Fabric-based lamina emergent MXene-based electrode for electrophysiological monitoring.

Commercial wearable biosignal sensing technologies encounter challenges associated with irritation or discomfort caused by unwanted objects in direct contact with the skin, which can discourage the widespread adoption of wearable devices. To address this issue, we propose a fabric-based lamina emergent MXene-based electrode, a lightweight and flexible shape-morphing wearable bioelectrode. This work offers an innovative approach to biosignal sensing by harnessing the high electrical conductivity and low skin-to-electrode contact impedance of MXene-based dry electrodes. Its design, inspired by Nesler's pneumatic interference actuator, ensures stable skin-to-electrode contact, enabling robust biosignal detection in diverse situations. Extensive research is conducted on key design parameters, such as the width and number of multiple semicircular legs, the radius of the anchoring frame, and pneumatic pressure, to accommodate a wide range of applications. Furthermore, a real-time wireless electrophysiological monitoring system has been developed, with a signal-to-noise ratio and accuracy comparable to those of commercial bioelectrodes. This work excels in recognizing various hand gestures through a convolutional neural network, ultimately introducing a shape-morphing electrode that provides reliable, high-performance biosignal sensing for dynamic users.

Garlic Bioconverted by Bacillus subtilis Stimulates the Intestinal Immune System and Modulates Gut Microbiota Composition.

SCOPE: This study evaluates the potential of bioconverted garlic ferments (BGFs) to stimulate the intestinal immune system and modulate cecal microbiota composition. METHODS AND RESULTS: In vitro, BGF significantly enhances Peyer's patch (PP)-mediated bone marrow cell proliferation and increases the production of interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, and immunoglobulin A (IgA) but not IL-4, IL-5, and immunoglobulin E (IgE). Oral administration of BGF to C3H/HeN mice for 4 weeks significantly increases the GM-CSF (42.1-45.8 pg mL-1) and IFN-γ (6.5-12.1 pg mL-1) levels in PP cells. BGF also significantly elevates the levels of tumor necrosis factor-alpha (TNF-α, 165.0-236.3 pg mg-1), GM-CSF (2.4-3.0 ng mg-1), and IFN-γ (1.5-3.2 ng mg-1) in the small intestinal fluid, and TNF-α (2.2-3.1 pg mL-1) and IFN-γ (10.3-0.21.5 pg mL-1) in the mouse serum. Cecal microbial analysis reveals that BGF increases Bacteroidota and Verrucomicrobiota and decreases Actinobacteria and Bacillota at the phylum level in mice. At the genus level, BGF significantly increases the abundance of Fusimonas (250 mg kg-1 BW-1 day-1), Bacteroides (125 and 250 mg kg-1 BW-1 day-1), and Akkermansia (125 mg kg-1 BW-1 day-1) and decreases that of Bifidobacterium (62.5 and 250 mg kg-1 BW-1 day-1) and Limosilactobacillus (125 and 250 mg kg-1 BW-1 day-1). CONCLUSION: This study provides the first evidence of BGF's ability to modulate the intestinal immune system and gut microbiota, supporting its potential as a novel functional material to enhance gut immunity.

Population genetic analysis of Plasmodium vivax vir genes in Pakistan.

Plasmodium vivax variant interspersed repeats (vir) refer to the key protein used for escaping the host immune system. Knowledge in the genetic variation of vir genes can be used for the development of vaccines or diagnostic methods. Therefore, we evaluated the genetic diversity of the vir genes of P. vivax populations of several Asian countries, including Pakistan, which is a malaria-endemic country experiencing a significant rise in malaria cases in recent years. We analyzed the genetic diversity and population structure of 4 vir genes (vir 4, vir 12, vir 21, and vir 27) in the Pakistan P. vivax population and compared these features to those of the corresponding vir genes in other Asian countries. In Pakistan, vir 4 (S=198, H=9, Hd=0.889, Tajima's D value=1.12321) was the most genetically heterogenous, while the features of vir 21 (S=8, H=7, Hd=0.664, Tajima's D value =-0.63763) and vir 27 (S =25, H =11, Hd =0.682, Tajima's D value=-2.10836) were relatively conserved. Additionally, vir 4 was the most genetically diverse among Asian P. vivax populations, although within population diversity was low. Meanwhile, vir 21 and vir 27 among all Asian populations were closely related genetically. Our findings on the genetic diversity of vir genes and its relationships between populations in diverse geographical locations contribute toward a better understanding of the genetic characteristics of vir. The high level of genetic diversity of vir 4 suggests that this gene can be a useful genetic marker for understanding the P. vivax population structure. Longitudinal genetic diversity studies of vir genes in P. vivax isolates obtained from more diverse geographical areas are needed to better understand the function of vir genes and their use for the development of malaria control measures, such as vaccines.

