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Abstract Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage’s influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.

Cereal, including barley, wheat, and oats, is a major winter food crop in Korea. Despite recent changes in agricultural environments in response to climate change, fungal diseases that could affect cereal productivity remain poorly understood. In this study, we investigated the incidence of diseases in barley, wheat, and oats in the southern part of Korea. We collected fungal pathogens from seven locations where cereals were grown. In March-April of 2020 and 2021, a total of 92 fungal isolates were collected, mainly from the stem base or leaves of cereal crops during the tillering and stem extension stages of cereals in Korea. The collected isolates were identified based on morphological and molecular biological characteristics. The dominant species was Ceratobasidium cereale (42.4%), followed by Pyrenophora teres (21.7%), P. avenae (10.9%), Alternaria alternata (6.5%), and Epicoccum tobaicum (6.5%). In addition, P. tritici-repentis (3.3%), Cladosporium sp. (3.3%), Fusarium sp. (3.3%), and Nigrospora sp. (2.2%) were also collected as minority groups. Our results will provide information on fungal pathogens that occur during the growing season of cereals in Korea, particularly during the tillering and stem extension stages. In addition, the isolates collected from this study can serve as a valuable resource for conducting simulations on climate change, focusing on temperature and humidity.

Abstract Post-surgical adhesions frequently occur after intra-abdominal surgery, leading to severe complications. Despite the development of various types of adhesion barriers to address post-surgical adhesions, several limitations persist, including off-target localization, handling difficulties, and potential immunogenicity. Here, we report a spray-type adhesion barrier for broad, fast application, forming two sequential networks. The first network is formed by a polyelectrolyte complex of sulfated hyaluronic acid and chitosan, while the second network is established through pluronic® F127 thermogelation. This sprayable barrier served as both a physical protector for the damaged peritoneum and an immunomodulator for peritoneal macrophages, as evidenced its effectiveness in a rat ischemic button model. Taken together, this efficient adhesion barrier presents a promising solution for post-surgical adhesions.

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

BackgroundThe risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children’s neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy.MethodsThis retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10–13 weeks) or amniocentesis (GA at 15–21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated.ResultsThe study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23–8.12], p = 0.016), after considering maternal characteristics.ConclusionPerforming CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.

Abstract Using updated emission inventories can enhance the accuracy of air quality forecast models. Given China’s rapid economic growth and Korea’s geographical and meteorological position on the windward side of China, updating China’s emission inventory has become particularly crucial for Korea’s air quality modeling. This study aimed to develop an updated version of China’s Emission Inventory in Comprehensive Regional Emissions for Atmospheric Transport Experiments version 3 for the base year of 2019 (CREATEv3 (YR 2019)). To achieve this goal, we utilized the Chinese emission inventory of CREATEv3 for the base year of 2015 (CREATEv3 (YR 2015)) as a framework to incorporate the latest Chinese emission data from the Multi-resolution Emission Inventory Model for Climate and Air Pollution Research for the base year of 2019 (MEIC COVID-19 (YR 2019)) and update the inventory. The updated China’s annual emissions are now reflected in CREATEv3 (YR 2019), and the amounts are as follows: 132 Tg for CO, 21 Tg for NO x , 8 Tg for SO2, 7 Tg for PM2.5, 9 Tg for NH3, and 28 Tg for volatile organic compound (VOC). By comparing previous Chinese emission inventories with the updated inventory developed in this study, it was found that SO2, NO x , VOC, and NH3 emissions were decreased. Therefore, using the updated inventory seemingly reduces the impact of China’s fine dust on Korea. By comparing emissions by pollutant and region in China using CREATEv3 (YR 2019), it was found that regions with high emissions of targeted pollutants strongly correlated with major industries operating in those areas. This study is expected to provide insights into China’s emission changes in 2019 and support air quality forecasting.

ABSTRACTCancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (n = 479) and immunocompromised individuals (n = 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or “Long-COVID”). Among immunocompromised individuals, 59% (n = 68) had an underlying hematologic malignancy; of those, 46% (n = 31) of individuals received cancer treatment 1,000 U/mL), and of these, 60% (n = 281) and 44% (n = 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (n = 12) cohorts (P < 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes.IMPORTANCEThe study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.

