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The liver partakes as a sensor and effector of peripheral metabolic changes and a regulator of systemic blood and nutrient circulation. As such, abnormalities arising from liver dysfunction can influence the brain in multiple ways, owing to direct and indirect bilateral communication between the liver and the brain. Interestingly, altered bile acid composition resulting from perturbed liver cholesterol metabolism influences systemic inflammatory responses, blood-brain barrier permeability, and neuron synaptic functions. Furthermore, bile acids produced by specific bacterial species may provide a causal link between dysregulated gut flora and neurodegenerative disease pathology through the gut-brain axis. This review will cover the role of bile acids—an often-overlooked category of active metabolites—in the development of neurological disorders associated with neurodegeneration. Further studies into bile acid signaling in the brain may provide insights into novel treatments against neurological disorders.

Attempts to image activated macrophages in vivo have been hampered by selectivity and delivery problems. Here the authors develop a small molecule fluorescent probe specific to activated M1 and M2 macrophages, identify the orphan receptor Slc18b1/SLC18B1 as the mechanism of uptake, and use it to image atherosclerosis in mice.

Abstract Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount.

Abstract T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/− mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases.

For a hygiene paper such as tissue and towel, strength, softness, and absorbency are known as attributes that a user is looking for. It is proposed here that purchasing decisions are likely to be influenced by in-use experiences, which may be quite different from the physical properties measured with current standardized tests. There have been continuous efforts on developing physical test methods to replace subjective in-use tests because the benefits of the former are too significant to be overlooked. This paper considered some in-use test methods for paper towel products that can be carried out by panel members quickly in the course of sensory panel testing. In addition, laboratory tests were developed in an attempt to quantify such input. The sensory panel testing showed that (wet) strength and absorbency were the key contributions to the performance of paper towels. Softness did not show any significant contribution to it. Wet strength showed a high correlation with absorbency. The (wet) ball burst strength had the highest correlation with the in-use strength. Although both the tensile strength and the ball burst strength had a high correlation with preference, the ball burst tester is preferred because more reproducible and simpler to operate.

The increasing rates of illicit behaviors, particularly financial crimes, e.g., bank fraud and tax evasion, adversely affect national economies. In such cases, using nondestructive methods, scientists must evaluate relevant documents carefully to preserve their value as evidence. When forensic laboratories analyze paper as evidence, they typically investigate its origin and date of manufacture. If a document’s date is earlier than the earliest availability of the paper used in its creation, then this anachronism indicates that the document has been backdated. This study investigated weave marks and drainage marks for forensic purposes. Machine learning models for forensic document examination were developed and evaluated. The partial least squares discriminant analysis (PLS-DA), support vector machine (SVM), and artificial neural network (ANN) classification models achieved F1-scores of 0.903, 0.952, and 0.931, respectively. In addition, to enhance model effectiveness and construct a robust model, variables were selected using the VIP scores generated by the PLS-DA model. As a result, the SoftMax classifier in the ANN model maintained its performance with an F1-score of 0.951 even with a 50% reduction in the number of input variables.

Sensors are applied to many fields nowadays because of their high sensitivity, low cost, time-saving, user-friendly, and excellent selectivity. Current biomedical and pharmaceutical science has one focus on developing nanoparticle-based sensors, especially biopolymeric nanoparticles. Alginate is a widely used biopolymer in a variety of applications. The hydrogel-forming characteristic, the chemical structure with hydroxy and carboxylate moieties, biocompatibility, biodegradability, and water solubility of alginate have expanded opportunities in material and biomedical sciences. Recently, research on alginate-based nanoparticles and their applications has begun. These materials are gaining popularity because of their wide usage potential in the biomedical and pharmaceutical fields. Many review papers describe applications of alginate in the drug delivery field. The current study covers the structural and physicochemical properties of alginate-based nanoparticles. The prospective applications of alginate-based nanomaterials in various domains are discussed, including drug delivery and environmental sensing applications for humidity, heavy metals, and hydrogen peroxide. Moreover, biomedical sensing applications of alginate-based nanoparticles regarding various analytes such as glucose, cancer cells, pharmaceutical drugs, and human motion will also be reviewed in this paper. Future research scopes highlight existing challenges and solutions.

