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Induction of differentiation is a therapeutic strategy in neuroblastoma, a common pediatric cancer of the sympathetic nervous system. The homeobox protein HOXC9 is a key regulator of neuroblastoma differentiation. To gain a molecular understanding of the function of HOXC9 in promoting differentiation of neuroblastoma cells, we conducted a genome-wide analysis of the HOXC9-induced differentiation program by microarray gene expression profiling and chromatin immunoprecipitation in combination with massively parallel sequencing (ChIP-seq). Here we describe in detail the experimental system, methods, and quality control for the generation of the microarray and ChIP-seq data associated with our recent publication [1].

Colistin is considered the last resort for treating infections caused by multidrug-resistant bacteria. However, the spread of the plasmid-borne colistin-resistance gene mcr-1 has become a public health threat. In this study, we identified mcr-1-harboring Leclercia adecarboxylata strain (WWCOL-134) isolated from wastewater in Seoul. The strain had a colistin MIC value of 2 µg/ml and was resistant to cefotaxime, gentamicin, tetracycline, trimethoprim and sulfamethoxazole. The mcr-1 gene, along with an array of resistance genes, was located on a 236-kb plasmid (pCOL134-1), which contained the typical IncHI2 backbone of reported mcr-1-carrying plasmids, and was transferred to an Escherichia coli strain by conjugation. To the best of our knowledge, this is the first study to report the emergence of mcr-1-harboring Leclercia sp. isolate. Our findings demonstrate the ongoing spread of colistin resistance among Enterobacterales species, emphasizing the need for surveillance of antimicrobial resistance in wastewater environments.

The prevalence of obesity is increasing globally, and dietary fiber supplementation can aid in its treatment. This 12-week randomized, double-blind, placebo-controlled trial examined the effect of Dyne-neoagarooligosaccharides (Dyne-NAOs), hydrolyzed from agar via β-agarase DagA, in overweight or obese adults. Eighty participants were randomly assigned using block randomization (1:1, block size 4) to receive either 15 g of Dyne-NAOs daily or a placebo (maltodextrin). After the intervention, body fat mass (−1.07 kg vs. −0.05 kg; p = 0.015) and body fat percentage (−1.04 % vs. −0.08 %; p = 0.018) were significantly lower in the NAO group than in the placebo group. The Constipation Scoring System (−1.42 vs. −0.06; p = 0.010) and Patient Assessment of Constipation-Symptoms (−3.28 vs. −0.42; p = 0.021), used to assess changes in bowel movements, also showed significant between-group differences. These findings suggest that Dyne-NAOs could be a promising anti-obesity dietary fiber supplement.

Ponatinib is a potent tyrosine kinase inhibitor that is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. To further expand its clinical applications, accurate quantification of ponatinib in plasma is essential. In this study, we developed and validated a sensitive and selective high-performance liquid chromatography (HPLC) method coupled with a fluorescence detector (FLD) to measure ponatinib concentrations in rat plasma using the Analytical Quality by Design approach. Briefly, we screened and optimized the critical method parameters using the Taguchi and Box-Behnken designs. The developed method had excellent linearity in the range of 1–1000 ng/mL, sensitivity, and reproducibility, and required minimal sample volume and a short run time. Compared with previously reported HPLC-ultraviolet (UV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, this HPLC-FLD method offers superior sensitivity, simpler sample preparation, and greater efficiency. We successfully used this method in a pharmacokinetic study in rats to obtain reliable data on ponatinib plasma concentrations. Altogether, this analytical method will be applicable in several analytical conditions and will support further pharmacokinetic and clinical investigations of ponatinib for various cancer treatments.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Serotonin (5-HT) is a biogenic monoamine that acts as a neurotransmitter in the central nervous system and as a paracrine, exocrine, or endocrine messenger in peripheral tissues. In this study, we hypothesized that inhibition of serotonin signaling using 5-HT receptor 2B (HTR2B) inhibitors could potentially impede the progression of CRC. We treated CT26 and COLO-205 cells with SB204741, an inhibitor of HTR2B, and evaluated CRC cell proliferation and migration. We then evaluated the effects of HTR2B inhibition in a xenograft mouse model of human colorectal cancer. We also evaluated the role of a novel inhibitor, GM-60186, using both in vitro and in vivo models. RNA sequencing analysis was performed to elucidate the underlying mechanism of the anti-tumor effects of pharmacological inhibition of HTR2B on CRC. In both CRC cell lines and xenograft mouse models, we show that pharmacological inhibition of HTR2B with SB204741 and GM-60186 significantly inhibits CRC cell proliferation and migration. HTR2B inhibition leads to the suppression of extracellular signal-regulated kinase (ERK) signaling, a critical pathway in CRC pathogenesis. Notably, transcriptomic analysis reveals distinct gene expression changes associated with HTR2B inhibition, providing insight into its therapeutic potential. In this study, we found that pharmacological inhibition of HTR2B suppressed CRC proliferation via ERK signaling. In addition, we proposed a novel HTR2B inhibitor for the treatment of CRC. This study highlights the potential role of HTR2B signaling in CRC. These inhibitors may contribute to new therapeutics for CRC treatment.

