagen 1, collagen 3, and elastin, were upregulated by J. chinensis L. and J. chinensis var. sargentii oil, which also significantly enhanced the contractile activity of skin cells in a three‐dimensional gel contraction assay. The results suggest that J. chinensis L. and J. chinensis var. sargentii essential oils may be potential anti‐wrinkling and anti‐oxidative agents for future consideration of use in the medical and cosmetic industry.

Black wood ear mushroom (Auricularia auricula-judae) is one of the most economically important mushrooms in China, Japan, and Korea. The cultivation of wood ear mushrooms on artificial substrates is more efficient in terms of time and cost compared with their natural growth on trees. However, if the substrate cultivation is infected by fast-growing fungi, the relatively slow-growing ear mushroom will be outcompeted, leading to economic losses. In this study, we investigated the competitive fungal isolates from substrates infected with fast-growing fungi for the cultivation of ear mushrooms in Jangheung and Sunchon, Korea. We collected 54 isolates and identified them by sequencing their internal transcribed spacer region with morphological identification. Among the isolates, the dominant isolates were Trichoderma spp. (92.6%), Penicillium spp. (5.6%), and Talaromyces sp. (1.8%). To find an appropriate eco-friendly biocontrol agent, we used five Streptomyces spp. and Benomyl, as controls against Trichoderma spp. and Penicillium spp. Among the six Streptomyces spp., Streptomyces sp. JC203-3 effectively controlled the fungi Trichoderma spp. and Penicillium spp., which pose a significant problem for the substrates of black wood ear mushrooms. This result indicated that this Streptomyces sp. JC203-3 can be used as biocontrol agents to protect against Trichoderma and Penicillium spp.

Abstract Background An enhanced monofocal intraocular lenses (IOLs) (Tecnis Eyhance ICB00 and Tecnis Eyhance Toric DIU) has been developed to enhance intermediate vision while avoiding the disadvantages of multifocal IOLs. Although many studies have demonstrated the improvement of intermediate visual acuity with enhanced monofocal IOLs, it is not known specifically for which patients these IOLs should be recommended or avoided. In this study, we aim to find out which ocular parameters affect vision performance and photic phenomenon of ICB00 or DIU at different distances. Methods Patients who underwent cataract surgery with ICB00 or DIU, performed by a single surgeon, were included. Before surgery, the patients’ age, gender, axial length, anterior chamber depth, spherical aberration Z (4,0), vertical coma, horizontal coma, angle kappa (κ), angle alpha (α), and other ocular parameters were investigated. One month after surgery, uncorrected near visual acuity (UNVA at 40 cm), uncorrected intermediate visual acuity (UIVA at 66 cm), uncorrected distance logMAR visual acuity (UDVA), IOL decentration, and quality of vision (QoV) questionnaires were conducted. Results A total of 43 patients (58 eyes) were included. The results of the univariate linear regression analyses showed a negative correlation between spherical aberration and logMAR UNVA and UIVA (p = 0.003, β=-0.51 and p = 0.018, β=-0.23, respectively) and a positive correlation between angle α and logMAR UIVA (p = 0.036, β = 0.19). Deeper anterior chamber depth (ACD) was associated with poorer total QoV (p = 0.018, β = 14.43), particularly in glare, halo, blur, and fluctuation perception. A higher degree of IOL decentration tended to decrease UNVA and UIVA (Pearson correlation coefficient, r = 0.336 and r = 0.221, respectively); however, no significant effect was observed on UDVA (Pearson correlation coefficient, r = 0.042). Conclusions In enhanced monofocal IOLs, a higher level of spherical aberration is associated with better performance in UNVA and UIVA, whereas a larger angle α has a negative impact. A deeper ACD negatively affects the QoV.

