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Population‐based studies of the familial aggregation of gout are scarce, and gene/environment interactions are not well studied. This study was undertaken to evaluate the familial aggregation of gout as well as assess interactions between family history and obesity or alcohol consumption on the development of gout. Using the Korean National Health Insurance database, which includes information regarding familial relationships and risk factor data, we identified 5,524,403 individuals from 2002 to 2018. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare the risk in individuals with and those without affected first‐degree relatives. Interactions between family history and obesity/alcohol consumption were assessed on an additive scale using the relative excess risk due to interaction (RERI). Individuals with a gout‐affected first‐degree relative had a 2.42‐fold (95% CI 2.39, 2.46) increased risk of disease compared to those with unaffected first‐degree relatives. Having both a family history of gout and being either overweight or having moderate alcohol consumption was associated with a markedly increased risk of disease, with HRs of 4.39 (95% CI 4.29, 4.49) and 2.28 (95% CI 2.22, 2.35), respectively, which exceeded the sum of their individual risks but was only statistically significant in overweight individuals (RERI 0.96 [95% CI 0.85, 1.06]). Obese individuals (RERI 1.88 [95% CI 1.61, 2.16]) and heavy drinkers (RERI 0.36 [95% CI 0.20, 0.52]) had a more prominent interaction compared to overweight individuals and moderate drinkers, suggesting a dose‐response interaction pattern. Our findings indicate the possibility of an interaction between gout‐associated genetic factors and obesity/alcohol consumption.

Hyperuricemia might have neuroprotective or neurodegenerative effects on dementia via oxidative stress or inflammatory response regulation. Few studies have explored the association of hyperuricemia or gout with dementia. This retrospective cohort study aimed to investigate the association between gout and dementia in Korea. Altogether, 5,052 gout patients and 25,260 age‐ and sex‐matched controls were selected from the National Health Insurance Service (NHIS)–National Sample Cohort database. The incidence and risk of dementia were evaluated by reviewing the NHIS record. We also performed a subgroup analysis according to age group (age <65 or ≥65 years) using the standard age of 65 years for elderly and nonelderly groups and sex. During follow‐up, 81 and 558 participants in the gout and control cohorts developed dementia, respectively. The mean follow‐up duration was 4.38 years in gout patients and 4.94 years in controls. Gout patients had a hazard ratio (HR) of 0.79 for overall dementia (95% confidence interval [95% CI] 0.62–1.00) and significantly lower Alzheimer's disease risk (HR 0.73 [95% CI 0.54–0.98]) after adjusting for age, sex, household income, and comorbidities. In subgroup analysis stratified by age and sex, the inverse association between gout and the risk of overall dementia (HR 0.71 [95% CI 0.52–0.97]) and Alzheimer's disease (HR 0.67 [95% CI 0.46–0.97]) were observed in the elderly male group. On the other hand, age‐ and sex‐adjusted analysis showed that the HR for vascular dementia of gout patients was 2.31 (95% CI 1.02–5.25) in the nonelderly male group. Gout decreased the risk of incident Alzheimer's disease–type dementia, especially in elderly patients. The association between gout and dementia risk may differ according to age and disease duration.

•High-contrast proximity between cities and wildland may be a model for resilience•A novel urban-wildland juxtaposition (UWJ) metric is calculated for 36 U.S. cities•Cities with high UWJ scores are negatively correlated with levels of obesity and diabetes