Background: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. Methods: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. Results: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. Conclusions: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

The use of biomaterials in additive manufacturing (AM) of medical devices has gained significant attention over the years, especially in areas such as wound care and orthopedics. This study aims to investigate the performance of bioresorbable peptide-incorporated polymers produced for fused deposition modelling (FDM) process. Herein, we report FDM 3D Printing process of bioactive polymers comprising polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or polylactic acid (PLA) or blended with peptide–containing brush copolymers bearing similar synthetic polymer side chains. Mechanical, thermal and rheological properties of the materials were carried out and we report that the incorporation of bioactive polymers into these biodegradable polymers does not result in significant changes to glass transition temperature, melt temperature, tensile properties of the base polymers. However, it was observed that flexural and rheological properties altered significantly. This study provides an insight into the thermomechanical performance of bioresorbable peptide-incorporated polymers for FDM utilization which allows for their use potential in medical device fabrication.

This study was conducted to confirm the effectiveness of kimchi starters (KSs) by investigating their growth characteristics. First, we assessed the growth characteristics of five lactic acid bacteria (LAB) strains (Lactococcus lactis WiKim0124; Companilactobacillus allii WiKim39; and Leuconostoc mesenteroides WiKim0121, WiKim33, and WiKim32) and assessed the effects of different parameters, including organic acids, salinity, acidity, and temperature, on the growth of these LAB. The findings showed that organic acids, particularly acetic and lactic acids that accumulated with the progress in fermentation, were the major players determining the microbial composition of kimchi and the growth of the KSs. Leuconostoc mesenteroides grew well in the presence of acetic and lactic acids than other starts, so it is confirmed that Leuconostoc mesenteroides can dominant in kimchi. In addition, malic acid, which is derived from kimchi ingredients, is used to induce malolactic fermentation by Lactobacillus species, and the progression of malolactic fermentation can be controlled through KSs. Our results suggest that KSs promote the production of organic acids, and the profiling of organic acids, as well as the progress of malolactic fermentation, can be controlled by selecting the suitable KS. Overall, this study demonstrates that kimchi fermentation can be controlled more effectively if the characteristics of KS are understood and used appropriately.

Objective: To examine children’s screen time use and sleep patterns over 2 years of the pandemic and the downstream associations with children’s executive functions and behavioural problems, as well as the moderating effects of parental factors. Method: This longitudinal cohort study examined school-aged children’s lifestyle and behavioural changes over 2 years of the pandemic across 6 timepoints (November 2020 to August 2022). Latent growth modeling (LGM) was used to identify changes in screen time and sleep duration and multivariate LGM was used to determine how parental stress, positive parenting, changes in children’s screen time and sleep over time were associated with children’s executive functions and mental health outcomes at the final time point. Results: A total of 198 parents (children’s mean age = 9.14 years) were recruited and followed up. Non-school screen time was elevated at the initial timepoint (3.6 ± 2.3 h). Positive parenting at the initial timepoint was associated with lower screen time use in children (β = −.19, p

The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.

Although the potent anti-inflammatory effects of irisin have been documented in various inflammatory disorders, its efficacy against inflammatory pain remains unexplored. Herein, we examined the therapeutic effects of irisin in a mouse model of inflammatory pain induced by complete Freund’s adjuvant (CFA). Mice were divided into three groups: normal control, CFA-injected (CFA), and CFA plus irisin-treated (CFA+Irisin). The irisin-treated group exhibited a gradual reduction in mechanical allodynia and thermal hyperalgesia when compared with the CFA group. Moreover, treatment with irisin significantly upregulated the expression of M2 macrophage markers (interleukin [IL]-4 and IL-10) and downregulated M1 macrophage markers (IL-1β, IL-6, and tumor necrosis factor-α) in the local paw tissue, dorsal root ganglion, and spinal cord tissue. However, there was no significant difference in the total number of F4/80+ macrophages in the paw tissue and dorsal root ganglion, indicating phenotypic exchange. Treatment with irisin also downregulated the expression of the glial cell activation-related markers Iba-1 and GFAP in the spinal cord tissue. To elucidate the underlying mechanisms, we detected the expression of Toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 5 (IRF5) in paw tissues, dorsal root ganglion, and spinal tissues, revealing that irisin could downregulate the expression of these proteins. Irisin alleviated inflammatory pain by modulating local tissue inflammation and peripheral and central neuroinflammation and reducing glial cell activation and M2 macrophage polarization by modulating the TLR4–MyD88–IRF5 signaling pathway. Accordingly, irisin is a promising candidate for treating inflammatory pain in various diseases.

Abstracts: Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.

Objective: We evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. Methods: Oropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). Results: Of 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P = 0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95% CI: 36.3-88.2), and serogroup C was particularly reduced (VEC = 83.0%, 95% CI: 50.6-94.1), whereas non-groupable isolates increased significantly after vaccination (VENG = -76.1%, 95% CI: -176.2 to -13.1). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. Conclusions: MenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.