Abstract Background Cell wall integrity (CWI) is crucial for fungal growth, pathogenesis, and adaptation to extracellular environments. Calcofluor white (CFW) is a cell wall perturbant that inhibits fungal growth, yet little is known about how phytopathogenic fungi respond to the CFW-induced stress. Results In this study, we unveiled a significant discovery that CFW triggered the translocation of the transcription factor CgCrzA from the cytoplasm to the nucleus in Colletotrichum gloeosporioides. This translocation was regulated by an interacting protein, CgMkk1, a mitogen-activated protein kinase involved in the CWI pathway. Further analysis revealed that CgMkk1 facilitated nuclear translocation by phosphorylating CgCrzA at the Ser280 residue. Using chromatin immunoprecipitation sequencing, we identified two downstream targets of CgCrzA, namely CgCHS5 and CgCHS6, which are critical for growth, cell wall integrity, and pathogenicity as chitin synthase genes. Conclusions These findings provide a novel insight into the regulatory mechanism of CgMkk1-CgCrzA-CgChs5/6, which enables response of the cell wall inhibitor CFW and facilitates infectious growth for C. gloeosporioides.

Abstract Background The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. Methods In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. Results Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was

Abstract Background Glycated albumin (GA) is an indicator of glycemic variability over the past 2–4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). Methods We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). Results In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10–9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01–1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14–3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. Conclusions High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Summary: This perspective focuses on functional models of photosynthesis to achieve molecular photocatalytic systems that mimic photosystems I and II (PSI and PSII). A long-lived and high-energy electron-transfer state of 9-mesityl-10-methylacridinium ion (Acr+-Mes) has been attained as a simple and useful model of the photosynthetic reaction center. Acr+-Mes has been used as an effective photoredox catalyst for photocatalytic hydrogen evolution and regioselective reduction of NAD(P)+ from plastoquinone analogs as a molecular functional model of PSI. A functional molecular model system to mimic the function of PSII has also been developed to oxidize water by plastoquinone analogs to produce O2 and plastoquinol analogs. The PSI molecular models have finally been integrated with the PSII molecular models to achieve production of a solar fuel (hydrogen) and NAD(P)H and its analogs from water by use of solar energy as a molecular artificial photosynthesis.

Backgrounds: Rapid response team or medical emergency team (MET) calls are typically activated by significant alterations of vital signs in inpatients. However, the clinical significance of a specific criterion, blood pressure elevations, is uncertain. Objectives: The aim of this study was to evaluate the likelihood ratios associated with MET-activating vital signs, particularly in-patient hypertension, for predicting in-hospital mortality among general medicine inpatients who met MET criteria at any point during admission in a South Australian metropolitan teaching hospital. Results: Among the 15,734 admissions over a two-year period, 4282 (27.2%) met any MET criteria, with a positive likelihood ratio of 3.05 (95% CI 2.93 to 3.18) for in-hospital mortality. Individual MET criteria were significantly associated with in-hospital mortality, with the highest positive likelihood ratio for respiratory rate ≤ 7 breaths per minute (9.83, 95% CI 6.90 to 13.62), barring systolic pressure ≥ 200 mmHg (LR + 1.26, 95% CI 0.86 to 1.69). Conclusions: Our results show that meeting the MET criteria for hypertension, unlike other criteria, was not significant associated with in-hospital mortality. This observation warrants further research in other patient cohorts to determine whether blood pressure elevations should be routinely included in MET criteria.

Key message Our case highlights the importance of follow‐up. Previous meta‐analysis has shown that patients with sub‐centimetre nodules may have extended follow‐up intervals before requiring intervention, unlike those with larger nodules exceeding 1 cm. However, referring to our case, we can see the importance of regular and dense follow‐up.