Study design: This is a retrospective study. Objectives: To detail respiratory management after a high cervical spinal cord injury (HCSCI). Setting: A tertiary university hospital’s pulmonary rehabilitation center to which most individuals with HCSCI and ventilatory insufficiency throughout Korea are referred. Methods: The medical records of individuals with complete or sensory incomplete HCSCI admitted to the pulmonary rehabilitation center and receiving the center’s standard treatment were retrospectively reviewed, focusing on respiratory state transitions. Results: In total, 133 individuals with a C1–4 neurological level of injury (A: 101 or B: 32 on the American Spinal Injury Association Impairment Scale) were identified; 110 (82.7%) had indwelling tracheostomy tubes at admission and 75 underwent successful decannulation during admission. At the final follow-up, 76 individuals (57.1%) still required mechanical ventilation (MV) and 37 (27.8%) still required indwelling tracheostomy tubes. Of the individuals who had tracheostomy tubes without ventilatory support, 30 underwent decannulation and were discharged without non-invasive MV support. Of those with MV via tracheostomy on admission, 25 were switched to non-invasive MV after decannulation. Conclusion: Respiratory management in complete or sensory incomplete HCSCI needs to be determined by reflecting the current ventilatory state with a comprehensive evaluation of pulmonary function and ventilatory state monitoring. Pulmonary rehabilitation in individuals with HCSCI should be emphasized in the aspect of improving quality of life by avoiding unwanted tracheostomy and changing management methods depending on their recovery.

Lymphadenopathy (LAP) after COVID-19 vaccination in patients with a diagnosis of cancer has been challenging. We analyzed imaging and clinical features from early cases of axillary LAP in six COVID-19 vaccine recipients with a history of breast cancer.

In this study an index is developed called the Transit Economic Equity Index, to enable quantitative assessment of transit service equity. The index measures convenience of travel for work trips for advantaged and disadvantaged populations, based on travel speed, using a multimodal network that includes transit lines, stop locations, transit schedules, and pedestrian connections via the street network. Non-peak hour service is compared with peak hour service to determine the degree to which operating resources are concentrated in times that might have greater benefits to advantaged populations. Finally, accessibility to the transit system is compared in relation to the number of transit stops in neighborhoods and employment centers, and these figures are compared between advantaged and disadvantaged locations. The scores for these three components are combined to create a single measure of transit economic equity. Disadvantage is defined using criteria established in Title VI of the Civil Rights Act of 1964. The index is constructed in a way that balances a robust and meaningful measure of transit equity that is decipherable by practitioners so that they can assess the equity of their systems as well as how potential service changes affect equity.

ABSTRACTThe most widely used influenza vaccines are prepared by chemical inactivation. However, chemical, especially formalin, treatment-induced modifications of the antigenic structure of the virus are frequently associated with adverse effects including low efficacy of protection, unexpected immune responses, or exacerbation of disease. Gamma-irradiation was suggested as an alternative influenza virus inactivation method due to its great features of completely inactivating virus while not damaging the structures of protein antigens, and cross-protective ability against heterologous strains. However, immunological features of gamma radiation-inactivated influenza vaccine have not been fully understood. In this study, we aimed to investigate the humoral and cellular immune responses of gamma radiation-inactivated influenza vaccine. The gamma irradiation-inactivated influenza vaccine (RADVAXFluA) showed complete viral inactivation but retained normal viral structure with functional activities of viral protein antigens. Intranasal immunization of RADVAXFluAprovided better protection against influenza virus infection than formalin-inactivated influenza virus (FIV) in mice. RADVAXFluAgreatly enhanced the production of virus-specific serum IgG and alveolar mucosal IgA, which effectively neutralized HA (hemagglutinin) and NA (neuraminidase) activities, and blocked viral binding to the cells, respectively. Further analysis of IgG subclasses showed RADVAXFluA-immunized sera had higher levels of IgG1 and IgG2a than those of FIV-immunized sera. In addition, analysis of cellular immunity found RADVAXFluAinduced strong dendritic cells (DC) activation resulting in higher DC-mediated activation of CD8+T cells than FIV. The results support improved immunogenicity by RADVAXFluA.