Cardiovascular disease remains a global health concern. Stem cell therapy utilizing human cardiac progenitor cells (hCPCs) shows promise in treating cardiac vascular disease. However, limited availability and senescence of hCPCs hinder their widespread use. To address these challenges, researchers are exploring innovative approaches. In this study, a bioengineered cell culture plate was developed to mimic the natural cardiac tissue microenvironment. It was coated with a combination of extracellular matrix (ECM) peptide motifs and mussel adhesive protein (MAP). The selected ECM peptide motifs, derived from fibronectin and vitronectin, play crucial roles in hCPCs. Results revealed that the Fibro-P and Vitro-P coated plates significantly improved hCPC adhesion, proliferation, migration, and differentiation compared to uncoated plates. Additionally, long-term culture on the coated plates delayed cellular senescence and maintained hCPC stemness. These enhancements were attributed to the activation of integrin downstream signaling pathways. The findings suggest that the engineered ECM peptide motif-MAP-coated plates hold potential for enhancing the therapeutic efficacy of stem cell-based therapies in cardiac tissue engineering and regenerative medicine.

This study explores the structure-property relationships in colorless polyimides (CPIs) synthesized from stereoisomeric (exo- and endo-form) alicyclic dianhydrides, combined with various diamines. The structural configurations of 5,5’-(1,4-phenylene)bis[hexahydro-(3aR,4R,5R,7S,7aS)-rel-4,7-Methanoisobenzofuran-1,3-dione] (BzDA-exo) and 5,5-(1,4-phenylene)bis(hexahydro-4,7-methanoisobenzofuran-1,3-dione) (BzDA-endo) were confirmed as exo- and endo-forms, respectively, through 1H NMR and 2D NOESY NMR analyses. Wide-angle X-ray scattering (WAXS) data revealed that stereoisomeric structures influence polymer chain packing in synthesized CPIs. The investigation extended to the chemical and physical structure-dependent properties such as physical, thermal and optical properties of the PIs. Notably, structure-dependent physical and thermal properties were evident, with a particularly strong structure-property relationship manifesting in the coloration and yellow index (Y.I.) of PIs. These systematic characterizations offer profound insights into the design and optimization of chemical and physical structures in CPIs, highlighting the versatility of stereoisomeric monomers for various applications.

Background: Deep brain stimulation (DBS) has been widely used to manage debilitating neurological symptoms in movement disorders such as Parkinson's disease (PD). Despite its well-established symptomatic benefits, our understanding of the mechanisms underlying DBS and its possible effect on the accumulation of pathological proteins in neurodegeneration remains limited. Accumulation and oligomerization of the protein alpha-synuclein (α-Syn) are implicated in the loss of dopaminergic neurons in the substantia nigra in PD, making α-Syn a potential therapeutic target for disease modification. Objective: We examined the effects of high frequency electrical stimulation on α-Syn levels and oligomerization in cell and rodent models. Methods: High frequency stimulation, mimicking DBS parameters used for PD, was combined with viral-mediated overexpression of α-Syn in cultured rat primary cortical neurons or in substantia nigra of rats. Bimolecular protein complementation with split fluorescent protein reporters was used to detect and quantify α-Syn oligomers. Results: High frequency electrical stimulation reduced the expression of PD-associated mutant α-Syn and mitigated α-Syn oligomerization in cultured neurons. Furthermore, DBS in the substantia nigra, but not the subthalamic nucleus, decreased overall levels of α-Syn, including oligomer levels, in the substantia nigra. Conclusions: Taken together, our results demonstrate that direct high frequency stimulation can reduce accumulation and pathological forms of α-Syn in cultured neurons in vitro and in substantia nigra in vivo. Thus, DBS therapy could have a role beyond symptomatic treatment, with potential disease-modifying properties that can be exploited to target pathological proteins in neurodegenerative diseases.

Background: The lack of headforms that accurately reflect the head characteristics of Koreans and the demographic composition of the Korean population can lead to inadequate FFR testing and reduced effectiveness of FFRs. Method: Direct measurements of 5,110 individuals and 3D measurements of 2,044 individuals, aged between 9 and 69 years, were sampled from the data pool of Size Korea surveys based on the age and gender ratios of the Korean resident demographics. Seven head dimensions were selected based on the ISO 16976-2, availability of Size Korea measurements, and their relevance to the fit performance of FFRs. A principal component analysis (PCA) was performed using the direct measurements to extract the main factors explaining the head characteristics and then the main factors were standardized and remapped to 3D measurements, creating five size categories representing Korean head shapes. Lastly, representative 3D headforms were constructed by averaging five head shapes for each size category. Results: The study identified two main factors explaining Korean head characteristics by the PCA procedure specified in ISO 16976-2 and developed five representative headforms reflecting the anthropometric features of Korean heads: medium, small, large, short & wide, and long & narrow. Conclusion: This study developed representative headforms tailored to the Korean population for conducting total inward leakage (TIL) tests on filtering facepiece respirators (FFRs). The representative headforms can be used for TIL testing by employing robotic headforms to enhance the performance of FFRs for the Korean target population.