Abstract The onset of osteoporosis leads to a gradual decrease in bone density due to an imbalance between bone formation and resorption. To achieve optimal drug efficacy with minimal side effects, targeted drug delivery to the bone is necessary. Previous studies have utilized peptides that bind to hydroxyapatite, a mineral component of bone, for bone‐targeted drug delivery. In this study, a hydroxyapatite binding (HAB) tag is fused to 30Kc19α‐Runt‐related transcription factor 2 (RUNX2) for bone‐targeting. This recombinant protein can penetrate the nucleus of human mesenchymal stem cells (hMSCs) and act as a master transcription factor for osteogenesis. The HAB tag increases the binding affinity of 30Kc19α‐RUNX2 to mineral deposition in mature osteoblasts and bone tissue, without affecting its osteogenic induction capability. In the osteoporosis mouse model, intravenous injection of HAB‐30Kc19α‐RUNX2 results in preferential accumulation in the femur and promotes bone formation while reducing toxicity in the spleen. These findings suggest that HAB‐30Kc19α‐RUNX2 may be a promising candidate for bone‐targeted therapy in osteoporosis.

Lab-on-a-chip (LOC) is a three-dimensional cell culture platform with a microfluidic flow that biomimics the physiological system of various organs. LOC emerged as a future replacement technology for in vitro cell-based models and in vivo animal models, gaining popularity in the field of physiology, pharmacology, and biology. Nowadays, sensors are incorporated into the LOC system to monitor real-time parameters of the cell and its microenvironment in response to biophysical and/or biochemical stimuli and maturation. A considerable amount of studies has been conducted to detect the mechanical, physical, electrical, and metabolic parameters of engineered organs. This paper aims to provide a comprehensive insight into how the biosensor-implemented LOC platform can be utilized for the analysis of tissue recapitulating systems with a focus on bone remodeling. We describe chip design, basic principles of sensors, and ongoing recent efforts to perform in-line analysis of engineered organoids. This review also presents various imaging techniques used as analytical tools for visualizing LOC.

Brown leaf spot disease caused by Alternaria spp. is among the most common diseases of potato crops. Typical brown spot symptoms were observed in commercial potato-cultivation areas of northern Korea from June to August 2020–2021. In total, 68 isolates were collected, and based on sequence analysis of the internal transcribed spacer (ITS) region, the collected isolates were identified as Alternaria spp. (80.9%). Phylogenetic analysis revealed that a majority of these isolates clustered within a clade that included A. alternata. Additionally, the ITS region and rpb2 yielded the most informative sequences for the identification of A. alternata. Pathogenicity tests confirmed that the collected pathogens elicited symptoms identical to those observed in the field. In pathogenicity tests performed on seven commercial cultivars, the pathogens exhibited strong virulence in both wound and non-wound inoculations. Among the cultivars tested, Arirang-1ho, Arirang-2ho, and Golden Ball were resistant to the pathogens. Furthermore, among the fungicides tested in vitro, mancozeb and difenoconazole were found to be effective for inhibiting mycelial growth. In summary, our findings suggest that A. alternata plays a critical role in leaf disease in potato-growing regions and emphasise the necessity of continuous monitoring and management to protect against this disease in Korea.

Phialemonium inflatum is a useful fungus known for its ability to mineralise lignin during primary metabolism and decompose polycyclic aromatic hydrocarbons (PAHs). However, no functional genetic analysis techniques have been developed yet for this fungus, specifically in terms of transformation. In this study, we applied an Agrobacterium tumefaciens-mediated transformation (ATMT) system to P. inflatum for a functional gene analysis. We generated 3689 transformants using the binary vector pSK1044, which carried either the hygromycin B phosphotransferase (hph) gene or the enhanced green fluorescent protein (eGFP) gene to label the transformants. A Southern blot analysis showed that the probability of a single copy of T-DNA insertion was approximately 50% when the co-cultivation of fungal spores and Agrobacterium tumefaciens cells was performed at 24–36 h, whereas at 48 h, it was approximately 35.5%. Therefore, when performing gene knockout using the ATMT system, the co-cultivation time was reduced to ≤36 h. The resulting transformants were mitotically stable, and a PCR analysis confirmed the genes’ integration into the transformant genome. Additionally, hph and eGFP gene expressions were confirmed via PCR amplification and fluorescence microscopy. This optimised transformation system will enable functional gene analyses to study genes of interest in P. inflatum.