Abstract To recharge lithium‐ion batteries quickly and safely while avoiding capacity loss and safety risks, a novel electrode design that minimizes cell polarization at a higher current is highly desired. This work presents a dual‐layer electrode (DLE) technology via sequential coating of two different anode materials to minimize the overall electrode resistance upon fast charging. Electrochemical impedance spectroscopy and distribution of relaxation times analysis revealed the dynamic evolution of electrode impedances in synthetic graphite (SG) upon a change in the state of charge (SOC), whereas the natural graphite (NG) maintains its original impedance regardless of SOC variation. This disparity dictates the sequence of the NG and SG coating layers within the DLE, considering the temporal SOC gradient developed upon fast charging. Simulation and experimental results suggest that DLE positioning NG and SG on the top (second‐layer) and bottom (first‐layer), respectively, can effectively reduce the overall resistance at a 4 C‐rate (15‐min charging), demonstrating two times higher capacity retention (61.0%) over 200 cycles than its counterpart with reversal sequential coating, and is higher than single‐layer electrodes using NG or NG/SG binary mixtures. Hence, this study can guide the combinatorial sequence for multi‐layer coating of various active materials for a lower‐resistivity, thick‐electrode design.

Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies. Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022. Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available. Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05–4.06, p = 0.036). Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.

Spermatogonial stem cells (SSCs) are germline stem cells that serve as the foundation of spermatogenesis to maintain fertility throughout a male's lifetime. To treat male infertility using stem cell banking systems and transplantation, it is important to be able to preserve SSCs for long periods of time. Therefore, this study was conducted to develop an optimal cryopreservation protocol for SSCs using antioxidants and apoptosis inhibitors in freezing medium. No differences were observed compared to controls when SSCs were cryopreserved in the presence of apoptosis inhibitors by themselves. However, mouse germ cells cryopreserved in basal medium containing the antioxidant hypotaurine (14 mM) resulted in significantly greater proliferation potential and mitochondrial activity. Furthermore, treatment groups with combinations containing 200 mM trehalose and 14 mM hypotaurine showed higher proliferation rates compared to controls. In addition, several serum free conditions were evaluated for SSC cryopreservation. Treatment media containing 10% or 20% knockout serum replacement resulted in similar cryopreservation results compared to media containing FBS. SSC transplantation was also performed to confirm the functionality of SSCs frozen in 14 mM hypotaurine. Donor SSCs formed normal spermatogenic colonies and sperm in the recipient testis. These data indicate that inclusion of 14 mM hypotaurine in cryopreservation media is an effective way to efficiently cryopreserve germ cells enriched for SSCs and that knockout serum replacement can replace FBS in germ cell cryopreservation media.

Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC) proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility.

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

Development of techniques to isolate, culture, and transplant human spermatogonial stem cells (SSCs) has the future potential to treat male infertility. To maximize the efficiency of these techniques, methods for SSC cryopreservation need to be developed to bank SSCs for extended periods of time. Although, it has been demonstrated that SSCs can reinitiate spermatogenesis after freezing, optimal cryopreservation protocols that maximize SSC proliferative capacity post-thaw have not been identified. The objective of this study was to develop an efficient cryopreservation technique for preservation of SSCs. To identify efficient cryopreservation methods for long-term preservation of SSCs, isolated testis cells enriched for SSCs were placed in medium containing dimethyl sulfoxide (DMSO) or DMSO and trehalose (50 mM, 100 mM, or 200 mM), and frozen in liquid nitrogen for 1 week, 1 month, or 3 months. Freezing in 50 mM trehalose resulted in significantly higher cell viability compared to DMSO at all thawing times and a higher proliferation rate compared to DMSO for the 1 week freezing period. Freezing in 200 mM trehalose did not result in increased cell viability; however, proliferation activity was significantly higher and percentage of apoptotic cells was significantly lower compared to DMSO after freezing for 1 and 3 months. To confirm the functionality of SSCs frozen in 200 mM trehalose, SSC transplantation was performed. Donor SSCs formed spermatogenic colonies and sperm capable of generating normal progeny. Collectively, these results indicate that freezing in DMSO with 200 mM trehalose serves as an efficient method for the cryopreservation of SSCs.