Peritonsillar abscess (PTA) is the most common deep neck infection in the United States. Timely treatment of PTA with antibiotics and aspiration or drainage is paramount, as delay in management may lead to further complications. The oral approach is the preferred route of drainage however may not always be accessible, warranting consideration of other routes of drainage. To the best of our knowledge, CT guidance for aspiration or drainage of a PTA has not been previously described. We present a 50-year-old patient with a PTA who initially presented with throat pain and dysphagia, rapidly developed upper airway obstruction, and required intubation. After the failure of clinical improvement and unsuccessful PTA aspiration via the conventional oral route, successful CT-guided percutaneous needle aspiration was performed by neuroradiology. Shortly thereafter, the patient clinically improved and was discharged with an oral course of antibiotics and follow-up on an as-needed basis. Total hospital length of stay was seven days. The complex patient may not allow for simple incision and drainage or needle aspiration of a suspected PTA. Assistance with ultrasound guidance is often utilized, however, challenges may persist depending on the anatomical location of the PTA and patient comorbidities. In cases where external drainage is considered and conventional ultrasound imaging is particularly challenging, CT-guided percutaneous aspiration may provide a useful alternative. PTAs are common with the possibility of complication. Although the usual route of drainage is oral, there are instances in which this cannot be performed. This case exhibits an uncommon approach to PTA aspiration via an external CT-guided percutaneous approach with rapid subsequent clinical improvement, exhibiting the utility of CT guidance.

Glycyrrhiza uralensis is a traditional herbal medicine with significant bioactivity. This study investigated the effect of G. uralensis crude water extract (GU-CWE) on nitric oxide synthase 2 (NOS2) expression during myogenesis. GU-CWE treatment increased myoblast differentiation by downregulating NOS2 and upregulating myogenic regulatory factors (MYOD, MYOG, and MYH). Notably, this effect was supported by an observed decrease in NOS2 expression in the gastrocnemius tissues of mice treated with GU-CWE. In addition, GU-CWE treatment and NOS2 knockdown were associated with reductions in reactive oxygen species levels. We further elucidate the role of the NOS2 gene in myoblast differentiation, demonstrating that its role was expression dependent, being beneficial at low expression but detrimental at high expression. High NOS2 gene expression induced oxidative stress, whereas its low expression impaired myotube formation. These findings highlight that the modulation of NOS2 expression by G. uralensis can potentially be use for managing muscle wasting disorders.

Summary: Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of NRF2 and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression.

The purpose of this study is to investigate the trajectory of depression over time among all registered individuals with disability, including the period since the onset of COVID-19. In this study, we analyzed the results of the 12th-16th Korea Welfare Panel Study(KoWePS) which was conducted from 2017 to 2021. 793 individuals who were able to estimate the change in depression all period were selected for the final analysis. There was a significant increase in depression among people with disabilities occurs over time, and the level of depression rose gradually. Individuals being women, the lower the household income, the more severe the disability, and not having a physical disability was associated with the likelihood of higher depression. The health care system needs to be improved to be more disability-friendly to promote the health of people with disability, who are relatively more vulnerable during an infectious disease pandemic, such as COVID-19.

With the increasing demand for highly efficient lighting in the automotive industry, flip-chip light-emitting diodes (LEDs) have become widely used for both interior and exterior lighting. Solder, serving as a crucial interconnecting material, often develops voids during the reflow process, compromising the integrity and reliability of the connections. Thus, understanding the impact of these voids on the mechanical and thermal properties of the product is vital for improving reliability accuracy. This work employs computational methods alongside experimental approaches to address the challenges of replicating solder voids and controlling the solder void fraction. A comprehensive study investigates the effects of solder voids on shearing properties and thermal conductance. Random voids were introduced into the solder pads of an LED assembly within a finite element model (FEM), leading to predictions of maximum shear stress and LED junction temperature. The findings correlate well with the experimental data, validating the FEM's applicability. Furthermore, a statistical analysis was conducted to explore the relationship between solder void fraction, position, and size, aiming to provide objective guidelines for analyzing soldered assembly tomography in reliability assessments.

The Jra antigen, the only antigen within the JR blood group system, is a high-prevalence red blood cell (RBC) antigen found in over 99 % of the global population. An induced pluripotent stem cell line (YUCMi020-A) was generated from peripheral blood drawn from a Jr(a−) phenotype individual, who was homozygous for a null mutation of ABCG2*01N.01 (rs72552713, c.376C>T; p.Gln126*). The generated line exhibited pluripotent characteristics and no chromosomal aberrations. This cell line will serve as a cell source, enabling us to produce RBCs with the Jr(a−) phenotype in vitro, which can be used for transfusing individuals with anti-Jra antibodies.

Background: Extracardiac conduit Fontan procedure (ECFP) employing a Gore-Tex conduit has been widely used for patients with single ventricle physiology; however, the long-term status of the conduit is unknown. We investigated the changes in a Gore-Tex conduit after ECFP and the factors associated with its narrowing. Methods: We conducted a retrospective analysis of 86 patients who underwent ECFP between January 1995 and December 2008 and had cardiac computed tomography (CT) during the follow-up period. Results: The median patient age at ECFP was 2.8 years (range 1.6–9.7), and a cardiac CT was obtained at 13.1 ± 3.4 years later. The minimum conduit area decreased by approximately two-thirds of the original due to calcification, pseudointimal hyperplasia, thrombus, and luminal irregularity. The normalized minimum conduit area was influenced by the time interval from ECFP and normalized original conduit area at ECFP. An oversized conduit was associated with a narrowing of both its sides and a high frequency of pseudointimal hyperplasia or mural thrombus. The ratio of minimum conduit-to-inferior vena cava areas was lower in patients with chronic liver disease than in those with a normal liver. The maximum percent stenosis of the conduit correlated with oxygen pulse and heart rate during peak exercise. Conclusions: Using a larger conduit at ECFP resulted in a larger minimum conduit area at follow-up. However, oversizing requires careful monitoring for stenosis near anastomotic sites and the occurrence of pseudointimal hyperplasia or thrombus.