We performed preoperative ultrasonography (US) to detect the anatomic course of the superficial radial nerve (SRN) and dominant pathologic tendon of the first extensor compartment in de Quervain tenosynovitis. We prospectively studied 27 patients (29 wrists) with de Quervain tenosynovitis who underwent surgical release of the first extensor compartment. Preoperatively, US was performed to evaluate the presence of the dominant pathologic tendon and the septum in the subcompartment, number of SRNs in the area of the surgical incision, and anatomic running course of the SRN. These variables were also checked intraoperatively. Cohen κ statistics were calculated to investigate agreement between US and surgical field findings. There were 7 men and 20 women (mean age, 47.8 years; range, 26–67 years). For the dominant pathologic tendon, there were 2 cases (6.9%) of an abductor pollicis longus, 11 cases (37.9%) of an extensor pollicis brevis, and 16 cases (55.2 %) of a nondominant tendon (κ = 0.94). For the subcompartment, there were 10 cases (34.5%) without a septum, 8 (27.6%) with an incomplete septum, and 11 (37.9%) with a complete septum (κ = 0.95). Most SRNs crossed over the first extensor compartment (κ = 0.78). Preoperative US can be useful in detecting the anatomic running course of the SRN and dominant pathologic tendon before surgery for de Quervain tenosynovitis. Classifying the anatomic course of the SRN could be essential to planning surgery, and it could be helpful to prevent injury of the SRN during surgery.

Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, such as cardiovascular diseases, diabetes, and Parkinson's disease. However, PSC transplantation has some associated risks, including teratoma formation from the remaining undifferentiated PSCs. Thus, for successful clinical application, it is essential to ablate the proliferative PSCs before or after transplantation. In this study, neural stem cell‐derived conditioned medium (NSC‐CM) inhibited the proliferation of PSCs and PSC‐derived neural precursor (NP) cells without influencing the potential of PSC‐NP cells to differentiate into neurons in vitro and prevented teratoma growth in vivo. Moreover, we found that the NSC‐CM remarkably decreased the expression levels of Oct4 and cyclin D1 that Oct4 directly binds to and increased the cleaved‐caspase 3‐positive cell death through the DNA damage response in PSCs and PSC‐NPs. Interestingly, we found that NSCs distinctly secreted the tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2 proteins. These proteins suppressed not only the proliferation of PSCs in cell culture but also teratoma growth in mice transplanted with PSCs through inhibition of matrix metalloproteinase (MMP)‐2 and MMP‐9 activity. Taken together, these results suggest that the TIMP proteins may improve the efficacy and safety of the PSC‐based transplantation therapy. Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, but PSC transplantation has a teratoma formation risk. Neural stem cell‐derived conditioned medium (NSC‐CM) prevented teratoma growth in vivo. NSCs distinctly secreted the tissue inhibitor of metalloproteinase TIMP proteins, which suppressed teratoma growth in mice transplanted with PSCs.

Duchenne muscular dystrophy (DMD) patients can have various issues that affect their quality of life, including eating and digestive conditions. We sought to identify the relationship between respiratory function and various eating and digestion related symptoms in patients with advanced Duchenne muscular dystrophy (DMD). Eating and digestive symptoms, including loss of appetite, nausea, vomiting, diarrhea, constipation, swallowing difficulty, mastication difficulty, early satiety, and aspiration, were evaluated among patients with advanced DMD who were nonambulatory and required noninvasive mechanical ventilatory support. In addition, various respiratory function parameters were measured, including forced vital capacity (FVC), maximal insufflation capacity (MIC), peak cough flow (PCF), assisted PCF (APCF), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). We then analyzed the relationship between gastrointestinal symptoms and respiratory function parameters. A total of 180 patients (age, 22.3±5.0 years) were included in the analysis. Loss of appetite and early satiety showed no correlation with any of the respiratory function parameters. Constipation was correlated with MEP; swallowing difficulty was correlated with MIC, APCF, MIP and MEP; and mastication difficulty was correlated with FVC, PCF, APCF, MIP, and MEP. Notably, age did not correlate with any gastrointestinal symptoms. Eating and digestive symptoms are more closely correlated with respiratory function than with age in patients with DMD. We think this correlation is mainly caused by the skeletal muscle strength, which is major determinant of both digestive and respiratory function.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Background: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. Results: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. Conclusions: These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Background: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. Results: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. Conclusions: Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