Introduction: This trial, conducted according to the request of the Korean Ministry of Food and Drug Safety, investigated the potential of oxiracetam in mitigating post-stroke cognitive decline, and whether physical activity could augment its efficacy. The mechanisms behind these effects were explored using functional neuroimaging. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, we enrolled patients reporting subjective cognitive decline more than three months post-stroke and at a high risk of dementia. Participants were randomly assigned to a 36-week regimen of either 800 mg oxiracetam or a placebo, administered twice daily, in conjunction with recommended physical activity. Physical activity levels were monitored using wrist actigraphy. Cognitive function was assessed using a mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) at baseline and 36 weeks. Other assessments included the 60-minute protocol of Vascular Cognitive Impairment Harmonization Standards, Euro QoL, patient's global assessment, and resting-state functional MRI-derived neural network attributes. Results: Of the 500 participants (mean age 68.9 years, male 76.1%, median interval between stroke and randomization 32 months), 457 were analyzed. Both groups have equally adhered to the exercise guidelines (moderate-to-vigorous physical activity per day; 23.7±26.1 vs. 24.1±28.7 minutes; p=0.75). No significant difference was observed in changes to MMSE and CDR-SB scores between the two groups (MMSE, 0.13±2.27 vs. 0.27±2.09, p=0.49; CDR-SB -0.14±0.70 vs. -0.08±0.80, p=0.38). Although increased baseline exercise time correlated with better MMSE scores, the correlation was weak (R= 0.11, p=0.02). Verbal memory, phonemic fluency, language, NPI-Q, and geriatric depression scale also improved significantly within each group. However, only the intervention group showed significant improvements in CDR-SB and EuroQoL scores. A predetermined multivariate analysis showed a significant change in the normalized clustering coefficient for the secondary efficacy endpoint (r=0.09, SE=0.04, p=0.03). Discussion: This study failed to confirm the efficacy of oxiracetam in preventing post-stroke cognitive decline. Nonetheless, adherence to the exercise guidelines appeared to help participants maintain their cognitive functions, despite being a chronic stage post-stroke and having a high dementia risk.

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h showed potential IC50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC50 (9.8 µM) but lower potency than miltefosine IC50 (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC50 of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to LdCALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.

Phenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, ortho-substituted compounds were more active than meta- or ortho-substituted compounds. They were potential anticancer agents against blood, lung, colon, CNS, ovary, renal, and prostate cancers but not against skin nor breast cancers. Compounds, 1b and 1a emerged as the most potential anticancer agents. Assessment of compound 1b impact on p38 MAPK and AKT confirmed it as an inhibitor of p38 MAPK but not AKT. In silico study suggested compounds 1b and 1a as possible binders to the lipid binding pocket of p38 MAPK. Overall, compounds 1b and 1a as novel broad spectrum antitumor lipids modulating activity of p38 MAPK for further development.

Abstract Ultrasound contrast agents (UCAs), which are groups of engineered microbubbles, have been recently studied for drug delivery applications, since the cavitation of bubbles can increase the temporary permeability of nearby cells. However, the internal volume of UCAs is generally filled with gas, hence loading drug molecules into UCAs is limited. In this study, an echogenic liposome with a liquid and gas core is proposed as an alternative carrier of genetic material for ultrasound‐mediated drug delivery. The structure of the synthesized echogenic liposome was analysed via transmission electron microscopy and confocal microscopy with fluorescent labels. The protection of siRNA by the echogenic liposomes was also verified by exposure to RNase. The results indicate that at least 10% of the total siRNA used in the experiment was successfully protected by the proposed echogenic liposome. Additionally, the release of siRNA from the liposomes could be successfully achieved with 1 W/cm2 ultrasound sonication at 1 MHz; parameters low enough to be used in generic ultrasound therapeutic systems. Although further studies to clarify the responses to incident ultrasound fields and to quantitatively analyse the internal liquid volume for drug loading are required, the proposed echogenic liposome has great potential for ultrasound‐mediated gene delivery.