Taraxacum coreanum (Korean Dandelion) Extract Protects against Lipopolysaccharide-Induced Blood-Brain Barrier Destruction via Regulation of Tight Junctions and Inflammatory Responses in bEnd.3 Cells.

Dysfunction of the blood-brain barrier (BBB) is closely related to neuroinflammation-mediated neurodegenerative disorders. Lipopolysaccharide (LPS), an endotoxin, can cause inflammation by impairing the brain endothelial barrier function and increasing the BBB permeability. Although Taraxacum coreanum NAKAI extract (TC), a traditional medicine widely used in Korea, has antioxidant and anti-inflammatory properties, the protective effects on neuroinflammation and BBB dysfunction are not fully understood. In the present study, bEnd.3 cerebral vascular endothelial cells were treated with TC followed by LPS exposure, and the effects on transendothelial electrical resistance (TEER) values, pro-inflammatory cytokine production, and expression of proteins related to inflammatory responses and tight junction integrity were assessed. The TC-treated group exhibited elevated TEER values in bEnd.3 monolayer compared to LPS-only treated group. In addition, TC treatment increased the expression of proteins involved in the tight junctions, such as ZO-1, claudin-5, and occludin. Furthermore, the TC-treated group suppressed the proteins expression-related to nuclear factor-κB (NF-κB) pathway. Taken together, TC attenuates LPS-induced neuroinflammatory responses by regulating NF-κB activation, which may contribute to protecting against BBB disruption. These findings suggest that TC may have the potential to be used as a material for functional foods to prevent neuroinflammation-related brain diseases.

Exploring phytochemicals and pharmacological properties of Populus × tomentiglandulosa.

Populus × tomentiglandulosa (PT), a tree endemic to Korea, shows promising potential as a natural therapeutic agent owing to its potent anti-inflammatory properties. However, the isolation and analysis of phytochemical compounds in PT and related species remains underexplored. Therefore, this study aims to investigate the biochemical profile of PT and evaluate its extracts and fractions for anti-inflammatory activities. Nine compounds were isolated, including two novel flavonoids (luteolin 7-O-ß-d-glucuronide butyl ester and chrysoeriol 7-O-ß-d-glucuronide butyl ester) from the Salicaceae family for the first time. The ethyl acetate fraction exhibited significant radical scavenging activity against various radicals, including DPPH, ABTS+, •OH, and O2 - radicals. PT extracts and the ethyl acetate fraction showed minimal cytotoxicity in Raw 264.7 macrophages at concentrations below 500 and 100 µg/mL, respectively. Furthermore, PT extracts and fractions significantly suppressed the protein expression of proinflammatory mediators (iNOS and IL-6) in LPS-stimulated Raw 264.7 macrophages, highlighting their potent anti-inflammatory effects. These findings suggest that PT holds promise as a valuable natural therapeutic intervention for various oxidative stress and inflammation-related disorders, underscoring the need for further exploration of its clinical applications.

Immunostimulatory effects of Bacillus subtilis-fermented garlic (Aglio): an in-depth in vitro and in vivo analysis.