Fusarium graminearum, the causal agent of Fusarium head blight (FHB) in cereal crops, employs the production of sexual fruiting bodies (perithecia) on plant debris as a strategy for overwintering and dissemination. In an artificial condition (e.g., carrot agar medium), the F. graminearum Z3643 strain was capable of producing perithecia predominantly in the central region of the fungal culture where aerial hyphae naturally collapsed. To unravel the intricate relationship between natural aerial hyphae collapse and sexual development in this fungus, we focused on 699 genes differentially expressed during aerial hyphae collapse, with 26 selected for further analysis. Targeted gene deletion and quantitative real-time PCR analyses elucidated the functions of specific genes during natural aerial hyphae collapse and perithecium formation. Furthermore, comparative gene expression analyses between natural collapse and artificial removal conditions reveal distinct temporal profiles, with the latter inducing a more rapid and pronounced response, particularly in MAT gene expression. Notably, FGSG_09210 and FGSG_09896 play crucial roles in sexual development and aerial hyphae growth, respectively. Taken together, it is plausible that if aerial hyphae collapse occurs on plant debris, it may serve as a physical cue for inducing perithecium formation in crop fields, representing a survival strategy for F. graminearum during winter. Insights into the molecular mechanisms underlying aerial hyphae collapse provides offer potential strategies for disease control against FHB caused by F. graminearum.

The home robot-based child activity service aims to cultivate children’s social emotions. A design theme was produced by interviewing child development experts and parents. The activity service is composed of 50 plays and 70 conversations. These were developed based on activities from psychomotor therapy and the guidelines of Ministry of Early Childhood Education in South Korea. In the field test, 50 children aged five–seven years participated to experience the activity services at home for 4 days. After completing the 4 days of field testing, we conducted customer satisfaction (CSAT) surveys, Godspeed evaluations and interviews to quantitatively and qualitatively verify the evaluations by the children and parents. As a result, 92% of the children and 80% of the parents evaluated that they were satisfied with the service. In addition, our results revealed that the social robot-based service contributed to improving the relationship between children and families by functioning as a messenger. Finally, the lessons learned from the service development and field tests were discussed to aid service designers and robotics engineers.

Ginsengs, widely acknowledged for their health-promoting properties, are predominantly grown for their roots, necessitating an extended cultivation period of a minimum of 4 to 6 years for maturation. The prolonged growth duration in a specific location makes ginseng plants susceptible to soil-borne ailments, such as root rot, leading to significant detrimental effects. Focusing on the crucial role of the plant microbial community in maintaining ginseng health, the study reveals that repeated and continuous cultivation leads to the collapse of the initial disease-suppressive rhizosphere community, resulting in severe root rot. The dominance of Pseudomonadaceae in the rhizosphere subsequently reinstates disease suppression, aligning with suppressive soil generation phenomena. The research investigates the applicability of identified patterns to field conditions and demonstrates that rhizosphere samples from the field closely resemble conditions observed in pot-based NH4Cl treatment experiments. These findings emphasize the critical role of the rhizosphere microbial community in ginseng health maintenance during extended cultivation, offering insights into disease prevention strategies. The study also suggests the potential of pot-based experiments in simulating field conditions and informs future approaches for sustainable ginseng cultivation.

Background Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear.Methods To identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets.Results We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161+ Trm and changes in tumor size.Conclusions We found that CD161+ Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers.Trial registration number NCT03737968.

Objectives We aimed to develop an automated method for measuring the volume of the psoas muscle using CT to aid sarcopenia research efficiently.Methods We used a data set comprising the CT scans of 520 participants who underwent health check-ups at a health promotion centre. We developed a psoas muscle segmentation model using deep learning in a three-step process based on the nnU-Net method. The automated segmentation method was evaluated for accuracy, reliability, and time required for the measurement.Results The Dice similarity coefficient was used to compare the manual segmentation with automated segmentation; an average Dice score of 0.927 ± 0.019 was obtained, with no critical outliers. Our automated segmentation system had an average measurement time of 2 min 20 s ± 20 s, which was 48 times shorter than that of the manual measurement method (111 min 6 s ± 25 min 25 s).Conclusion We have successfully developed an automated segmentation method to measure the psoas muscle volume that ensures consistent and unbiased estimates across a wide range of CT images.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment. Given this context, our study aimed to target the GBM TME, with a special focus on pericytes expressing CD19, to evaluate the potential effectiveness of CD19 CAR-iNK cells against GBM. We performed CD19 CAR transduction in induced pluripotent stem cell-derived NK (iNK) cells. To determine whether CD19 CAR targets the TME pericytes in GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing GBM spheroids with blood vessel organoids. When co-cultured with GBVA, CD19 CAR-iNK cells migrated towards the pericytes surrounding the GBM. Using a microfluidic chip, we demonstrated CD19 CAR-iNK cells’ targeted action and cytotoxic effects in a perfusion-like environment. GBVA xenografts recapitulated the TME including human CD19-positive pericytes, thereby enabling the application of an in vivo model for validating the efficacy of CD19 CAR-iNK cells against GBM. Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