AbstractFungal contamination of built-in furniture is a frequent problem in Korea when new apartment is built. However, domestic information on the contaminating fungi is very limited. This study was conducted to isolate, identify and characterize the fungi of the problem in one of the apartment houses where the fungi were claimed in the built-in furniture before the house owner moves in. Fungi present in the furniture installed in a main room, dress room, and kitchen side were visually and microscopically confirmed and purely isolated on PDA. The isolated fungi were identified by analyzing the morphological characteristics and nucleotide sequence of the ITS, calmodulin gene, and TEF-1α gene. Aspergillus creber, A. niger, A. pseudoglacus, A. ruber, Cladosporium perangustumand Penicillium communewere identified. Four out of the six fungal species were positive for at least one enzyme in six kinds of extracellular enzyme assays. When these four species (A. creber, A. niger, C. perangustumand P. commune) were inoculated onto four kinds of wood chips of furniture materials, they were able to colonize all of the wood chips. Their settlement was better at 95% humidity condition than at 30% humidity condition. Among the four species, C. perangustumcaused the darkest discoloration and secreted the most number of extracellular enzymes. The four species were re-isolated from the colonized wood chips and confirmed as the problematic fungi in the built-in furniture.

Study design: A single-blind crossover study. Objectives: This study aimed to evaluate neuropathic pain in persons with spinal cord injury (SCI) after the application of transcutaneous spinal direct current stimulation (tsDCS). Setting: Outpatient Clinic of the Rehabilitation Department, Seoul National University Hospital. Methods: The effect of single sessions of both anodal and sham tsDCS (2 mA, 20 min) on chronic neuropathic pain in ten volunteers with complete motor cervical SCI was assessed. The active electrode was placed over the spinal process of the tenth thoracic vertebra and the reference electrode, at the top of the head. Pre- to post-tsDCS intervention changes in pain intensity (numeric rating scale, NRS), patient global assessment, and present pain intensity (PPI) were assessed before and after the tsDCS session (immediately post stimulation, and at 1 and 2 h post stimulation). Results: All participants underwent the stimulation procedure without dropout. Our results showed no significant pre- to post-treatment difference in pain intensity between the active and sham tsDCS groups. Only in the sham tsDCS stimulation, NRS and PPI scores were reduced after the stimulation session. Furthermore, in the mixed effect model analysis, the response in the second period appeared to be more favorable. Conclusion: The results suggest that a single session of anodal tsDCS with the montage used in this study is feasible but does not have a significant analgesic effect in individuals with chronic cervical SCI. Sponsorship: The study was funded by Seoul National University Hospital (No. 0420160470) and Korea Workers’ Compensation & Welfare Service.

The physical characteristics of wireless channels, in particular the channel impulse response (CIR), have become an attractive source of shared secrecy between two communicating parties for many wireless applications. However, ensuring high-entropy secret bits from the CIR may not be always feasible, including in IoT and/or indoor environments, where the coherence time may not be easy to obtain, or mobility is limited. Many techniques have been developed to resolve the above problems, including privacy amplification for higher entropy output, and pre-processing for data distillation. In this paper, we develop a framework for extracting entropy from sequentially arriving channel impulse response observation samples, and propose algorithms for both online and offline versions of the problem. We fully characterize the optimal solutions to these problems through a series of analytic results, and establish the optimality of our proposed online and offline algorithms, namely A_EMSON and A_EMSOFF to solve the problem. We also verify the performance of the algorithms through comparisons with the existing related techniques, and evaluate their capability to ensure high-entropy under different channel models using MATLAB simulations.