This study evaluated the immunostimulatory potential of garlic fermented with Bacillus subtilis (Aglio) and identified the underlying mechanisms using in vitro and in vivo models. Aglio significantly enhanced macrophage activity, with increased TNF-α (9.3-46.6 fold), MCP-1 (5.3-41.4 fold), IL-6 (2.1-32.1 fold), and IL-12 (1.1-5.5 fold) secretion compared to those of the standard garlic extract. This macrophage-stimulatory activity was associated with MAPK (ERK, JNK, and p38) and NF-κB (IκBα and p65) signaling pathway activation. Aglio significantly increased splenocyte proliferation (1.8-2.9 fold) and TNF-α (32.5-96.6 fold), IFN-γ (26.6-362.3 fold), GM-CSF (2.1-3.9 fold), and IL-6 (10.3-11.6 fold) secretion. Gene expression analysis revealed Th1-related T-Bet upregulation and Th2- and Th17-related GATA3 and FOXP3 downregulation, indicating a Th1-mediated splenocyte activation mechanism. Oral administration of Aglio (125 and 250 mg kg-1) to BALB/c mice increased splenocyte proliferation (2.1-3.3 fold) and elevated splenic cytokine (TNF-α, 1.9-2.7 fold; GM-CSF, 2.2-2.3 fold; IL-6, 1.9 fold) and antibody (IgA, 1.4-1.8 fold; IgG, 1.0-1.7 fold) levels. Aglio administration also increased serum TNF-α (2.1-3.3 fold), IL-6 (1.0-1.1 fold), and IgG (1.6-1.9 fold) levels. Nutrient analysis indicated that Aglio lacked detectable carbohydrates and had negligible protein and polyphenol contents compared to standard garlic extract, suggesting complete biotransformation during fermentation. These findings demonstrate Aglio-mediated immune activation, highlighting its potential as a functional food or nutraceutical agent for immune enhancement.

A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma.

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.

Cu-Catalyzed Three-Component Alkene Carboamination: Mechanistic Insights and Rational Design to Overcome Limitations.

Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with α-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring the reaction reveals the formation of transient atom transfer radical addition (ATRA) intermediates with both electron-neutral and deficient vinyl arenes as well as unactivated alkenes. Based on our experimental studies and density functional theory calculations, the oxocarbenium is generated through atom transfer and subsequent intramolecular substitution. Further, mechanistic factors that dictate the regioselectivity of the nucleophilic attack onto the oxocarbenium to afford the γ-amino ester, γ-iminolactone, or γ-lactone are discussed. A strategy to overcome scope limitation with respect to unactivated alkenes is developed using the mechanistic insights gained herein. Finally, we demonstrate that under modified conditions, our Cu catalyst enables the ATRA reaction between a variety of alkyl halides and vinyl arenes/α-olefins, and we present a one-pot, two-step carbofunctionalization with an array of nucleophiles through ATRA/SN2.

Wearable heart rate sensing and critical power-based whole-body fatigue monitoring in the field.

Whole-body fatigue (WBF) presents a concerning risk to construction workers, which can impact function and ultimately lead to accidents and diminished productivity. This study proposes a new WBF monitoring technique by applying the Critical Power (CP) model, a bioenergetic model, with a wrist-worn heart rate sensor. The authors modified the CP model to calculate WBF from the percentage of heart rate reserve (%HRR) and generated a personalized model via WBF perception surveys. Data were collected for two days from 33 workers at four construction sites. The results showed that the proposed technique can monitor field workers' perceived WBF with a mean absolute error of 12.8% and Spearman correlation coefficient of 0.83. This study, therefore, demonstrates the viability of wearable WBF monitoring on construction sites to support programs aimed at improving workplace safety and productivity.

2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

Geraniin from the methanol extract of Pilea mongolica suppresses LPS-induced inflammatory responses by inhibiting IRAK4/MAPKs/NF-κB/AP-1 pathway in HaCaT cells.