Abstract Background The number of patients suffering from osteoporosis is increasing as the elderly population increases. The demand for investigating bone regeneration strategies naturally arises. One of the approaches to induce bone regeneration is somatic cell transdifferentiation. Among the transcriptional regulators for transdifferentiation, octamer-binding transcription factor 4 (OCT4) is famous for its role in the regulation of pluripotency of stem cells. Bone morphogenetic protein 4 (BMP4) is another factor that is known to have a significant role in osteogenic differentiation. Previous studies have achieved transdifferentiation of cells into osteoblasts using viral and plasmid deliveries of these factors. Although these methods are efficient, viral and plasmid transfection have safety issues such as permanent gene incorporations and bacterial DNA insertions. Herein, we developed a cell penetrating protein-based strategy to induce transdifferentiation of endothelial cells into osteoblasts via nuclear delivery of OCT4 recombinant protein combined with the BMP4 treatment. For the nuclear delivery of OCT4 protein, we fused the protein with 30Kc19, a cell-penetrating and protein stabilizing protein derived from a silkworm hemolymph of Bombyx mori with low cytotoxic properties. This study proposes a promising cell-based therapy without any safety issues that existing transdifferentiation approaches had. Methods OCT4-30Kc19 protein with high penetrating activities and stability was synthesized for a protein-based osteogenic transdifferentiation system. Cells were treated with OCT4-30Kc19 and BMP4 to evaluate their cellular penetrating activity, cytotoxicity, osteogenic and angiogenic potentials in vitro. The osteogenic potential of 3D cell spheroids was also analyzed. In addition, in vivo cell delivery into subcutaneous tissue and cranial defect model was performed. Results OCT4-30Kc19 protein was produced in a soluble and stable form. OCT4-30Kc19 efficiently penetrated cells and were localized in intracellular compartments and the nucleus. Cells delivered with OCT4-30Kc19 protein combined with BMP4 showed increased osteogenesis, both in 2D and 3D culture, and showed increased angiogenesis capacity in vitro. Results from in vivo subcutaneous tissue delivery of cell-seeded scaffolds confirmed enhanced osteogenic properties of transdifferentiated HUVECs via treatment with both OCT4-30Kc19 and BMP4. In addition, in vivo mouse cranial defect experiment demonstrated successful bone regeneration of HUVECs pretreated with both OCT4-30Kc19 and BMP4. Conclusions Using a protein-based transdifferentiation method allows an alternative approach without utilizing any genetic modification strategies, thus providing a possibility for safer use of cell-based therapies in clinical applications.

Acute disseminated encephalomyelitis (ADEM) is a monophasic central nervous system inflammatory demyelinating disorder clinically defined by multifocal neurologic symptoms with encephalopathy. Brain magnetic resonance imaging most often reveals multiple T2 hyperintense lesions consistent with demyelination. High-dose corticosteroids are the current treatment of choice, and intravenous immunoglobulin or plasmapheresis is considered in steroid-unresponsive cases. The majority of patients show favorable outcomes with full clinical recovery and complete or partial resolution of previous lesions. For patients who are refractory to multiple immunomodulatory agents, other treatments such as rituximab have been used. We present a patient who developed ADEM after Epstein-Barr virus infection who achieved full recovery with immunotherapy including rituximab.

This review examined recently published (July 2014 to June 2017), randomized controlled trials (RCTs) which investigated the safety and effectiveness of combined Korean medicine/complementary alternative medicine (CAM) and Western medicine, to indicate the direction for integrative medical practice. The Korean Medicine Convergence Research Information Center evidence-based medicine database (KMCRIC EBM DB) was used to retrieve relevant RCTs indexed in the last 3 years. Study design, country, sample size, disease/condition with the Korean Standard Classification of Diseases code, interventions, direction of outcomes, and adverse events were extracted and summarized. A total of 93 RCTs were included in this review. Acupuncture/moxibustion was the most commonly used intervention (n = 47; 51%), and 19% (n = 18) of the studies treated musculoskeletal disorders, followed by circulatory disorders (n = 16; 17%), and mental and behavioral disorders (n = 9; 10%). Integrative treatment was reported as more effective than monotherapy in approximately 83% of these studies. Adverse events were poorly reported in most studies. This review suggests that integrative treatments are feasible, effective, and safe for various diseases/conditions, based on the evidence from recently published RCTs. Future studies on integrative healthcare are warranted.