Introduction. Buspirone, as a partial agonist for a 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), has been prescribed as an anxiolytic drug for patients. In addition, the lowering effect of serotonin on blood pressure was reported in hypertensive animal model. We investigated the therapeutic mechanism of buspirone against lipid metabolism disturbed by hypertension of early stage via hypertensive and obese animal model. Methods. The levels of various biomarkers related to lipid metabolism and hypertension were estimated through the measurement of body weight and fat weight, blood analysis, western blotting, immunohistochemistry, and staining methods. Results. The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 μM compared with untreated differentiated control. Body weight and abdominal fat weight were lowered in spontaneously hypertensive rats (SHRs) administered with buspirone of 10 mg/kg/day for 4 weeks than 8-week untreated group. Triglyceride (TG) level was decreased in SHRs administered with buspirone of 5 and 10 mg/kg/day compared to 8-week untreated group. High-density lipoprotein (HDL)-cholesterol concentration was elevated by buspirone 10 mg/kg/day treatment compared to 8-week untreated group. Blood pressures in SHRs were lowered by buspirone treatments of 5 and 10 mg/kg/day compared with 8-week untreated group. Protein levels for peroxisome proliferator-activated receptor δ (PPARδ), 5′ adenosine monophosphate-activated protein kinase (AMPK), and PPARγ coactivator-1 alpha (PGC-1α) were increased both in C2C12 cells treated by buspirone of 100 μM and in SHRs administered by buspirone of 1, 5, and 10 mg/kg/day compared to untreated control cells and 8-week untreated group. Fat cell numbers decreased in 8-week untreated group were increased in SHRs administered by buspirone treats of 1, 5, and 10 mg/kg/day. Protein expression levels for angiotensin II type 1 receptor (AT1R) and vascular cell adhesion molecule 1 (VCAM1) were increased in 8-week untreated group compared to 4-week group, however, they were decreased by buspirone treatments of 1, 5, and 10 mg/kg/day. Conclusion. Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPARδ dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.

A digital twin has recently received considerable attention in various industry domains. The digital twin replicates physical objects (e.g., people, objects, spaces, systems, and processes) in the real world into digital objects in the digital world. It also provides various simulations to solve problems in the real world or to improve situational operations. Therefore, the digital twin is a convergence of various technologies, such as advanced machine-learning algorithms, data analytics, super-resolution visualization and modeling, and simulation. Because the digital twin is a complicated technology, a step-by-step implementation that includes many technology elements should be considered to create a digital twin model. In this study, implementation layers are introduced to guide practical implementations of the digital twin. In addition, technology elements were suggested for the presented implementation layers. Because the suggested technology elements include clear technology definitions, various application domains (e.g., energy, transportation, logistics, environment, manufacturing, and smart cities) can easily utilize the introduced implementation layers and technology elements according to the intended purpose. Furthermore, this paper describes the evolution of digital twins. Digital twin technology has evolved continuously since 2002, when the digital twin concept was first introduced. In the described evolution levels, we show the future aspects of digital twin technology, according to the technological evolution direction. Therefore, the digital twin model can be efficiently created by considering the evolution direction and future aspects by using the suggested digital twin evolution levels.