The skin acts as a vital barrier, shielding the body from external threats that can trigger dryness, itching, and inflammation. Pilea mongolica, a traditional Chinese medicinal herb, holds promise for various ailments, yet its anti-inflammatory properties remain understudied. This study aimed to explore the potential anti-inflammatory effects of the methanol extract of P. mongolica (MEPM) and its underlying molecular mechanisms and active compounds in LPS-stimulated human keratinocytes. MEPM treatment, at concentrations without cytotoxicity, significantly decreased NO productions and the iNOS, IL-6, IL-1ß, and TNF-α levels in LPS-induced HaCaT cells. Moreover, MEPM suppressed IRAK4 expression and phosphorylation of JNK, ERK, p38, p65, and c-Jun, suggesting that the anti-inflammatory effects of MEPM result from the inhibition of IRAK4/MAPK/NF-κB/AP-1 signaling pathway. Through LC/MS/MS analysis, 30 compounds and 24 compounds were estimated in negative and positive modes, respectively, including various anti-inflammatory compounds, such as corilagin and geraniin. Through HPLC analysis, geraniin was found to be present in MEPM at a concentration of 18.87 mg/g. Similar to MEPM, geraniin reduced iNOS mRNA expression and inhibited NO synthesis. It also decreased mRNA and protein levels of inflammatory cytokines, including IL-6 and TNF-α, and inhibited IRAK4 expression and the phosphorylation of MAPKs, NF-κB, and AP-1 pathways. Therefore, it can be inferred that the anti-inflammatory effects of MEPM are attributable to geraniin. Thus, MEPM and its active compound geraniin are potential candidates for use in natural functional cosmetics.

The neonatal Fc receptor and DPP4 are human astrovirus receptors.

Human astroviruses (HAstV) are major global causes of gastroenteritis, but little is known about host factors required for their cellular entry. Here, we utilized complementary CRISPR-Cas9-based knockout and activation screening approaches and identified neonatal Fc receptor (FcRn) and dipeptidyl-peptidase IV (DPP4) as entry factors for HAstV infection of human intestinal epithelial cells. Disruption of FcRn or DPP4 reduced HAstV infection in permissive cells and, reciprocally, overexpression of these factors in non-permissive cells was sufficient to promote infection. We observed direct binding between FcRn and HAstV virions as well as purified spike protein. Finally, inhibitors for DPP4 and FcRn currently in clinical use prevent HAstV infection in cell lines and primary human enteroids. Thus, our results reveal mechanisms of HAstV entry as well as druggable targets. One-Sentence Summary: Targeting FcRn or DPP4 using available therapies effectively prevents human astrovirus infection in human enteroid cultures.

Phytochemical Profile, Antioxidant, Anti-Atopic, and Anti-Inflammatory Activities of Filipendula glaberrima Nakai at Different Growth Stages.

Since atopic dermatitis is an inflammatory skin disease, natural remedies, such as Filipendula glaberrima Nakai (FG), with anti-inflammatory properties are possible promising therapeutic options. This study aimed to investigate the therapeutic potential of FG extracts at different growth stages. Seven compounds were isolated from the FG leaf extracts using open-column chromatography, and they were analyzed using HPLC. The extracts were further evaluated for their total polyphenol and flavonoid content (TPC and TFC). The in vitro antioxidant properties of the FG extracts were evaluated using radical scavenging assays, whereas their anti-inflammatory activities were assessed by evaluating their ability to inhibit the production of inflammation-associated biomarkers using the Griess assay and ELISA, respectively. The MTT assay was used to evaluate the viability and cytotoxicity of the FG extracts in keratinocyte cell lines. The results showed that the full-flowering stage exhibited the highest TPC, TFC, and antioxidant activities, thus suggesting a positive correlation between these properties. All FG extracts showed significant anti-inflammatory activity by inhibiting the production of pro-inflammatory biomarkers in lipopolysaccharide-stimulated macrophages. Additionally, the FG extracts suppressed the production of cytokines and chemokines in keratinocytes, indicating their anti-atopic potential. HPLC analysis revealed that the full-flowering stage had the highest content of all the analyzed phytochemicals (gallic acid, (+)-catechin, hyperin, miquelianin, astragalin, afzelin, and quercetin). These results suggest that the full-flowering stage of FG is the most promising source for therapeutic applications owing to its superior phytochemical profile and biological activities. This study highlights the potential of FG extracts, particularly in its full-flowering stage, as a natural therapeutic agent for the management of inflammation-related diseases, and it can also serve as a reference for further research on FG.

2023 Korean Society of Echocardiography position paper for diagnosis and management of valvular heart disease, part I: aortic valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the clinical management of valvular heart diseases with reference to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee tried to reflect the recently published results on the topic of valvular heart diseases and Korean data by a systematic literature search based on validity and relevance. In part I of this article, we will review and discuss the current position of aortic valve disease in Korea.

Characteristics of Korean medical care utilization in patients with traffic injury: Analysis of 3 hospital electronic health record databases.