Abstract Background Until recently, it is generally considered safe to perform magnetic resonance imaging (MRI) in patients with an intrathecal drug administration system (ITDAS) device. In this study, we presented a case of morphine overdose due to ITDAS malfunction during MRI evaluation for the diagnosis of stroke. Case presentation A 58-year-old woman was referred to the emergency department for left-sided hemiparesis and dysarthria. She had undergone ITDAS implantation 4 years ago because of intractable back pain. Her brain MRI examination did not show any abnormalities except an old hemorrhagic infarction in the right basal ganglia. After MRI was performed, her symptoms completely resolved. Approximately 3 h after the MRI scan, the patient showed progressive stuporous consciousness and decreased respiration with decreased peripheral oxygen saturation of 80%. Initial arterial blood gas analysis revealed respiratory acidosis with hypoxia and hypercapnia. We suspected the opioid overdose for her unconciousness, small and sluggish pupils, and slow respiration. The patient regained consciousness within 3 min after the administration of naloxone with severe anxiety and irritability, without any respiratory symptoms or focal neurological deficits. In the pump interrogation and actual reservoir checks performed 6 h after the MRI scan, there was no significant difference between the expected reservoir volume and actual reservoir volume. Follow-up MRI performed to rule out posterior circulation infarction showed no structural lesions. The patient was eventually discharged without further neurologic or functional deterioration, with diagnosis of transient ischemia attack for initial symptoms of focal neurologic deficits. Conclusion Although both ex vivo and in vivo studies have provided evidence that ITDAS devices are MRI-compatible, the pump is made of titanium and has ferromagnetic components. Since misdiagnosis of overinfusion could lead to mortality, early awareness of overinfusion of the intrathecal drug is needed to all clinicians in case of performing MRI in ITDAS implanted patients.

The cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2) gene is associated with epilepsy, intellectual disability (ID), and developmental delay, suggesting its critical role in proper neuronal development and function. CYFIP2 is involved in regulating cellular actin dynamics and also interacts with RNA-binding proteins. However, the adult brain function of CYFIP2 remains unclear because investigations thus far are limited to Cyfip2 heterozygous (Cyfip2+/−) mice owing to the perinatal lethality of Cyfip2-null mice. Therefore, we generated Cyfip2 conditional knock-out (cKO) mice with reduced CYFIP2 expression in postnatal forebrain excitatory neurons (CaMKIIα-Cre). We found that in the medial prefrontal cortex (mPFC) of adult Cyfip2 cKO mice, CYFIP2 expression was decreased in both layer 2/3 (L2/3) and layer 5 (L5) neurons, unlike the L5-specific CYFIP2 reduction observed in adult Cyfip2+/− mice. Nevertheless, filamentous actin (F-actin) levels were increased only in L5 of Cyfip2 cKO mPFC possibly because of a compensatory increase in CYFIP1, the other member of CYFIP family, in L2/3 neurons. Abnormal dendritic spines on basal, but not on apical, dendrites were consistently observed in L5 neurons of Cyfip2 cKO mPFC. Meanwhile, neuronal excitability and activity were enhanced in both L2/3 and L5 neurons of Cyfip2 cKO mPFC, suggesting that CYFIP2 functions of regulating F-actin and excitability/activity may be mediated through independent mechanisms. Unexpectedly, adult Cyfip2 cKO mice did not display locomotor hyperactivity or reduced anxiety observed in Cyfip2+/− mice. Instead, both exhibited enhanced social dominance accessed by the tube test. Together, these results provide additional insights into the functions of CYFIP2 in the adult brain.

High grade serous ovarian cancer (HGSC) is the most common and deadly type of ovarian cancer, largely due to difficulties in early diagnosis and rapid metastasis throughout the peritoneal cavity. Previous studies have shown that expression of Notch3 correlates with worse prognosis and increased tumorigenic cell behaviors in HGSC. We investigated the mechanistic role of Notch3 in a model of metastatic ovarian cancer using the murine ovarian surface epithelial cell line, ID8 IP2. Notch3 was activated in ID8 IP2 cells via expression of the Notch3 intracellular domain (Notch3IC). Notch3IC ID8 IP2 cells injected intraperitoneally caused accelerated ascites and reduced survival compared to control ID8 IP2, particularly in early stages of disease. We interrogated downstream targets of Notch3IC in ID8 IP2 cells by RNA sequencing and found significant induction of genes that encode adhesion and extracellular matrix proteins. Notch3IC ID8 IP2 showed increased expression of ITGA1 mRNA and cell-surface protein. Notch3IC-mediated increase of ITGA1 was also seen in two human ovarian cancer cells. Notch3IC ID8 IP2 cells showed increased adhesion to collagens I and IV in vitro. We propose that Notch3 activation in ovarian cancer cells causes increased adherence to collagen-rich peritoneal surfaces. Thus, the correlation between increased Notch3 signaling and poor prognosis may be influenced by increased metastasis of HGSC via increased adherence of disseminating cells to new metastatic sites in the peritoneum.