Background and objective: In many real-world scenarios, including the blood smear domain, it is difficult for detection networks to achieve good performance because image annotation is usually time consuming and expensive. To address this issue, similarity-based distillation (SD) methods, considered the soft version of contrastive learning, are applied to learn a better visual representation without requiring any supervision of the downstream task. Motivated by our theoretical analysis, we treat standard SD methods as the maximization of common 1-hop neighboring key points between two queries in an attributed graph, where nodes represent query and key data points. However, such first-order graph heuristic methods that calculate the likelihood of an unseen link between target nodes by using up to 1-hop neighborhoods are normally limited by insufficient representation power and even lack of generalization ability. Methods: Therefore, in this paper, we propose a novel higher-order heuristic distillation (H2D) method that distills knowledge about more general and powerful higher-order heuristic features based on a more than 1-hop relationship in the attributed graph. To do this, we utilize a graph neural network model to learn the higher-order heuristic features on the attributed graph constructed by query and key data representations and transfer the knowledge from the teacher to the student encoder. Results: Our method outperforms the previous state-of-the-art SD methods in the cell detection task on the blood smear dataset as well on open databases (Pascal VOC and MS COCO). Conclusions: Our proposed model allow teacher encoder to transfer the knowledge about more general and powerful higher-order heuristic embeddings to the student and enables better learning for visual representation on cell detection task using blood smear images.

Traditional questionnaires do not capture the complexity of how people are viewed by others and grouped into categories on the basis of what is inferred (or not) about them. This is critical in applying an intersectionality framework in research because people are negatively impacted because of “who they are” but also based on “how others see them.” The purpose of this project was to develop and validate a questionnaire, grounded in intersectionality theory and a nuanced understanding of social position, that can be applied in large-scale, population-based surveys and studies.Drawing on 61 existing quantitative surveys collecting identity-based information and 197 qualitative studies on intersectionality describing the complex ways in which people's social positions are constructed and experienced, we created a draft questionnaire comprising five parts: 1) Sex and Gender, 2) Sexuality and Sexual Orientation, 3) Cultural Context, 4) Disability, Health, and Physical Characteristics, and 5) Socioeconomic Status. A draft of the questionnaire was then reviewed by experts via the Delphi process, which gauged the accessibility of the questionnaire (e.g., language used, length) and the relevance of its content using a 5-point scale and open-ended questions. These responses were ranked, analyzed, and synthesized to refine the questionnaire and, ultimately, to obtain ≥75 % consensus on each questionnaire item and response option.The SAFE questionnaire provides an opportunity to take a significant step forward in advancing our understanding of the complex, intersectional nature of social participation and marginalization.

The electrochemical behavior and catalytic properties of nickel oxide (NiOx) are enhanced through cathodic electroplating and subsequent electrochemical activation in an alkaline aqueous electrolyte. The electrochemical detection of ʟ-glutamate becomes feasible by introducing an amine group through immobilizing APTES ((3-aminopropyl)triethoxysilane) on the NiOx surface, resulting in a positive charge. The synergistic effect of electrochemically activated electroplated NiOx and the APTES-modified surface facilitates the effective electrochemical detection of trace ʟ-glutamate. The APTES-activated NiOx electrode exhibits a linear detection range of 0.2 nM to 2 mM for glutamate. This relatively wide concentration range is promising for the analysis of human biological fluids.

Objective: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. Methods: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. Results: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the “early” period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the “late” period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). Conclusion: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Bioactive non-woven dressings can be prepared by dip coating of non-woven cloth in solutions containing bioactive polyethylene bearing pendant arms of polyethylene (PE5000) and modified PEG3400-biomolecules including linear Arg-Gly-Asp (RGD), collagen fragment (Gly-Pro-Hyp)3, laminin-derived peptide (AGQWHRVSVRWGC) (A5G81) and hyaluronic acid (HA). Obtainment of ultimate coating concentration for each type of non-woven cloth is achieved such that the technically demanding bioactive polyethylene does not delaminate from the non-woven cloth itself but is of sufficient quantity for bioactivity. Scanning electron microscopy images show uniform polyethylene deposition on the non-woven cloth. Good water absorption and permeability allow the use of such bioactive polyethylene coated non-woven cloth as wound dressings. Material biocompatibility is demonstrated using in vitro human skin fibroblast assays. In vivo porcine full thickness excisional wound model shows PE5000-coated non-woven cloth can remarkably accelerate skin regeneration to close the wounds faster than clinical gold standard dressing. Thus, the results presented here may provide a promising guide for bioactive polyethylene-modified non-woven materials for wound dressing applications.