Objective: To evaluate the effects of Capsosiphon fulvescens (C. fulvescens) ethanolic extract on inflammation in lipopolysaccharide (LPS)-induced RAW296.7 macrophages. Methods: The protective effects of C. fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis, including enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis. To examine reactive oxygen species (ROS) production, flow cytometry analysis, and immunofluorescence staining were used. Furthermore, the modulatory effect of C. fulvescens ethanolic extract on NF-κB activation was investigated. Results: C. fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases. In addition, C. fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway. Conclusions: C. fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages. C. fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

Abstract Distant metastasis is the leading cause of death in breast cancer (BC). The timing of distant metastasis differs according to subtypes of BCs and there is a need for identification of biomarkers for the prediction of early and late metastasis. To identify biomarker candidates whose abundance level can discriminate metastasis types, we performed a high-throughput proteomics assay using tissue samples from BCs with no metastasis, late metastasis, and early metastasis, processed data with machine learning-based feature selection, and found that low VWA5A could be responsible for shorter duration of metastasis-free interval. Low expression of VWA5A gene in METABRIC cohort was associated with poor survival in BCs, especially in hormone receptor (HR)-positive BCs. In-vitro experiments confirmed tumor suppressive effect of VWA5A on BCs in HR+ and triple-negative BC cell lines. We found that expression of VWA5A can be assessed by immunohistochemistry (IHC) on archival tissue samples. Decreasing nuclear expression of VWA5A was significantly associated with advanced T stage and lymphatic invasion in consecutive BCs of all subtypes. We discovered lower expression of VWA5A as the potential biomarker for metastasis-prone BCs, and our results support the clinical utility of VWA5A IHC, as an adjunctive tools for prognostication of BCs.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

Respiratory epithelial adenomatoid hamartoma (REAH) in the head and neck is a rare benign lesion containing glandular tissue covered with ciliated respiratory epithelium. In the head and neck, REAH of the nasal cavity, paranasal sinuses, and nasopharynx have been reported in literature. Due to rareness of REAH and insufficient knowledge of its imaging features, the diagnosis can be challenging when we encounter a non-specific cystic mass at an uncommon site in the head or neck. Here, we report the case of a pathologically confirmed REAH showing a cystic mass centered at the buccal space (retromaxillary fat pad) with CT and MRI findings.

Objective To analyze the changes in muscle mass and quality with time on the paretic and non-paretic sides in subacute stroke patients and identify correlations between the variation of muscle mass and quality and lower limb functions. Methods Thirty hemiplegia patients diagnosed with stroke participated in this study. To evaluate poststroke muscle changes, longitudinal measurement of muscle mass and quality was conducted with bilateral lower limbs. The elastic shear modulus was measured using shear wave elastography and muscle thickness (MT) of rectus femoris, vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, and gastrocnemius (GCM) muscles. Functional evaluation was performed using Berg Balance Scale (BBS), Five Times Sit to Stand Test (FTSST). Follow-up was performed at discharge. The muscle mass and quality were compared according to time. We analyzed whether muscle quantity and quality were related to function. Results MT demonstrated no significant change with time. The elastic shear modulus increased significantly in the paretic VL and GCM muscles and did not change significantly in the muscles on the non-paretic side. Correlation analysis detected that elastic shear modulus in the VL has a cross-sectional negative relationship between BBS and positive relationship between FTSST. There were significant correlation between variation of FTSST and the variation of the elastic shear modulus in VL. Conclusion Only paretic VL and GCM muscle quality changed in subacute stroke patients and muscle’s property related to lower limb functions. Therefore, the lower extremity requires an approach to muscle quality rather than quantity for subacute stroke patients.