Objective: Advancements in AVM surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. Methods : We retrospectively reviewed 55 patients (36 males and 19 females; average age 37.4 years) with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2022. Results : In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow coma scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms through multivariate logistic regression. Postoperative seizures noted in nine patients, were exclusive to the ruptured AVM group. Conclusion : Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissuebased techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC. Materials and methods: The study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control. Results: The combination of seven epigenetic biomarkers (HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and KRAS mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%. Conclusion: Our study suggests that analyzing seven differentially methylated genes with KRAS mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC. [ABSTRACT FROM AUTHOR]

The mineralization of inorganic components in paper sludge offers potential for their re-use in various fields. This study synthesized carbonates based on the minerals present in paper sludge and aimed to investigate the control of particle size distribution and particle shape of the synthesized carbonates. First, the physicochemical and thermal properties of paper mill sludge and ash were evaluated using a spectrophotometer, XRF, and TGA. Paper sludge ash was obtained by incinerating the paper sludge, followed by a carbonation reaction using CO2 gas injection and pH neutralization to produce recycled fillers. The average particle size, crystal lattice structure, and morphology of the recycled fillers were analyzed using a particle size analyzer, XRD, and FE-SEM. The results indicate that the recycled filler produced from coating paper sludge exhibited similar brightness and morphology to conventional paper-based fillers, suggesting its potential to replace commercial PCC (Precipitated Calcium Carbonate). In contrast, the recycled filler manufactured using old corrugated container mill sludge was deemed unsuitable due to its low hydration activity. [ABSTRACT FROM AUTHOR]

A sodium bentonite product (nanoclay) was added to a polyhydroxybutyrate/ethyl cellulose (PHB/EC) blend coating agent, and the impact of the nanoclay content on the properties of the coated paper was investigated. The organically treated nanoclay exhibited enhanced compatibility with the PHB/EC blend, ensuring uniform dispersion within the coating layer and improving the barrier properties of the coated paper. The mechanical properties of the PHB/EC blend-coated paper with nanoclay demonstrated ductile behavior, reducing the tensile strength and increasing the elongation. However, at higher nanoclay loadings, specifically up to 25%, aggregation among nanoclay particles occurred. This hindered the enhancement of barrier properties, thereby decreasing the degree of elongation. Incorporating nanoclay as a filler in the PHB/EC blend at suitable levels showed potential for further enhancing the barrier properties and ensuring economic feasibility in the production of packaging paper. [ABSTRACT FROM AUTHOR]

Purpose: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. Materials and Methods: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. Results: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140--6.649, p=0.024; OR=2.986, 95% CI=1.451--6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064--4.617, p=0.034). Conclusion: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD. [ABSTRACT FROM AUTHOR]

Species distribution modeling is widely used for evaluating invasion risk, and for prioritizing areas for the control and management of invasive species. However, selecting a modeling tool that accurately predicts species invasion risk requires a systematic approach. In this study, five species distribution models (SDMs), namely, artificial neural network (ANN), generalized linear model (GLM), multivariate adaptive regression splines (MARS), maximum entropy (MaxEnt), and random forest (RF), were performed and evaluated their model performance using the mean value of area under the curve (AUC), true skill statistics (TSS), and Kappa scores of 12 ecosystem disturbing alien plant species (EDAPS). The mean evaluation metric scores were highest in RF (AUC = 0.924 ± 0.058, TSS = 0.789 ± 0.109, Kappa = 0.671 ± 0.096, n = 12) and lowest in ANN. The ANOVA of AUC, TSS, and Kappa metrics revealed the RF model was significantly different from other SDMs and was therefore selected as the relatively best model. The potential distribution area and invasion risk for each EDAPS were quantified. Under the current climate conditions of South Korea, the average potential distribution area of EDAPS was estimated to be 13,062 km2. However, in future climate change scenarios, the average percentage change of EDAPS distribution relative to the current climate was predicted to be increased over 219.93%. Furthermore, under the current climate, 0.16% of the area of the country was estimated to be under a very high risk of invasion, but this would increase to 60.43% by 2070. Invasion risk under the current climate conditions was highest in the northwestern, southern, and southeastern regions, and in densely populated cities, such as Seoul, Busan, and Daegu. By 2070, invasion risk was predicted to expand across the whole country except in the northeastern region. These results suggested that climate change induced the risk of EDAPS invasiveness, and SDMs could be valuable tools for alien and invasive plant species risk assessment.