This retrospective study aimed to identify the characteristics of Korean medical care utilization in patients with traffic injury (TI) and to explore the clinical effectiveness of Korean medical interventions for TI through a multicenter chart review. This multicenter, retrospective registry study gathered electronic health records from 3 hospitals between January 1, 2018 and December 31, 2021. Data included treatment dates, demographic information, the Korean Standard Classification of Diseases codes, collision data, Korean medicine treatment modalities, and treatment outcomes. In total, 384 patients (182 inpatients and 202 outpatients) were included in the analysis. Patients were categorized into acute (207 patients, 53.9%), subacute (77 patients, 20.1%), and chronic (100 patients, 26.0%) phases based on the period until the visit. The most frequent Korean Standard Classification of Diseases code was "sprain and strain of cervical spine (S13.4)." All patients, except one, received Korean physiotherapy, followed by acupuncture and cupping. Comparative intragroup analysis revealed significant pain reduction in patients treated with the combination of Chuna manual therapy, herbal medicine, and pharmacopuncture and those treated with pharmacopuncture and herbal medicine only. This study highlights the characteristics of patients with TI visiting medical institutions providing Korean medicine and describes the effectiveness of Korean medicine interventions. Further comprehensive analysis with more data is necessary for future research.

Modeling the impact of measured and projected climate and management systems on agricultural fields: Surface runoff, soil moisture, and soil erosion.

As global climate change poses a challenge to crop production, it is imperative to prioritize effective adaptation of agricultural systems based on a scientific understanding of likely impacts. In this study, we applied an integrated watershed modeling framework to examine the impacts of projected climate on runoff, soil moisture, and soil erosion under different management systems in Central Oklahoma. The proposed model uses measured climate data and three downscaled ensembles from the Coupled Model Intercomparison Project Phase 6 (CMIP6) at the water resources and erosion watershed to understand the impact of climate change and various climate conditions under three management systems: (1) continuous winter wheat (Triticum aestivum) under conventional tillage (WW-CT; baseline system), (2) continuous winter wheat under no-till (WW-NT), and (3) cool and warm season forage cover crop mixes under no-till (CC-NT). The study indicates that the occurrence of agricultural drought is projected to increase while erosion rates will remain unchanged under the WW-CT. In contrast, climate simulations imposed on the WW-NT and CC-NT systems significantly reduce runoff and sediment while preserving soil moisture levels. Especially, implementing the CC-NT system can bolster food security and foster sustainable farming practices in Central Oklahoma in the face of a changing climate.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Corrigendum to "Glucose-lowering effect of Reducose® enriched with 1-deoxynojirimycin and l-leucine: Studies on insulin secretion in INS-1 cells and reduction of blood glucose in diabetic rats" <[Heliyon Volume 10, Issue 3, 15 February 2024, article e25499]>.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e25499.].

Nanostructured Substrate-Mediated Bubble Degassing in Microfluidic Systems.

Microfluidic platforms have been widely used in a variety of fields owing to their numerous advantages. The prevention and prompt removal of air bubbles from microchannels are important to ensuring the optimal functioning of microfluidic devices. The entrapment of bubbles in the microchannels can result in flow instability and device performance disruption. Active and passive methods are the primary categories of degassing technologies. Active methods rely on external equipment, and passive methods operate autonomously without any external sources. This study proposed a passive degassing method that employs a nanoscale surface morphology integrated into the substrate of a microfluidic device. Nanostructures exhibit a microchannel geometry and are fabricated based on surface micromachining technology using silver ink and chemical etching. Consequently, the gas permeability is enhanced, resulting in effective degassing through the nanostructure. The performance of this degassing method was characterized under varying substrate permeabilities and input pressure conditions, and it was found that increased permeability facilitates the degassing performance. Furthermore, the applicability of our method was demonstrated by using a serpentine channel design prone to gas entrapment, particularly in the corner regions. The nanostructured substrate exhibited significantly improved degassing performance under the given pressure conditions in comparison to the glass substrate.

Intestinal tuft cell immune privilege enables norovirus persistence.

The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (just EGFP death inducing) CD8+ T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8+ T cell-mediated killing-unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells-despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8+ T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8+ T cells neither cleared nor prevented MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8+ T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.