Gamma-aminobutyric acid (GABA) neuronal system-related transcription factors (TFs) play a critical role in GABA production, and GABA modulates diabetic neuropathic pain (DNP). The present study investigated the therapeutic effects of intrathecal delivery of two TFs achaete-scute homolog 1 (Ascl1) and LIM homeobox protein 6 (Lhx6) in a mouse model of DNP and elucidated their underlying mechanisms. GABA-related specific TFs, including Ascl1, Lhx6, distal-less homeobox 1, distal-less homeobox 5, the Nkx2.1 homeobox gene, and the Nkx2.2 homeobox gene, were investigated under normal and diabetic conditions. Among these, the expression of Ascl1 and Lhx6 was significantly downregulated in mice with diabetes. Therefore, a single intrathecal injection of combined lenti-Ascl1/Lhx6 was performed. Intrathecal delivery of lenti-Ascl1/Lhx6 significantly relieved mechanical allodynia and heat hyperalgesia in mice with DNP. Ascl1/Lhx6 delivery also reduced microglial activation, decreased the levels of pro-inflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-1β, increased the levels of anti-inflammatory cytokines including IL-4, IL-10, and IL-13, and reduced the activation of p38, c-Jun N-terminal kinase, and NF-κB in the spinal cord of mice with DNP, thereby reducing DNP. The results of this study suggest that intrathecal Ascl1/Lhx6 delivery attenuates DNP via upregulating spinal GABA neuronal function and inducing anti-inflammatory effects.

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9–12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9–12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

Summary: To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO2) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO2 gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.

Objectives: Sufficient trials of acupuncture manipulations should be practiced to obtain proficiency. However, there is not an adequate quantitative methodology for selecting a tissue-mimicking phantom that effectively reproduces the mechanical behavior that occurs during acupuncture. The objective of this study was to determine the proper mixing ratio of polydimethylsiloxane (PDMS) to obtain tissue phantom that is the most similar to porcine phantoms. Design: An automatic needle manipulator equipped with a six-degrees-of-freedom force/torque sensor was installed to monitor the interaction force that occurred when the acupuncture needle performed lifting–thrusting and twirling manipulations. Four types of PDMS phantoms, composed of two silicone elastomers with different hardener ratios, were studied alongside four control groups consisting of different porcine sites. A Visual Analog Scale was used to quantify the similarity of the PDMS phantoms to the controls by 11 Korean medical doctors. Results: Using the lifting–thrusting method, PDMS D (mixing ratio of 1:4.5) and control 2 (porcine blade shoulder) revealed no significant difference in the dynamic friction coefficients or maximum and minimum friction force values (P

Summary: Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

Objectives: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. Methods: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. Results: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). Conclusion: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.

Background: Numerous fascial closure techniques have been used to reduce donor site morbidities after transverse rectus abdominis myocutaneous (TRAM) flap harvest. A leaflet-shaped acellular dermal matrix (ADM) with a thickness gradient was designed to cover the defect effectively and to withstand the pressure applied to the lower portion of the defect. The complication and functional recovery rates of the donor site of the custom ADM were compared with those of previous methods of fascial closure (primary closure and polypropylene mesh assisted closure). Materials and methods: A retrospective review of patients undergoing immediate or delayed breast reconstruction using muscle-sparing TRAM flaps was performed. Abdominal bulging, hernia, wound dehiscence, infection, seroma, and hematoma rates were compared. The Back Performance Scale measured four months postoperatively was compared to evaluate the donor site's recovery rate. Results: A total of 173 patients were analyzed. The three groups did not differ in hernia, wound dehiscence, infection, and hematoma rates. However, the abdominal bulging rate was lower in the primary closure group, while the seroma rate was higher in the mesh group. Functional recovery was the fastest in the custom ADM group. Conclusion: A thickness-gradient, leaflet-shaped ADM can be effectively used as an onlay graft to cover the abdominal fascial defect, with similar complication rates, while providing a faster recovery of abdominal function.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and is characterized by the formation of renal cysts and the eventual development of end-stage kidney disease. One approach to treating ADPKD is through inhibition of the mammalian target of rapamycin (mTOR) pathway, which has been implicated in cell overproliferation, contributing to renal cyst expansion. However, mTOR inhibitors, including rapamycin, everolimus, and RapaLink-1, have off-target side effects including immunosuppression. Thus, we hypothesized that the encapsulation of mTOR inhibitors in drug delivery carriers that target the kidneys would provide a strategy that would enable therapeutic efficacy while minimizing off-target accumulation and associated toxicity. Toward eventual in vivo application, we synthesized cortical collecting duct (CCD) targeted peptide amphiphile micelle (PAM) nanoparticles and show high drug encapsulation efficiency (>92.6%). In vitro analysis indicated that drug encapsulation into PAMs enhanced the anti-proliferative effect of all three drugs in human CCD cells. Analysis of in vitro biomarkers of the mTOR pathway via western blotting confirmed that PAM encapsulation of mTOR inhibitors did not reduce their efficacy. These results indicate that PAM encapsulation is a promising way to deliver mTOR inhibitors to CCD cells and potentially treat ADPKD. Future studies will evaluate the therapeutic effect of PAM-drug formulations and ability to prevent off-target side effects associated with mTOR inhibitors in mouse models of ADPKD.