Objective.We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc).Methods.We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc.Results.We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death.Conclusion.Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

ABSTRACTIntroduction: Huntington’s disease (HD) is an inherited neurodegenerative disease characterized by chorea, dementia, and depression caused by progressive nerve cell degeneration, which is triggered by expanded CAG repeats in the huntingtin (Htt) gene. Currently, there is no cure for this disease, nor is there an effective medicine available to delay or improve the physical, mental, and behavioral severities caused by it.Areas covered: In this review, the authors describe the use of induced neural stem cells (iNSCs) by direct conversion technology, which offers great advantages as a therapeutic cell type to treat HD.Expert opinion: Cell conversion of somatic cells into a desired stem cell type is one of the most promising treatments for HD because it could be facilitated for the generation of patient-specific neural stem cells. The induced pluripotent stem cells (iPSCs) have a powerful potential for differentiation into neurons, but they may cause teratoma formation due to an undifferentiated pluripotent stem cell after transplantation Therefore, direct conversion of somatic cells into iNSCs is a promising alternative technology in regenerative medicine and the iNSCs may be provided as a therapeutic cell source for Huntington’s disease.

The prevalence of diabetes has become a huge health burden in parts of quality of life and economic cost for overcoming this chronic disease. We followed a bioactivity-guided isolation using α-glucosidase inhibitory assay, four major compounds were isolated, and their structures were elucidated using nuclear magnetic resonance, mass spectrometry, and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry in litchi seed. As a result, the IC50of α-glucosidase inhibitory assay of the crude extract, sugar-removed layer, pavetannin B2, procyanidin A2, and acarbose was 0.691 μg/mL, 3.686 μg/mL, 0.04 μM, 0.08 μM, and 55.845 μg/mL, respectively. With those compounds, we examined the protein tyrosine phosphatase 1B inhibitory activity. And the IC50of pavetannin B2, procyanidin A2, and ursolic acid was 450.295, 338.257, and 19.686 μM, respectively. Contents analysis method for bioactive compounds, which can be used in manufacturing for extract preparations, was established. The findings of this study, litchi seed can be a cost-effective medicinal food in terms of recyclable resources in the litchi food industry and as a natural alternative medicine against type-2 diabetes.

Oral Wound Healing In article 2200527by Eun Ha Choi, Jae Jun Ryu, and co‐workers, nonthermal biocompatible plasma (NBP) stimulates human gingival fibroblast (HGF) cell migration through focal adhesion kinase (FAK) pathway. NBP inhibits colony formation and induces matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration. NBP plays a role in cell motility to regulate AKT and p21 signals in HGF cells, through actin modification of cytoskeleton.

This study hypothesizes that the application of low‐dose nonthermal biocompatible dielectric barrier discharge plasma (DBD‐NBP) to human gingival fibroblasts (HGFs) will inhibit colony formation but not cell death and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration, which can result in enhanced wound healing. HGFs treated with plasma for 3 min migrate to each other across the gap faster than those in the control and 5‐min treatment groups on days 1 and 3. The plasma‐treated HGFs show significantly high expression levels of the cell cycle arrest‐related p21gene and enhanced MMP activity. Focal adhesion kinase (FAK) mediated attenuation of wound healing or actin cytoskeleton rearrangement, and plasma‐mediated reversal of this attenuation support the migratory effect of DBD‐NBP. Further, this work performs computer simulations to investigate the effect of oxidation on the stability and conformation of the catalytic kinase domain (KD) of FAK. It is found that the oxidation of highly reactive amino acids (AAs) Cys427, Met442, Cys559, Met571, Met617, and Met643 changes the conformation and increases the structural flexibility of the FAK protein and thus modulates its function and activity. Low‐dose DBD‐NBP‐induces host cell cycle arrest, ECM breakdown, and subsequent migration, thus contributing to the enhanced wound healing process. Nonthermal biocompatible plasma (NBP) stimulates human gingival fibroblast (HGF) cell migration through focal adhesion kinase (FAK) pathway. NBP would inhibit colony formation and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration. NBP plays a role in cell motility to regulate AKT and p21 signals in HGF cells, through actin modification of cytoskeleton.