In order to quickly and effectively respond to a newly received criminal case, information regarding the type and severity of the case is crucial for authorities. This paper designs and develops a crime type and risk level prediction technique based on machine learning technology and verifies its performance. The designed technology can predict crime type and crime risk level using a text-based criminal case summary, which is criminal case receipt data. For the text-based criminal case summary data, the KICS data format is considered, which is actual policing data that contains information about criminal cases. For the crime type, 21 representative types of crimes are considered; therefore, the system can predict one of 21 types of crime for each criminal case. Furthermore, to predict the crime risk level, we developed a crime risk calculation formula. The developed formula calculates the crime risk level and outputs the risk score in numerical terms considering the severity and damage level of the criminal case. To predict the crime type and crime risk score, both DNN and CNN-based prediction models were designed and developed. The performance evaluation section shows that, in the case of crime type prediction, the proposed prediction models can achieve better performance than traditional classification algorithms such as naïve Bayes and SVM. The performance of the CNN-based crime type prediction model is about 7% and 8% better than those of the SVM algorithm and the naïve Bayes algorithm, respectively. The performance of the designed technology was comprehensively analyzed and verified through various performance measurement parameters. It is also developed in the form of a software platform with a GUI, allowing field personnel (e.g. police officers) to intuitively identify the type of criminal case and the level of risk from a text-based criminal case summary upon receipt of a new criminal case.

Purpose: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. Materials and Methods: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. Results: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). Conclusion: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase. [ABSTRACT FROM AUTHOR]

Background: This study investigates the relationship between changes in physical activity levels and risk of metabolic syndrome. Methods: This study examined 1,686 adults aged 40 to 69 years from a community-based cohort study with complete 1st to 4th follow-up data between 2011 and 2020. Changes in physical activity were evaluated through baseline and follow-up surveys using physical activity questionnaires. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. A survival analysis was conducted using a multivariate extended Cox regression model with a significance level set at P<0.05. Results: Participants were divided into groups according to physical activity levels. The newly inactive group (vigorous physical activity ≤150 minutes at first follow-up) had a 36% increase in the hazard ratio (HR) for metabolic syndrome compared with the consistently inactive group (≤150 minutes at both baseline and first followup) (HR, 1.36; 95% confidence interval [CI], 1.04 to 1.79). The newly active group (walking ≤420 minutes per week at baseline and >420 minutes per week at first follow-up) had a 25% decrease in the HR for metabolic syndrome compared with the consistently inactive group (walking ≤420 minutes per week at both baseline and first follow-up) (HR, 0.75; 95% CI, 0.57 to 0.98). Conclusion: Changes in physical activity levels are associated with risk of metabolic syndrome. These results provide important insights for future investigations into the link between physical activity changes and disease occurrence. [ABSTRACT FROM AUTHOR]

Symbiotic microbes are essential for developing and growing Gastrodia elata, an achlorophyllous orchid of high medicinal value. Recently, the cultivation of G. elata in greenhouses has been adopted in Korea to produce mature tubers in a short time. However, no studies have been conducted on the microbial community structure of G. elata cultivated in greenhouse environments. Therefore, we analyzed the temporal features of bacterial and fungal communities in the rhizosphere of G. elata at the juvenile [JT; 2 months after sowing (MAS)], young (YT; 6 MAS), and mature (MT; 11 MAS) tuber stages using culture-dependent and high-throughput sequencing technology. The richness and diversity of the bacterial and fungal communities decreased with tuber growth of G. elata. The symbiotic fungi Mycena sp. and Armillaria sp. as well as tuber extract inhibited the growth of various soil-inhabiting fungal and bacterial strains, indicating that G. elata and its symbiotic fungi play important roles in the selection of rhizosphere microbes. Mortierella rishikesha was the most abundant fungal species in the rhizosphere. We also identified the microorganisms potentially beneficial for G. elata development during greenhouse cultivation. Tubers and symbiotic fungi actively exert selective pressure on rhizosphere microbes, influencing the diversity and abundance of bacterial and fungal communities as G. elata grows. This study is a first report on the temporal microbial community structure of G. elata cultivated in greenhouse. The results on the associated microbiome of G. elata will help understand their beneficial interactions with G. elata and contribute to improvement in cultivation. [ABSTRACT FROM AUTHOR]