Background/purpose: Human dental pulp stem cells (hDPSCs) possess excellent proliferative and osteogenic differentiation potentials. This study aimed to elucidate the role of lysophosphatidic acid (LPA) signaling in the proliferation and osteogenic differentiation of hDPSCs. Materials and methods: hDPSCs were treated with LPA and proliferation was measured using the cell counting kit-8 assay. Following the osteogenic differentiation of hDPSCs using osteogenic medium in the presence or absence of LPA, alkaline phosphatase (ALP) staining, ALP activity measurements, and RT-qPCR were performed to analyze the osteoblast differentiation. Small interfering RNA (siRNA)-mediated LPAR3 silencing and extracellular signal-regulated (ERK)/mitogen-activated protein (MAP) kinase inhibitors were used to elucidate the molecular mechanisms underlying LPA-induced proliferation and differentiation of hDPSCs. Results: LPA treatment significantly induced proliferation and osteogenic differentiation of hDPSCs. The depletion of LPAR3 expression by LPAR3-speicifc siRNA in hDPSCs diminished LPA-induced proliferation and osteogenic differentiation. The LPAR3-mediated proliferation and osteogenic differentiation of hDPSCs in response to LPA were significantly suppressed by U0126, a selective inhibitor of ERK. Conclusion: These findings suggest that LPA induces the proliferation and osteogenic differentiation of hDPSCs via LPAR3-ERK-dependent pathways.

Background: This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. Methods: All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. Results: Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48–5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. Conclusions: Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.

Cultured meat (CM) is an alternative protein food and is produced by cultivating muscle satellite (stem) cells (MSCs) derived from livestock animals (bovine, chickens, and porcine) through myogenesis leading to generate muscle mass. Myostatin (MSTN) is well well-known negative regulator of myogenesis, and in the present study, in silico screening of natural compounds was performed to identify MSTN inhibitors. Interestingly, quercetin was found to inhibit MSTN (binding energy −7.40 kcal/mol), and this was further validated by a 100 ns molecular dynamics simulation. Quercetin was added to culture media to boost myogenesis, and its potent antioxidant property helped maintain media pH. Furthermore, quercetin increased the myotube thickness and length, increased MSC differentiation, and upregulated the gene and protein expressions of myoblast determination protein 1 (MYOD), Myogenin (MYOG), and Myosin heavy chains (MYH) in vitro. In addition, quercetin inhibited the activities of MSTN, activin receptor type-2B (ACVR2B), and SMAD2 and 3, and thus significantly enhanced MSC differentiation and myotube formation. Overall, this study shows that quercetin might be useful for enhancing large-scale CM production. It is hoped that this study provides a starting point for research in the CM area aimed to enhancing product quality, nutritional values, and the efficacy of large-scale production.

Although rutin and isoquercitrin have many effects, they are insoluble substances, making it difficult to obtain pure substances. This study was to investigate whether Morus alba leaves containing rutin and isoquercitrin could improve intestinal health by making a sustained-release formulation through a hot-melt extrusion (HME) process with improved stability and solubility and determine whether it could upregulate the balance of intestinal microorganisms and intestinal epithelial cells. A sustained-release formulation was prepared by the HME process using Morus alba leaves and a hydrophilic polymer matrix. Antibacterial activities of pathogenic microorganisms (Escherichia coli, Streptococcus aureus, Enterococcus faecalis) and proliferative effect of probiotics (Lactobacillus rhamnosus, Pediococcus pentosaceus) were tested against intestinal microorganisms. Regarding intestinal epithelial cells, a co-culture model of Caco-2 cells and RAW 264.7 cells was used. It was confirmed that the extrudate exhibited high antibacterial activities against pathogenic microorganisms and affected the proliferation of probiotics. Furthermore, after inducing inflammation through LPS, it recovered transepithelial electrical resistance-increased levels of tight junction proteins and decreased expression levels of pro-inflammatory cytokines. HME of Morus alba leaves containing rutin and isoquercitrin can upregulate intestinal microbial balance and intestinal epithelial cells.

MicroRNAs (miRNAs) are small, non-coding RNAs crucial for gene regulation and implicated in various human diseases. Their potential as clinical prognostic and diagnostic biomarkers in biological fluids necessitates reliable detection methods. In this study, a combination of streptavidin-coupled magnetic beads and capillary electrophoresis with laser-induced fluorescence (CE-LIF) was used to extract and analyze plasma miRNAs. Specifically, miRNAs hybridized with a biotinylated fluorescent DNA probe were isolated from plasma using magnetic beads. These hybridized miRNAs were then directly injected into the CE-LIF system for analysis, eliminating the need for additional processing steps. Both the hybridization and bead-to-probe binding were executed concurrently, regulated by temperature and time. Through the optimization of magnetic bead extraction and CE-LIF conditions, we developed a highly sensitive assay for miR-21 quantification in plasma. The assay displayed remarkable linearity (R2 = 0.9975) within a 0.1–5 pM range and exhibited favorable precision (0.22–1.26 %) and accuracy (98.31–111.19 %). Importantly, we successfully detected endogenous miR-21 in plasma samples from both a lung cancer patient and healthy adults, revealing a 1.7-fold overexpression of miR-21 in lung cancer plasma relative to normal samples. Our findings suggest that this developed system offers a simple and sensitive approach for detecting endogenous miRNAs in plasma, showing its potential utility in disease diagnostics. To our knowledge, this is the first study to utilize CE-LIF for plasma miRNA detection.