AbstractBreeding the button mushroom requires genetic information about its strains. This study was undertaken to genetically characterize four domestically bred button mushroom strains (Saea, Saejung, Saedo, Saeyeon cultivars) and to assess the possibility of using the intergenic spacer 1 (IGS1) region of rDNA as a genetically variable region in the genetic characterization. For the experiment, 34 strains of Agaricus bisporus, two strains of A. bitorquis, and one strain of A. silvaticus, from 17 countries were used. Nucleotide sequence analysis of IGS1 rDNA in these 37 Agaricusstrains confirmed that genetic variations exist, not only among the four domestic strains, but also between the four domestic strains and foreign strains. Crossing two different haploid strains of A. bisporusseems to generate genetic variation in the IGS1 region in their off-spring haploid strains. Phylogenetic analysis based on the IGS1 sequence revealed all A. bisporusstrains could be differentiated from A. silvaticusand A. bitorquisstrains. Five genetic groups were resolved among A. bisporusstrains. Saejung and Saeyeon cultivars formed a separate genetic group. Our results suggest that IGS1 could be complementarily applied in the polymorphism analysis of button mushroom.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions: This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Uric acid acts as both an antioxidant and a pre-oxidant that induces oxidative stress; thus, it plays a paradoxical role in inflammation. However, the effect of gout, a hallmark of hyperuricemia, on osteoporosis remains unclear. Therefore, this study aimed to investigate the association between gout and osteoporosis. This retrospective cohort study used data from the Korean National Health Insurance Service Database. In total, 628,565 participants who were diagnosed with gout and prescribed medications for gout for at least 90 days were selected. The control cohort included patients with no history of gout or use of gout medication. Age and sex 1:1 propensity score matching and Cox proportional hazards models were used to investigate risk factors for osteoporosis. In total, 305,810 patients with gout met the inclusion criteria. Compared with the control group, both men and women with gout showed an increased incidence rate ratio of osteoporosis. In the stratified analysis by age, patients with gout showed an increased incidence rate ratio for osteoporosis in all age groups, except for those over 80 years of age (P< .001). Gout showed an increased hazard ratio of 1.48 (95% CI: 1.45–1.51, P< .001). The female sex has also been identified as a risk factor for osteoporosis. Patients in their 70s had the highest HR. Gout is significantly associated with the risk of osteoporosis. In particular, the results of this study showed that the incidence of osteoporosis increased up to four times in male patients in their 20s with gout compared to without gout.

Several types of hair loss result from the inability of hair follicles to initiate the anagen phase of the hair regeneration cycle. Modulating signaling pathways in the hair follicle niche can stimulate entry into the anagen phase. Despite much effort, stem cell-based or pharmacological therapies to activate the hair follicle niche have not been successful. Here, we set out to test the effect of neural stem cell (NSC) extract on the hair follicle niche for hair regrowth. NSC extracts were applied to the immortalized cell lines HaCaT keratinocytes and dermal papilla cells (DPCs) and the shaven dorsal skin of mice. Treatment with NSC extract dramatically improved the growth of HaCaT keratinocytes and DPCs. In addition, NSC extract enhanced the hair growth of the shaven dorsal skin of mice. In order to determine the molecular signaling pathways regulated by NSCs, we evaluated the expression levels of multiple growth and signaling factors, such as insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and bone morphogenetic protein (BMP) family members. We found that treatment with an NSC extract enhanced hair growth by activating hair follicle niches via coregulation of TGF-β and BMP signaling pathways in the telogen phase. We also observed activation and differentiation of intrafollicular hair follicle stem cells, matrix cells, and extrafollicular DPCs in vivo and in vitro. We tested whether activation of growth factor pathways is a major effect of NSC treatment on hair growth by applying the growth factors to mouse skin. Combined growth factors, including TGF-β, significantly increased the hair shaft length and growth rate. DNA damage and cell death were not observed in skin cells of mice treated with the NSC extract for a prolonged period. Overall, our data demonstrate that NSC extract provides an effective approach for promoting hair growth by directly regulating hair follicle niches through TGF-β and BMP signaling pathways as well as induction of core growth factors.

Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell–derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons. Interestingly, low doses of SHH and RA induced MGE-like progenitors, which expressed low levels of DARPP32 and Nkx2.1 and high levels of Irx3 and Pax6. These cells subsequently generated the majority of the DARPP32-GABAergic neurons after in vitro differentiation. The spinal mESC-NPCs were intrathecally transplanted into the lesion area of the spinal cord around T10–T11 at 21 days after SCI. The engrafted spinal GABAergic neurons remarkably increased both the paw withdrawal threshold (PWT) below the level of the lesion and the vocalization threshold (VT) to the level of the lesion (T12, T11, and T10 vertebrae), which indicates attenuation of chronic neuropathic pain by the spinal GABAergic neurons. The transplanted cells were positive for GABA antibody staining in the injured region, and cells migrated to the injured spinal site and survived for more than 7 weeks in L4–L5. The mESC-NPC-derived spinal GABAergic neurons dramatically attenuated the chronic neuropathic pain following SCI, suggesting that the spinal GABAergic mESC-NPCs cultured with low doses of SHH and RA could be alternative cell sources for treatment of SCI neuropathic pain by stem cell-based therapies.

AbstractBy using a longitudinal data-set from the Korean Labor and Income Panel Study, the present study examines the poverty reduction effectiveness of public income transfers in South Korea from 1998 to 2011. Findings indicate that the average poverty rate fell from over 20% between 1998 and 2000, to 14% from 2001 to 2006, rose to 17% by 2008, and declined to 15% in 2011. However, the poverty-rate reduction effectiveness continuously increased from 5.5% in 1998 to 32.8% in 2011. The poverty-gap reduction effectiveness also improved sixfold from 6.8 to 39.6% over the same period.

The long-term clinical outcome of pediatric intracranial epepdymoma is poor with a high rate of recurrence. One of the main reasons for this poor outcome is the tumor’s inherent resistance to chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is overactive in many human cancers, and inhibition of STAT3 signaling is an emerging area of interest in oncology. In this study, the possibility of STAT3 inhibition as a treatment was investigated in pediatric intracranial ependymoma tissues and cell lines. STAT3 activation status was checked in ependymoma tissues. The responses to conventional chemotherapeutic agents and a STAT3 inhibitor WP1066 in primarily cultured ependymoma cells were measured by cell viability assay. Apoptosis assays were conducted to reveal the cytotoxic mechanism of applied agents. Knockdown of STAT3 was tried to confirm the effects of STAT3 inhibition in ependymoma cells. High levels of phospho-STAT3 (p-STAT3) expression were observed in ependymoma tissue, especially in the anaplastic histology group. There was no cytotoxic effect of cisplatin, ifosfamide, and etoposide. Both brain tumor-initiating cells (BTICs) and bulk tumor cells (BCs) showed considerably decreased viability after WP1066 treatment. However, BTICs had fewer responses than BCs. No additive or synergistic effect was observed for combination therapy of WP1066 and cisplatin. WP1066 effectively abrogated p-STAT3 expression. An increased apoptosis and decreased Survivin expression were observed after WP1066 treatment. Knockdown of STAT3 also decreased cell survival, supporting the critical role of STAT3 in sustaining ependymoma cells. In this study, we observed a cytotoxic effect of STAT3 inhibitor on ependymoma BTICs and BCs. There is urgent need to develop new therapeutic agents for pediatric ependymoma. STAT3 inhibitors may be a new group of drugs for clinical application.