In this work we describe a soft and ultrastretchable fiber with a magnetic liquid metal (MLM) core for electrical switches used in remote magnetic actuation. MLM was prepared by removing the oxide layer on the liquid metal and subsequent mixing with magnetic iron particles. We used SEBS (poly[styrene-b-(ethylene-co-butylene)-b-styrene]) and silicone to prepare stretchable elastic fibers. Once hollow elastic fibers form, MLM was injected into the core of the fiber at ambient pressure. The fibers are soft (Young’s modulus of 1.6~4.4 MPa) and ultrastretchable (elongation at break of 600~5000%) while maintaining electrical conductivity and magnetic property due to the fluidic nature of the core. Magnetic strength of the fibers was characterized by measuring the maximum effective distance between the magnet and the fiber as a function of iron particle concentration in the MLM core and the polymeric shell. The MLM core facilitates the use of the fiber in electrical switches for remote magnetic actuation. This ultrastretchable and elastic fiber with MLM core can be used in soft robotics, and wearable and conformal electronics.

BACKGROUND AND OBJECTIVE:Trial registration is widely endorsed as it is considered not only to enhance transparency and quality of reporting but also to help safeguard against outcome reporting bias and probably spin, known as specific reporting that could distort the interpretation of results thus mislead readers. We planned to investigate the current registration status of recently published randomized controlled trials (RCTs) of acupuncture, outcome reporting bias in the prospectively registered trials, and the association between trial registration and presence of spin and methodological factors in acupuncture RCTs. METHODS:Acupuncture RCTs published in English in recent 5 years (January 2013 to December 2017) were searched in PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Trial registration records identified in the publications and trial registries were classified into prospectively registered, retrospectively registered, or unregistered. Primary outcomes were identified and the direction of the results was judged as statistically significant (positive) or statistically nonsignificant (negative). We compared registered and published primary outcomes to assess outcome reporting bias and assessed whether discrepancies favored statistically significant outcomes. Frequency and strategies of spin in published reports with statistically nonsignificant results for primary outcomes were then identified. We also analyzed whether the trial registration status was associated with spin and quality of methodological factors. RESULTS:Of the 322 included RCTs, 41.9% (n = 135) were prospectively registered. Among 64 studies that were prospectively registered and specified primary outcomes, 25 trials had the discrepancies between the registered and published primary outcomes and 60% of them (15 trials) favored the statistically significant findings. Among 169 studies that specified primary outcomes, trial registration status was not associated with the direction of results, i.e., statistically significant or not. Spin was identified in 56.4% out of 78 studies with statistically nonsignificant primary outcomes and claiming efficacy with no consideration of statistically nonsignificant primary outcomes was the most common strategy for spin. Trial registration status was not statistically different between studies with and without spin. CONCLUSION:While trial registration seemed to have improved over time, primary outcomes in registered records and publications were often inconsistent, tending to favor statistically significant findings and spin was common in studies with statistically nonsignificant primary outcomes. Journal editors and researchers in this field should be alerted to still prevalent reporting bias and spin.

Adipogenesis is a crucial cellular process that contributes to the expansion of adipose tissue in obesity. Shockwaves are mechanical stimuli that transmit signals to cause biological responses. The purpose of this study is to evaluate the effects of shockwaves on adipogenesis. We treated 3T3L-1 cells and human primary preadipocytes for differentiation with or without shockwaves. Western blots and quantitative real-time reverse transcriptase PCR (qRT-PCR) for adipocyte markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPα) were performed. Extracellular adenosine triphosphate (ATP) and intracellular cyclic adenosine monophosphate (cAMP) levels, which are known to affect adipocyte differentiation, were measured. Shockwave treatment decreased intracellular lipid droplet accumulation in primary human preadipocytes and 3T3-L1 cells after 11−12 days of differentiation. Levels of key adipogenic transcriptional factors PPARγ and/or C/EBPα were lower in shockwave-treated human primary preadipocytes and 3T3L-1 cells after 12−13 days of differentiation than in shockwave-untreated cells. Shockwave treatment induced release of extracellular ATP from preadipocytes and decreased intracellular cAMP levels. Shockwave-treated preadipocytes showed a higher level of β-catenin and less PPARγ expression than shockwave-untreated cells. Supplementation with 8-bromo-cAMP analog after shockwave treatment rescued adipocyte differentiation by preventing the effect of shockwaves on β-catenin, Wnt10b mRNA, and PPARγ expression. Low-energy shockwaves suppressed adipocyte differentiation by decreasing PPARγ. Our study suggests an insight into potential uses of shockwave-treatment for obesity.