Background/Aims: Reports on the association between sarcopenic visceral obesity and nonalcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities. Methods: The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (<0.789 for men and <0.512 for women). Results: In total, 82.0% (n=1,205) of the entire study population had NAFLD, and 14.6% of these individuals (n=176) exhibited significant liver fibrosis. Individuals with the lowest SV ratio had a significantly increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk (all p<0.05). Individuals with both the lowest SV ratio and sarcopenia had the highest risk of developing NAFLD (odds ratio [OR]=3.11), significant liver fibrosis (OR=2.03), and high ASCVD risk (OR=4.15), compared with those with a higher SV ratio and without sarcopenia (all p<0.05). Conclusions: Low SV ratio combined with sarcopenia was significantly associated with an increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk among individuals with a high risk of NAFLD [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted. [ABSTRACT FROM AUTHOR]

Background: The metabolic score for insulin resistance index (METS-IR) is a novel non insulin-based marker that indicates the risk for metabolic syndrome and type 2 diabetes mellitus (T2DM). However, METS-IR has not been investigated in relation to all-cause mortality. We investigated the longitudinal effect of METS-IR on all-cause mortality in a significantly large cohort of Korean adults over 60 years old. Methods: Data were assessed from 30,164 Korean participants over 60 years of age from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort data, linked with the death certificate database of the National Statistical Office. The participants were grouped into three according to METS-IR tertiles. We used multivariate Cox proportional-hazard regression models to prospectively assess hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) over an 11-year postbaseline period. Results: During the mean 11.7 years of follow-up, 2,821 individuals expired. The HRs of mortality for METS-IR tertiles were 1.16 (95% CI, 1.01-1.34) in T3 after adjustment for metabolic parameters, but the T2 did not show statistical significance towards increases for incident mortality respectively. In subgroup analysis depending on the cause of mortality, higher METS-IR was associated with cancer mortality (HR, 1.23, 95% CI, 1.01-1.51) but not with cardiovascular mortality (HR, 1.14, 95% CI, 0.83-1.57) after adjustment for the same confounding variables. Conclusion: The METS-IR may be a useful predictive marker for all-cause mortality and cancer mortality, but not for cardiovascular mortality in subjects over 60 years of age. This implies that early detection and intervention strategies for metabolic syndrome could potentially benefit this identified group. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan. Methods: This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10-24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression. Results: The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category. Conclusion: This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or of glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that the cerebellum is critically involved in modulating non-motor behaviors, including cognition and emotional processing. Both imaging and lesion studies strongly suggest that the cerebellum is a component of the fear memory network. Given the well-established role of the cerebellum in adaptive prediction of movement and cognition, the cerebellum is likely to be engaged in the prediction of learned threats. The cerebellum is activated by fear learning, and fear learning induces changes at multiple synaptic sites in the cerebellum. Furthermore, recent technological advances have enabled the investigation of causal relationships between intra- and extra-cerebellar circuits and fear-related behaviors such as freezing. Here, we review the literature on the mechanisms underlying the modulation of cerebellar circuits in a mammalian brain by fear conditioning at the cellular and synaptic levels to elucidate the contributions of distinct cerebellar structures to fear learning and memory. This knowledge may facilitate a deeper understanding and development of more effective treatment strategies for fear-related affective disorders including post-traumatic stress or anxiety related disorders.