Nowadays, diabetes mellitus has emerged as a significant global public health concern with a remarkable increase in its prevalence. This review article focuses on the definition of diabetes mellitus and its classification into different types, including type 1 diabetes (idiopathic and fulminant), type 2 diabetes, gestational diabetes, hybrid forms, slowly evolving immune-mediated diabetes, ketosis-prone type 2 diabetes, and other special types. Diagnostic criteria for diabetes mellitus are also discussed. The role of inflammation in both type 1 and type 2 diabetes is explored, along with the mediators and potential anti-inflammatory treatments. Furthermore, the involvement of various organs in diabetes mellitus is highlighted, such as the role of adipose tissue and obesity, gut microbiota, and pancreatic β-cells. The manifestation of pancreatic Langerhans β-cell islet inflammation, oxidative stress, and impaired insulin production and secretion are addressed. Additionally, the impact of diabetes mellitus on liver cirrhosis, acute kidney injury, immune system complications, and other diabetic complications like retinopathy and neuropathy is examined. Therefore, further research is required to enhance diagnosis, prevent chronic complications, and identify potential therapeutic targets for the management of diabetes mellitus and its associated dysfunctions.

Skeletal muscle (SM) plays a vital role in energy and glucose metabolism by regulating insulin sensitivity, glucose uptake, and blood glucose homeostasis. Impaired SM metabolism is strongly linked to several diseases, particularly type 2 diabetes (T2D). Insulin resistance in SM may result from the impaired activities of insulin receptor tyrosine kinase, insulin receptor substrate 1, phosphoinositide 3-kinase, and AKT pathways. This review briefly discusses SM myogenesis and the critical roles that SM plays in insulin resistance and T2D. The pharmacological targets of T2D which are associated with SM metabolism, such as DPP4, PTB1B, SGLT, PPARγ, and GLP-1R, and their potential modulators/inhibitors, especially natural compounds, are discussed in detail. This review highlights the significance of SM in metabolic disorders and the therapeutic potential of natural compounds in targeting SM-associated T2D targets. It may provide novel insights for the future development of anti-diabetic drug therapies. We believe that scientists working on T2D therapies will benefit from this review by enhancing their knowledge and updating their understanding of the subject.

Objective: To examine screen time (ST) before and during the pandemic and changes between the two time points in children and youth aged 0 to 21 years, and to identify moderating factors (mean age, male%, report type, geography, and study design). Study design: A literature search of five databases was conducted. Studies written in English, reported ST in minutes or hours before and/or during the pandemic, and were published between January 2020-June 2022 were included. 109 studies were selected from the first screening of 4845 studies, and 91 studies that reported either ST during the pandemic (N = 91) or both ST before and during the pandemic (N = 51) were included in the final analyses. Random-effects meta-analyses were used to derive the mean STs across the studies. Results: The pre-pandemic ST mean was 2.67 ± 0.21 h/d, which was increased to 4.38 ± 0.20 h during the pandemic. Older children (p = 0.006) and boys (p = 0.005) spent more time on screens before the pandemic, but sex differences were no longer evident during the pandemic. In children under 5 years, the pre-pandemic ST mean was 1.91 h/d, which increased to 2.65 h/d during the pandemic, with 0.89 h/d changes. Conclusions: Children and youth's ST exceeded pediatric guidelines before the pandemic, even in children under 5 years, but the current study found significant increases in ST during the pandemic across all ages. This study suggests that ST increases need to be understood in terms of contextual perspectives. Further, identifying vulnerable groups is important to establish practical guidelines and interventions.

Summary: Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson’s disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.

Background: The role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of hepatic encephalopathy (HE) is unclear. Mitochondrial reactive oxygen species (mtROS) is a signal for NLRP3 inflammasome activation. Therefore, we aimed to determine whether mtROS-dependent NLRP3 inflammasome activation is involved in HE, using in vivo and in vitro models. Methods: Bile duct ligation (BDL) in C57/BL6 mice was used as an in vivo HE model. NLRP3 activation was assessed in the hippocampus. Immunofluorescence staining was performed to determine the cellular source of NLRP3 in the hippocampal tissue. For the in vitro experiment, BV-2 microglial cells were primed with lipopolysaccharide (LPS), followed by ammonia treatment. NLRP3 activation and mitochondrial dysfunction were measured. Mito-TEMPO was used to suppress mtROS production. Results: BDL mice showed cognitive impairment with hyperammonemia. Both the priming and activation steps of NLRP3 inflammasome activation were processed in the hippocampus of BDL mice. Moreover, intracellular ROS levels increased in the hippocampus, and NLRP3 was mainly expressed in the microglia of the hippocampus. In LPS-primed BV-2 cells, ammonia treatment induced NLRP3 inflammasome activation and pyroptosis, with elevation of mtROS and altered mitochondrial membrane potential. Pretreatment with Mito-TEMPO suppressed mtROS production and the subsequent NLRP3 inflammasome activation and pyroptosis under LPS and ammonia treatment in BV-2 cells. Conclusions: Hyperammonemia in HE may be involved in mtROS overproduction and subsequent NLRP3 inflammasome activation. Further studies using NLRP3-specific inhibitor or NLRP3 knockout mice are needed to elucidate the important role of NLRP3 inflammasome in HE development.