Type I interferon (IFN-I, including IFN-α and IFN-β) response has been implicated in eosinophilic inflammation, in addition to antiviral function. This study aimed to investigate the role of IFN-I in the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). IFN-α, IFN-β, cytokine expression, and IFN-β cellular localization in the sinonasal tissue from control subjects and ECRS patients with nasal polyps (NP) were determined using real time-PCR, ELISA, and immunohistochemistry. ECRS was induced in wild-type (WT) and IFNAR1 knockout (Ifnar1−/−) mice by intranasal challenge with Aspergillus protease and ovalbumin. Stromal cells cultured from NP tissue were stimulated by exogenous IFN-β, and their CCL11 production and IRF3, IRF7, STAT1, STAT2, and IRF9 gene and/or protein expression were measured. IFN-β, IL-5, IL-13, and CCL11 expression was higher in the NP tissue from ECRS patients, compared to the control group. IFN-β was highly colocalized with the CD11c+ cells in NP. IFN-β levels positively correlated with IL-5, IL-13, and CCL11 levels as well as the number of eosinophils in the NP tissue and CT score. The histological severity of ECRS, levels of IL-4, IL-5, IL-13, and CCL11 in the nasal lavage fluid, and total serum IgE levels were less in Ifnar1−/− mice than in WT mice. CCL11 production, and STAT1 and STAT2 mRNA and STAT1, phospho-STAT1, and phospho-STAT2 protein expression were significantly increased by exogenous IFN-β in NP stromal cells. Our data suggest that IFN-β response was upregulated in ECRS and may play role in ECRS development. IFN-β may contribute to ECRS by enhancing CCL11 production. Thus, increased IFN-β response in the sinonasal mucosa may underlie ECRS pathogenesis.

Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifolium pratense. In this study, we investigated the effects of pratol on melanogenesis. We also studied the mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were treated with various concentrations (6.25, 12.5, 25, and 50 μM) of pratol to observe its effects. The results showed that pratol significantly increased melanin content and tyrosinase activity in the cells without being cytotoxic. In addition, pratol strongly increased the expression of tyrosinase and tyrosinase-related protein-1 and 2 by enhancing the expression of microphthalmia-associated transcription factor. Furthermore, pratol stimulated melanogenesis via the phosphorylation of p38, c-Jun N-terminal kinases (JNK), and extracellular signal–regulated kinase (ERK). The findings from an assay searching for the inhibitor revealed that SB203580 (a specific p38 inhibitor) or SP600125 (a p-JNK inhibitor) attenuated pratol-induced cellular tyrosinase activity whereas PD98059 (an ERK inhibitor) did not. Additionally, pratol interfered with the phosphorylation of p-AKT. We also found that pratol-induced melanogenesis was reversed by H89, which is a specific protein kinase A inhibitor. The results suggest that, owing to its multi-functional properties, pratol may be a potential tanning agent or a therapeutic agent for hair depigmentation in the cosmetic industry.

Based on the investigation of logistic regression models utilizing sparse triangulation within a compact domain in R², this study addresses the limited research extending the triogram model to logistic regression. A primary challenge arises from the potential instability induced by a large number of vertices, hindering the effective modeling of complex relationships. To mitigate this challenge, we propose introducing sparsity to boundary vertices of the triangulation based on the Ramer-Douglas-Peucker algorithm and employing the K-means algorithm for adaptive vertex initialization. A second order coordinate-wise descent algorithm is adopted to implement the proposed method. Validation of the proposed algorithm’s stability and performance assessment are conducted using synthetic and handwritten digit data (LeCun et al., 1989). Results demonstrate the advantages of our method over existing methodologies, particularly when dealing with non-rectangular data domains. [ABSTRACT FROM AUTHOR]